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Sample records for form scar-like perivascular

  1. Hepatic perivascular epithelioid cell tumor

    PubMed Central

    Tang, Da; Wang, Jianmin; Tian, Yuepeng; Li, Qiuguo; Yan, Haixiong; Wang, Biao; Xiong, Li; Li, Qinglong

    2016-01-01

    Abstract Rational: Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm which expresses both myogenic and melanocytic markers. PEComas are found in a variety locations in the body, but up to now only approximately 30 cases about hepatic perivascular epithelioid cell tumor are reported in English language worldwide. Patient concerns: A 32-year-old woman was admitted in our hospital with intermittent right upper quadrant pain for 1 month and recent (1 day) progressive deterioration. Diagnoses: Based on the results of the laboratory examinations and the findings of the computed tomography, the diagnosis of hepatic hamartoma or the hepatocecullar carcinoma with hemorrhage was made. Interventions: The patient underwent a segmentectomy of the liver, and the finally diagnosis of hepatic PEComa was made with immunohistochemical confirmation with HMB-45 and SMA. Outcomes: There is no clinical or radiographic evidence of recurrence 9 months after surgery. Lessons: This kind of tumor is extremely rare and the natural history of PEComa is uncertain, as the treatment protocol for hepatic PEComa has not reached a consensus. But the main treatment of the disease may be surgical resection. Only after long term follow-up can we know whether the tumor is benign or malignant. It appears that longer clinical follow-up is necessary in all patients with hepatic PEComas. PMID:28002331

  2. Perivascular fluid cuffs decrease lung compliance by increasing tissue resistance

    PubMed Central

    Lowe, Kevin; Alvarez, Diego F.; King, Judy A.; Stevens, Troy

    2010-01-01

    Objective Lung inflammation causes perivascular fluid cuffs to form around extra-alveolar blood vessels; however, the physiologic consequences of such cuffs remain poorly understood. Herein, we tested the hypothesis that perivascular fluid cuffs, without concomitant alveolar edema, are sufficient to decrease lung compliance. Design Prospective, randomized, controlled study. Setting Research laboratory. Subjects One hundred twenty male CD40 rats. Interventions To test this hypothesis, the plant alkaloid thapsigargin was used to activate store-operated calcium entry and increase cytosolic calcium in endothelium. Thapsigargin was infused into a central venous catheter of intact, sedated, and mechanically ventilated rats. Measurements Static and dynamic lung mechanics and hemodynamics were measured continuously. Main Results Thapsigargin produced perivascular fluid cuffs along extra-alveolar vessels but did not cause alveolar flooding or blood gas abnormalities. Lung compliance dose-dependently decreased after thapsigargin infusion, attributable to an increase in tissue resistance that was attributed to increased tissue damping and tissue elastance. Airway resistance was not changed. Neither central venous pressure nor left ventricular end diastolic pressure was altered by thapsigargin. Heart rate did not change, although thapsigargin decreased pressure over time sufficient to reduce cardiac output by 50%. Infusion of the type 4 phosphodiesterase inhibitor, rolipram, prevented thapsigargin from inducing perivascular cuffs and decreasing lung compliance. Rolipram also normalized pressure over time and corrected the deficit in cardiac output. Conclusions Our findings resolve for the first time that perivascular cuff formation negatively impacts mechanical coupling between the bronchovascular bundle and the lung parenchyma, decreasing lung compliance without impacting central venous pressure. PMID:20400904

  3. EARLY SENESCENCE1 Encodes a SCAR-LIKE PROTEIN2 That Affects Water Loss in Rice1[OPEN

    PubMed Central

    Rao, Yuchun; Yang, Yaolong; Xu, Jie; Li, Xiaojing; Leng, Yujia; Dai, Liping; Huang, Lichao; Shao, Guosheng; Ren, Deyong; Hu, Jiang; Guo, Longbiao; Pan, Jianwei; Zeng, Dali

    2015-01-01

    The global problem of drought threatens agricultural production and constrains the development of sustainable agricultural practices. In plants, excessive water loss causes drought stress and induces early senescence. In this study, we isolated a rice (Oryza sativa) mutant, designated as early senescence1 (es1), which exhibits early leaf senescence. The es1-1 leaves undergo water loss at the seedling stage (as reflected by whitening of the leaf margin and wilting) and display early senescence at the three-leaf stage. We used map-based cloning to identify ES1, which encodes a SCAR-LIKE PROTEIN2, a component of the suppressor of cAMP receptor/Wiskott-Aldrich syndrome protein family verprolin-homologous complex involved in actin polymerization and function. The es1-1 mutants exhibited significantly higher stomatal density. This resulted in excessive water loss and accelerated water flow in es1-1, also enhancing the water absorption capacity of the roots and the water transport capacity of the stems as well as promoting the in vivo enrichment of metal ions cotransported with water. The expression of ES1 is higher in the leaves and leaf sheaths than in other tissues, consistent with its role in controlling water loss from leaves. GREEN FLUORESCENT PROTEIN-ES1 fusion proteins were ubiquitously distributed in the cytoplasm of plant cells. Collectively, our data suggest that ES1 is important for regulating water loss in rice. PMID:26243619

  4. The perivascular phenotype and behaviors of dedifferentiated cells derived from human mature adipocytes.

    PubMed

    Song, Ning; Kou, Liang; Lu, Xiao-Wen; Sugawara, Atsunori; Shimizu, Yutaka; Wu, Min-Ke; Du, Li; Wang, Hang; Sato, Soh; Shen, Jie-Fei

    2015-02-13

    Derived from mature adipocytes, dedifferentiated fat (DFAT) cells represent a special group of multipotent cells. However, their phenotype and cellular nature remain unclear. Our study found that human DFAT cells adopted perivascular characteristics and behaviors. Flow cytometry and immunofluorescent staining revealed that human DFAT cells positively expressed markers highly related to perivascular cell lineages, such as CD140b, NG2 and desmin, but were negative for common endothelial markers, including CD31, CD34, and CD309. Furthermore, DFAT cells displayed vascular network formation ability in Matrigel, and they noticeably promoted and stabilized the vessel structures formed by human umbilical vascular endothelial cells (HUVECs) in vitro. These results provide novel evidence on the pericyte nature of human DFAT cells, further supporting the recent model for the perivascular origin of adult stem cells, in which tissue-specific progenitor cells in mesenchymal tissues associate with blood vessels, exhibiting perivascular characteristics and functions.

  5. Changes in the population of perivascular cells in the bone tissue remodeling zones under microgravity

    NASA Astrophysics Data System (ADS)

    Katkova, Olena; Rodionova, Natalia; Shevel, Ivan

    2016-07-01

    Microgravity and long-term hypokinesia induce reduction both in bone mass and mineral saturation, which can lead to the development of osteoporosis and osteopenia. (Oganov, 2003). Reorganizations and adaptive remodeling processes in the skeleton bones occur in the topographical interconnection with blood capillaries and perivascular cells. Radioautographic studies with 3H- thymidine (Kimmel, Fee, 1980; Rodionova, 1989, 2006) have shown that in osteogenesis zones there is sequential differentiation process of the perivascular cells into osteogenic. Hence the study of populations of perivascular stromal cells in areas of destructive changes is actual. Perivascular cells from metaphysis of the rat femoral bones under conditions of modeling microgravity were studied using electron microscopy and cytochemistry (hindlimb unloading, 28 days duration) and biosatellite «Bion-M1» (duration of flight from April 19 till May 19, 2013 on C57, black mice). It was revealed that both control and test groups populations of the perivascular cells are not homogeneous in remodeling adaptive zones. These populations comprise of adjacent to endothelium poorly differentiated forms and isolated cells with signs of differentiation (specific increased volume of rough endoplasmic reticulum in cytoplasm). Majority of the perivascular cells in the control group (modeling microgravity) reveals reaction to alkaline phosphatase (marker of the osteogenic differentiation). In poorly differentiated cells this reaction is registered in nucleolus, nucleous and cytoplasm. In differentiating cells activity of the alkaline phosphatase is also detected on the outer surface of the cellular membrane. Unlike the control group in the bones of experimental animals reaction to the alkaline phosphatase is registered not in all cells of perivascular population. Part of the differentiating perivascular cells does not contain a product of the reaction. Under microgravity some poorly differentiated perivascular

  6. Pericyte Antigens in Perivascular Soft Tissue Tumors

    PubMed Central

    Shen, Jia; Shrestha, Swati; Yen, Yu-Hsin; Asatrian, Greg; Mravic, Marco; Soo, Chia; Ting, Kang; Dry, Sarah M.; Peault, Bruno; James, Aaron W.

    2015-01-01

    Introduction Perivascular soft tissue tumors are relatively uncommon neoplasms of unclear line of differentiation, although most are presumed to originate from pericytes or modified perivascular cells. Among these, glomus tumor, myopericytoma, and angioleiomyoma share a spectrum of histologic findings and a perivascular growth pattern. In contrast, solitary fibrous tumor (previously termed hemangiopericytoma) was once hypothesized to have pericytic differentiation. Methods Here, we systematically examine pericyte immunohistochemical markers among glomus tumor (including malignant glomus tumor), myopericytoma, angioleiomyoma, and solitary fibrous tumor. Immunohistochemical staining and semiquantification was performed using well-defined pericyte antigens, including αSMA, CD146, and PDGFRβ. Results Glomus tumor and myopericytoma demonstrate diffuse staining for all pericyte markers, including immunohistochemical reactivity for αSMA, CD146, and PDGFRβ. Malignant glomus tumors all showed some degree of pericyte marker immunoreactivity, although it was significantly reduced. Angioleiomyoma shared a similar αSMA + CD146 + PDGFRβ+ immunophenotype; however, this was predominantly seen in the areas of perivascular tumor growth. Solitary fibrous tumors showed patchy PDGFRβ immunoreactivity only. Discussion In summary, pericyte marker expression is a ubiquitous finding in glomus tumor, myopericytoma, and angioleiomyoma. Malignant glomus tumor shows a comparative reduction in pericyte marker expression, which may represent partial loss of pericytic differentiation. Pericyte markers are essentially not seen in solitary fibrous tumor. The combination of αSMA, CD146, and PDGFRβ immunohistochemical stainings may be of utility for the evaluation of pericytic differentiation in soft tissue tumors. PMID:26085647

  7. Differentiation potentials of perivascular cells in the bone tissue remodeling zones under microgravity

    NASA Astrophysics Data System (ADS)

    Rodionova, Natalia; Katkova, Olena

    Adaptive remodeling processes in the skeleton bones occur in the close topographical interconnection with blood capillaries followed by perivascular cells. Radioautographic studies with 3Н- thymidine (Kimmel D.B., Fee W.S., 1980; Rodionova N.V., 1989, 2006) has shown that in osteogenesis zones there is sequential differentiation process of the perivascular cells into osteogenic ones. Using electron microscopy and cytochemistry we studied perivsacular cells in metaphysis of the rats femoral bones under conditions of modeling microgravity (28 days duration) and in femoral bonеs metaphyses of rats flown on board of the space laboratory (Spacelab - 2) It was revealed that population of the perivascular cells is not homogeneous in adaptive zones of the remodeling in both control and test groups (lowering support loading). This population comprises adjacent to endothelium little differentiated forms and isolated cells with differentiation features (specific volume of rough endoplasmic reticulum in cytoplasm is increased). Majority of the perivascular cells in the control group reveals reaction to alkaline phosphatase (marker of the osteogenic differentiation). In little differentiated cells this reaction is registered in nucleolus, nucleous and cytoplasm. In differentiating cells activity of the alkaline phosphatase is also detected on the outer surface of the cellular membrane. Unlike the control group in the bones of animals under microgravitaty reaction to the alkaline phosphatase is registered not for all cells of perivascular population. Part of the differentiating perivascular cells does not contain a product of the reaction. There is also visible trend of individual alkaline phosphatase containing perivascular cells amounts decrease (i.e. osteogenic cells-precursors). Under microgravity some little differentiated perivascular cells reveal destruction signs. Found decrease trend of the alkaline phosphatase containing cells (i.e. osteogenic cells) number in

  8. Spontaneous Regression and Recurrence of a Tumefactive Perivascular Space

    PubMed Central

    Muttikkal, Thomas Jose Eluvathingal; Raghavan, Prashant

    2014-01-01

    Summary Perivascular spaces can occasionally appear mass-like (tumefactive or giant perivascular space), and can be associated with clinical symptoms. Spontaneous regression of a tumefactive perivascular space is a very rare phenomenon with only two reported cases in the English medical literature. Spontaneous regression of a tumefactive perivascular space along with resolution of clinical symptoms, followed by spontaneous recurrence associated with symptom recurrence is an extremely rare occurrence, which to the best of our knowledge, has not been reported in the medical literature. We describe a case of spontaneous regression of a tumefactive perivascular space, three years after its initial detection, followed by spontaneous recurrence after two years. PMID:24750709

  9. Fluid mechanics in the perivascular space.

    PubMed

    Wang, Peng; Olbricht, William L

    2011-04-07

    Perivascular space (PVS) within the brain is an important pathway for interstitial fluid (ISF) and solute transport. Fluid flowing in the PVS can affect these transport processes and has significant impacts on physiology. In this paper, we carry out a theoretical analysis to investigate the fluid mechanics in the PVS. With certain assumptions and approximations, we are able to find an analytical solution to the problem. We discuss the physical meanings of the solution and particularly examine the consequences of the induced fluid flow in the context of convection-enhanced delivery (CED). We conclude that peristaltic motions of the blood vessel walls can facilitate fluid and solute transport in the PVS.

  10. How do culture media influence in vitro perivascular cell behavior?

    PubMed

    Huber, Birgit; Volz, Ann-Cathrin; Kluger, Petra Juliane

    2015-12-01

    Perivascular cells are multilineage cells located around the vessel wall and important for wall stabilization. In this study, we evaluated a stem cell media and a perivascular cell-specific media for the culture of primary perivascular cells regarding their cell morphology, doubling time, stem cell properties, and expression of cell type-specific markers. When the two cell culture media were compared to each other, perivascular cells cultured in the stem cell medium had a more elongated morphology and a faster doubling rate and cells cultured in the pericyte medium had a more typical morphology, with several filopodia, and a slower doubling rate. To evaluate stem cell properties, perivascular cells, CD146(-) cells, and mesenchymal stem cells (MSCs) were differentiated into the adipogenic, osteogenic, and chondrogenic lineages. It was seen that perivascular cells, as well as CD146(-) cells and MSCs, cultured in stem cell medium showed greater differentiation than cells cultured in pericyte-specific medium. The expression of pericyte-specific markers CD146, neural/glial antigen 2 (NG2), platelet-derived growth factor receptor-β (PDGFR-β), myosin, and α-smooth muscle actin (α-SMA) could be found in both pericyte cultures, as well as to varying amounts in CD146(-) cells, MSCs, and endothelial cells. The here presented work shows that perivascular cells can adapt to their in vitro environment and cell culture conditions influence cell functionality, such as doubling rate or differentiation behavior. Pericyte-specific markers were shown to be expressed also from cells other than perivascular cells. We can further conclude that CD146(+) perivascular cells are inhomogeneous cell population probably containing stem cell subpopulations, which are located perivascular around capillaries.

  11. Constitutively active Notch1 converts cranial neural crest-derived frontonasal mesenchyme to perivascular cells in vivo

    PubMed Central

    Miller, Sophie R.; Perera, Surangi N.; Baker, Clare V. H.

    2017-01-01

    ABSTRACT Perivascular/mural cells originate from either the mesoderm or the cranial neural crest. Regardless of their origin, Notch signalling is necessary for their formation. Furthermore, in both chicken and mouse, constitutive Notch1 activation (via expression of the Notch1 intracellular domain) is sufficient in vivo to convert trunk mesoderm-derived somite cells to perivascular cells, at the expense of skeletal muscle. In experiments originally designed to investigate the effect of premature Notch1 activation on the development of neural crest-derived olfactory ensheathing glial cells (OECs), we used in ovo electroporation to insert a tetracycline-inducible NotchΔE construct (encoding a constitutively active mutant of mouse Notch1) into the genome of chicken cranial neural crest cell precursors, and activated NotchΔE expression by doxycycline injection at embryonic day 4. NotchΔE-targeted cells formed perivascular cells within the frontonasal mesenchyme, and expressed a perivascular marker on the olfactory nerve. Hence, constitutively activating Notch1 is sufficient in vivo to drive not only somite cells, but also neural crest-derived frontonasal mesenchyme and perhaps developing OECs, to a perivascular cell fate. These results also highlight the plasticity of neural crest-derived mesenchyme and glia. PMID:28183698

  12. Perivascular macrophages mediate neutrophil recruitment during bacterial skin infection

    PubMed Central

    Abtin, Arby; Jain, Rohit; Mitchell, Andrew J.; Roediger, Ben; Brzoska, Anthony J.; Tikoo, Shweta; Cheng, Qiang; Ng, Lai Guan; Cavanagh, Lois L.; von Andrian, Ulrich H.; Hickey, Michael J.; Firth, Neville; Weninger, Wolfgang

    2014-01-01

    Transendothelial migration of neutrophils in post-capillary venules is a key event in the inflammatory response against pathogens and tissue damage. The precise regulation of this process is incompletely understood. We report that perivascular macrophages are critical for neutrophil migration into skin infected with the pathogen Staphylococcus aureus. Using multiphoton intravital microscopy we show that neutrophils extravasate from inflamed dermal venules in close proximity to perivascular macrophages, which are a major source of neutrophil chemoattractants. The virulence factor alpha-hemolysin lyses perivascular macrophages leading to decreased neutrophil transmigration. Our data illustrate a previously unrecognized role for perivascular macrophages in neutrophil recruitment to inflamed skin, and indicate that Staphylococcus aureus uses hemolysin-dependent killing of these cells as an immune evasion strategy. PMID:24270515

  13. The pericyte antigen RGS5 in perivascular soft tissue tumors.

    PubMed

    Shen, Jia; Shrestha, Swati; Yen, Yu-Hsin; Scott, Michelle A; Soo, Chia; Ting, Kang; Peault, Bruno; Dry, Sarah M; James, Aaron W

    2016-01-01

    Perivascular soft tissue tumors are relatively uncommon neoplasms of unclear lineage of differentiation, although most are presumed to originate from or differentiate to pericytes or a modified perivascular cell. Among these, glomus tumor, myopericytoma, and angioleiomyoma share a spectrum of histologic findings and a perivascular growth pattern. In contrast, solitary fibrous tumor was once hypothesized to have pericytic differentiation--although little bona fide evidence of pericytic differentiation exists. Likewise the perivascular epithelioid cell tumor (PEComa) family shares a perivascular growth pattern, but with distinctive dual myoid-melanocytic differentiation. RGS5, regulator of G-protein signaling 5, is a novel pericyte antigen with increasing use in animal models. Here, we describe the immunohistochemical expression patterns of RGS5 across perivascular soft tissue tumors, including glomus tumor (n = 6), malignant glomus tumor (n = 4), myopericytoma (n = 3), angioleiomyoma (n = 9), myofibroma (n = 4), solitary fibrous tumor (n = 10), and PEComa (n = 19). Immunohistochemical staining and semi-quantification was performed, and compared to αSMA (smooth muscle actin) expression. Results showed that glomus tumor (including malignant glomus tumor), myopericytoma, and angioleiomyoma shared a similar diffuse immunoreactivity for RGS5 and αSMA across all tumors examined. In contrast, myofibroma, solitary fibrous tumor and PEComa showed predominantly focal to absent RGS5 immunoreactivity. These findings further support a common pericytic lineage of differentiation in glomus tumors, myopericytoma and angioleiomyoma. The pericyte marker RGS5 may be of future clinical utility for the evaluation of pericytic differentiation in soft tissue tumors.

  14. Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation

    PubMed Central

    Davalos, Dimitrios; Kyu Ryu, Jae; Merlini, Mario; Baeten, Kim M.; Le Moan, Natacha; Petersen, Mark A.; Deerinck, Thomas J.; Smirnoff, Dimitri S.; Bedard, Catherine; Hakozaki, Hiroyuki; Gonias Murray, Sara; Ling, Jennie B.; Lassmann, Hans; Degen, Jay L.; Ellisman, Mark H.; Akassoglou, Katerina

    2012-01-01

    Blood-brain barrier disruption, microglial activation and neurodegeneration are hallmarks of multiple sclerosis. However, the initial triggers that activate innate immune responses and their role in axonal damage remain unknown. Here we show that the blood protein fibrinogen induces rapid microglial responses toward the vasculature and is required for axonal damage in neuroinflammation. Using in vivo two-photon microscopy, we demonstrate that microglia form perivascular clusters before myelin loss or paralysis onset and that, of the plasma proteins, fibrinogen specifically induces rapid and sustained microglial responses in vivo. Fibrinogen leakage correlates with areas of axonal damage and induces reactive oxygen species release in microglia. Blocking fibrin formation with anticoagulant treatment or genetically eliminating the fibrinogen binding motif recognized by the microglial integrin receptor CD11b/CD18 inhibits perivascular microglial clustering and axonal damage. Thus, early and progressive perivascular microglial clustering triggered by fibrinogen leakage upon blood-brain barrier disruption contributes to axonal damage in neuroinflammatory disease. PMID:23187627

  15. Mechanisms of Glioma Formation: Iterative Perivascular Glioma Growth and Invasion Leads to Tumor Progression, VEGF-Independent Vascularization, and Resistance to Antiangiogenic Therapy12

    PubMed Central

    Baker, Gregory J.; Yadav, Viveka Nand; Motsch, Sebastien; Koschmann, Carl; Calinescu, Anda-Alexandra; Mineharu, Yohei; Camelo-Piragua, Sandra Ines; Orringer, Daniel; Bannykh, Serguei; Nichols, Wesley S.; deCarvalho, Ana C.; Mikkelsen, Tom; Castro, Maria G.; Lowenstein, Pedro R.

    2014-01-01

    As glioma cells infiltrate the brain they become associated with various microanatomic brain structures such as blood vessels, white matter tracts, and brain parenchyma. How these distinct invasion patterns coordinate tumor growth and influence clinical outcomes remain poorly understood. We have investigated how perivascular growth affects glioma growth patterning and response to antiangiogenic therapy within the highly vascularized brain. Orthotopically implanted rodent and human glioma cells are shown to commonly invade and proliferate within brain perivascular space. This form of brain tumor growth and invasion is also shown to characterize de novo generated endogenous mouse brain tumors, biopsies of primary human glioblastoma (GBM), and peripheral cancer metastasis to the human brain. Perivascularly invading brain tumors become vascularized by normal brain microvessels as individual glioma cells use perivascular space as a conduit for tumor invasion. Agent-based computational modeling recapitulated biological perivascular glioma growth without the need for neoangiogenesis. We tested the requirement for neoangiogenesis in perivascular glioma by treating animals with angiogenesis inhibitors bevacizumab and DC101. These inhibitors induced the expected vessel normalization, yet failed to reduce tumor growth or improve survival of mice bearing orthotopic or endogenous gliomas while exacerbating brain tumor invasion. Our results provide compelling experimental evidence in support of the recently described failure of clinically used antiangiogenics to extend the overall survival of human GBM patients. PMID:25117977

  16. Perivascular medical devices and drug delivery systems: Making the right choices.

    PubMed

    Mylonaki, Ioanna; Allémann, Éric; Saucy, François; Haefliger, Jacques-Antoine; Delie, Florence; Jordan, Olivier

    2017-02-28

    Perivascular medical devices and perivascular drug delivery systems are conceived for local application around a blood vessel during open vascular surgery. These systems provide mechanical support and/or pharmacological activity for the prevention of intimal hyperplasia following vessel injury. Despite abundant reports in the literature and numerous clinical trials, no efficient perivascular treatment is available. In this review, the existing perivascular medical devices and perivascular drug delivery systems, such as polymeric gels, meshes, sheaths, wraps, matrices, and metal meshes, are jointly evaluated. The key criteria for the design of an ideal perivascular system are identified. Perivascular treatments should have mechanical specifications that ensure system localization, prolonged retention and adequate vascular constriction. From the data gathered, it appears that a drug is necessary to increase the efficacy of these systems. As such, the release kinetics of pharmacological agents should match the development of the pathology. A successful perivascular system must combine these optimized pharmacological and mechanical properties to be efficient.

  17. Perivascular Arrest of CD8+ T Cells Is a Signature of Experimental Cerebral Malaria

    PubMed Central

    Strangward, Patrick; Dandamudi, Durga B.; Coles, Jonathan A.; Villegas-Mendez, Ana; Gallego-Delgado, Julio; van Rooijen, Nico; Zindy, Egor; Rodriguez, Ana; Brewer, James M.; Couper, Kevin N.; Dustin, Michael L.

    2015-01-01

    There is significant evidence that brain-infiltrating CD8+ T cells play a central role in the development of experimental cerebral malaria (ECM) during Plasmodium berghei ANKA infection of C57BL/6 mice. However, the mechanisms through which they mediate their pathogenic activity during malaria infection remain poorly understood. Utilizing intravital two-photon microscopy combined with detailed ex vivo flow cytometric analysis, we show that brain-infiltrating T cells accumulate within the perivascular spaces of brains of mice infected with both ECM-inducing (P. berghei ANKA) and non-inducing (P. berghei NK65) infections. However, perivascular T cells displayed an arrested behavior specifically during P. berghei ANKA infection, despite the brain-accumulating CD8+ T cells exhibiting comparable activation phenotypes during both infections. We observed T cells forming long-term cognate interactions with CX3CR1-bearing antigen presenting cells within the brains during P. berghei ANKA infection, but abrogation of this interaction by targeted depletion of the APC cells failed to prevent ECM development. Pathogenic CD8+ T cells were found to colocalize with rare apoptotic cells expressing CD31, a marker of endothelial cells, within the brain during ECM. However, cellular apoptosis was a rare event and did not result in loss of cerebral vasculature or correspond with the extensive disruption to its integrity observed during ECM. In summary, our data show that the arrest of T cells in the perivascular compartments of the brain is a unique signature of ECM-inducing malaria infection and implies an important role for this event in the development of the ECM-syndrome. PMID:26562533

  18. Perivascular graft heparin delivery using biodegradable polymer wraps.

    PubMed

    Edelman, E R; Nathan, A; Katada, M; Gates, J; Karnovsky, M J

    2000-11-01

    Heparin remains the gold-standard inhibitor of the processes involved in the vascular response to injury. Though this compound has profound and wide-reaching effects on vascular cells in culture and animal models, its clinical utility has been questionable at best. It is clear that the mode of heparin delivery is critical to its potential and it may well be that routine forms of administration are insufficient to observe benefit given the heparin's short half-life and complex pharmacokinetics. When ingested orally, heparin is degraded to inactive oligomer fragments while systemic administration is complicated by the need for continuous infusion and the potential for uncontrolled hemorrhage. Thus alternative heparin delivery systems have been proposed to maximize regional effects while limiting systemic toxicity. Yet, as heparin is such a potent antithrombotic compound and since existing local delivery systems lack the ability to precisely regulate release kinetics, even site-specific therapy is prone to bleeding. We now describe the design and development of a novel biodegradable system for the perivascular delivery of heparin to the blood vessel wall with well-defined release kinetics. This system consists of heparin-encapsulated poly(DL lactide-co-glycolide) (pLGA) microspheres sequestered in an alginate gel. Controlled release of heparin from this heterogeneous system could be obtained over a period of 25 days in vitro. The experimental variables affecting heparin release from these matrices were investigated. Gel permeation chromatography (GPC) and scanning electron microscopy (SEM) were used to monitor the degradation process and found to correlate well with the release kinetics. Heparin-releasing gels inhibited growth of bovine vascular smooth muscle cells in tissue culture in a dose-dependent manner. Moreover, gel release controlled vascular injury in denuding and interposition vascular graft animal models of disease even when uncontrolled bleeding was

  19. The perivascular environment along the vertebral artery governs segment-specific structural and mechanical properties.

    PubMed

    Zhou, Boran; Alshareef, Mohammed; Prim, David; Collins, Michael; Kempner, Michael; Hartstone-Rose, Adam; Eberth, John F; Rachev, Alexander; Shazly, Tarek

    2016-11-01

    The vertebral arteries (VAs) are anatomically divided into four segments (V1-V4), which cumulatively transport blood flow through neck and ultimately form the posterior circulation of the brain. The vital physiological function of these conduit vessels depends on their geometry, composition and mechanical properties, all of which may vary among the defined arterial segments. Despite their significant role in blood circulation and susceptibility to injury, few studies have focused on characterizing the mechanical properties of VAs, and none have investigated the potential for segmental variation that could arise due to distinct perivascular environments. In this study, we compare the passive mechanical response of the central, juxtaposed arterial segments of porcine VAs (V2 and V3) via inflation-extension mechanical testing. Obtained experimental data and histological measures of arterial wall composition were used to adjust parameters of structure-motivated constitutive models that quantify the passive mechanical properties of each arterial segment and enable prediction of wall stress distributions under physiologic loads and boundary conditions. Our findings reveal significant segmental differences in the arterial wall geometry and structure. Nevertheless, similar wall stress distributions are predicted in these neighboring arterial segments if calculations account for their specific perivascular environments. These findings allow speculation that segmental differences in wall structure and geometry are a consequence of a previously introduced principle of optimal operation of arteries, which ensures effective bearing of physiological load and a favorable mechanical environment for mechanosensitive vascular smooth muscle cells.

  20. Perivascular Enhancement in a Patient with Neuromyelitis Optica Spectrum Disease during an Optic Neuritis Attack.

    PubMed

    Pekcevik, Yeliz; Izbudak, Izlem

    2015-01-01

    We present a case with neuromyelitis optica spectrum disease (NMOSD) who had perivascular enhancement during an optic neuritis attack. Cloud-like enhancement, pencil-thin enhancement, and leptomeningeal enhancement have been defined as specific enhancement patterns to neuromyelitis optica (NMO). Perivascular enhancement has not been described before in NMO/NMOSD. This finding suggests that perivascular enhancement may also be seen in NMO/NMOSD patients.

  1. Disproportionate subarachnoid space hydrocephalus—outcome and perivascular space

    PubMed Central

    Akiguchi, Ichiro; Shirakashi, Yoshitomo; Budka, Herbert; Watanabe, Yuko; Watanabe, Toshiyuki; Shiino, Akihiko; Ogita, Mihoko; Kawamoto, Yasuhiro; Jungwirth, Susanne; Krampla, Wolfgang; Fischer, Peter

    2014-01-01

    Objective We sought to identify the prevalence of MRI features of disproportionately enlarged subarachnoid space hydrocephalus in possible idiopathic normal pressure hydrocephalus (DESH-iNPH) and to describe the clinico-radiological features and outcomes of a community-based investigation (The Vienna Trans-Danube Aging study). Methods Of the 697 inhabitants (all 75 years old), 503 completed extensive neurological examinations at baseline and were followed up every 30 months thereafter with MRIs, mini-mental state examination (MMSE), and the Unified Parkinson Disease Rating Scale-Motor Section (UPDRSM). The DESH-iNPH participant data were compared with the data from participants with Evans index ratios >0.3 (ex vacuo hydrocephalus), cerebral small-vessel diseases, and normal MRIs. The widening of perivascular space was also evaluated by MRI in these groups. Results Eight participants with DESH-iNPH (1.6%) and 76 with ex vacuo hydrocephalus (16.1%) at baseline were identified. The mean MMSE in DESH-iNPH, ex vacuo hydrocephalus, and normal MRIs was 26.4, 27.9, and 28.3, respectively, and the mean UPDRSM was 9.75, 2.96, and 1.87, respectively. After a 90-month follow-up, the mortality rates for DESH-iNPH, ex vacuo hydrocephalus, and normal MRIs were 25.0%, 21.3%, and 10.9%, respectively. The perivascular-space widening scores were significantly smaller in the DESH-iNPH cases, particularly at the centrum semiovale, compared to cerebral small-vessel disease and ex vacuo hydrocephalus cases. Interpretation The prevalence of DESH-iNPH was 1.6% for participants aged 75 years and revealed significantly lower MMSE and higher UPDRSM scores compared to the ex vacuo hydrocephalus and controls. Moreover, it is suggested that perivascular-space narrowing is a morphological and pathophysiological marker of DESH-iNPH. PMID:25356428

  2. A systematic review: perivascular epithelioid cell tumor of gastrointestinal tract

    PubMed Central

    Chen, Zehong; Han, Siqi; Wu, Jialin; Xiong, Minmin; Huang, Yanqiao; Chen, Jianhui; Yuan, Yujie; Peng, Jianjun; Song, Wu

    2016-01-01

    Abstract Perivascular epithelioid cell tumor (PEComa) is a rare entity with distinctive morphology and of expressing myomelanocytic markers. Gastrointestinal tract (GI) is one of the most common anatomic sites of origin and counts for 20% to 25% of all reported cases of perivascular epithelioid cell tumors not otherwise specified (PEComas-NOS). However, the biologic behavior of perivascular epithelioid cell tumors of gastrointestinal tract (GI PEComas-NOS) is still unclear. The aim of conducting this systematic review is to sum up what is known so far of the epidemiology, natural history, management and prognosis of GI PEComas-NOS. A systematic research was performed on PubMed and EMBASE using the following terms: (“perivascular epithelioid cell tumor” or “PEComa”) and (“gastrointestinal tract” or “GI” or “oral ” or “mouth” or “esophagus” or “gullet” or “gastric” or “stomach” or “duodenum” or “jejunum” or “ileum” or “cecum” or “colon” or “colorectal” or “sigmoid” or “rectum” or “anus” or “mesentery”) up to December 1, 2015. Retrieved GI PEComas-NOS publications, which included these terms, contains case reports, case series to case characteristic researches. A total of 168 articles were reviewed, 41 GI PEComa-NOS English studies among which were retrieved for analysis. We reviewed epidemiology, natural history, management and prognosis of GI PEComa-NOS. Generally GI PEComa-NOS is believed to have women predomination. The most frequently involved location is colon with non-specific clinical signs. Pathologically, GI PEComas-NOS shows epithelioid predominance (70%), meanwhile coexpresses melanocytic and muscle markers characteristically, while immunohistochemistry is a useful tool for identify, which indicates that HMB-45 is regarded as the most sensitive reagent. Complete resection served as mainstay of treatment, while chemotherapy should be unanimously considered to apply in malignant

  3. Ang-2 but not Ang-1 expression in perivascular soft tissue tumors.

    PubMed

    Shrestha, Swati; Shen, Jia; Giacomelli, Paulina; Scott, Michelle A; Soo, Chia; Ting, Kang; Péault, Bruno; Dry, Sarah M; James, Aaron W

    2017-03-01

    Perivascular soft tissue tumors are relatively uncommon neoplasms of unclear line of differentiation, although most are presumed to originate from pericytes. Previously, we reported a shared immunophenotype across these related tumor types. Here, we extend these findings to examine the expression of the pericyte markers angiopoietin-1 and -2 (Ang-1 and -2) among perivascular soft tissue tumors. Results showed consistent Ang-2 but not Ang-1 expression across tumor types. In summary, the absence of Ang-1 expression distinguishes perivascular from vascular soft tissue tumors. Ang-2 expression is present across perivascular soft tissue tumors, with some variation between histologic subtypes.

  4. Perivascular Stem Cells at the Tip of Mouse Incisors Regulate Tissue Regeneration.

    PubMed

    Pang, Yvonne Wy; Feng, Jifan; Daltoe, Felipe; Fatscher, Robert; Gentleman, Eileen; Gentleman, Molly M; Sharpe, Paul T

    2016-03-01

    Cells with in vitro properties similar to those of bone marrow stromal stem cells are present in tooth pulp as quiescent cells that are mobilized by damage. These dental pulp stem cells (DPSCs) respond to damage by stimulating proliferation and differentiation into odontoblast-like cells that form dentine to repair the damage. In continuously growing mouse incisors, tissue at the incisor tips is continuously being damaged by the shearing action between the upper and lower teeth acting to self-sharpen the tips. We investigated mouse incisor tips as a model for the role of DPSCs in a continuous natural repair/regeneration process. We show that the pulp at the incisor tip is composed of a disorganized mass of mineralized tissue produced by odontoblast-like cells. These cells become embedded into the mineralized tissue that is rapidly formed and then lost during feeding. Tetracycline labeling not only revealed the expected incorporation into newly synthesized dentine formation of the incisor but also a zone covering the pulp cavity at the tips of the incisors that is mineralized very rapidly. This tissue was dentine-like but had a significantly lower mineral content than dentine as determined by Raman spectroscopy. The mineral was more crystalline than dentine, indicative of small, defect-free mineral particles. To identify the origin of cells responsible for deposition of this mineralized tissue, we genetically labeled perivascular cells by crossing NG2(ERT2) Cre and Nestin Cre mice with reporter mice. A large number of pericyte-derived cells were visible in the pulp of incisor tips with some having elongated, odontoblast-like shapes. These results show that in mouse incisors, rapid, continuous mineralization occurs at the tip to seal off the pulp tissue from the external environment. The mineral is formed by perivascular-derived cells that differentiate into cells expressing dentin sialo-phosphoprotein (DSPP) and produce a dentine-like material in a process that

  5. Follicular Dendritic Cells Emerge from Ubiquitous Perivascular Precursors

    PubMed Central

    Krautler, Nike Julia; Kana, Veronika; Kranich, Jan; Tian, Yinghua; Perera, Dushan; Lemm, Doreen; Schwarz, Petra; Armulik, Annika; Browning, Jeffrey L.; Tallquist, Michelle; Buch, Thorsten; Oliveira-Martins, José B.; Zhu, Caihong; Hermann, Mario; Wagner, Ulrich; Brink, Robert; Heikenwalder, Mathias; Aguzzi, Adriano

    2013-01-01

    Summary The differentiation of follicular dendritic cells (FDC) is essential to the remarkable microanatomic plasticity of lymphoid follicles. Here we show that FDC arise from ubiquitous perivascular precursors (preFDC) expressing platelet-derived growth factor receptor β (PDGFRβ). PDGFRβ-Cre-driven reporter gene recombination resulted in FDC labeling, whereas conditional ablation of PDGFRβ+-derived cells abolished FDC, indicating that FDC originate from PDGFRβ+ cells. Lymphotoxin-α-overexpressing prion protein (PrP)+ kidneys developed PrP+ FDC after transplantation into PrP mice, confirming that preFDC exist outside lymphoid organs. Adipose tissue-derived PDGFRβ+ stromal-vascular cells responded to FDC maturation factors and, when transplanted into lymphotoxin β receptor (LTβR) kidney capsules, differentiated into Mfge8+CD21/35+ FcγRIIβ+PrP+ FDC capable of trapping immune complexes and recruiting B cells. Spleens of lymphocyte-deficient mice contained perivascular PDGFRβ+ FDC precursors whose expansion required both lymphoid tissue inducer (LTi) cells and lymphotoxin. The ubiquity of preFDC and their strategic location at blood vessels may explain the de novo generation of organized lymphoid tissue at sites of lymphocytic inflammation. PMID:22770220

  6. Intrastriatal convection-enhanced delivery results in widespread perivascular distribution in a pre-clinical model

    PubMed Central

    2012-01-01

    Background Convection-enhanced delivery (CED), a direct method for drug delivery to the brain through intraparenchymal microcatheters, is a promising strategy for intracerebral pharmacological therapy. By establishing a pressure gradient at the tip of the catheter, drugs can be delivered in uniform concentration throughout a large volume of interstitial fluid. However, the variables affecting perivascular distribution of drugs delivered by CED are not fully understood. The aim of this study was to determine whether the perivascular distribution of solutes delivered by CED into the striatum of rats is affected by the molecular weight of the infused agent, by co-infusion of vasodilator, alteration of infusion rates or use of a ramping regime. We also wanted to make a preliminary comparison of the distribution of solutes with that of nanoparticles. Methods We analysed the perivascular distribution of 4, 10, 20, 70, 150 kDa fluorescein-labelled dextran and fluorescent nanoparticles at 10 min and 3 h following CED into rat striatum. We investigated the effect of local vasodilatation, slow infusion rates and ramping on the perivascular distribution of solutes. Co-localisation with perivascular basement membranes and vascular endothelial cells was identified by immunohistochemistry. The uptake of infusates by perivascular macrophages was quantified using stereological methods. Results Widespread perivascular distribution and macrophage uptake of fluorescein-labelled dextran was visible 10 min after cessation of CED irrespective of molecular weight. However, a significantly higher proportion of perivascular macrophages had taken up 4, 10 and 20 kDa fluorescein-labelled dextran than 150 kDa dextran (p < 0.05, ANOVA). Co-infusion with vasodilator, slow infusion rates and use of a ramping regime did not alter the perivascular distribution. CED of fluorescent nanoparticles indicated that particles co-localise with perivascular basement membranes throughout the striatum but

  7. Cat-scratch disease: unusual perivascular chorioretinal lesions.

    PubMed

    Sahin, Ozlem

    2014-01-01

    This study is a case report of bilateral perivascular chorioretinal lesions associated with Bartonella henselae. A 37-year-old woman presented with headache and blurred vision in both eyes aggravating occasionally during five years. She was otherwise healthy, with best-corrected visual acuities were 20/20 in both eyes. History of close contact with cats was more than merely eye-catching upon examination of her fundus. In both eyes, fundi were coated with yellow-brown pigmented perivenous chorioretinal lesions along the superotemporal and inferotemporal vascular arcades and their branches. The perivenous lesions were associated with vascular fibrous bands and corresponding changes in vascular calibers. There were no associated intraocular inflammatory signs in both eyes. The serologic tests confirmed the diagnosis of cat-scratch disease. The patient received no treatment, and she was followed for three years without any signs of ocular inflammation.

  8. Circulating perivascular progenitors: a target of PDGFR inhibition.

    PubMed

    Mancuso, Patrizia; Martin-Padura, Ines; Calleri, Angelica; Marighetti, Paola; Quarna, Jessica; Rabascio, Cristina; Braidotti, Paola; Bertolini, Francesco

    2011-09-15

    Cancer blood vessels consist of two interacting types of cells: inner lining endothelial cells (ECs) and surrounding perivascular cells (pericytes, vascular smooth muscle cells or mural cells). PDGFRbeta(CD140b)+ progenitor perivascular cells (PPC) can differentiate into pericytes and regulate vessel stability and vascular survival in tumors. Similarly to what we have done with circulating ECs and progenitors, we developed a flow cytometry procedure for the enumeration of circulating PPCs and the study of their viability in murine models of cancer and in cancer patients. DNA+CD45-CD31-CD140b+ cells were enumerated by six-colour flow cytometry, their morphology was studied by electron microscopy, PPC specificity confirmed by reverse trascription-PCR (RT-PCR) expression of CD140b mRNA, and viability assessed by Syto16 and 7AAD. In preclinical marrow transplantation studies, 9 ± 4% of circulating PPCs were derived from the marrow donor. PPCs were increased in cancer-bearing mice and in patients affected by some types of cancer. At variance with the kinetic of circulating endothelial progenitors, high-dose cyclophosphamide reduced the number of viable PPCs. The administration of sunitinib, a drug known to inhibit PDGFR, was associated in murine models and in cancer patients with an increase of apoptotic/necrotic circulating PPC, suggesting a direct targeting of these cells. PPC enumeration might be studied as a tool for the definition of the optimal biologic dose of anti-PDGFR drugs and investigated clinically as a possible predictive/prognostic tool in patients receiving anti-PDGFR drugs.

  9. Multivalent proteoglycan modulation of FGF mitogenic responses in perivascular cells.

    PubMed

    Cattaruzza, Sabrina; Ozerdem, Ugur; Denzel, Martin; Ranscht, Barbara; Bulian, Pietro; Cavallaro, Ugo; Zanocco, Daniela; Colombatti, Alfonso; Stallcup, William B; Perris, Roberto

    2013-04-01

    Sprouting of angiogenic perivascular cells is thought to be highly dependent upon autocrine and paracrine growth factor stimulation. Accordingly, we report that corneal angiogenesis induced by ectopic FGF implantation is strongly impaired in NG2/CSPG4 proteoglycan (PG) null mice known to harbour a putative deficit in pericyte proliferation/mobilization. Conversely, no significant differences were seen between wild type and knockout corneas when VEGF was used as an angiocrine factor. Perturbed responsiveness of NG2-deficient pericytes to paracrine and autocrine stimulation by several FGFs could be confirmed in cells isolated from NG2 null mice, while proliferation induced by other growth factors was equivalent in wild type and knockout cells. Identical results were obtained after siRNA-mediated knock-down of NG2 in human smooth muscle-like cell lines, as also demonstrated by the decreased levels of FGF receptor phosphorylation detected in these NG2 deprived cells. Binding assays with recombinant proteins and molecular interactions examined on live cells asserted that FGF-2 bound to NG2 in a glycosaminoglycan-independent, core protein-mediated manner and that the PG was alone capable of retaining FGF-2 on the cell membrane for subsequent receptor presentation. The use of dominant-negative mutant cells, engineered by combined transduction of NG2 deletion constructs and siRNA knock-down of the endogenous PG, allowed us to establish that the FGF co-receptor activity of NG2 is entirely mediated by its extracellular portion. In fact, forced overexpression of the NG2 ectodomain in human smooth muscle-like cells increased their FGF-2-induced mitosis and compensated for low levels of FGF receptor surface expression, in a manner equivalent to that produced by overexpression of the full-length NG2. Upon FGF binding, the cytoplasmic domain of NG2 is phosphorylated, but there is no evidence that this event elicits signal transductions that could bypass the FGFR-mediated ones

  10. A role for ion channels in perivascular glioma invasion

    PubMed Central

    Thompson, Emily G.

    2017-01-01

    Malignant gliomas are devastating tumors, frequently killing those diagnosed in little over a year. The profuse infiltration of glioma cells into healthy tissue surrounding the main tumor mass is one of the major obstacles limiting the improvement of patient survival. Migration along the abluminal side of blood vessels is one of the salient features of glioma cell invasion. Invading glioma cells are attracted to the vascular network, in part by the neuro-peptide bradykinin, where glioma cells actively modify the gliovascular interface and undergo volumetric alterations to navigate the confined space. Critical to these volume modifications is a proposed hydrodynamic model that involves the flux of ions in and out of the cell, followed by osmotically obligated water. Ion and water channels expressed by the glioma cell are essential in this model of invasion and make opportune therapeutic targets. Lastly, there is growing evidence that vascular-associated glioma cells are able to control the vascular tone, presumably to free up space for invasion and growth. The unique mechanisms that enable perivascular glioma invasion may offer critical targets for therapeutic intervention in this devastating disease. Indeed, a chloride channel-blocking peptide has already been successfully tested in human clinical trials. PMID:27424110

  11. A role for ion channels in perivascular glioma invasion.

    PubMed

    Thompson, Emily G; Sontheimer, Harald

    2016-10-01

    Malignant gliomas are devastating tumors, frequently killing those diagnosed in little over a year. The profuse infiltration of glioma cells into healthy tissue surrounding the main tumor mass is one of the major obstacles limiting the improvement of patient survival. Migration along the abluminal side of blood vessels is one of the salient features of glioma cell invasion. Invading glioma cells are attracted to the vascular network, in part by the neuropeptide bradykinin, where glioma cells actively modify the gliovascular interface and undergo volumetric alterations to navigate the confined space. Critical to these volume modifications is a proposed hydrodynamic model that involves the flux of ions in and out of the cell, followed by osmotically obligated water. Ion and water channels expressed by the glioma cell are essential in this model of invasion and make opportune therapeutic targets. Lastly, there is growing evidence that vascular-associated glioma cells are able to control the vascular tone, presumably to free up space for invasion and growth. The unique mechanisms that enable perivascular glioma invasion may offer critical targets for therapeutic intervention in this devastating disease. Indeed, a chloride channel-blocking peptide has already been successfully tested in human clinical trials.

  12. Use of human perivascular stem cells for bone regeneration.

    PubMed

    James, Aaron W; Zara, Janette N; Corselli, Mirko; Chiang, Michael; Yuan, Wei; Nguyen, Virginia; Askarinam, Asal; Goyal, Raghav; Siu, Ronald K; Scott, Victoria; Lee, Min; Ting, Kang; Péault, Bruno; Soo, Chia

    2012-05-25

    Human perivascular stem cells (PSCs) can be isolated in sufficient numbers from multiple tissues for purposes of skeletal tissue engineering. PSCs are a FACS-sorted population of 'pericytes' (CD146+CD34-CD45-) and 'adventitial cells' (CD146-CD34+CD45-), each of which we have previously reported to have properties of mesenchymal stem cells. PSCs, like MSCs, are able to undergo osteogenic differentiation, as well as secrete pro-osteogenic cytokines. In the present protocol, we demonstrate the osteogenicity of PSCs in several animal models including a muscle pouch implantation in SCID (severe combined immunodeficient) mice, a SCID mouse calvarial defect and a femoral segmental defect (FSD) in athymic rats. The thigh muscle pouch model is used to assess ectopic bone formation. Calvarial defects are centered on the parietal bone and are standardly 4 mm in diameter (critically sized). FSDs are bicortical and are stabilized with a polyethylene bar and K-wires. The FSD described is also a critical size defect, which does not significantly heal on its own. In contrast, if stem cells or growth factors are added to the defect site, significant bone regeneration can be appreciated. The overall goal of PSC xenografting is to demonstrate the osteogenic capability of this cell type in both ectopic and orthotopic bone regeneration models.

  13. Survival-associated heterogeneity of marker-defined perivascular cells in colorectal cancer

    PubMed Central

    Mezheyeuski, Artur; Dragomir, Anca; Pfeiffer, Per; Kure, Elin H.; Ikdahl, Tone; Skovlund, Eva; Corvigno, Sara; Strell, Carina; Pietras, Kristian; Ponten, Fredrik; Mulder, Jan; Qvortrup, Camilla; Portyanko, Anna; Tveit, Kjell Magne; Östman, Arne

    2016-01-01

    Perivascular cells (PC) were recently implied as regulators of metastasis and immune cell activity. Perivascular heterogeneity in clinical samples, and associations with other tumor features and outcome, remain largely unknown. Here we report a novel method for digital quantitative analyses of vessel characteristics and PC, which was applied to two collections of human metastatic colorectal cancer (mCRC). Initial analyses identified marker-defined subsets of PC, including cells expressing PDGFR-β or α-SMA or both markers. PC subsets were largely independently expressed in a manner unrelated to vessel density and size. Association studies implied specific oncogenic mutations in malignant cells as determinants of PC status. Semi-quantitative and digital-image-analyses-based scoring of the NORDIC-VII cohort identified significant associations between low expression of perivascular PDGFR-α and -β and shorter overall survival. Analyses of the SPCRC cohort confirmed these findings. Perivascular PDGFR-α and -β remained independent factors for survival in multivariate analyses. Overall, our study identified host vasculature and oncogenic status as determinants of tumor perivascular features. Perivascular PDGFR-α and -β were identified as novel independent markers predicting survival in mCRC. The novel methodology should be suitable for similar analyses in other tumor collections. PMID:27248825

  14. Microscopic endometrial perivascular epithelioid cell nodules: a case report with the earliest presentation of a uterine perivascular epithelioid cell tumor.

    PubMed

    Fang, Chia-Lang; Lin, Yun-Ho; Chen, Wei-Yu

    2012-09-03

    Perivascular epithelioid cell (PEC) tumors (PEComas) are a family of related mesenchymal tumors composed of PECs which co-express melanocytic and smooth muscle markers. Although their distinctive histologic, immunohistochemical, ultrastructural, and genetic features have been clearly demonstrated, their histogenesis and normal counterpart remain largely unknown. Precursor lesions of PEComas have rarely been reported. We herein describe a tuberous sclerosis patient with microscopic PEC nodules in the endometrium of adenomyosis, pelvic endometriosis, an ovarian endometriotic cyst, and the endometrium of the uterine cavity. The nodules showed a mixture of spindle-shaped and epithelioid cells concentrically arranged around small arteries. The cells exhibited uniform nuclei, light eosinophilic cytoplasm, and immunoreactivity with HMB-45 and CD10. Some nodules revealed continuity with a PEComa in the myometrium. These findings support microscopic endometrial PEC nodules possibly being precursor lesions of uterine PEComas. The wide distribution of the nodules in the pelvis may be related to the multicentricity of PEComas in tuberous sclerosis patients. Owing to the immunoreactivity with CD10, microscopic endometrial PEC nodules may be misinterpreted as endothelial stromal cells unless melanocytic markers are stained. To the best of our knowledge, this is a case with the earliest manifestation of PEC lesions occurring in the endometrium. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9658280017862643.

  15. Divergent phenotype of rat thoracic and abdominal perivascular adipose tissues

    PubMed Central

    Jenkins, Nathan T.; Vieira-Potter, Victoria J.; Laughlin, M. Harold

    2013-01-01

    Perivascular adipose tissue (PVAT) is implicated as a source of proatherogenic cytokines. Phenotypic differences in local PVAT depots may contribute to differences in disease susceptibility among arteries and even regions within an artery. It has been proposed that PVAT around the abdominal and thoracic aorta shares characteristics of white and brown adipose tissue (BAT), respectively; however, a detailed comparison of the phenotype of these PVAT depots has not been performed. Using young and older adult rats, we compared the phenotype of PVATs surrounding the abdominal and thoracic aorta to each other and also to epididymal white and subscapular BAT. Compared with young rats, older rats exhibited greater percent body fat (34.5 ± 3.1 vs. 10.4 ± 0.9%), total cholesterol (112.2 ± 7.5 vs. 58.7 ± 6.3 mg/dl), HOMA-insulin resistance (1.7 ± 0.1 vs. 0.9 ± 0.1 a.u.), as well as reduced ACh-induced relaxation of the aorta (maximal relaxation: 54 ± 10 vs. 77 ± 6%) (all P < 0.05). Expression of inflammatory genes and markers of immune cell infiltration were greater in abdominal PVAT than in thoracic PVAT, and overall, abdominal and thoracic PVATs resembled the phenotype of white adipose tissue (WAT) and BAT, respectively. Histology and electron microscopy indicated structural similarity between visceral WAT and abdominal PVAT and between BAT and thoracic PVAT. Our data provide evidence that abdominal PVAT is more inflamed than thoracic PVAT, a difference that was by and large independent of sedentary aging. Phenotypic differences in PVAT between regions of the aorta may be relevant in light of the evidence in large animals and humans that the abdominal aorta is more vulnerable to atherosclerosis than the thoracic aorta. PMID:23389108

  16. A renal epithelioid angiomyolipoma/perivascular epithelioid cell tumor with TFE3 gene break visualized by FISH.

    PubMed

    Ohe, Chisato; Kuroda, Naoto; Hes, Ondrej; Michal, Michal; Vanecek, Tomas; Grossmann, Petr; Tanaka, Yukichi; Tanaka, Mio; Inui, Hidekazu; Komai, Yoshihiro; Matsuda, Tadashi; Uemura, Yoshiko

    2012-12-01

    We present a case of renal epithelioid angiomyolipoma (eAML)/perivascular epithelioid cell tumor (PEComa) with a TFE3 gene break visible by fluorescence in situ hybridization (FISH). Histologically, the tumor was composed of mainly epithelioid cells forming solid arrangements with small foci of spindle cells. In a small portion of the tumor, neoplastic cells displayed nuclear pleomorphism, such as polygonal and enlarged vesicular nuclei with prominent nucleoli. Marked vascularity was noticeable in the background, and perivascular hyaline sclerosis was also seen. Immunohistochemically, neoplastic cells were diffusely positive for α-smooth muscle actin and melanosome in the cytoplasm. Nuclei of many neoplastic cells were positive for TFE3. FISH analysis of the TFE3 gene break using the Poseidon TFE3 (Xp11) Break probe revealed positive results. Reverse transcriptase-polymerase chain reactions (RT-PCR) for ASPL/TFE3, PRCC/TFE3, CLTC/TFE3, PSF/TFE3, and NonO/TFE3 gene fusions all revealed negative results. This is the first reported case of renal eAML/PEComa with a TFE3 gene break, and it has unique histological findings as compared to previously reported TFE3 gene fusion-positive PEComas. Pathologists should recognize that PEComa with TFE3 gene fusion can arise even in the kidney.

  17. Perivascular oxygen tensions in a transplantable mammary tumor growing in a dorsal flap window chamber.

    PubMed

    Dewhirst, M W; Ong, E T; Klitzman, B; Secomb, T W; Vinuya, R Z; Dodge, R; Brizel, D; Gross, J F

    1992-05-01

    Fischer 344 rats with R3230 Ac mammary carcinomas implanted in dorsal flap window chambers served as a model to obtain measurements of perivascular and stromal oxygen tension in normal and tumor tissues using Whalen recessed-tip microelectrodes (3- to 6-microns tip). Perivascular measurements were made adjacent to vessels with continuous blood flow. Thus the measurements and models provided are reflective of conditions leading to chronic hypoxia. Perivascular oxygen tensions averaged 72 +/- 13 mmHg in normal tissue vessels adjacent to tumor, 26 +/- 5 mmHg in tumor periphery, and 12 +/- 3 mmHg in tumor central vessels. There was a significant trend toward lower perivascular oxygen tensions in the tumor center (Kruskal-Wallis test, P = 0.002). A similar tendency was seen with a limited number of stromal measurements. Krogh cylinder models, which incorporate these data for perivascular oxygen tension, along with morphometric data obtained from the same tumor model suggest that hypoxic regions will exist between tumor vessels in the tumor center unless O2 consumption rates are well below 0.6 ml/100 g/min. The low perivascular measurements observed near the tumor center combined with the theoretical considerations suggest, for this model at least, that tissue oxygenation may best be improved by increasing red cell velocity and input pO2 and reducing oxygen consumption. The low perivascular oxygen tensions observed near the center also suggest that conditions conducive to increased red cell rigidity exist, that drugs which can decrease red cell rigidity could improve tumor blood flow and oxygenation, and that the endothelium of those vessels may be susceptible to hypoxia-reoxygenation injury.

  18. Imaging the Perivascular Space as a Potential Biomarker of Neurovascular and Neurodegenerative Diseases.

    PubMed

    Ramirez, Joel; Berezuk, Courtney; McNeely, Alicia A; Gao, Fuqiang; McLaurin, JoAnne; Black, Sandra E

    2016-03-01

    Although the brain lacks conventional lymphatic vessels found in peripheral tissue, evidence suggests that the space surrounding the vasculature serves a similar role in the clearance of fluid and metabolic waste from the brain. With aging, neurodegeneration, and cerebrovascular disease, these microscopic perivascular spaces can become enlarged, allowing for visualization and quantification on structural MRI. The purpose of this review is to: (i) describe some of the recent pre-clinical findings from basic science that shed light on the potential neurophysiological mechanisms driving glymphatic and perivascular waste clearance, (ii) review some of the pathobiological etiologies that may lead to MRI-visible enlarged perivascular spaces (ePVS), (iii) describe the possible clinical implications of ePVS, (iv) evaluate existing qualitative and quantitative techniques used for measuring ePVS burden, and (v) propose future avenues of research that may improve our understanding of this potential clinical neuroimaging biomarker for fluid and metabolic waste clearance dysfunction in neurodegenerative and neurovascular diseases.

  19. Perivascular instruction of cell genesis and fate in the adult brain.

    PubMed

    Goldman, Steven A; Chen, Zhuoxun

    2011-10-26

    The perivascular niche for neurogenesis was first reported as the co-association of newly generated neurons and their progenitors with both dividing and mitotically quiescent endothelial cells in restricted regions of the brain in adult birds and mammals alike. This review attempts to summarize our present understanding of the interaction of blood vessels with neural stem and progenitor cells, addressing both glial and neuronal progenitor cell interactions in the perivascular niche. We review the molecular interactions that are most critical to the endothelial control of stem and progenitor cell mobilization and differentiation. The focus throughout will be on defining those perivascular ligand-receptor interactions shared among these systems, as well as those that clearly differ as a function of cell type and setting, by which specificity may be achieved in the development of targeted therapeutics.

  20. Acute lacunar infarcts in CLIPPERS: is the chronic infiltrative lymphocytic perivascular disease process to blame?

    PubMed

    Saigal, Gaurav; Quencer, Robert

    2013-12-01

    CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is a recently described chronic inflammatory disorder involving the brainstem with characteristic imaging findings. Since it was originally described in 2002, only a handful of cases have been reported in the literature. We describe two additional cases of CLIPPERS with characteristic clinical and radiological findings. Besides the previously described MR findings, one of the cases also demonstrated multiple basal ganglia lacunar infarcts, a finding which has not been previously reported. We hypothesize that the lacunar infarcts are caused by this chronic infiltrative perivascular disease process.

  1. Acute Lacunar Infarcts in CLIPPERS: Is the Chronic Infiltrative Lymphocytic Perivascular Disease Process to Blame?

    PubMed Central

    Saigal, Gaurav; Quencer, Robert

    2013-01-01

    Summary CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is a recently described chronic inflammatory disorder involving the brainstem with characteristic imaging findings. Since it was originally described in 2002, only a handful of cases have been reported in the literature. We describe two additional cases of CLIPPERS with characteristic clinical and radiological findings. Besides the previously described MR findings, one of the cases also demonstrated multiple basal ganglia lacunar infarcts, a finding which has not been previously reported. We hypothesize that the lacunar infarcts are caused by this chronic infiltrative perivascular disease process. PMID:24355180

  2. Perivascular Spaces--MRI Marker of Inflammatory Activity in the Brain?

    ERIC Educational Resources Information Center

    Wuerfel, Jens; Haertle, Mareile; Waiczies, Helmar; Tysiak, Eva; Bechmann, Ingo; Wernecke, Klaus D.; Zipp, Frauke; Paul, Friedemann

    2008-01-01

    The Virchow-Robin spaces (VRS), perivascular compartments surrounding small blood vessels as they penetrate the brain parenchyma, are increasingly recognized for their role in leucocyte trafficking as well as for their potential to modulate immune responses. In the present study, we investigated VRS numbers and volumes in different brain regions…

  3. The dance of the perivascular and endothelial cells: mechanisms of brain response to immune signaling.

    PubMed

    Saper, Clifford B

    2010-01-14

    The mechanisms underlying the brain response to systemic inflammation remain unclear. In this issue of Neuron, Serrats and colleagues demonstrate that two cell types that produce prostaglandins that act on the brain, perivascular and endothelial cells, have an unexpectedly complex interaction in regulating the timing and types of brain responses that occur.

  4. A Rapamycin-Releasing Perivascular Polymeric Sheath Produces Highly Effective Inhibition of Intimal Hyperplasia

    PubMed Central

    Yu, Xaohua; Takayama, Toshio; Goel, Shakti A.; Shi, Xudong; Zhou, Yifan; Kent, K. Craig; Murphy, William L.; Guo, Lian-Wang

    2014-01-01

    Intimal hyperplasia produces restenosis (re-narrowing) of the vessel lumen following vascular intervention. Drugs that inhibit intimal hyperplasia have been developed, however there is currently no clinical method of perivascular drug-delivery to prevent restenosis following open surgical procedures. Here we report a poly(ε-caprolactone) (PCL) sheath that is highly effective in preventing intimal hyperplasia through perivascular delivery of rapamycin. We first screened a series of bioresorbable polymers, i.e., poly(lactide-co-glycolide) (PLGA), poly(lactic acid) (PLLA), PCL, and their blends, to identify desired release kinetics and sheath physical properties. Both PLGA and PLLA sheaths produced minimal (<30%) rapamycin release within 50 days in PBS buffer. In contrast, PCL sheaths exhibited more rapid and near-linear release kinetics, as well as durable integrity (>90 days) as evidenced in both scanning electron microscopy and subcutaneous embedding experiments. Moreover, a PCL sheath deployed around balloon-injured rat carotid arteries was associated with a minimum rate of thrombosis compared to PLGA and PLLA. Morphometric analysis and immunohistochemistry revealed that rapamycin-loaded perivascular PCL sheaths produced pronounced (85%) inhibition of intimal hyperplasia (0.15±0.05 vs 1.01±0.16), without impairment of the luminal endothelium, the vessel’s anti-thrombotic layer. Our data collectively show that a rapamycin-loaded PCL delivery system produces substantial mitigation of neointima, likely due to its favorable physical properties leading to a stable yet flexible perivascular sheath and steady and prolonged release kinetics. Thus, a PCL sheath may provide useful scaffolding for devising effective perivascular drug delivery particularly suited for preventing restenosis following open vascular surgery. PMID:24852098

  5. A rapamycin-releasing perivascular polymeric sheath produces highly effective inhibition of intimal hyperplasia.

    PubMed

    Yu, Xiaohua; Takayama, Toshio; Goel, Shakti A; Shi, Xudong; Zhou, Yifan; Kent, K Craig; Murphy, William L; Guo, Lian-Wang

    2014-10-10

    Intimal hyperplasia produces restenosis (re-narrowing) of the vessel lumen following vascular intervention. Drugs that inhibit intimal hyperplasia have been developed, however there is currently no clinical method of perivascular drug-delivery to prevent restenosis following open surgical procedures. Here we report a poly(ε-caprolactone) (PCL) sheath that is highly effective in preventing intimal hyperplasia through perivascular delivery of rapamycin. We first screened a series of bioresorbable polymers, i.e., poly(lactide-co-glycolide) (PLGA), poly(lactic acid) (PLLA), PCL, and their blends, to identify desired release kinetics and sheath physical properties. Both PLGA and PLLA sheaths produced minimal (<30%) rapamycin release within 50days in PBS buffer. In contrast, PCL sheaths exhibited more rapid and near-linear release kinetics, as well as durable integrity (>90days) as evidenced in both scanning electron microscopy and subcutaneous embedding experiments. Moreover, a PCL sheath deployed around balloon-injured rat carotid arteries was associated with a minimum rate of thrombosis compared to PLGA and PLLA. Morphometric analysis and immunohistochemistry revealed that rapamycin-loaded perivascular PCL sheaths produced pronounced (85%) inhibition of intimal hyperplasia (0.15±0.05 vs 1.01±0.16), without impairment of the luminal endothelium, the vessel's anti-thrombotic layer. Our data collectively show that a rapamycin-loaded PCL delivery system produces substantial mitigation of neointima, likely due to its favorable physical properties leading to a stable yet flexible perivascular sheath and steady and prolonged release kinetics. Thus, a PCL sheath may provide useful scaffolding for devising effective perivascular drug delivery particularly suited for preventing restenosis following open vascular surgery.

  6. A case of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) in East Asia.

    PubMed

    Tohge, Rie; Nagao, Masahiro; Yagishita, Akira; Matsubara, Shiro

    2012-01-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome is a clinically and radiologically distinct pontine-predominant perivascular neuroinflammation showing T lymphocyte infiltration. It is assumed to have an autoimmune or other inflammatory mediated pathogenesis. We report the first known case of CLIPPERS in East Asia, characterized by multiple punctate enhancement of the brainstem extending to the bilateral posterior limb of the internal capsule and caudal to the spinal cord conus. The patient had elevated IgE levels and a history of allergies, suggesting that lesions may arise from neuroinflammation in response to T lymphocyte infiltration into perivascular spaces.

  7. CD1a immunopositivity in perivascular epithelioid cell neoplasms: true expression or technical artifact? A streptavidin-biotin and polymer-based detection system immunohistochemical study of perivascular epithelioid cell neoplasms and their morphologic mimics.

    PubMed

    Ahrens, William A; Folpe, Andrew L

    2011-03-01

    Perivascular epithelioid cell neoplasms comprise a family of rare neoplasms composed of morphologically distinctive perivascular epithelioid cells exhibiting a "myomelanocytic" immunophenotype. The distinction of perivascular epithelioid cell neoplasms from other tumors with melanocytic and smooth muscle differentiation can be difficult. A recent study has suggested that perivascular epithelioid cell neoplasms routinely express CD1a, a Langerhans cell-associated transmembrane glycoprotein involved in antigen presentation and that expression of this marker may be helpful in the distinction of perivascular epithelioid cell neoplasms from various mimics. We evaluated a series of perivascular epithelioid cell neoplasms and potential mimics for CD1a expression. A total of 54 cases (27 perivascular epithelioid cell neoplasms, 11 leiomyosarcomas, 10 melanomas, 6 clear cell sarcomas) were evaluated in 2 laboratories (Mayo Clinic Rochester: 31 cases, Carolinas Medical Center: 23 cases). Selected positive cases were retested at Carolinas Medical Center (11 cases) and Mayo Clinic Rochester (10 cases). Mayo Clinic Rochester methods were as follows: MTB1 clone (1:20, Novocastra, Newcastle-upon-Tyne, UK), heat-induced epitope retrieval in EDTA (pH 8.0), and Dako Advance detection system (Dako Corp, Carpinteria, CA) with background-reducing diluent. Carolinas Medical Center methods were as follows: MTB1 clone (1:30; CellMarque, Rocklin, CA), heat-induced epitope retrieval in Medium Cell Conditioner #1 (pH 8.0-9.0), and streptavidin-biotin detection system with diaminobenzidine chromogen, with and without biotin blocking. Scores were as follows: 1+, 5% to 25%; 2+, 26% to 50%; and 3+, more than 51%. Langerhans cells served as a positive internal control in all tested cases. All Mayo Clinic Rochester cases were negative. Sixteen Carolinas Medical Center perivascular epithelioid cell neoplasms (14 renal angiomyolipomas, 1 soft tissue perivascular epithelioid cell neoplasm, 1

  8. Cutaneous perivascular epithelioid cell tumors: A review on an infrequent neoplasm

    PubMed Central

    Llamas-Velasco, Mar; Requena, Luis; Mentzel, Thomas

    2016-01-01

    Perivascular epithelioid cutaneous” cell tumors (PEComa) are a family of mesenchymal tumors with shared microscopic and immunohistochemical properties: They exhibit both smooth muscle cell and melanocytic differentiation. Non-neoplastic counterpart of PEComa’s cells are unknown, as well as the relationship between extracutaneous PEComa and primary cutaneous ones. We will review the clinical setting, histopathologic features, chromosomal abnormalities, differential diagnosis and treatment options for cutaneous PEComa. PMID:27019799

  9. Pulsed ultrasound expands the extracellular and perivascular spaces of the brain.

    PubMed

    Hersh, David S; Nguyen, Ben A; Dancy, Jimena G; Adapa, Arjun R; Winkles, Jeffrey A; Woodworth, Graeme F; Kim, Anthony J; Frenkel, Victor

    2016-09-01

    Diffusion within the extracellular and perivascular spaces of the brain plays an important role in biological processes, therapeutic delivery, and clearance mechanisms within the central nervous system. Recently, ultrasound has been used to enhance the dispersion of locally administered molecules and particles within the brain, but ultrasound-mediated effects on the brain parenchyma remain poorly understood. We combined an electron microscopy-based ultrastructural analysis with high-resolution tracking of non-adhesive nanoparticles in order to probe changes in the extracellular and perivascular spaces of the brain following a non-destructive pulsed ultrasound regimen known to alter diffusivity in other tissues. Freshly obtained rat brain neocortical slices underwent sham treatment or pulsed, low intensity ultrasound for 5min at 1MHz. Transmission electron microscopy revealed intact cells and blood vessels and evidence of enlarged spaces, particularly adjacent to blood vessels, in ultrasound-treated brain slices. Additionally, ultrasound significantly increased the diffusion rate of 100nm, 200nm, and 500nm nanoparticles that were injected into the brain slices, while 2000nm particles were unaffected. In ultrasound-treated slices, 91.6% of the 100nm particles, 20.7% of the 200nm particles, 13.8% of the 500nm particles, and 0% of the 2000nm particles exhibited diffusive motion. Thus, pulsed ultrasound can have meaningful structural effects on the brain extracellular and perivascular spaces without evidence of tissue disruption.

  10. Heterogeneous perivascular cell coverage affects breast cancer metastasis and response to chemotherapy

    PubMed Central

    Kim, Jiha; de Sampaio, Pedro Correa; Lundy, Donna Marie; Peng, Qian; Evans, Kurt W.; Sugimoto, Hikaru; Kienast, Yvonne; do Amaral, Nayra Soares; Rocha, Rafael Malagoli; Eikesdal, Hans Petter; Meric-Bernstam, Funda; LeBleu, Valerie S.

    2016-01-01

    Angiogenesis and co-optive vascular remodeling are prerequisites of solid tumor growth. Vascular heterogeneity, notably perivascular composition, may play a critical role in determining the rate of cancer progression. The contribution of vascular pericyte heterogeneity to cancer progression and therapy response is unknown. Here, we show that angiopoietin-2 (Ang2) orchestrates pericyte heterogeneity in breast cancer with an effect on metastatic disease and response to chemotherapy. Using multispectral imaging of human breast tumor specimens, we report that perivascular composition, as defined by the ratio of PDGFRβ– and desmin+ pericytes, provides information about the response to epirubicin but not paclitaxel. Using 17 distinct patient-derived breast cancer xenografts, we demonstrate a cancer cell–derived influence on stromal Ang2 production and a cancer cell–defined control over tumor vasculature and perivascular heterogeneity. The aggressive features of tumors and their distinct response to therapies may thus emerge by the cancer cell–defined engagement of distinct and heterogeneous angiogenic programs. PMID:28018977

  11. Vascular wound healing and neointima formation induced by perivascular electric injury in mice.

    PubMed Central

    Carmeliet, P.; Moons, L.; Stassen, J. M.; De Mol, M.; Bouché, A.; van den Oord, J. J.; Kockx, M.; Collen, D.

    1997-01-01

    Vascular interventions for atherothrombotic disease frequently induce neointima formation, which can contribute to restenosis of blood vessels. As the molecular mechanisms of this process remain largely unknown, quantitative models of arterial injury in transgenic animals may be useful to study this process at the genetic level. Here, an injury model is proposed in which surgically exposed femoral arteries in mice were injured perivascularly via a single delivery of an electric current. Transmission electron microscopy, light microscopy, and immunohistochemistry revealed that electric injury destroyed all medial smooth muscle cells, denuded the injured segment of intact endothelium, and transiently induced platelet-rich mural thrombosis. A vascular wound-healing response resulted that was characterized by degradation of the mural thrombus, transient infiltration of the vessel wall by inflammatory cells, and progressive removal of the necrotic debris. Topographic analysis revealed repopulation of the media and accumulation in the neointima of smooth muscle cells originating from the uninjured borders and progressing into the necrotic center. Within 3 weeks after injury, a neointima of 0.026 +/- 0.003 mm2 (n = 7 arteries) was formed that contained a maximum of 12 +/- 1 layers of smooth muscle alpha-actin-immunoreactive cells. Evans blue staining in five electrically injured arteries revealed a denuded distance of 2.8 +/- 0.2 mm immediately after injury, which became progressively re-endothelialized from the uninjured borders to 2.2 +/- 0.08 mm (P = 0.013 vs freshly injured by analysis of variance), 0.8 +/- 0.22 mm (P < 0.001), and 0.005 +/- 0.003 mm (P < 0.001) within 2, 7, and 14 days after injury, respectively. Analysis of 5'-bromo-2'-deoxyuridine incorporation revealed that a maximum of 35 +/- 10% endothelial cells proliferated within 2 days after injury and that in the media and neointima, a maximum of, respectively, 12 +/- 2% and 18 +/- 3% smooth muscle cells

  12. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS).

    PubMed

    Pittock, Sean J; Debruyne, Jan; Krecke, Karl N; Giannini, Caterina; van den Ameele, Jelle; De Herdt, Veerle; McKeon, Andrew; Fealey, Robert D; Weinshenker, Brian G; Aksamit, Allen J; Krueger, Bruce R; Shuster, Elizabeth A; Keegan, B Mark

    2010-09-01

    The classification and pathological mechanisms of many central nervous system inflammatory diseases remain uncertain. In this article we report eight patients with a clinically and radiologically distinct pontine-predominant encephalomyelitis we have named 'chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids' (CLIPPERS). The patients were assessed clinically, radiologically and pathologically at Mayo Clinic, USA and Ghent University Hospital, Belgium from 1999 to 2009. Median follow-up duration from clinical onset was 22 months (range 7-144 months). Patients underwent extensive laboratory (serum and cerebrospinal fluid), radiological and pathological testing (conjunctival, transbronchial and brain biopsies) to search for causes of an inflammatory central nervous system disorder. All eight patients (five female, three male) presented with episodic diplopia or facial paresthesias with subsequent brainstem and occasionally myelopathic symptoms and had a favourable initial response to high dose glucocorticosteroids. All patients had symmetric curvilinear gadolinium enhancement peppering the pons and extending variably into the medulla, brachium pontis, cerebellum, midbrain and occasionally spinal cord. Radiological improvement accompanied clinical response to glucocorticosteroids. Patients routinely worsened following glucocorticosteroid taper and required chronic glucocorticosteroid or other immunosuppressive therapy. Neuropathology of biopsy material from four patients demonstrated white matter perivascular, predominantly T lymphocytic, infiltrate without granulomas, infection, lymphoma or vasculitis. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids is a definable, chronic inflammatory central nervous system disorder amenable to immunosuppressive treatment. The T cell predominant inflammatory pathology in affected central nervous system lesions and the clinical and radiological

  13. An extended chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids phenotype.

    PubMed

    Lane, Chris; Phadke, Rahul; Howard, Robin

    2014-06-25

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described central nervous system inflammatory condition. In this case report we describe a patient initially with features consistent with this syndrome, who represented with seizures (not previously reported in this syndrome) and corresponding prominent cortical involvement on imaging (also not previously noted). Owing to diagnostic uncertainty, cerebral biopsy was performed revealing histology consistent with CLIPPERS, excluding other differentials. Following a further brainstem relapse, this patient was treated with high-dose steroids, subsequently switched to a tapering oral regime and now, azathioprine, a steroid-sparing agent. She remains well on this.

  14. [CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids)].

    PubMed

    Kan, Shinichi

    2016-09-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) has been recently identified as an inflammatory central nervous system (CNS) disorder. Punctate and curvilinear gadolinium enhancement (peppering) the pons is a characteristic magnetic resonance imaging (MRI) feature of CLIPPERS. Pathogenesis of this disorder remains unknown. A specific serum or cerebrospinal fluid biomarker for this disorder is currently unknown. Whether CLIPPERS is an actual new disease or just represents overlapping symptoms from multiple diseases is still debated. Many differential diagnoses exist even when using imaging as a tool. Pre-lymphoma states, such as grade I LYG (lymphomatoid granulomatosis) and sentinel lesions of primary CNS lymphoma are the most difficult to distinguish.

  15. An extended chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids phenotype

    PubMed Central

    Lane, Chris; Phadke, Rahul; Howard, Robin

    2014-01-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described central nervous system inflammatory condition. In this case report we describe a patient initially with features consistent with this syndrome, who represented with seizures (not previously reported in this syndrome) and corresponding prominent cortical involvement on imaging (also not previously noted). Owing to diagnostic uncertainty, cerebral biopsy was performed revealing histology consistent with CLIPPERS, excluding other differentials. Following a further brainstem relapse, this patient was treated with high-dose steroids, subsequently switched to a tapering oral regime and now, azathioprine, a steroid-sparing agent. She remains well on this. PMID:24966263

  16. Intracerebroventricular infusions of TNF-alpha preferentially recruit blood lymphocytes and induce a perivascular leukocyte infiltrate.

    PubMed

    Seabrook, T J; Hay, J B

    2001-02-01

    Tumour necrosis factor (TNF)-alpha is important in several central nervous system (CNS) inflammatory diseases, however, its role in the recruitment of leukocytes into the cerebral spinal fluid (CSF) and CNS is incompletely understood. Therefore, we examined the effect of intracerebroventricular (icv) and parenchymal infusions of TNF-alpha on the type of leukocyte, the pool and subset of lymphocytes recruited into CSF and brain parenchyma. Parenchymal injections of 500 ng of recombinant human TNF-alpha did not induce inflammation, whereas an icv infusion of TNF-alpha caused CSF leuckocytosis and a perivascular infiltrate. Twenty-four hours after the icv infusion neutrophils predominated, with CD4+ T cells being the major lymphocyte subset in CSF. By 48 h lymphocytes were the dominant cell type with CD8+ cells surpassing CD4+ cells in both the CSF and the perivascular infiltrate. The labeled recirculating lymphocyte pool prevailed in normal CSF, but after the infusion of TNF-alpha, the blood pool of lymphocytes was preferentially recruited. These results have implications for the immune surveillance of the CNS.

  17. Human coronary artery perivascular adipocytes overexpress genes responsible for regulating vascular morphology, inflammation, and hemostasis

    PubMed Central

    Aronow, Bruce J.; Tong, Wilson S.; Manka, David; Tang, Yaoliang; Bogdanov, Vladimir Y.; Unruh, Dusten; Blomkalns, Andra L.; Piegore, Mark G.; Weintraub, Daniel S.; Rudich, Steven M.; Kuhel, David G.; Hui, David Y.; Weintraub, Neal L.

    2013-01-01

    Inflammatory cross talk between perivascular adipose tissue and the blood vessel wall has been proposed to contribute to the pathogenesis of atherosclerosis. We previously reported that human perivascular (PV) adipocytes exhibit a proinflammatory phenotype and less adipogenic differentiation than do subcutaneous (SQ) adipocytes. To gain a global view of the genomic basis of biologic differences between PV and SQ adipocytes, we performed genome-wide expression analyses to identify differentially expressed genes between adipocytes derived from human SQ vs. PV adipose tissues. Although >90% of well-expressed genes were similarly regulated, we identified a signature of 307 differentially expressed genes that were highly enriched for functions associated with the regulation of angiogenesis, vascular morphology, inflammation, and blood clotting. Of the 156 PV upregulated genes, 59 associate with angiogenesis, vascular biology, or inflammation, noteworthy of which include TNFRSF11B (osteoprotegerin), PLAT, TGFB1, THBS2, HIF1A, GATA6, and SERPINE1. Of 166 PV downregulated genes, 21 associated with vascular biology and inflammation, including ANGPT1, ANGPTL1, and VEGFC. Consistent with the emergent hypothesis that PV adipocytes differentially regulate angiogenesis and inflammation, cell culture-derived adipocyte-conditioned media from PV adipocytes strongly enhanced endothelial cell tubulogenesis and monocyte migration compared with media from SQ adipocytes. These findings demonstrate that PV adipocytes have the potential to significantly modulate vascular inflammatory crosstalk in the setting of atherosclerosis by their ability to signal to both endothelial and inflammatory cells. PMID:23737535

  18. Selective capture of endothelial and perivascular cells from brain microvessels using laser capture microdissection.

    PubMed

    Kinnecom, Katie; Pachter, Joel S

    2005-12-01

    Laser capture microdissection (LCM) of the major cell types comprising brain microvessels offers a powerful technology to explore the molecular basis of the blood-brain barrier in health and disease. However, the ability to selectively retrieve endothelial or perivascular cells, without cross-contamination from the other, has proven difficult. Additionally, histochemical methods previously described for use with LCM have not allowed for identification of all the different size branches of the microvascular tree. Here, we describe a double immunostaining method, combining bright-field and fluorescence microscopy, and using an extensive dehydration with xylene, to clearly identify and spatially resolve endothelial from perivascular cells within all size microvascular branches in frozen brain sections. LCM of these sections, coupled with RNA analysis by reverse-transcription polymerase chain reaction, revealed that captured endothelial cells show endothelial markers but no detectable markers for astrocytes or smooth muscle cells/pericytes. Conversely, captured astrocytes or smooth muscle cells/pericytes demonstrate their respective markers, but not those of endothelial cells. This approach has applicability to microarray analysis, thereby enabling global gene profiling of the different cell types along the entirety of the brain microvascular tree.

  19. Effects of the perivascular space on convection-enhanced delivery of liposomes in primate putamen.

    PubMed

    Krauze, Michal T; Saito, Ryuta; Noble, Charles; Bringas, John; Forsayeth, John; McKnight, Tracy R; Park, John; Bankiewicz, Krystof S

    2005-11-01

    Convection-enhanced delivery has recently entered the clinic and represents a promising new therapeutic option in the field of neurodegenerative diseases and treatment of brain tumors. Understanding of the principles governing delivery and flow of macromolecules within the CNS is still poorly understood and requires more investigation of the microanatomy and fluid dynamics of the brain. Our previously established, reflux-free convection-enhanced delivery (CED) technique and real-time imaging MR method for monitoring CED delivery of liposomes in primate CNS allowed us to closely monitor infusions of putamen. Our findings indicate that CED in putamen is associated with perivascular transport of liposomes, throughout CNS arteries. The results may explain side effects seen in current clinical trials using CED. In addition, they clearly show the necessity for a monitoring technique for future direct delivery of therapeutic agents to the human central nervous system. Based on these findings, we believe that the physiological concept that the perivascular space serves as a conduit for distribution of endogenous molecules within the CNS also applies to interstitially infused agents.

  20. Perivascular iron deposits are associated with protein nitration in cerebral experimental autoimmune encephalomyelitis.

    PubMed

    Sands, Scott A; Williams, Rachel; Marshall, Sylvester; LeVine, Steven M

    2014-10-17

    Nitration of proteins, which is thought to be mediated by peroxynitrite, is a mechanism of tissue damage in multiple sclerosis (MS). However, protein nitration can also be catalyzed by iron, heme or heme-associated molecules independent of peroxynitrite. Since microhemorrhages and perivascular iron deposits are present in the CNS of MS patients, we sought to determine if iron is associated with protein nitration. A cerebral model of experimental autoimmune encephalomyelitis (cEAE) was utilized since this model has been shown to have perivascular iron deposits similar to those present in MS. Histochemical staining for iron was used together with immunohistochemistry for nitrotyrosine, eNOS, or iNOS on cerebral sections. Leakage of the blood-brain barrier (BBB) was studied by albumin immunohistochemistry. Iron deposits were colocalized with nitrotyrosine staining around vessels in cEAE mice while control animals revealed minimal staining. This finding supports the likelihood that nitrotyrosine formation was catalyzed by iron or iron containing molecules. Examples of iron deposits were also observed in association with eNOS and iNOS, which could be one source of substrates for this reaction. Extravasation of albumin was present in cEAE mice, but not in control animals. Extravasated albumin may act to limit tissue injury by binding iron and/or heme as well as being a target of nitration, but the protection is incomplete. In summary, iron-catalyzed nitration of proteins is a likely mechanism of tissue damage in MS.

  1. Rapid transport within cerebral perivascular spaces underlies widespread tracer distribution in the brain after intranasal administration.

    PubMed

    Lochhead, Jeffrey J; Wolak, Daniel J; Pizzo, Michelle E; Thorne, Robert G

    2015-03-01

    The intranasal administration route is increasingly being used as a noninvasive method to bypass the blood-brain barrier because evidence suggests small fractions of nasally applied macromolecules may reach the brain directly via olfactory and trigeminal nerve components present in the nasal mucosa. Upon reaching the olfactory bulb (olfactory pathway) or brainstem (trigeminal pathway), intranasally delivered macromolecules appear to rapidly distribute within the brains of rodents and primates. The mechanisms responsible for this distribution have yet to be fully characterized. Here, we have used ex vivo fluorescence imaging to show that bulk flow within the perivascular space (PVS) of cerebral blood vessels contributes to the rapid central distribution of fluorescently labeled 3 and 10 kDa dextran tracers after intranasal administration in anesthetized adult rats. Comparison of tracer plasma levels and fluorescent signal distribution associated with the PVS of surface arteries and internal cerebral vessels showed that the intranasal route results in unique central access to the PVS not observed after matched intravascular dosing in separate animals. Intranasal targeting to the PVS was tracer size dependent and could be regulated by modifying nasal epithelial permeability. These results suggest cerebral perivascular convection likely has a key role in intranasal drug delivery to the brain.

  2. Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension

    PubMed Central

    Faraco, Giuseppe; Sugiyama, Yukio; Garcia-Bonilla, Lidia; Chang, Haejoo; Santisteban, Monica M.; Racchumi, Gianfranco; Murphy, Michelle; Anrather, Joseph

    2016-01-01

    Hypertension is a leading risk factor for dementia, but the mechanisms underlying its damaging effects on the brain are poorly understood. Due to a lack of energy reserves, the brain relies on continuous delivery of blood flow to its active regions in accordance with their dynamic metabolic needs. Hypertension disrupts these vital regulatory mechanisms, leading to the neuronal dysfunction and damage underlying cognitive impairment. Elucidating the cellular bases of these impairments is essential for developing new therapies. Perivascular macrophages (PVMs) represent a distinct population of resident brain macrophages that serves key homeostatic roles but also has the potential to generate large amounts of reactive oxygen species (ROS). Here, we report that PVMs are critical in driving the alterations in neurovascular regulation and attendant cognitive impairment in mouse models of hypertension. This effect was mediated by an increase in blood-brain barrier permeability that allowed angiotensin II to enter the perivascular space and activate angiotensin type 1 receptors in PVMs, leading to production of ROS through the superoxide-producing enzyme NOX2. These findings unveil a pathogenic role of PVMs in the neurovascular and cognitive dysfunction associated with hypertension and identify these cells as a putative therapeutic target for diseases associated with cerebrovascular oxidative stress. PMID:27841763

  3. EphrinB2 drives perivascular invasion and proliferation of glioblastoma stem-like cells

    PubMed Central

    Krusche, Benjamin; Ottone, Cristina; Clements, Melanie P; Johnstone, Ewan R; Goetsch, Katrin; Lieven, Huang; Mota, Silvia G; Singh, Poonam; Khadayate, Sanjay; Ashraf, Azhaar; Davies, Timothy; Pollard, Steven M; De Paola, Vincenzo; Roncaroli, Federico; Martinez-Torrecuadrada, Jorge; Bertone, Paul; Parrinello, Simona

    2016-01-01

    Glioblastomas (GBM) are aggressive and therapy-resistant brain tumours, which contain a subpopulation of tumour-propagating glioblastoma stem-like cells (GSC) thought to drive progression and recurrence. Diffuse invasion of the brain parenchyma, including along preexisting blood vessels, is a leading cause of therapeutic resistance, but the mechanisms remain unclear. Here, we show that ephrin-B2 mediates GSC perivascular invasion. Intravital imaging, coupled with mechanistic studies in murine GBM models and patient-derived GSC, revealed that endothelial ephrin-B2 compartmentalises non-tumourigenic cells. In contrast, upregulation of the same ephrin-B2 ligand in GSC enabled perivascular migration through homotypic forward signalling. Surprisingly, ephrin-B2 reverse signalling also promoted tumourigenesis cell-autonomously, by mediating anchorage-independent cytokinesis via RhoA. In human GSC-derived orthotopic xenografts, EFNB2 knock-down blocked tumour initiation and treatment of established tumours with ephrin-B2-blocking antibodies suppressed progression. Thus, our results indicate that targeting ephrin-B2 may be an effective strategy for the simultaneous inhibition of invasion and proliferation in GBM. DOI: http://dx.doi.org/10.7554/eLife.14845.001 PMID:27350048

  4. Perivascular innervation: A multiplicity of roles in vasomotor control and myoendothelial signaling

    PubMed Central

    Westcott, Erika B.; Segal, Steven S.

    2013-01-01

    The control of vascular resistance and tissue perfusion reflect coordinated changes in the diameter of feed arteries and the arteriolar networks they supply. Against a background of myogenic tone and metabolic demand, vasoactive signals originating from perivascular sympathetic and sensory nerves are integrated with endothelium-derived signals to produce vasodilation or vasoconstriction. PVNs release adrenergic, cholinergic, peptidergic, purinergic, and nitrergic neurotransmitters that lead to SMC contraction or relaxation via their actions on SMCs, ECs, or other PVNs. ECs release autacoids that can have opposing actions on SMCs. Respective cell layers are connected directly to each other through GJs at discrete sites via MEJs projecting through holes in the IEL. Whereas studies of intercellular communication in the vascular wall have centered on endothelium-derived signals that govern SMC relaxation, attention has increasingly focused on signaling from SMCs to ECs. Thus, via MEJs, neurotransmission from PVNs can evoke distinct responses from ECs subsequent to acting on SMCs. To integrate this emerging area of investigation in light of vasomotor control, the present review synthesizes current understanding of signaling events that originate within SMCs in response to perivascular neurotransmission in light of EC feedback. Though often ignored in studies of the resistance vasculature, PVNs are integral to blood flow control and can provide a physiological stimulus for myoendothelial communication. Greater understanding of these underlying signaling events and how they may be affected by aging and disease will provide new approaches for selective therapeutic interventions. PMID:23289720

  5. Local Control of Perivascular Malignant Liver Lesions Using Percutaneous Irreversible Electroporation: Initial Experiences

    SciTech Connect

    Eller, Achim Schmid, Axel; Schmidt, Joachim; May, Matthias Brand, Michael Saake, Marc Uder, Michael Lell, Michael

    2015-02-15

    PurposeThis study was designed to assess efficacy and safety in the treatment of perivascular malignant liver lesions using percutaneous, computed tomography (CT)-guided irreversible electroporation (IRE).MethodsFourteen patients (mean age 58 ± 11 years) with 18 malignant liver lesions were consecutively enrolled in this study. IRE was performed in patients not eligible for surgery and lesions abutting large vessels or bile ducts. Follow-up exams were performed using multislice-CT (MS-CT) or MRI.ResultsMedium lesion diameter was 20 ± 5 mm. Ten of 14 (71 %) were successfully treated with no local recurrence to date (mean follow-up 388 ± 160 days). One case left initial tumor control unclear and additional RFA was performed 4 weeks after IRE. Complications occurred in 4 of 14 (29 %) cases. In one case, intervention was terminated and abdominal bleeding required laparotomy. In two cases, a postinterventional hematothorax required intervention. In another case, abdominal bleeding could be managed conservatively. No complications related to the bile ducts occurred.ConclusionsPercutaneous IRE seems to be effective in perivascular lesions but is associated with a higher complication rate compared with thermoablative techniques.

  6. Perivascular inflammatory cells in ovine Visna/maedi encephalitis and their possible role in virus infection and lesion progression.

    PubMed

    Polledo, Laura; González, Jorge; Benavides, Julio; Martínez-Fernández, Beatriz; Ferreras, Ma Carmen; Marín, Juan F García

    2012-12-01

    We examined the distribution in the perivascular spaces of Visna/maedi antigen, T cells (CD3+, CD4+ and CD8+), B cells and macrophages by immunohistochemistry in 22 natural cases of Visna/maedi encephalitis. Sheep showed lymphocytic or histiocytic lesions. In mild lymphocytic lesions, the viral antigen was detected in perivascular cuffs where CD8+ T cells predominated, but in severe lymphocytic lesions, sparse antigen was identified, and CD8+/CD4+ T cells appeared in a similar proportion in multilayer perivascular sleeves. In histiocytic lesions, vessels were surrounded by macrophages with abundant viral antigen, with CD8+/CD4+ T cells and B cells in the periphery. These results could reflect different stages of virus neuroinvasion and clarify the neuropathogenesis of Visna/maedi encephalitis.

  7. Isolated Anxa5{sup +}/Sca-1{sup +} perivascular cells from mouse meningeal vasculature retain their perivascular phenotype in vitro and in vivo

    SciTech Connect

    Brachvogel, Bent . E-mail: bent.brachvogel@uni-koeln.de; Pausch, Friederike; Farlie, Peter; Gaipl, Udo; Etich, Julia; Zhou, Zhigang; Cameron, Trevor; Mark, Klaus von der; Bateman, John F.; Poeschl, Ernst . E-mail: e.poschl@uea.ac.uk

    2007-07-15

    Pericytes are closely associated with endothelial cells, contribute to vascular stability and represent a potential source of mesenchymal progenitor cells. Using the specifically expressed annexin A5-LacZ fusion gene (Anxa5-LacZ), it became possible to isolate perivascular cells (PVC) from mouse tissues. These cells proliferate and can be cultured without undergoing senescence for multiple passages. PVC display phenotypic characteristics of pericytes, as they express pericyte-specific markers (NG2-proteoglycan, desmin, {alpha}SMA, PDGFR-{beta}). They also express stem cell marker Sca-1, whereas endothelial (PECAM), hematopoietic (CD45) or myeloid (F4/80, CD11b) lineage markers are not detectable. These characteristics are in common with the pericyte-like cell line 10T1/2. PVC also display a phagocytoic activity higher than 10T1/2 cells. During coculture with endothelial cells both cell types stimulate angiogenic processes indicated by an increased expression of PECAM in endothelial cells and specific deposition of basement membrane proteins. PVC show a significantly increased induction of endothelial specific PECAM expression compared to 10T1/2 cells. Accordingly, in vivo grafts of PVC aggregates onto chorioallantoic membranes of quail embryos recruit endothelial cells, get highly vascularized and deposit basement membrane components. These data demonstrate that isolated Anxa5-LacZ{sup +} PVC from mouse meninges retain their capacity for differentiation to pericyte-like cells and contribute to angiogenic processes.

  8. Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche.

    PubMed

    Hayakawa, Yoku; Ariyama, Hiroshi; Stancikova, Jitka; Sakitani, Kosuke; Asfaha, Samuel; Renz, Bernhard W; Dubeykovskaya, Zinaida A; Shibata, Wataru; Wang, Hongshan; Westphalen, Christoph B; Chen, Xiaowei; Takemoto, Yoshihiro; Kim, Woosook; Khurana, Shradha S; Tailor, Yagnesh; Nagar, Karan; Tomita, Hiroyuki; Hara, Akira; Sepulveda, Antonia R; Setlik, Wanda; Gershon, Michael D; Saha, Subhrajit; Ding, Lei; Shen, Zeli; Fox, James G; Friedman, Richard A; Konieczny, Stephen F; Worthley, Daniel L; Korinek, Vladimir; Wang, Timothy C

    2015-12-14

    The regulation and stem cell origin of normal and neoplastic gastric glands are uncertain. Here, we show that Mist1 expression marks quiescent stem cells in the gastric corpus isthmus. Mist1(+) stem cells serve as a cell-of-origin for intestinal-type cancer with the combination of Kras and Apc mutation and for diffuse-type cancer with the loss of E-cadherin. Diffuse-type cancer development is dependent on inflammation mediated by Cxcl12(+) endothelial cells and Cxcr4(+) gastric innate lymphoid cells (ILCs). These cells form the perivascular gastric stem cell niche, and Wnt5a produced from ILCs activates RhoA to inhibit anoikis in the E-cadherin-depleted cells. Targeting Cxcr4, ILCs, or Wnt5a inhibits diffuse-type gastric carcinogenesis, providing targets within the neoplastic gastric stem cell niche.

  9. Changes in fine structure of pericytes and novel desmin-immunopositive perivascular cells during postnatal development in rat anterior pituitary gland.

    PubMed

    Jindatip, Depicha; Fujiwara, Ken; Horiguchi, Kotaro; Tsukada, Takehiro; Kouki, Tom; Yashiro, Takashi

    2013-09-01

    Pericytes are perivascular cells associated with capillaries. We previously demonstrated that pericytes, identified by desmin immunohistochemistry, produce type I and III collagens in the anterior pituitary gland of adult rats. In addition, we recently used desmin immunoelectron microscopy to characterize a novel type of perivascular cell, dubbed a desmin-immunopositive perivascular cell, in the anterior pituitary. These two types of perivascular cells differ in fine structure. The present study attempted to characterize the morphological features of pituitary pericytes and novel desmin-immunopositive perivascular cells during postnatal development, in particular their role in collagen synthesis. Desmin immunostaining revealed numerous perivascular cells at postnatal day 5 (P5) and P10. Transmission electron microscopy showed differences in the fine structure of the two cell types, starting at P5. Pericytes had well-developed rough endoplasmic reticulum and Golgi apparatus at P5 and P10. The novel desmin-immunopositive perivascular cells exhibited dilated cisternae of rough endoplasmic reticulum at P5-P30. In addition, during early postnatal development in the gland, a number of type I and III collagen-expressing cells were observed, as were high expression levels of these collagen mRNAs. We conclude that pituitary pericytes and novel desmin-immunopositive perivascular cells contain well-developed cell organelles and that they actively synthesize collagens during the early postnatal period.

  10. 'Browning' the cardiac and peri-vascular adipose tissues to modulate cardiovascular risk.

    PubMed

    Aldiss, Peter; Davies, Graeme; Woods, Rachel; Budge, Helen; Sacks, Harold S; Symonds, Michael E

    2017-02-01

    Excess visceral adiposity, in particular that located adjacent to the heart and coronary arteries is associated with increased cardiovascular risk. In the pathophysiological state, dysfunctional adipose tissue secretes an array of factors modulating vascular function and driving atherogenesis. Conversely, brown and beige adipose tissues utilise glucose and lipids to generate heat and are associated with improved cardiometabolic health. The cardiac and thoracic perivascular adipose tissues are now understood to be composed of brown adipose tissue in the healthy state and undergo a brown-to-white transition i.e. during obesity which may be a driving factor of cardiovascular disease. In this review we discuss the risks of excess cardiac and vascular adiposity and potential mechanisms by which restoring the brown phenotype i.e. "re-browning" could potentially be achieved in clinically relevant populations.

  11. A biodegradable perivascular wrap for controlled, local and directed drug delivery

    PubMed Central

    Sanders, William G.; Hogrebe, Paul C.; Grainger, David W.; Cheung, Alfred K.; Terry, Christi M.

    2012-01-01

    Perivascular delivery of anti-proliferative agents is an attractive approach to inhibit hyperplasia that causes stenosis of synthetic hemodialysis grafts and other vascular grafts. Perivascular drug delivery systems typically release drugs to both the vascular wall and non-target extravascular tissue. The objective of this study was to develop a biodegradable, perivascular delivery system for localized, sustained and unidirectional drug release in the context of synthetic arteriovenous (AV) grafts used for chronic hemodialysis. To this end, a dense non-porous polymer barrier layer was laminated to either i) a drug-loaded non-porous polymer layer, or ii) a porous polymer layer. To provide tuneability, the porous layer could be loaded with drug during casting or later infused with a drug-loaded hydrogel. The polymer bilayer wraps were prepared by a solvent casting, thermal-phase inversion technique using either polylactide-co-glycolide (PLGA) or polycaprolactone (PCL). Sunitinib, a multi-target receptor tyrosine kinase inhibitor, was used as a model drug. In a modified transwell chamber system, the barrier function of the non-porous PLGA backing was superior to the non-porous PCL backing although both markedly inhibited drug diffusion. As assessed by in vitro release assays, drug release duration from the drug-loaded non-porous PCL construct was almost 4-fold greater than release from the porous PCL construct infused with drug-laden hydrogel (22 days vs. 5 days); release duration from the drug-loaded non-porous PLGA construct was prolonged approximately 3-fold over release from the porous PLGA construct infused with drug-laden hydrogel (9 days vs. 3 days). Complete in vitro degradation of the PLGA porous and non-porous constructs occurred by approximately 35 days whereas the PCL constructs remained intact even after most drug was released (49 days). The PLGA non-porous bilayer wrap containing 143±5.5 mg sunitinib in the inner layer was chosen for further

  12. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids following influenza vaccination.

    PubMed

    Hillesheim, Paul B; Parker, John R; Parker, Joseph C; Escott, Edward; Berger, Joseph R

    2012-06-01

    Inflammatory processes within the central nervous system are challenging for the clinician, radiologist, and pathologist alike. They often can mimic other more well-known and defined disease processes. We present the case of a patient with a newly described inflammatory process that primarily involves the pons and adjacent structures, which is called chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). An 80-year-old man presented with numbness of his right hand that ultimately progressed to involve both lower extremities and face and was associated with mild dysarthria and ataxia. He had received the influenza vaccination 2 weeks prior. The biopsy revealed primarily reactive T-cell lymphocytic infiltrates with macrophages and gliosis. Treatment required long-term immunosuppressive therapy. CLIPPERS is a recently described central nervous system inflammatory condition that should be considered in the differential diagnosis when a prominent lymphocytic inflammatory infiltrate is encountered in brainstem, spinal cord, midbrain, or cerebellar biopsies.

  13. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) after treatment for Hodgkin's lymphoma.

    PubMed

    Mashima, Kyoko; Suzuki, Shigeaki; Mori, Takehiko; Shimizu, Toshihiko; Yamada, Satoshi; Hirose, Shigemichi; Okamoto, Shinichiro; Suzuki, Norihiro

    2015-12-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare central nervous system (CNS) disorder with distinct radiological features. However, CLIPPERS may mimic CNS lymphoma, and several cases in which CLIPPERS occurred premonitory to CNS lymphoma have been reported. We report a 31-year-old man presenting with progressive gait ataxia and the characteristic MRI features of CLIPPERS. He was diagnosed with stage II Hodgkin's lymphoma at the age of 15, and we considered the possibility of newly emerged CNS lymphoma occurring in the immunosuppressive condition after the treatment of Hodgkin's lymphoma. Histological findings showed no evidence of CNS lymphoma and the neurological symptoms were resolved by steroids. Although CLIPPERS developed in the reverse order in this case, CLIPPERS should be considered in different diagnosis for CNS lymphoma.

  14. Dilated perivascular spaces: an informative radiologic finding in Sanfilippo syndrome type A.

    PubMed

    Kara, Simay; Sherr, Elliott H; Barkovich, A James

    2008-05-01

    Mucopolysaccharidosis type IIIA, or Sanfilippo syndrome type A, is a lysosomal storage disorder caused by deficiency of heparan N-sulfamidase, resulting in defective degradation and subsequent storage of heparan sulfate. It is characterized by progressive nervous system involvement. Cribriform changes in the corpus callosum, basal ganglia, and white matter, diffuse high-intensity signal in the white matter, and cerebral atrophy have been described in patients with this disorder. This case report describes a child with Sanfilippo syndrome type A who exhibited fairly mild clinical findings but an unusual magnetic resonance imaging pattern that included multiple moderate-sized cysts (probably enlarged perivascular spaces) within the corpus callosum and an abnormal appearance of the clivus and cervical vertebrae. This case calls attention to the variety of appearances possible with magnetic resonance imaging in Sanfilippo syndrome type A.

  15. Perivascular adipose tissue in vascular function and disease: a review of current research and animal models.

    PubMed

    Brown, Nicholas K; Zhou, Zhou; Zhang, Jifeng; Zeng, Rong; Wu, Jiarui; Eitzman, Daniel T; Chen, Y Eugene; Chang, Lin

    2014-08-01

    Perivascular adipose tissue (PVAT), long assumed to be nothing more than vessel-supporting connective tissue, is now understood to be an important, active component of the vasculature, with integral roles in vascular health and disease. PVAT is an adipose tissue with similarities to both brown and white adipose tissue, although recent evidence suggests that PVAT develops from its own precursors. Like other adipose tissue depots, PVAT secretes numerous biologically active substances that can act in both autocrine and paracrine fashion. PVAT has also proven to be involved in vascular inflammation. Although PVAT can support inflammation during atherosclerosis via macrophage accumulation, emerging evidence suggests that PVAT also has antiatherosclerotic properties related to its abilities to induce nonshivering thermogenesis and metabolize fatty acids. We here discuss the accumulated knowledge of PVAT biology and related research on models of hypertension and atherosclerosis.

  16. Hepatic perivascular epithelioid cell tumor (PEComa): a case report with a review of literatures

    PubMed Central

    Son, Hyun-Jin; Kang, Dong Wook; Kim, Joo Heon; Han, Hyun Young; Lee, Min Koo

    2017-01-01

    Hepatic perivascular epithelioid cell tumors (PEComas) are very rare. We report a primary hepatic PEComa with a review of the literature. A 56-year-old women presented with a nodular mass detected during the management of chronic renal failure and chronic hepatitis C. Diagnostic imaging studies suggested a nodular hepatocellular carcinoma in segment 5 of the liver. The patient underwent partial hepatectomy. A brown-colored expansile mass measuring 3.2×3.0 cm was relatively demarcated from the surrounding liver parenchyma. The tumor was mainly composed of epithelioid cells that were arranged in a trabecular growth pattern. Adipose tissue and thick-walled blood vessels were minimally identified. A small amount of extramedullary hematopoiesis was observed in the sinusoidal spaces between tumor cells. Tumor cells were diffusely immunoreactive for human melanoma black 45 (HMB45) and Melan A, focally immunoreactive for smooth muscle actin, but not for hepatocyte specific antigen (HSA). PMID:28288506

  17. Post-radiation fibrosarcoma of the cerebrum associated with a prominent, lace-like, perivascular, desmoplastic change.

    PubMed

    Shintaku, Masayuki; Adachi, Yasushi; Takeuchi, Yasuhide; Yamamoto, Daisuke; Koyama, Junji

    2016-04-01

    An intra-axial tumor measuring about 4 cm was excised from the right temporal lobe of a 35-year-old woman, who had a past history of resection of craniopharyngioma and postoperative radiation 21 years earlier. The tumor involved both the cortex and white matter, but was not attached to the dura mater. It consisted of a dense, interlacing, fascicular proliferation of atypical fibroblastic cells and was associated with an extensive, lace-like, desmoplastic change mainly involving the perivascular region around the tumor and overlying the subarachnoid space. The histopathological features of the desmoplastic change resembled meningioangiomatosis, but no proliferation of meningothelial cells was noted. The patient has been free from recurrence for 12 months since the operation. The association of primary cerebral fibrosarcoma with an extensive, lace-like, perivascular, desmoplastic change has not been documented in the literature. The radiation administered 21 years previously may have played some pathogenetic role in the perivascular desmoplastic change, and a malignant transformation of fibroblasts within the perivascular collagenous tissue is considered the most likely origin of the fibrosarcoma.

  18. Differential effects of statins on endogenous H2S formation in perivascular adipose tissue.

    PubMed

    Wójcicka, Grażyna; Jamroz-Wiśniewska, Anna; Atanasova, Pepa; Chaldakov, George N; Chylińska-Kula, Beata; Bełtowski, Jerzy

    2011-01-01

    Hydrogen sulfide (H(2)S) is a new gasotransmitter synthesized enzymatically from l-cysteine in cytosol and is oxidized in mitochondria. In the cardiovascular system, H(2)S regulates vascular tone, inhibits atherogenesis, and protects against myocardial ischemia-reperfusion injury. We examined the effect of statins on vascular H(2)S production. Male Wistar rats received pravastatin (40mg/kg/day) or atorvastatin (20mg/kg/day) for 3 weeks and then H(2)S formation was measured in aortic media, periaortic adipose tissue (PAAT) and the liver. Only atorvastatin increased H(2)S production in PAAT whereas both statins stimulated its formation in the liver. Neither statin affected H(2)S production in aortic media. H(2)S formation in post-mitochondrial supernatant was higher than in mitochondria-containing supernatant and was not influenced by statins in any tissue. In addition, oxidation of exogenous H(2)S in isolated liver mitochondria was slower in statin-treated than in control rats. These data indicate that statins increase net H(2)S production by inhibiting its mitochondrial oxidation. Statins had no effect on the activity of H(2)S-metabolizing enzyme, sulfide:quinone oxidoreductase, measured at saturating coenzyme Q concentration. Both statins reduced CoQ(9) concentration in plasma and liver, but only atorvastatin decreased CoQ(9) in PAAT. Atorvastatin attenuated phenylephrine-induced contraction of PAAT+ but not of PAAT- aortic rings. Effects of atorvastatin on net H(2)S production, mitochondrial H(2)S oxidation and aortic contractility were abolished by supplementation of exogenous CoQ(9). In conclusion, lipophilic atorvastatin, but not hydrophilic pravastatin, increases net H(2)S production in perivascular adipose tissue by inhibiting its mitochondrial oxidation. This effect is mediated by statin-induced CoQ(9) deficiency and results in the augmentation of anticontractile effect of perivascular adipose tissue.

  19. Role of chemokine RANTES in the regulation of perivascular inflammation, T-cell accumulation, and vascular dysfunction in hypertension

    PubMed Central

    Mikolajczyk, Tomasz P.; Nosalski, Ryszard; Szczepaniak, Piotr; Budzyn, Klaudia; Osmenda, Grzegorz; Skiba, Dominik; Sagan, Agnieszka; Wu, Jing; Vinh, Antony; Marvar, Paul J.; Guzik, Bartlomiej; Podolec, Jakub; Drummond, Grant; Lob, Heinrich E.; Harrison, David G.; Guzik, Tomasz J.

    2016-01-01

    Recent studies have emphasized the role of perivascular inflammation in cardiovascular disease. We studied mechanisms of perivascular leukocyte infiltration in angiotensin II (Ang II)-induced hypertension and their links to vascular dysfunction. Chronic Ang II infusion in mice increased immune cell content of T cells (255 ± 130 to 1664 ± 349 cells/mg; P < 0.01), M1 and M2 macrophages, and dendritic cells in perivascular adipose tissue. In particular, the content of T lymphocytes bearing CC chemokine receptor (CCR) 1, CCR3, and CCR5 receptors for RANTES chemokine was increased by Ang II (CCR1, 15.6 ± 1.5% vs. 31 ± 5%; P < 0.01). Hypertension was associated with an increase in perivascular adipose tissue expression of the chemokine RANTES (relative quantification, 1.2 ± 0.2 vs. 3.5 ± 1.1; P < 0.05), which induced T-cell chemotaxis and vascular accumulation of T cells expressing the chemokine receptors CCR1, CCR3, and CCR5. Mechanistically, RANTES−/− knockout protected against vascular leukocyte, and in particular T lymphocyte infiltration (26 ± 5% in wild type Ang II vs. 15 ± 4% in RANTES−/−), which was associated with protection from endothelial dysfunction induced by Ang II. This effect was linked with diminished infiltration of IFN-γ-producing CD8+ and double-negative CD3+CD4−CD8− T cells in perivascular space and reduced vascular oxidative stress while FoxP3+ T-regulatory cells were unaltered. IFN-γ ex vivo caused significant endothelial dysfunction, which was reduced by superoxide anion scavenging. In a human cohort, a significant inverse correlation was observed between circulating RANTES levels as a biomarker and vascular function measured as flow-mediated dilatation (R = −0.3, P < 0.01) or endothelial injury marker von Willebrand factor (R = +0.3; P < 0.01). Thus, chemokine RANTES is important in the regulation of vascular dysfunction through modulation of perivascular inflammation.—Mikolajczyk, T. P., Nosalski, R., Szczepaniak, P

  20. Perivascular Accumulation of β-Sheet-Rich Proteins in Offspring Brain following Maternal Exposure to Carbon Black Nanoparticles

    PubMed Central

    Onoda, Atsuto; Kawasaki, Takayasu; Tsukiyama, Koichi; Takeda, Ken; Umezawa, Masakazu

    2017-01-01

    Environmental stimulation during brain development is an important risk factor for the development of neurodegenerative disease. Clinical evidence indicates that prenatal exposure to particulate air pollutants leads to diffuse damage to the neurovascular unit in the developing brain and accelerates neurodegeneration. Maternal exposure to carbon black nanoparticles (CB-NPs), used as a model for particulate air pollution, induces long-lasting diffuse perivascular abnormalities. We aimed to comprehensively characterize the perivascular abnormalities related to maternal NPs exposure using Fourier transform infrared microspectroscopy (in situ FT-IR) and classical staining analysis. Pregnant ICR mice were intranasally treated with a CB-NPs suspension (95 μg/kg at a time) on gestational days 5 and 9. Brains were collected 6 weeks after birth and sliced to prepare 10-μm-thick serial sections. Reflective spectra of in situ FT-IR were acquired using lattice measurements (x-axis: 7, y-axis: 7, 30-μm apertures) around a centered blood vessel. We also performed mapping analysis of protein secondary structures. Serial sections were stained with using periodic acid-Schiff or immunofluorescence to examine the phenotypes of the perivascular areas. Peaks of amide I bands in spectra from perivascular areas were shifted by maternal NPs exposure. However, there were two types of peak-shift in one mouse in the exposure group. Some vessels had a large peak-shift and others had a small peak-shift. In situ FT-IR combined with traditional staining revealed that the large peak-shift was induced around blood vessel adjacent to astrocytes with glial fibrillary acidic protein and aquaporin-4 over-expression and perivascular macrophages (PVMs) with enlarged lysosome granules. Furthermore, protein secondary structural analysis indicated that maternal NPs exposure led to increases in β-sheet content and decreases in α-helix content in areas that are mostly close to the centered blood vessel

  1. CXCR4 increases in-vivo glioma perivascular invasion, and reduces radiation induced apoptosis: A genetic knockdown study

    PubMed Central

    Yadav, Viveka Nand; Zamler, Daniel; Baker, Gregory J.; Kadiyala, Padma; Erdreich-Epstein, Anat; DeCarvalho, Ana C.; Mikkelsen, Tom; Castro, Maria G.; Lowenstein, Pedro R.

    2016-01-01

    Glioblastoma (GBM) is a highly invasive brain tumor. Perivascular invasion, autovascularization and vascular co-option occur throughout the disease and lead to tumor invasion and progression. The molecular basis for perivascular invasion, i.e., the interaction of glioma tumor cells with endothelial cells is not well characterized. Recent studies indicate that glioma cells have increased expression of CXCR4. We investigated the in-vivo role of CXCR4 in perivascular invasion of glioma cells using shRNA-mediated knock down of CXCR4. We show that primary cultures of human glioma stem cells HF2303 and mouse glioma GL26-Cit cells exhibit significant migration towards human (HBMVE) and mouse (MBVE) brain microvascular endothelial cells. Blocking CXCR4 on tumor cells with AMD3100 in-vitro, inhibits migration of GL26-Cit and HF2303 toward MBVE and HBMVE cells. Additionally, genetic down regulation of CXCR4 in mouse glioma GL26-Cit cells inhibits their in-vitro migration towards MBVE cells; in an in-vivo intracranial mouse model, these cells display reduced tumor growth and perivascular invasion, leading to increased survival. Quantitative analysis of brain sections showed that CXCR4 knockdown tumors are less invasive. Lastly, we tested the effects of radiation on CXCR4 knock down GL26-Cit cells in an orthotopic brain tumor model. Radiation treatment increased apoptosis of CXCR4 downregulated tumor cells and prolonged median survival. In summary, our data suggest that CXCR4 signaling is critical for perivascular invasion of GBM cells and targeting this receptor makes tumors less invasive and more sensitive to radiation therapy. Combination of CXCR4 knock down and radiation treatment might improve the efficacy of GBM therapy. PMID:27863376

  2. Paracrine influence of human perivascular cells on the proliferation of adenocarcinoma alveolar epithelial cells

    PubMed Central

    Kim, Eunbi; Na, Sunghun; An, Borim; Yang, Se-Ran; Kim, Woo Jin; Ha, Kwon-Soo; Han, Eun-Taek; Park, Won Sun; Lee, Chang-Min; Lee, Ji Yoon

    2017-01-01

    Understanding the crosstalk mechanisms between perivascular cells (PVCs) and cancer cells might be beneficial in preventing cancer development and metastasis. In this study, we investigated the paracrine influence of PVCs derived from human umbilical cords on the proliferation of lung adenocarcinoma epithelial cells (A549) and erythroleukemia cells (TF-1α and K562) in vitro using Transwell® co-culture systems. PVCs promoted the proliferation of A549 cells without inducing morphological changes, but had no effect on the proliferation of TF-1α and K562 cells. To identify the factors secreted from PVCs, conditioned media harvested from PVC cultures were analyzed by antibody arrays. We identified a set of cytokines, including persephin (PSPN), a neurotrophic factor, and a key regulator of oral squamous cell carcinoma progression. Supplementation with PSPN significantly increased the proliferation of A549 cells. These results suggested that PVCs produced a differential effect on the proliferation of cancer cells in a cell-type dependent manner. Further, secretome analyses of PVCs and the elucidation of the molecular mechanisms could facilitate the discovery of therapeutic target(s) for lung cancer. PMID:28280409

  3. Lymphatic Clearance of the Brain: Perivascular, Paravascular and Significance for Neurodegenerative Diseases.

    PubMed

    Bakker, Erik N T P; Bacskai, Brian J; Arbel-Ornath, Michal; Aldea, Roxana; Bedussi, Beatrice; Morris, Alan W J; Weller, Roy O; Carare, Roxana O

    2016-03-01

    The lymphatic clearance pathways of the brain are different compared to the other organs of the body and have been the subject of heated debates. Drainage of brain extracellular fluids, particularly interstitial fluid (ISF) and cerebrospinal fluid (CSF), is not only important for volume regulation, but also for removal of waste products such as amyloid beta (Aβ). CSF plays a special role in clinical medicine, as it is available for analysis of biomarkers for Alzheimer's disease. Despite the lack of a complete anatomical and physiological picture of the communications between the subarachnoid space (SAS) and the brain parenchyma, it is often assumed that Aβ is cleared from the cerebral ISF into the CSF. Recent work suggests that clearance of the brain mainly occurs during sleep, with a specific role for peri- and para-vascular spaces as drainage pathways from the brain parenchyma. However, the direction of flow, the anatomical structures involved and the driving forces remain elusive, with partially conflicting data in literature. The presence of Aβ in the glia limitans in Alzheimer's disease suggests a direct communication of ISF with CSF. Nonetheless, there is also the well-described pathology of cerebral amyloid angiopathy associated with the failure of perivascular drainage of Aβ. Herein, we review the role of the vasculature and the impact of vascular pathology on the peri- and para-vascular clearance pathways of the brain. The different views on the possible routes for ISF drainage of the brain are discussed in the context of pathological significance.

  4. Hoxb5 marks long-term haematopoietic stem cells revealing a homogenous perivascular niche

    PubMed Central

    Chen, James Y.; Miyanishi, Masanori; Wang, Sean K.; Yamazaki, Satoshi; Sinha, Rahul; Kao, Kevin S.; Nakauchi, Hiromitsu; Weissman, Irving L.

    2016-01-01

    The hematopoietic stem cell (HSC) is arguably the most extensively characterized tissue stem cell. Since its identification by prospective isolation1, complex multi-parameter flow cytometric isolation of phenotypic subsets has facilitated studies on many aspects of HSC biology including, self-renewal2–4, differentiation, aging, niche5, and diversity6–8. Here we demonstrate by unbiased multi-step screening, identification of a single gene, Hoxb5 (homeobox B5 also known as Hox-2.1), whose expression in the bone marrow (BM) is limited to the long-term HSC (LT-HSC) in mice. Utilizing a single-color tri-mCherry reporter mouse driven by endogenous Hoxb5 regulation, only the Hoxb5-positive HSCs exhibit long-term reconstitution capacity after transplantation in primary transplant recipients, and critically, in secondary recipients. Only 7–35% of various previously defined immunophenotypic HSCs are LT-HSCs. Finally, by in situ imaging of mouse BM, we show that >94% of LT-HSC (Hoxb5+) are directly attached to VE-cadherin-positive cells, implicating a perivascular space as a near homogenous localization of the LT-HSC. PMID:26863982

  5. sdf1 Expression Reveals a Source of Perivascular-Derived Mesenchymal Stem Cells in Zebrafish

    PubMed Central

    Lund, Troy C.; Patrinostro, Xiaobai; Kramer, Ashley C.; Stadem, Paul; Higgins, LeeAnn; Markowski, Todd W.; Wroblewski, Matt S.; Lidke, Diane S.; Tolar, Jakub; Blazar, Bruce R.

    2014-01-01

    There is accumulating evidence that mesenchymal stem cells (MSC) have their origin as perivascular cells (PVC) in vivo, but precisely identifying them has been a challenge, as they have no single definitive marker and are rare. We have developed a fluorescent transgenic vertebrate model in which PVC can be visualized in vivo based upon sdf1 expression in the zebrafish. Prospective isolation and culture of sdf1DsRed PVC demonstrated properties consistent with MSC including prototypical cell surface marker expression; mesodermal differentiation into adipogenic, osteogenic and chondrogenic lineages; and the ability to support hematopoietic cells. Global proteomic studies performed by 2-dimensional liquid chromatography and tandem mass spectrometry revealed a high degree of similarity to human MSC and discovery of novel markers (CD99, CD151 and MYOF) that were previously unknown to be expressed by hMSC. Dynamic in vivo imaging during fin regeneration showed that PVC may arise from undifferentiated mesenchyme providing evidence of a PVC – MSC relationship. This is the first model, established in zebrafish, in which MSC can be visualized in vivo and will allow us to better understand their function in a native environment. PMID:24905975

  6. Interaction of perivascular adipose tissue and sympathetic nerves in arteries from normotensive and hypertensive rats.

    PubMed

    Török, J; Zemančíková, A; Kocianová, Z

    2016-10-24

    The inhibitory action of perivascular adipose tissue (PVAT) in modulation of arterial contraction has been recently recognized and contrasted with the prohypertensive effect of obesity in humans. In this study we demonstrated that PVAT might have opposing effect on sympatho-adrenergic contractions in different rat conduit arteries. In superior mesenteric artery isolated from normotensive Wistar-Kyoto rats (WKY), PVAT exhibited inhibitory influence on the contractions to exogenous noradrenaline as well as to endogenous noradrenaline released from arterial sympathetic nerves during transmural electrical stimulation or after application of tyramine. In contrast, the abdominal aorta with intact PVAT responded with larger contractions to transmural electrical stimulation and tyramine when compared to the aorta after removing PVAT; the responses to noradrenaline were similar in both. This indicates that PVAT may contain additional sources of endogenous noradrenaline which could be responsible for the main difference in the modulatory effect of PVAT on adrenergic contractions between abdominal aortas and superior mesenteric arteries. In spontaneously hypertensive rats (SHR), the anticontractile effect of PVAT in mesenteric arteries was reduced, and the removal of PVAT completely eliminated the difference in the dose-response curves to exogenous noradrenaline between SHR and WKY. These results suggest that in mesenteric artery isolated from SHR, the impaired anticontractile influence of PVAT might significantly contribute to its increased sensitivity to adrenergic stimuli.

  7. Dual Roles for Perivascular Macrophages in Immune-to-Brain Signaling

    PubMed Central

    Serrats, Jordi; Schiltz, Jennifer C.; García-Bueno, Borja; van Rooijen, Nico; Reyes, Teresa M.; Sawchenko, Paul E.

    2009-01-01

    Cytokines produced during infection/inflammation activate adaptive CNS responses, including acute stress responses mediated by the hypothalamo-pituitary-adrenal (HPA) axis. The mechanisms by which cytokines engage HPA control circuitry remain unclear, though stimulated release of prostanoids from neighboring vascular cells has been implicated in this regard. How specific vascular cell types, endothelial cells (ECs) vs. perivascular cells (PVCs; a subset of brain-resident macrophages), participate in this response remains unsettled. We exploited the phagocytic activity of PVCs to deplete them in rats by central injection of a liposome-encapsulated pro-apoptotic drug. This manipulation abrogated CNS and hormonal indices of HPA activation under immune challenge conditions (interleukin-1; IL-1) that activated prostanoid synthesis only in PVCs, while enhancing these responses to stimuli (lipopolysaccaride; LPS) that engaged prostanoid production by ECs as well. Thus, PVCs provide both prostanoid-mediated drive to the HPA axis, and an anti-inflammatory action that constrains endothelial, and overall CNS, responses to inflammatory insults. PMID:20152116

  8. Gene transfer corrects acute GM2 gangliosidosis--potential therapeutic contribution of perivascular enzyme flow.

    PubMed

    Cachón-González, M Begoña; Wang, Susan Z; McNair, Rosamund; Bradley, Josephine; Lunn, David; Ziegler, Robin; Cheng, Seng H; Cox, Timothy M

    2012-08-01

    The GM2 gangliosidoses are fatal lysosomal storage diseases principally affecting the brain. Absence of β-hexosaminidase A and B activities in the Sandhoff mouse causes neurological dysfunction and recapitulates the acute Tay-Sachs (TSD) and Sandhoff diseases (SD) in infants. Intracranial coinjection of recombinant adeno-associated viral vectors (rAAV), serotype 2/1, expressing human β-hexosaminidase α (HEXA) and β (HEXB) subunits into 1-month-old Sandhoff mice gave unprecedented survival to 2 years and prevented disease throughout the brain and spinal cord. Classical manifestations of disease, including spasticity-as opposed to tremor-ataxia-were resolved by localized gene transfer to the striatum or cerebellum, respectively. Abundant biosynthesis of β-hexosaminidase isozymes and their global distribution via axonal, perivascular, and cerebrospinal fluid (CSF) spaces, as well as diffusion, account for the sustained phenotypic rescue-long-term protein expression by transduced brain parenchyma, choroid plexus epithelium, and dorsal root ganglia neurons supplies the corrective enzyme. Prolonged survival permitted expression of cryptic disease in organs not accessed by intracranial vector delivery. We contend that infusion of rAAV into CSF space and intraparenchymal administration by convection-enhanced delivery at a few strategic sites will optimally treat neurodegeneration in many diseases affecting the nervous system.

  9. Rare case of uterine PEC-oma (perivascular epithelioid cell tumor) recurrence. Case report and literature review.

    PubMed

    Issat, Tadeusz; Maciejewski, Tomasz; Beta, Jarosław; Jakimiuk, J Artur

    2012-07-01

    Perivascular epithelioid cell tumor (PEC-oma) is a rare mesenchymal neoplasm. Literature reports more than 100 cases of PEC-oma, a third of which is of uterine or uterine retroperitoneum origin. The case of a 59-year-old woman presented here is, to the best of our knowledge, the first described fast uterine PEC-oma recurrence of the tumor of the gastrointestinal tract origin. In this text the authors also present literature review concerning this rare female tumor

  10. Real-Time Imaging of Perivascular Transport of Nanoparticles During Convection Enhanced Delivery in the Rat Cortex

    PubMed Central

    Foley, Conor P.; Nishimura, Nozomi; Neeves, Keith B.; Schaffer, Chris B.; Olbricht., William L.

    2012-01-01

    Convection enhanced delivery (CED) is a promising technique for administering large therapeutics that do not readily cross the blood brain barrier to neural tissue. It is of vital importance to understand how large drug constructs move through neural tissue during CED to optimize construct and delivery parameters so that drugs are concentrated in the targeted tissue, with minimal leakage outside the targeted zone. Experiments have shown that liposomes, viral vectors, high molecular weight tracers, and nanoparticles infused into neural tissue localize in the perivascular spaces of blood vessels within the brain parenchyma. In this work, we used two-photon excited fluorescence microscopy to monitor the real-time distribution of nanoparticles infused in the cortex of live, anesthetized rats via CED. Fluorescent nanoparticles of 24-nm and 100-nm nominal diameters were infused into rat cortex through microfluidic probes. We found that perivascular spaces provide a high permeability path for rapid convective transport of large nanoparticles through tissue, and that the effects of perivascular spaces on transport are more significant for larger particles that undergo hindered transport through the extra cellular matrix. This suggests that the vascular topology of the target tissue volume must be considered when delivering large therapeutic constructs via CED. PMID:22009318

  11. THE PERIVASCULAR POOL OF AQUAPORIN-4 MEDIATES THE EFFECT OF OSMOTHERAPY IN POST-ISCHEMIC CEREBRAL EDEMA

    PubMed Central

    Zeynalov, Emil; Chen, Chih-Hung; Froehner, Stanley C.; Adams, Marvin E.; Ottersen, Ole Petter; Amiry-Moghaddam, Mahmood; Bhardwaj, Anish

    2009-01-01

    Objective Osmotherapy with hypertonic saline (HS) ameliorates cerebral edema associated with experimental ischemic stroke. We tested the hypothesis that HS exerts its anti-edema effect by promoting an efflux of water from brain via the perivascular aquaporin-4 (AQP4) pool. We utilized mice with targeted disruption of the gene encoding α-syntrophin (α-Syn−/−) that lack the perivascular AQP4 pool but retain the endothelial pool of this protein. Design Prospective laboratory animal study. Setting Research laboratory in a university teaching hospital. Measurements and Main Results Halothane-anesthetized adult male wildtype (WT) C57B/6 and α-Syn−/− mice were subjected to 90 min of transient middle cerebral artery occlusion (MCAO) and treated with either a continuous intravenous infusion of 0.9% saline (NS) or 3% HS (1.5 mL/Kg/hr) for 48 hr. In the first series of experiments (n = 59), brain water content analyzed by wet-to-dry ratios in the ischemic hemisphere of WT mice was attenuated after HS (79.9 ± 0.5%mean ± SEM) but not after NS (82.3 ± 1.0%) treatment. In contrast in α-Syn−/− mice, HS had no effect on the postischemic edema (HS: 80.3 ± 0.7% NS: 80.3 ± 0.4%). In the second series of experiments (n = 31), treatment with HS attenuated post-ischemic BBB disruption at 48 hr in WT mice but not in α-Syn−/− mice; α-Syn deletion alone had no effect on BBB integrity. In the third series of experiments (n=34), α-Syn−/− mice treated with either HS or NS had smaller infarct volume as compared with their WT counterparts. Conclusions These data demonstrate that: 1) osmotherapy with HS exerts anti-edema effects via the perivascular pool of AQP4 2) HS attenuates BBB disruption depending on the presence of perivascular AQP4, and 3) deletion of the perivascular pool of AQP4 alleviates tissue damage following stroke, in mice subjected to osmotherapy as well as in non-treated mice. PMID:18679106

  12. Alterations in perivascular innervation function in mesenteric arteries from offspring of diabetic rats

    PubMed Central

    de Queiroz, D B; Sastre, E; Caracuel, L; Callejo, M; Xavier, F E; Blanco-Rivero, J; Balfagón, G

    2015-01-01

    Background and Purpose We have reported that exposure to a diabetic intrauterine environment during pregnancy increases blood pressure in adult offspring, but the mechanisms involved are not completely understood. This study was designed to analyse a possible role of perivascular sympathetic and nitrergic innervation in the superior mesenteric artery (SMA) in this effect. Experimental Approach Diabetes was induced in pregnant Wistar rats by a single injection of streptozotocin. Endothelium-denuded vascular rings from the offspring of control (O-CR) and diabetic rats (O-DR) were used. Vasomotor responses to electrical field stimulation (EFS), NA and the NO donor DEA-NO were studied. The expressions of neuronal NOS (nNOS) and phospho-nNOS (P-nNOS) and release of NA, ATP and NO were determined. Sympathetic and nitrergic nerve densities were analysed by immunofluorescence. Key Results Blood pressure was higher in O-DR animals. EFS-induced vasoconstriction was greater in O-DR animals. This response was decreased by phentolamine more in O-DR animals than their controls. L-NAME increased EFS-induced vasoconstriction more strongly in O-DR than in O-CR segments. Vasomotor responses to NA or DEA-NO were not modified. NA, ATP and NO release was increased in segments from O-DR. nNOS expression was not modified, whereas P-nNOS expression was increased in O-DR. Sympathetic and nitrergic nerve densities were similar in both experimental groups. Conclusions and Implications The activity of sympathetic and nitrergic innervation is increased in SMA from O-DR animals. The net effect is an increase in EFS-induced contractions in these animals. These effects may contribute to the increased blood pressure observed in the offspring of diabetic rats. PMID:26177571

  13. Alterations in Perivascular Sympathetic and Nitrergic Innervation Function Induced by Late Pregnancy in Rat Mesenteric Arteries

    PubMed Central

    Caracuel, Laura; Callejo, María; Balfagón, Gloria

    2015-01-01

    Background and Purpose We investigated whether pregnancy was associated with changed function in components of perivascular mesenteric innervation and the mechanism/s involved. Experimental Approach We used superior mesenteric arteries from female Sprague-Dawley rats divided into two groups: control rats (in oestrous phase) and pregnant rats (20 days of pregnancy). Modifications in the vasoconstrictor response to electrical field stimulation (EFS) were analysed in the presence/absence of phentolamine (alpha-adrenoceptor antagonist) or L-NAME (nitric oxide synthase-NOS- non-specific inhibitor). Vasomotor responses to noradrenaline (NA), and to NO donor DEA-NO were studied, NA and NO release measured and neuronal NOS (nNOS) expression/activation analysed. Key Results EFS induced a lower frequency-dependent contraction in pregnant than in control rats. Phentolamine decreased EFS-induced vasoconstriction in segments from both experimental groups, but to a greater extent in control rats. EFS-induced vasoconstriction was increased by L-NAME in arteries from both experimental groups. This increase was greater in segments from pregnant rats. Pregnancy decreased NA release while increasing NO release. nNOS expression was not modified but nNOS activation was increased by pregnancy. Pregnancy decreased NA-induced vasoconstriction response and did not modify DEA-NO-induced vasodilation response. Conclusions and Implications Neural control of mesenteric vasomotor tone was altered by pregnancy. Diminished sympathetic and enhanced nitrergic components both contributed to the decreased vasoconstriction response to EFS during pregnancy. All these changes indicate the selective participation of sympathetic and nitrergic innervations in vascular adaptations produced during pregnancy. PMID:25951331

  14. Perivascular Adipose Tissue's Impact on Norepinephrine-Induced Contraction of Mesenteric Resistance Arteries

    PubMed Central

    Ayala-Lopez, Nadia; Thompson, Janice M.; Watts, Stephanie W.

    2017-01-01

    Background: Perivascular adipose tissue (PVAT) can decrease vascular contraction to NE. We tested the hypothesis that metabolism and/or uptake of vasoactive amines by mesenteric PVAT (MPVAT) could affect NE-induced contraction of the mesenteric resistance arteries. Methods: Mesenteric resistance vessels (MRV) and MPVAT from male Sprague-Dawley rats were used. RT-PCR and Western blots were performed to detect amine metabolizing enzymes. The Amplex® Red Assay was used to quantify oxidase activity by detecting the oxidase reaction product H2O2 and the contribution of PVAT on the mesenteric arteries' contraction to NE was measured by myography. Results: Semicarbazide sensitive amine oxidase (SSAO) and monoamine oxidase A (MAO-A) were detected in MRV and MPVAT by Western blot. Addition of the amine oxidase substrates tyramine or benzylamine (1 mM) resulted in higher amine oxidase activity in the MRV, MPVAT, MPVAT's adipocyte fraction (AF), and the stromal vascular fraction (SVF). Inhibiting SSAO with semicarbazide (1 mM) decreased amine oxidase activity in the MPVAT and AF. Benzylamine-driven, but not tyramine-driven, oxidase activity in the MRV was reduced by semicarbazide. By contrast, no reduction in oxidase activity in all sample types was observed with use of the monoamine oxidase inhibitors clorgyline (1 μM) or pargyline (1 μM). Inhibition of MAO-A/B or SSAO individually did not alter contraction to NE. However, inhibition of both MAO and SSAO increased the potency of NE at mesenteric arteries with PVAT. Addition of MAO and SSAO inhibitors along with the H2O2 scavenger catalase reduced PVAT's anti-contractile effect to NE. Inhibition of the norepinephrine transporter (NET) with nisoxetine also reduced PVAT's anti-contractile effect to NE. Conclusions: PVAT's uptake and metabolism of NE may contribute to the anti-contractile effect of PVAT. MPVAT and adipocytes within MPVAT are a source of SSAO. PMID:28228728

  15. Wild blueberry consumption attenuates local inflammation in the perivascular adipose tissue of obese Zucker rats.

    PubMed

    Vendrame, Stefano; Tsakiroglou, Panagiotis; Kristo, Aleksandra S; Schuschke, Dale A; Klimis-Zacas, Dorothy

    2016-10-01

    Perivascular adipose tissue (PVAT) has been shown to play important roles in regulating vascular tone and linking local and systemic vascular inflammation. We examined the impact of PVAT on phenylephrine-mediated vasoconstriction in the aorta of obese Zucker rats (OZR) and their lean littermates (LZR) by comparing aortic rings with or without PVAT. Subsequently we placed OZR and LZR on a control (C) or an 8% wild blueberry (WB) diet and evaluated the effect of WB consumption on such response. PVAT-released adipokine concentrations were also measured as a function of WB diet. Maximal constrictor force (Fmax) in aortic rings without PVAT was significantly lower in OZR-C compared with LZR-C (0.41 ± 0.05 and 0.71 ± 0.06 g, respectively). Following WB diet, Fmax significantly increased in OZR (0.54 ± 0.06 g). In aortas with intact PVAT, Fmax was significantly lower in all groups (0.31 ± 0.06 OZR-C, 0.30 ± 0.05 OZR-WB, 0.29 ± 0.03 LZR-C, and 0.30 ± 0.04 g LZR-WB), but no difference was observed between treatments. PVAT concentrations of monocyte chemoactractant protein 1 (MCP-1), tumor necrosis factor alpha, and adiponectin were significantly higher in OZR compared with LZR (+102%, +108%, and +45%, respectively). Following WB diet, PVAT concentrations of interleukin-8 were significantly lower in both OZR (-37%) and LZR (-30%), while adiponectin concentrations significantly increased in both OZR (+11%) and LZR (+16%). MCP-1 concentrations significantly decreased (-31%) in the PVAT of OZR with the WB diet. WB consumption appears to attenuate local inflammation in PVAT, which may impact systemic vascular inflammation and endothelial function.

  16. Effect of resveratrol and orchidectomy on the vasorelaxing influence of perivascular adipose tissue.

    PubMed

    Boydens, Charlotte; Pauwels, Bart; Van de Voorde, Johan

    2016-04-01

    Perivascular adipose tissue (PVAT) releases several adipo(cyto)kines. Some are vasoactive substances that elicit a net beneficial anticontractile effect. Resveratrol and testosterone are known to modulate adipo(cyto)kine release from adipose tissue and could therefore influence the anticontractile effect of PVAT. In vitro tension measurements were performed using thoracic aorta segments with and without adipose tissue from sham-operated or orchidectomized male Swiss mice. Concentration-response curves to norepinephrine (NOR) were constructed in the presence and absence of resveratrol (10 μM, 15 min) or the relaxant effect of resveratrol (10-100 μM) was investigated after inducing tone with NOR (5 μM). Aortas with PVAT displayed significantly attenuated contractions to NOR compared with aortas without PVAT. In aortas without PVAT, resveratrol (10 μM) significantly decreased NOR responses and elicited concentration-dependent (10-100 µM) relaxations. However, in aortas with adherent PVAT, resveratrol (10 μM) neither decreased NOR responses, nor did resveratrol (10-100 µM) induce arterial relaxations. The anticontractile effect of PVAT was less pronounced in the presence of resveratrol and unaltered by orchidectomy. Orchidectomy did not influence contractions induced by NOR. Orchidectomy does not modulate the anticontractile capacity of PVAT, while resveratrol decreases the vasorelaxing influence of PVAT. The positive effects associated with resveratrol addition are neutralized by the presence of PVAT. This is thought to result from a dual effect of resveratrol: (1) inhibition of the influence of vasodilatory adipo(cyto)kines and (2) a direct relaxant effect on the vascular smooth muscle. Overall, the beneficial relaxing effect of resveratrol is lost in mice thoracic aorta surrounded by PVAT.

  17. Vascular and Perivascular NO Release and Transport: Biochemical Pathways of NOS1 and NOS3

    PubMed Central

    Chen, Kejing; Popel, Aleksander S.

    2007-01-01

    Nitric oxide (NO) derived from nitric oxide synthase (NOS) is an important paracrine effector that maintains vascular tone. The release of NO mediated by NOS isozymes under various O2 conditions critically determines the NO bioavailability in tissues. Because of experimental difficulties, there has been no direct information on how enzymatic NO production and distribution change around arterioles under various oxygen conditions. In this study, we used computational models based on the analysis of biochemical pathways of enzymatic NO synthesis and the availability of NOS isozymes to quantify the NO production by neuronal NOS (NOS1) and endothelial NOS (NOS3). We compared the catalytic activities of NOS1 and NOS3 and their sensitivities to the concentration of substrate O2. Based on the NO release rates predicted from kinetic models, the geometric distribution of NO sources and mass balance analysis, we predicted the NO concentration profiles around an arteriole under various O2 conditions. The results indicated that NOS1-catalyzed NO production was significantly more sensitive to ambient O2 concentration than that catalyzed by NOS3. Also, the high sensitivity of NOS1 catalytic activity to O2 was associated with significantly reduced NO production and therefore NO concentrations, upon hypoxia. Moreover, the major source determining the distribution of NO was NOS1, which was abundantly expressed in the nerve fibers and mast cells close to arterioles, rather than NOS3, which was expressed in the endothelium. Finally, the perivascular NO concentration predicted by the models under conditions of normoxia was paradoxically at least an order of magnitude lower than a number of experimental measurements, suggesting a higher abundance of NOS1 or NOS3 and/or the existence of other enzymatic or non-enzymatic sources of NO in the microvasculature. PMID:17320763

  18. Transcriptional Networks in Single Perivascular Cells Sorted from Human Adipose Tissue Reveal a Hierarchy of Mesenchymal Stem Cells.

    PubMed

    Hardy, W Reef; Moldovan, Nicanor I; Moldovan, Leni; Livak, Kenneth J; Datta, Krishna; Goswami, Chirayu; Corselli, Mirko; Traktuev, Dmitry O; Murray, Iain R; Péault, Bruno; March, Keith

    2017-02-24

    Adipose tissue is a rich source of multipotent mesenchymal stem-like cells, located in the perivascular niche. Based on their surface markers, these have been assigned to two main categories: CD31(-) /CD45(-) /CD34(+) /CD146(-) cells (adventitial stromal/stem cells [ASCs]) and CD31(-) /CD45(-) /CD34(-) /CD146(+) cells (pericytes [PCs]). These populations display heterogeneity of unknown significance. We hypothesized that aldehyde dehydrogenase (ALDH) activity, a functional marker of primitivity, could help to better define ASC and PC subclasses. To this end, the stromal vascular fraction from a human lipoaspirate was simultaneously stained with fluorescent antibodies to CD31, CD45, CD34, and CD146 antigens and the ALDH substrate Aldefluor, then sorted by fluorescence-activated cell sorting. Individual ASCs (n = 67) and PCs (n = 73) selected from the extremities of the ALDH-staining spectrum were transcriptionally profiled by Fluidigm single-cell quantitative polymerase chain reaction for a predefined set (n = 429) of marker genes. To these single-cell data, we applied differential expression and principal component and clustering analysis, as well as an original gene coexpression network reconstruction algorithm. Despite the stochasticity at the single-cell level, covariation of gene expression analysis yielded multiple network connectivity parameters suggesting that these perivascular progenitor cell subclasses possess the following order of maturity: (a) ALDH(br) ASC (most primitive); (b) ALDH(dim) ASC; (c) ALDH(br) PC; (d) ALDH(dim) PC (least primitive). This order was independently supported by specific combinations of class-specific expressed genes and further confirmed by the analysis of associated signaling pathways. In conclusion, single-cell transcriptional analysis of four populations isolated from fat by surface markers and enzyme activity suggests a developmental hierarchy among perivascular mesenchymal stem cells supported by markers and

  19. Human Perivascular Stem Cells Show Enhanced Osteogenesis and Vasculogenesis with Nel-Like Molecule I Protein

    PubMed Central

    Askarinam, Asal; James, Aaron W.; Zara, Janette N.; Goyal, Raghav; Corselli, Mirko; Pan, Angel; Liang, Pei; Chang, Le; Rackohn, Todd; Stoker, David; Zhang, Xinli; Ting, Kang; Péault, Bruno

    2013-01-01

    An ideal mesenchymal stem cell (MSC) source for bone tissue engineering has yet to be identified. Such an MSC population would be easily harvested in abundance, with minimal morbidity and with high purity. Our laboratories have identified perivascular stem cells (PSCs) as a candidate cell source. PSCs are readily isolatable through fluorescent-activated cell sorting from adipose tissue and have been previously shown to be indistinguishable from MSCs in the phenotype and differentiation potential. PSCs consist of two distinct cell populations: (1) pericytes (CD146+, CD34−, and CD45−), which surround capillaries and microvessels, and (2) adventitial cells (CD146−, CD34+, and CD45−), found within the tunica adventitia of large arteries and veins. We previously demonstrated the osteogenic potential of pericytes by examining pericytes derived from the human fetal pancreas, and illustrated their in vivo trophic and angiogenic effects. In the present study, we used an intramuscular ectopic bone model to develop the translational potential of our original findings using PSCs (as a combination of pericytes and adventitial cells) from human white adipose tissue. We evaluated human PSC (hPSC)-mediated bone formation and vascularization in vivo. We also examined the effects of hPSCs when combined with the novel craniosynostosis-associated protein, Nel-like molecule I (NELL-1). Implants consisting of the demineralized bone matrix putty combined with NELL-1 (3 μg/μL), hPSC (2.5×105 cells), or hPSC+NELL-1, were inserted in the bicep femoris of SCID mice. Bone growth was evaluated using microcomputed tomography, histology, and immunohistochemistry over 4 weeks. Results demonstrated the osteogenic potential of hPSCs and the additive effect of hPSC+NELL-1 on bone formation and vasculogenesis. Comparable osteogenesis was observed with NELL-1 as compared to the more commonly used bone morphogenetic protein-2. Next, hPSCs induced greater implant vascularization than the

  20. Organic cation transporter 3 contributes to norepinephrine uptake into perivascular adipose tissue.

    PubMed

    Ayala-Lopez, Nadia; Jackson, William F; Burnett, Robert; Wilson, James N; Thompson, Janice M; Watts, Stephanie W

    2015-12-01

    Perivascular adipose tissue (PVAT) reduces vasoconstriction to norepinephrine (NE). A mechanism by which PVAT could function to reduce vascular contraction is by decreasing the amount of NE to which the vessel is exposed. PVATs from male Sprague-Dawley rats were used to test the hypothesis that PVAT has a NE uptake mechanism. NE was detected by HPLC in mesenteric PVAT and isolated adipocytes. Uptake of NE (10 μM) in mesenteric PVAT was reduced by the NE transporter (NET) inhibitor nisoxetine (1 μM, 73.68 ± 7.62%, all values reported as percentages of vehicle), the 5-hydroxytryptamine transporter (SERT) inhibitor citalopram (100 nM) with the organic cation transporter 3 (OCT3) inhibitor corticosterone (100 μM, 56.18 ± 5.21%), and the NET inhibitor desipramine (10 μM) with corticosterone (100 μM, 61.18 ± 6.82%). Aortic PVAT NE uptake was reduced by corticosterone (100 μM, 53.01 ± 10.96%). Confocal imaging of mesenteric PVAT stained with 4-[4-(dimethylamino)-styrl]-N-methylpyridinium iodide (ASP(+)), a fluorescent substrate of cationic transporters, detected ASP(+) uptake into adipocytes. ASP(+) (2 μM) uptake was reduced by citalopram (100 nM, 66.68 ± 6.43%), corticosterone (100 μM, 43.49 ± 10.17%), nisoxetine (100 nM, 84.12 ± 4.24%), citalopram with corticosterone (100 nM and 100 μM, respectively, 35.75 ± 4.21%), and desipramine with corticosterone (10 and 100 μM, respectively, 50.47 ± 5.78%). NET protein was not detected in mesenteric PVAT adipocytes. Expression of Slc22a3 (OCT3 gene) mRNA and protein in PVAT adipocytes was detected by RT-PCR and immunocytochemistry, respectively. These end points support the presence of a transporter-mediated NE uptake system within PVAT with a potential mediator being OCT3.

  1. Perivascular Adipose Tissue Inflammation and Coronary Artery Disease: An Autopsy Study Protocol

    PubMed Central

    Farias-Itao, Daniela Souza; Pasqualucci, Carlos Augusto; Nishizawa, Aline; Silva, Luiz Fernando Ferraz; Campos, Fernanda Marinho; da Silva, Karen Cristina Souza; Leite, Renata Elaine Paraizo; Grinberg, Lea Tenenholz; Ferretti-Rebustini, Renata Eloah Lucena; Jacob Filho, Wilson

    2016-01-01

    Background Perivascular adipose tissue (PAT) inflammation may have a role in coronary artery disease (CAD) pathophysiology. However, most evidence has come from samples obtained during surgical procedures that may imply in some limitations. Moreover, the role of B lymphocytes and inflammation in PAT that is adjacent to unstable atheroma plaques has not been investigated in humans using morphometric measurements. Objective The objective of this study is to investigate the inflammation in PAT, subcutaneous, and perirenal adipose tissues (SAT and PrAT) among chronic CAD, acute CAD, and control groups in an autopsy study. Methods Heart, SAT, and PrAT samples are collected from autopsied subjects in a general autopsy service, with the written informed consent of the next-of-kin (NOK). Sociodemographic and clinical data are obtained from a semistructure interview with the NOK. Coronary arteries are dissected and PAT are removed. Sections with the greatest arterial obstruction or unstable plaques, and the local with absence of atherosclerosis in all coronary arteries are sampled. PAT are represented adjacent to these fragments. Adipose tissues are fixed in 4% buffered paraformaldehyde solution and analyzed immunohistochemically for macrophages (CD68), macrophage polarization (CD11c for proinflammatory and CD206 for anti-inflammatory), B lymphocytes (CD20), and T lymphocytes (CD3). Slides will be scanned, and inflammatory cells will be quantified in 20 random fields. Participants will be categorized in CAD groups, after morphometric measurement of arterial obstruction and plaque composition analysis in accordance with American Heart Association classification. Three study groups will be investigated: acute CAD (at least one unstable plaque); chronic CAD (≥50% arterial obstruction); and controls (<50% arterial obstruction). Inflammatory cells in PAT, SAT, and PrAT will be counted and compared between groups using multivariate linear regression, adjusted for age, body mass

  2. Nerve growth factor facilitates redistribution of adrenergic and non-adrenergic non-cholinergic perivascular nerves injured by phenol in rat mesenteric resistance arteries.

    PubMed

    Yokomizo, Ayako; Takatori, Shingo; Hashikawa-Hobara, Narumi; Goda, Mitsuhiro; Kawasaki, Hiromu

    2016-01-05

    We previously reported that nerve growth factor (NGF) facilitated perivascular sympathetic neuropeptide Y (NPY)- and calcitonin gene-related peptide (CGRP)-containing nerves injured by the topical application of phenol in the rat mesenteric artery. We also demonstrated that mesenteric arterial nerves were distributed into tyrosine hydroxylase (TH)-, substance P (SP)-, and neuronal nitric oxide synthase (nNOS)-containing nerves, which had axo-axonal interactions. In the present study, we examined the effects of NGF on phenol-injured perivascular nerves, including TH-, NPY-, nNOS-, CGRP-, and SP-containing nerves, in rat mesenteric arteries in more detail. Wistar rats underwent the in vivo topical application of 10% phenol to the superior mesenteric artery, proximal to the abdominal aorta, under pentobarbital-Na anesthesia. The distribution of perivascular nerves in the mesenteric arteries of the 2nd to 3rd-order branches isolated from 8-week-old Wistar rats was investigated immunohistochemically using antibodies against TH-, NPY-, nNOS-, CGRP-, and SP-containing nerves. The topical phenol treatment markedly reduced the density of all nerves in these arteries. The administration of NGF at a dose of 20µg/kg/day with an osmotic pump for 7 days significantly increased the density of all perivascular nerves over that of sham control levels. These results suggest that NGF facilitates the reinnervation of all perivascular nerves injured by phenol in small resistance arteries.

  3. Minute perivascular epithelioid cell (PEC) nests in the abdominal lymph nodes--a putative precursor of PEComa.

    PubMed

    Nagasaka, Toru; Murakami, Yoshiko; Sasaki, Eiichi; Hosoda, Waki; Nakanishi, Toru; Yatabe, Yasushi

    2015-04-01

    A perivascular epithelioid cell tumor (PEComa) is a peculiar growth defined as a mesenchymal tumor composed of histologically and immunohistochemically distinct perivascular epithelioid cells (PECs). Because neither normal counterparts nor precursor lesions of PEComa have been identified, we examined minute PEC nests, ranged from 0.8 mm to 10 mm, to investigate the possible origin of the PEComa. We examined a total of 80 677 para-aortic and pelvic lymph nodes that were systematically dissected from 1656 patients for gynecological malignancies. The identified lesions were confirmed immunohistochemically with multiple PEC markers, including smooth muscle actin, HMB45, melan-A, MiTF, ER and PgR. A total of 66 minute PEC nests were found in 21 patients (1.3% of the total population) with an average frequency of 3.1 lesions per patient. In cases of multiple involvement, 11 of 13 nests were located at the same level of multiple lymph node or on continuous levels. The lesions were preferentially distributed at the level of para-aortic and high pelvic lymph nodes. All nests were positive for actin and HMB45, whereas the other markers were positive with varying frequencies. The minute PEC nests may be associated with the possible normal counterpart of PEComas.

  4. Induction of Perivascular Neural Stem Cells and Possible Contribution to Neurogenesis Following Transient Brain Ischemia/Reperfusion Injury.

    PubMed

    Nakata, Masayo; Nakagomi, Takayuki; Maeda, Mitsuyo; Nakano-Doi, Akiko; Momota, Yoshihiro; Matsuyama, Tomohiro

    2017-04-01

    Recent therapeutic advances have increased the likelihood of recanalizing the obstructed brain arteries in patients with stroke. Therefore, it is important to understand the fate of neural cells under transient ischemia/reperfusion injury. Accumulating evidence shows that neurogenesis occurs in perivascular regions following brain injury, although the precise mechanism and origin of these newborn neurons under transient ischemia/reperfusion injury remain unclear. Using a mouse model of transient brain ischemia/reperfusion injury, we found that neural stem cells (NSCs) develop within injured areas. This induction of NSCs following ischemia/reperfusion injury was observed even in response to nonlethal ischemia, although massive numbers of NSCs were induced by lethal ischemia. Immunohistochemical and immunoelectron microscopic studies indicated that platelet-derived growth factor receptor beta-positive (PDGFRβ(+)) pericytes within injured areas following nonlethal ischemia began to express the NSC marker nestin as early as 3 days after transient ischemia/reperfusion. Some PDGFRβ(+) pericytes expressed the immature neuronal marker doublecortin at day 7. These findings indicate that brain pericytes are a potential source of the perivascular NSCs that generate neuronal cells under lethal and nonlethal ischemic conditions following transient ischemia/reperfusion. Thus, brain pericytes might be a target for neurogenesis mediation in patients with nonlethal and lethal ischemia following transient ischemia/reperfusion injury.

  5. Expanding the clinical, radiological and neuropathological phenotype of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS).

    PubMed

    Simon, Neil G; Parratt, John D; Barnett, Michael H; Buckland, Michael E; Gupta, Ruta; Hayes, Michael W; Masters, Lynette T; Reddel, Stephen W

    2012-01-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described inflammatory disease of the CNS with a predilection for the hindbrain and responsive to immunotherapy. Five further cases are described with detailed pathology and long term evaluation. CLIPPERS does not represent a benign condition, and without chronic immunosuppression the disease may relapse. The radiological distribution is focused not only in the pons but also in the brachium ponti and cerebellum. Pontocerebellar atrophy occurred early, even in cases treated promptly. Significant cognitive impairment was seen in some cases and was associated with additional cerebral atrophy. The pathology included distinctive histiocytic as well as lymphocytic components and evidence of neuro-axonal injury. Additional subclinical systemic findings on investigation were identified. Relapse was associated with withdrawal of corticosteroids, and disability was least marked in cases where both the presentation and relapses were treated promptly. We propose that the title of the syndrome be amended to chronic lymphocytic inflammation with pontocerebellar perivascular enhancement responsive to steroids to more accurately reflect the distribution of the radiological findings.

  6. [Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) associated with swelling in the brainstem: a case report].

    PubMed

    Tani, Hiroki; Nakajima, Hideto; Yamane, Kazushi; Ohnishi, Hiroyuki; Kimura, Fumiharu; Hanafusa, Toshiaki

    2014-01-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare central nervous system inflammatory disease characterized by the punctate gadolinium enhancement peppering the pons and the cerebellar peduncles as neuroimaging. We report the case of a 66-year-old woman who presented with CLIPPERS associated with swelling in the brainstem. She was hospitalized because of gait ataxia and consciousness disturbance. MRI of the brain showed FLAIR hyperintense lesions in the pons, cerebellar peduncles, cerebellum and the subcortical white matter lesion in the right occipital lobe with significant swelling in the brainstem. Diffusion-weighted MRI did not show an abnormal signal, indicating vasogenic edema. Post-contrast T1-weighted MRI showed enhanced area in the right occipital lobe and panctate gadolinium enhancement peppering brainstem. Treatment with steroids led to rapid improvement. However, she showed exacerbation of clinical and radiological findings during the tapering schedule of steroid. The biopsy from the occipital lobe revealed intense perivascular and parenchymal lymphocytic infiltrates composed of primarily T cells, B cells and macrophages. The patient was diagnosed with CLIPPERS, and treatment with increased dose of corticosteroid induced a clinical improvement. Previous reports well described a characteristic MRI finding of punctate enhancement peppering the pons. In addition, the pons and cerebellar peduncles swelling can occur in this disorder.

  7. S1P lyase in thymic perivascular spaces promotes egress of mature thymocytes via up-regulation of S1P receptor 1.

    PubMed

    Maeda, Yasuhiro; Yagi, Hideki; Takemoto, Kana; Utsumi, Hiroyuki; Fukunari, Atsushi; Sugahara, Kunio; Masuko, Takashi; Chiba, Kenji

    2014-05-01

    Sphingosine 1-phosphate (S1P) and S1P receptor 1 (S1P1) play an important role in the egress of mature CD4 or CD8 single-positive (SP) thymocytes from the thymus. Fingolimod hydrochloride (FTY720), an S1P1 functional antagonist, induced significant accumulation of CD62L(high)CD69(low) mature SP thymocytes in the thymic medulla. Immunohistochemical staining using anti-S1P1 antibody revealed that S1P1 is predominantly expressed on thymocytes in the thymic medulla and is strongly down-regulated even at 3h after FTY720 administration. 2-Acetyl-4-tetrahydroxybutylimidazole (THI), an S1P lyase inhibitor, also induced accumulation of mature SP thymocytes in the thymic medulla with an enlargement of the perivascular spaces (PVS). At 6h after THI administration, S1P1-expressing thymocytes reduced partially as if to form clusters and hardly existed in the proximity of CD31-expressing blood vessels in the thymic medulla, suggesting S1P lyase expression in the cells constructing thymic medullary PVS. To determine the cells expressing S1P lyase in the thymus, we newly established a mAb (YK19-2) specific for mouse S1P lyase. Immunohistochemical staining with YK19-2 revealed that S1P lyase is predominantly expressed in non-lymphoid thymic stromal cells in the thymic medulla. In the thymic medullary PVS, S1P lyase was expressed in ER-TR7-positive cells (reticular fibroblasts and pericytes) and CD31-positive vascular endothelial cells. Our findings suggest that S1P lyase expressed in the thymic medullary PVS keeps the tissue S1P concentration low around the vessels and promotes thymic egress via up-regulation of S1P1.

  8. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): A case report and review of literature.

    PubMed

    Reddy, Soma Madhan; Lath, Rahul; Swain, Meenakshi; Ranjan, Alok

    2015-01-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described inflammatory disease of central nervous system with distinct clinical and radiological features. The etiopathogenesis of this rare entity remains to be understood. The histopathological findings closely resemble chronic inflammatory diseases like sarcoidosis and malignancies like lymphoma. With advancements in serology, immunopathology and radiology CLIPPERS is identified as a distinct entity that differs considerably in its clinical presentation, immunopathology, radiological findings and response to steroids. We describe a case that presented to us with progressive quadriparesis and lower cranial nerve deficits whose radiological and pathological findings were consistent with CLIPPERS. The patient had a good outcome with long term immunosuppression.

  9. Phenotypic analysis of pulmonary perivascular mononuclear infiltrates that occur as a direct result of acute lethal graft-versus-host disease describes the onset of interstitial pneumonitis.

    PubMed Central

    Workman, D. L.; Clancy, J.

    1995-01-01

    We recently determined that the sequential development of interstitial pneumonitis and lymphocytic bronchiolitis/bronchitis occurs as a direct result of acute lethal graft-versus-host disease. Interstitial pneumonitis develops before lymphocytic bronchiolitis/bronchitis primarily from the dissemination of perivascular mononuclear infiltrates. We have used the adult, nonirradiated (DA x LEW) F1 hybrid rat in the absence of chemotherapy, immunosuppression, or overt infection to determine the phenotype of infiltrating perivascular mononuclear cells throughout acute lethal graft-versus-host disease. F1 animals were intravenously injected with 1 x 10(6) DA parental lymphoid cells/g body weight, which produced 100% morbidity and mortality by day 21. Graft-versus-host disease animals were killed on days 3, 7, 10, 14, and 15 to 21 after injection. Whole left lung lobes were frozen, serially sectioned (4 microns), and incubated with a panel of mouse anti-rat monoclonal antibodies. Labeled antibody density was determined by computerized image analysis. Perivascular infiltration was observed first for ED1+, OX8+, and W3/25+ cells, and then OX41+, W3/13+ and OX19/25+ populations. OX6 was expressed in control tissues and at all time points tested. OX12+, OX39+ and MOM/3F12/F2+ cells were not quantifiable. The present study has determined that the process of perivascular infiltration was produced through a biphasic influx of OX6+, T-cell, and macrophage populations. Images Figure 1 Figure 4 PMID:7485398

  10. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) with intracranial Epstein–Barr virus infection

    PubMed Central

    Ma, Yue; Sun, Xiaolong; Li, Wen; Li, Yi; Kang, Tao; Yang, Xiai; Jiang, Wen

    2016-01-01

    Abstract Background: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder in the central nervous system (CNS) with distinct clinical, radiological, and pathological features. The pathophysiology of CLIPPERS still remains unclear and the reports are quite few. Although the radiological lesions were reported to be located predominantly in the pons, brachium pontis, and cerebellum, other adjacent structures such as the white matter and spinal cord were very recently reported as involved regions in CLIPPERS. In this study, we report a case of CLIPPERS presenting with intracranial Epstein–Barr virus (EBV) infection and diffuse white matter involvement. Case summary: A 37-year-old male was diagnosed with mediastinal Hodgkin's lymphoma (lymphocyte predominance type) at the age of 26, and then obtained complete remission after treatment and remained free of relapse for 11 years. He was admitted with 7 months’ history of mental disorder, and 20 days’ history of gait and limb ataxia, dysphagia, and cough. The diagnosis of CLIPPERS was established based on the findings of punctate and nodular enhancing lesions in the bilateral pons, the basal ganglia, the mid-brain, the pontine brachium, and diffuse white matter in magnetic resonance imaging (MRI), together with CD3+ T-lymphocytic inflammatory infiltration in perivascular and parenchymal area revealed by bilateral parietal lobe brain biopsy. Also, our patient exhibited a good response to steroid therapy and remained free of relapse for 5 months. Importantly, we found intracranial Epstein–Barr virus infection in this patient. Conclusion: CLIPPERS might be an autoimmune disorder, and intracranial EBV-infection raises the possibility that EBV-associated autoimmunity is associated with CLIPPERS pathogenesis. PMID:27861371

  11. Clinical-Grade Isolated Human Kidney Perivascular Stromal Cells as an Organotypic Cell Source for Kidney Regenerative Medicine.

    PubMed

    Leuning, Daniëlle G; Reinders, Marlies E J; Li, Joan; Peired, Anna J; Lievers, Ellen; de Boer, Hetty C; Fibbe, Willem E; Romagnani, Paola; van Kooten, Cees; Little, Melissa H; Engelse, Marten A; Rabelink, Ton J

    2017-02-01

    Mesenchymal stromal cells (MSCs) are immunomodulatory and tissue homeostatic cells that have shown beneficial effects in kidney diseases and transplantation. Perivascular stromal cells (PSCs) identified within several different organs share characteristics of bone marrow-derived MSCs (BM-MSCs). These PSCs may also possess tissue-specific properties and play a role in local tissue homeostasis. We hypothesized that human kidney-derived PSCs (hkPSCs) would elicit improved kidney repair in comparison with BM-MSCs. Here we introduce a novel, clinical-grade isolation method of hkPSCs from cadaveric kidneys by enriching for the perivascular marker, NG2. hkPSCs show strong transcriptional similarities to BM-MSCs but also show organotypic expression signatures, including the HoxD10 and HoxD11 nephrogenic transcription factors. Comparable to BM-MSCs, hkPSCs showed immunosuppressive potential and, when cocultured with endothelial cells, vascular plexus formation was supported, which was specifically in the hkPSCs accompanied by an increased NG2 expression. hkPSCs did not undergo myofibroblast transformation after exposure to transforming growth factor-β, further corroborating their potential regulatory role in tissue homeostasis. This was further supported by the observation that hkPSCs induced accelerated repair in a tubular epithelial wound scratch assay, which was mediated through hepatocyte growth factor release. In vivo, in a neonatal kidney injection model, hkPSCs reintegrated and survived in the interstitial compartment, whereas BM-MSCs did not show this potential. Moreover, hkPSCs gave protection against the development of acute kidney injury in vivo in a model of rhabdomyolysis-mediated nephrotoxicity. Overall, this suggests a superior therapeutic potential for the use of hkPSCs and their secretome in the treatment of kidney diseases. Stem Cells Translational Medicine 2017;6:405-418.

  12. Fractalkine Signaling Attenuates Perivascular Clustering of Microglia and Fibrinogen Leakage during Systemic Inflammation in Mouse Models of Diabetic Retinopathy

    PubMed Central

    Mendiola, Andrew S.; Garza, Rolando; Cardona, Sandra M.; Mythen, Shannon A.; Lira, Sergio A.; Akassoglou, Katerina; Cardona, Astrid E.

    2017-01-01

    Fractalkine (FKN) is a chemokine expressed constitutively by healthy neurons and signals to microglia upon interaction with the FKN receptor, CX3CR1. Signaling between FKN and CX3CR1 transduces inhibitory signals that ameliorate microglial activation and proinflammatory cytokine release in neuroinflammatory conditions. The aim of this study is to determine the mechanisms associated with microglial activation and vascular leakage during diabetic retinopathy (DR) and under conditions of low-level endotoxemia, common in diabetic patients. Utilizing the Ins2Akita strain (Akita), a mouse model of type 1 diabetes, our results show that leakage of the blood-protein fibrin(ogen) into the retina occurs as a result of chronic (4 months) but not acute (1.5 months) hyperglycemia. Conversely, inducing endotoxin-mediated systemic inflammation during acute diabetes resulted in fibrinogen deposition in the retina, a phenotype that was exacerbated in mice lacking CX3CR1 signaling. Systemic inflammation in Cx3cr1−/− mice led to robust perivascular clustering of proliferating microglia in areas of fibrinogen extravasation, and induced IL-1β expression in microglia and astrocytes. Lastly, we determined a protective effect of modulating FKN/CX3CR1 signaling in the diabetic retina. We show that intravitreal (iv) administration of recombinant FKN into diabetic FKN-KO mice, reduced fibrinogen deposition and perivascular clustering of microglia in the retina during systemic inflammation. These data suggest that dysregulated microglial activation via loss of FKN/CX3CR1 signaling disrupts the vascular integrity in retina during systemic inflammation. PMID:28119571

  13. Endothelial nitric oxide synthase uncoupling and perivascular adipose oxidative stress and inflammation contribute to vascular dysfunction in a rodent model of metabolic syndrome.

    PubMed

    Marchesi, Chiara; Ebrahimian, Talin; Angulo, Orlando; Paradis, Pierre; Schiffrin, Ernesto L

    2009-12-01

    The metabolic syndrome represents a constellation of cardiovascular risk factors that promote the development of cardiovascular disease. Oxidative stress is a mediator of endothelial dysfunction and vascular remodeling. We investigated vascular dysfunction in the metabolic syndrome and the oxidant mechanisms involved. New Zealand obese (NZO) mice with metabolic syndrome and New Zealand black control mice were studied. NZO mice showed insulin resistance and increased visceral fat and blood pressure compared with New Zealand black mice. Mesenteric resistance arteries from NZO mice exhibited increased media:lumen ratio and media cross-sectional area, demonstrating hypertrophic vascular remodeling. Endothelium-dependent relaxation to acetylcholine, assessed by pressurized myography, was impaired in NZO mice, not affected by N(G)-nitro-l-arginine methyl ester, inhibitor of endothelial NO synthase, and improved by the antioxidant Tempol, suggesting reduced NO bioavailability and increased oxidative stress. Dimer:monomer ratio of endothelial NO synthase was decreased in NZO mice compared with New Zealand black mice, suggesting endothelial NO synthase uncoupling. Furthermore, vascular superoxide and peroxynitrite production was increased, as well as adhesion molecule expression. Perivascular adipose tissue of NZO mice showed increased superoxide production and NADPH oxidase activity, as well as adipocyte hypertrophy, associated with inflammatory Mac-3-positive cell infiltration. Vasoconstriction to norepinephrine decreased in the presence of perivascular adipose tissue in New Zealand black mice but was unaffected by perivascular adipose tissue in NZO mice, suggesting loss of perivascular adipose tissue anticontractile properties. Our data suggest that this rodent model of metabolic syndrome is associated with perivascular adipose inflammation and oxidative stress, hypertrophic resistance artery remodeling, and endothelial dysfunction, the latter a result of decreased NO

  14. Celecoxib, but not indomethacin, ameliorates the hypertensive and perivascular fibrotic actions of cyclosporine in rats: Role of endothelin signaling

    SciTech Connect

    El-Mas, Mahmoud M.; Helmy, Maged W.; Ali, Rabab M.; El-Gowelli, Hanan M.

    2015-04-01

    The immunosuppressant drug cyclosporine (CSA) is used with nonsteroidal antiinflammatory drugs (NSAIDs) in arthritic conditions. In this study, we investigated whether NSAIDs modify the deleterious hypertensive action of CSA and the role of endothelin (ET) receptors in this interaction. Pharmacologic, protein expression, and histopathologic studies were performed in rats to investigate the roles of endothelin receptors (ET{sub A}/ET{sub B}) in the hemodynamic interaction between CSA and two NSAIDs, indomethacin and celecoxib. Tail-cuff plethysmography measurements showed that CSA (20 mg kg{sup −1} day{sup −1}, 10 days) increased systolic blood pressure (SBP) and heart rate (HR). CSA hypertension was associated with renal perivascular fibrosis and divergent changes in immunohistochemical signals of renal arteriolar ET{sub A} (increases) and ET{sub B} (decreases) receptors. While these effects of CSA were preserved in rats treated concomitantly with indomethacin (5 mg kg{sup −1} day{sup −1}), celecoxib (10 mg kg{sup −1} day{sup −1}) abolished the pressor, tachycardic, and fibrotic effects of CSA and normalized the altered renal ET{sub A}/ET{sub B} receptor expressions. Selective blockade of ET{sub A} receptors by atrasentan (5 mg kg{sup −1} day{sup −1}) abolished the pressor response elicited by CSA or CSA plus indomethacin. Alternatively, BQ788 (ET{sub B} receptor blocker, 0.1 mg kg{sup −1} day{sup −1}) caused celecoxib-sensitive elevations in SBP and potentiated the pressor response evoked by CSA. Together, the improved renovascular fibrotic and endothelin receptor profile (ET{sub A} downregulation and ET{sub B} upregulation) mediate, at least partly, the protective effect of celecoxib against the hypertensive effect of CSA. Clinically, the use of celecoxib along with CSA in the management of arthritic conditions might provide hypertension-free regimen. - Highlights: • Chronic CSA causes hypertension and renal perivascular fibrosis in rats.

  15. The Infrapatellar Fat Pad as a Source of Perivascular Stem Cells with Increased Chondrogenic Potential for Regenerative Medicine.

    PubMed

    Hindle, Paul; Khan, Nusrat; Biant, Leela; Péault, Bruno

    2017-01-01

    Perivascular stem cells (PSCs) are the natural ancestors of mesenchymal stem cells (MSCs) and are the stem cells responsible for homeostasis and repair in vivo. Prospectively identified and isolated PSCs have demonstrated increased plasticity and osteogenic potential. Cells from the infrapatellar fat pad (IFP) have demonstrated increased chondrogenic potential compared with those from subcutaneous fat. This research assessed the chondrogenic potential of IFP PSCs compared with MSCs from the IFP and bone marrow. Immunohistochemistry demonstrated the location of perivascular markers (CD146, CD34, neural/glial antigen 2 [NG2], platelet-derived growth factor receptor-β [PDGFRβ], and α-smooth muscle actin [α-SMA]) in relation to endothelial markers (CD31, CD144, von Willebrand factor [vWF]). Pericytes and adventitial cells were isolated from the stromal vascular fraction (3.8% and 21.2%, respectively) using flow cytometry with a viability of 88%. The mean numbers of pericytes and adventitial cells isolated were 4.6 ± 2.2 × 10(4) and 16.2 ± 3.2 × 10(4) , respectively, equating to 7.9 ± 4.4 × 10(3) and 20.8 ± 4.3 × 10(3) cells per gram of harvested tissue. Fluorescence-activated cell sorting demonstrated that cultured PSCs were CD44+CD90+CD105+; polymerase chain reaction and immunocytochemistry demonstrated that pericytes retained their CD146+ phenotype and expressed the pericyte markers PDGFRβ and NG2. Differentiation was confirmed using histochemical stains and genetic expression. Using a pellet model, the IFP PSCs and the MSCs generated significantly more extracellular matrix than bone marrow MSCs (p < .001 and p = .011, respectively). The IFP PSCs generated significantly more extracellular matrix than IFP MSCs (p = .002). Micromass culture demonstrated that differentiated PSCs were upregulated compared with MSCs for COL2A1, ACAN, and SOX9 expression by factors of 4.8 ± 1.3, 4.3 ± 0.9, and 7.0 ± 1.7, respectively. The IFP was a significantly better

  16. The Infrapatellar Fat Pad as a Source of Perivascular Stem Cells With Increased Chondrogenic Potential for Regenerative Medicine.

    PubMed

    Hindle, Paul; Khan, Nusrat; Biant, Leela; Péault, Bruno

    2016-08-05

    : Perivascular stem cells (PSCs) are the natural ancestors of mesenchymal stem cells (MSCs) and are the stem cells responsible for homeostasis and repair in vivo. Prospectively identified and isolated PSCs have demonstrated increased plasticity and osteogenic potential. Cells from the infrapatellar fat pad (IFP) have demonstrated increased chondrogenic potential compared with those from subcutaneous fat. This research assessed the chondrogenic potential of IFP PSCs compared with MSCs from the IFP and bone marrow. Immunohistochemistry demonstrated the location of perivascular markers (CD146, CD34, neural/glial antigen 2 [NG2], platelet-derived growth factor receptor-β [PDGFRβ], and α-smooth muscle actin [α-SMA]) in relation to endothelial markers (CD31, CD144, von Willebrand factor [vWF]). Pericytes and adventitial cells were isolated from the stromal vascular fraction (3.8% and 21.2%, respectively) using flow cytometry with a viability of 88%. The mean numbers of pericytes and adventitial cells isolated were 4.6 ± 2.2 × 10(4) and 16.2 ± 3.2 × 10(4), respectively, equating to 7.9 ± 4.4 × 10(3) and 20.8 ± 4.3 × 10(3) cells per gram of harvested tissue. Fluorescence-activated cell sorting demonstrated that cultured PSCs were CD44+CD90+CD105+; polymerase chain reaction and immunocytochemistry demonstrated that pericytes retained their CD146+ phenotype and expressed the pericyte markers PDGFRβ and NG2. Differentiation was confirmed using histochemical stains and genetic expression. Using a pellet model, the IFP PSCs and the MSCs generated significantly more extracellular matrix than bone marrow MSCs (p < .001 and p = .011, respectively). The IFP PSCs generated significantly more extracellular matrix than IFP MSCs (p = .002). Micromass culture demonstrated that differentiated PSCs were upregulated compared with MSCs for COL2A1, ACAN, and SOX9 expression by factors of 4.8 ± 1.3, 4.3 ± 0.9, and 7.0 ± 1.7, respectively. The IFP was a significantly better

  17. Direct contact with perivascular tumor cells enhances integrin αvβ3 signaling and migration of endothelial cells

    PubMed Central

    Burgett, Monica E.; Lathia, Justin D.; Roth, Patrick; Nowacki, Amy S.; Galileo, Deni S.; Pugacheva, Elena; Huang, Ping; Vasanji, Amit; Li, Meizhang; Byzova, Tatiana; Mikkelsen, Tom; Bao, Shideng; Rich, Jeremy N.; Weller, Michael; Gladson, Candece L.

    2016-01-01

    The secretion of soluble pro-angiogenic factors by tumor cells and stromal cells in the perivascular niche promotes the aggressive angiogenesis that is typical of glioblastoma (GBM). Here, we show that angiogenesis also can be promoted by a direct interaction between brain tumor cells, including tumor cells with cancer stem-like properties (CSCs), and endothelial cells (ECs). As shown in vitro, this direct interaction is mediated by binding of integrin αvβ3 expressed on ECs to the RGD-peptide in L1CAM expressed on CSCs. It promotes both EC network formation and enhances directed migration toward basic fibroblast growth factor. Activation of αvβ3 and bone marrow tyrosine kinase on chromosome X (BMX) is required for migration stimulated by direct binding but not for migration stimulated by soluble factors. RGD-peptide treatment of mice with established intracerebral GBM xenografts significantly reduced the percentage of Sox2-positive tumor cells and CSCs in close proximity to ECs, decreased integrin αvβ3 and BMX activation and p130CAS phosphorylation in the ECs, and reduced the vessel surface area. These results reveal a previously unrecognized aspect of the regulation of angiogenesis in GBM that can impact therapeutic anti-angiogenic targeting. PMID:27270311

  18. Influence of exercise and perivascular adipose tissue on coronary artery vasomotor function in a familial hypercholesterolemic porcine atherosclerosis model

    PubMed Central

    Bunker, Aaron K.

    2010-01-01

    Our lab has shown that left circumflex coronary artery (LCX) perivascular adipose tissue (PAT) blunts endothelin-1 (ET-1)-induced maximal contractions in normal pigs on low- and high-fat diets. Other studies report that PAT exerts anticontractile effects on agonist-induced arterial contraction via release of a relaxing factor that acts on the underlying vasculature. The purpose of this study was to test the hypotheses that PAT blunts LCX contraction in familial hypercholesterolemic pigs and that exercise training (Ex) augments this anticontractile effect. Male familial hypercholesterolemic pigs were divided into Ex (n = 13) and sedentary (Sed) (n = 15) groups. LCX reactivity to angiotensin II (ANG II), bradykinin (BK), ET-1, and sodium nitroprusside (SNP) was evaluated in vitro with intact or removed PAT in Sed and Ex familial hypercholesterolemic pigs. LCX relaxation induced by BK and SNP was not altered by Ex or PAT removal. LCX contractions stimulated by ANG II and ET-1 were not significantly altered by Ex or PAT removal across doses; however, Ex did act to significantly reduce ET-1 maximal contractions in familial hypercholesterolemic pig LCX compared with Sed familial hypercholesterolemic pig LCX, independent of PAT (P < 0.05). We conclude that LCX PAT in Sed and Ex familial hypercholesterolemic pigs exerts no substantial anticontractile influence over LCX vasomotor responses to endogenous constrictors such as ANG II and ET-1. Our results suggest that exercise training significantly reduces familial hypercholesterolemic pig LCX maximal contractile responses to the endogenous constrictor ET-1, independent of PAT. PMID:19959766

  19. Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids with a Significant Elevation of β-2 Microglobulin Levels

    PubMed Central

    Fujisawa, Naoaki; Mori, Harushi; Matsui, Toru

    2015-01-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a relapsing-remitting disorder for which steroid administration is a key to control the progression. CLIPPERS can exhibit radiological features similar to malignant lymphoma, whose diagnosis is confounded by prior steroid administration. We report a case of CLIPPERS accompanied by abnormal elevation of β-2 microglobulin in the cerebrospinal fluid (CSF). A 62-year-old man started to experience numbness in all fingers of his left hand one year ago, which gradually extended to his body trunk and legs on both sides. Magnetic resonance imaging demonstrated numerous small enhancing spots scattered in his brain and spinal cord. CSF levels of β-2 microglobulin were elevated; although this often indicates central nervous system involvement in leukemia and lymphoma, the lesions were diagnosed as CLIPPERS based on the pathological findings from a biopsy specimen. We emphasize the importance of biopsy to differentiate between CLIPPERS and malignant lymphoma because the temporary radiological response to steroid might be the same in both diseases but the treatment strategies regarding the use of steroid are quite different. PMID:26713153

  20. In Vitro Differentiation of First Trimester Human Umbilical Cord Perivascular Cells into Contracting Cardiomyocyte-Like Cells

    PubMed Central

    Szaraz, Peter; Librach, Matthew; Maghen, Leila; Iqbal, Farwah; Barretto, Tanya A.; Kenigsberg, Shlomit; Gauthier-Fisher, Andrée; Librach, Clifford L.

    2016-01-01

    Myocardial infarction (MI) causes an extensive loss of heart muscle cells and leads to congestive heart disease (CAD), the leading cause of mortality and morbidity worldwide. Mesenchymal stromal cell- (MSC-) based cell therapy is a promising option to replace invasive interventions. However the optimal cell type providing significant cardiac regeneration after MI is yet to be found. The aim of our study was to investigate the cardiomyogenic differentiation potential of first trimester human umbilical cord perivascular cells (FTM HUCPVCs), a novel, young source of immunoprivileged mesenchymal stromal cells. Based on the expression of cardiomyocyte markers (cTnT, MYH6, SIRPA, and CX43) FTM and term HUCPVCs achieved significantly increased cardiomyogenic differentiation compared to bone marrow MSCs, while their immunogenicity remained significantly lower as indicated by HLA-A and HLA-G expression and susceptibility to T cell mediated cytotoxicity. When applying aggregate-based differentiation, FTM HUCPVCs showed increased aggregate formation potential and generated contracting cells within 1 week of coculture, making them the first MSC type with this ability. Our results indicate that young FTM HUCPVCs have superior cardiomyogenic potential coupled with beneficial immunogenic properties when compared to MSCs of older tissue sources, suggesting that in vitro predifferentiation could be a potential strategy to increase their effectiveness in vivo. PMID:27123009

  1. Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids with a Significant Elevation of β-2 Microglobulin Levels.

    PubMed

    Fujisawa, Naoaki; Oya, Soichi; Mori, Harushi; Matsui, Toru

    2015-11-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a relapsing-remitting disorder for which steroid administration is a key to control the progression. CLIPPERS can exhibit radiological features similar to malignant lymphoma, whose diagnosis is confounded by prior steroid administration. We report a case of CLIPPERS accompanied by abnormal elevation of β-2 microglobulin in the cerebrospinal fluid (CSF). A 62-year-old man started to experience numbness in all fingers of his left hand one year ago, which gradually extended to his body trunk and legs on both sides. Magnetic resonance imaging demonstrated numerous small enhancing spots scattered in his brain and spinal cord. CSF levels of β-2 microglobulin were elevated; although this often indicates central nervous system involvement in leukemia and lymphoma, the lesions were diagnosed as CLIPPERS based on the pathological findings from a biopsy specimen. We emphasize the importance of biopsy to differentiate between CLIPPERS and malignant lymphoma because the temporary radiological response to steroid might be the same in both diseases but the treatment strategies regarding the use of steroid are quite different.

  2. CNS invasion by CD14+/CD16+ peripheral blood-derived monocytes in HIV dementia: perivascular accumulation and reservoir of HIV infection.

    PubMed

    Fischer-Smith, T; Croul, S; Sverstiuk, A E; Capini, C; L'Heureux, D; Régulier, E G; Richardson, M W; Amini, S; Morgello, S; Khalili, K; Rappaport, J

    2001-12-01

    Increases in circulating CD14+/CD16+ monocytes have been associated with HIV dementia; trafficking of these cells into the CNS has been proposed to play an important role in the pathogenesis of HIV-induced neurological disorders. This model suggests that events outside the CNS leading to monocyte activation initiate the process leading to HIV dementia. To investigate the role of this activated monocyte subset in the pathogenesis of HIV dementia, we examined brain specimens from patients with HIV encephalopathy (HIVE), HIV without encephalopathy, and seronegative controls. An accumulation of perivascular macrophages was observed in HIVE. The majority of these cells identified in microglial nodules and in the perivascular infiltrate were CD14+/CD16+. P24 antigen colocalized with both CD14 and CD16 suggesting that the CD14+/CD16+ macrophage is a major reservoir of HIV-1 infection in CNS. Using CD45/LCA staining, the perivascular macrophage was distinguished from resident microglia. In addition to perivascular and nodular localizations, CD16 also stained ramified cells throughout the white matter. These cells were more ramified and abundant than cells positive for CD14 in white matter. Double staining for p24 and CD16 suggests that these cells were often infected with HIV-1. The prominent distribution of CD14+ cells in HIVE prompted our analysis of soluble CD14 levels in cerebrospinal fluid. Higher levels of soluble CD14 (sCD14) were observed in patients with moderate-to-severe HIV dementia, suggesting the utility of sCD14 as a surrogate marker. CD14+/CD16+ monocytes may play a role in other neurological disorders and sCD14 may be useful for evaluating these conditions.

  3. Vascular and perivascular niches, but not the osteoblastic niche, are numerically restored following allogeneic hematopoietic stem cell transplantation in patients with aplastic anemia.

    PubMed

    Wu, Liangliang; Mo, Wenjian; Zhang, Yuping; Zhou, Ming; Li, Yumiao; Zhou, Ruiqing; Xu, Shiling; Pan, Shiyi; Deng, Hui; Mao, Ping; Wang, Shunqing

    2017-03-16

    Bone marrow (BM) niches, including the osteoblastic, vascular, and perivascular niches, are numerically impaired in patients with aplastic anemia (AA). It remains unclear whether these niches are numerically restored in AA patients after allogenic hematopoietic stem cell transplantation (allo-HSCT). To investigate changes in BM niches, we monitored 52 patients with AA who had undergone allo-HSCT and performed immunohistochemical studies of BM niches using antibodies against CD34, CD146, and osteopontin. After allo-HSCT, patients with AA exhibited a remarkable increase in the number of cellular elements in the BM niches, including the vascular and perivascular cells. However, no significant differences in endosteal cells were detected. We explored the cause of this restoration by analyzing the origin of BM mesenchymal stem cells (BM-MSCs) and the expression of cytokines in BM plasma. STR-PCR revealed that the BM-MSCs were derived from the host, not the donor. In addition, significantly elevated levels of vascular endothelial growth factor (VEGF) were found after allo-HSCT. Our data indicates that vascular and perivascular niches are numerically restored, but the endosteal niche remains numerically impaired in patients with AA after allo-HSCT, and that levels of VEGF, but not donor-derived BM-MSCs, may correlate with the restoration of BM niches.

  4. Effects of Maternal Exposure to Ultrafine Carbon Black on Brain Perivascular Macrophages and Surrounding Astrocytes in Offspring Mice

    PubMed Central

    Onoda, Atsuto; Umezawa, Masakazu; Takeda, Ken; Ihara, Tomomi; Sugamata, Masao

    2014-01-01

    Perivascular macrophages (PVMs) constitute a subpopulation of resident macrophages in the central nervous system (CNS). They are located at the blood-brain barrier and can contribute to maintenance of brain functions in both health and disease conditions. PVMs have been shown to respond to particle substances administered during the prenatal period, which may alter their phenotype over a long period. We aimed to investigate the effects of maternal exposure to ultrafine carbon black (UfCB) on PVMs and astrocytes close to the blood vessels in offspring mice. Pregnant mice were exposed to UfCB suspension by intranasal instillation on gestational days 5 and 9. Brains were collected from their offspring at 6 and 12 weeks after birth. PVM and astrocyte phenotypes were examined by Periodic Acid Schiff (PAS) staining, transmission electron microscopy and PAS-glial fibrillary acidic protein (GFAP) double staining. PVM granules were found to be enlarged and the number of PAS-positive PVMs was decreased in UfCB-exposed offspring. These results suggested that in offspring, “normal” PVMs decreased in a wide area of the CNS through maternal UfCB exposure. The increase in astrocytic GFAP expression level was closely related to the enlargement of granules in the attached PVMs in offspring. Honeycomb-like structures in some PVM granules and swelling of astrocytic end-foot were observed under electron microscopy in the UfCB group. The phenotypic changes in PVMs and astrocytes indicate that maternal UfCB exposure may result in changes to brain blood vessels and be associated with increased risk of dysfunction and disorder in the offspring brain. PMID:24722459

  5. Accelerated wound healing in a diabetic rat model using decellularized dermal matrix and human umbilical cord perivascular cells.

    PubMed

    Milan, P Brouki; Lotfibakhshaiesh, N; Joghataie, M T; Ai, J; Pazouki, A; Kaplan, D L; Kargozar, S; Amini, N; Hamblin, M R; Mozafari, M; Samadikuchaksaraei, A

    2016-11-01

    There is an unmet clinical need for novel wound healing strategies to treat full thickness skin defects, especially in diabetic patients. We hypothesized that a scaffold could perform dual roles of a biomechanical support and a favorable biochemical environment for stem cells. Human umbilical cord perivascular cells (HUCPVCs) have been recently reported as a type of mesenchymal stem cell that can accelerate early wound healing in skin defects. However, there are only a limited number of studies that have incorporated these cells into natural scaffolds for dermal tissue engineering. The aim of the present study was to promote angiogenesis and accelerate wound healing by using HUCPVCs and decellularized dermal matrix (DDM) in a rat model of diabetic wounds. The DDM scaffolds were prepared from harvested human skin samples and histological, ultrastructural, molecular and mechanical assessments were carried out. In comparison with the control (without any treatment) and DDM alone group, full thickness excisional wounds treated with HUCPVCs-loaded DDM scaffolds demonstrated an accelerated wound closure rate, faster re-epithelization, more granulation tissue formation and decreased collagen deposition. Furthermore, immunofluorescence analysis showed that the VEGFR-2 expression and vascular density in the HUCPVCs-loaded DDM scaffold treated group were also significantly higher than the other groups at 7days post implantation. Since the rates of angiogenesis, re-epithelization and formation of granulation tissue are directly correlated with full thickness wound healing in patients, the proposed HUCPVCs-loaded DDM scaffolds may fulfil a role neglected by current treatment strategies. This pre-clinical proof-of-concept study warrants further clinical evaluation.

  6. Design, fabrication and perivascular implantation of bioactive scaffolds engineered with human adventitial progenitor cells for stimulation of arteriogenesis in peripheral ischemia.

    PubMed

    Carrabba, M; De Maria, C; Oikawa, A; Reni, C; Rodriguez-Arabaolaza, I; Spencer, H; Slater, S; Avolio, E; Dang, Z; Spinetti, G; Madeddu, P; Vozzi, G

    2016-03-24

    Cell therapy represents a promising option for revascularization of ischemic tissues. However, injection of dispersed cells is not optimal to ensure precise homing into the recipient's vasculature. Implantation of cell-engineered scaffolds around the occluded artery may obviate these limitations. Here, we employed the synthetic polymer polycaprolactone for fabrication of 3D woodpile- or channel-shaped scaffolds by a computer-assisted writing system (pressure assisted micro-syringe square), followed by deposition of gelatin (GL) nanofibers by electro-spinning. Scaffolds were then cross-linked with natural (genipin, GP) or synthetic (3-glycidyloxy-propyl-trimethoxy-silane, GPTMS) agents to improve mechanical properties and durability in vivo. The composite scaffolds were next fixed by crown inserts in each well of a multi-well plate and seeded with adventitial progenitor cells (APCs, 3 cell lines in duplicate), which were isolated/expanded from human saphenous vein surgical leftovers. Cell density, alignment, proliferation and viability were assessed 1 week later. Data from in vitro assays showed channel-shaped/GPTMS-crosslinked scaffolds confer APCs with best alignment and survival/growth characteristics. Based on these results, channel-shaped/GPTMS-crosslinked scaffolds with or without APCs were implanted around the femoral artery of mice with unilateral limb ischemia. Perivascular implantation of scaffolds accelerated limb blood flow recovery, as assessed by laser Doppler or fluorescent microspheres, and increased arterial collaterals around the femoral artery and in limb muscles compared with non-implanted controls. Blood flow recovery and perivascular arteriogenesis were additionally incremented by APC-engineered scaffolds. In conclusion, perivascular application of human APC-engineered scaffolds may represent a novel option for targeted delivery of therapeutic cells in patients with critical limb ischemia.

  7. Endothelial dysfunction and enhanced contractility in microvessels from ovariectomized rats: roles of oxidative stress and perivascular adipose tissue.

    PubMed

    Wang, Dan; Wang, Cheng; Wu, Xie; Zheng, Wei; Sandberg, Kathryn; Ji, Hong; Welch, William J; Wilcox, Christopher S

    2014-05-01

    Ovarian hormone loss increases reactive oxidative species, endothelial dysfunction, and cardiovascular disease. Because perivascular adipose tissue (PVAT) regulates endothelial function, we hypothesized that reactive oxidative species in PVAT mediate adverse microvascular effects of ovarian hormone deficiency. Rats were ovariectomized or sham operated and given vehicle or tempol for 6 weeks. Mesenteric resistance arterioles from ovariectomized compared with sham-operated rats had dysfunctional responses to acetylcholine (ACh) including decreased ACh-induced endothelium-dependent relaxation (50±6% versus 72±2%) and endothelium-dependent relaxation factor (17±4% versus 37±2%) and increased endothelium-dependent contracting factor (27±5% versus 9±3%). OVX rat mesenteric arterioles had increased contractions to the thromboxane/prostanoid receptor agonist U-46 619 (58±3% versus 40±5%) and increased reactive oxidative species (tempo-9-AC fluorescence) with U-46 619 (0.65±0.17 versus 0.14±0.06 Δ unit) or ACh (0.49±0.09 versus 0.09±0.05 Δ unit) and increased p22(phox) protein expression (0.89±0.05 versus 0.18±0.04 Δ unit), whereas nitric oxide activity (DAF-FM [4-amino-5-methylamino-2',7'-difluorofluorescein diacetate] fluorescence) with ACh was reduced (0.39±0.1 versus 0.70±0.10 Δ unit). No differences were found in endothelium-dependent hyperpolarizing factor or contractile responses to phenylephrine. PVAT enhanced ACh-induced relaxation, endothelium-dependent relaxation factor, and nitric oxide only in sham-operated rats. Tempol prevented ovariectomy-induced endothelial dysfunction and restored the enhancing effects of PVAT on ACh-induced relaxation, endothelium-dependent relaxation factor, and nitric oxide in ovariectomized rat vessels, but both tempol and PVAT were required to normalize the enhanced U-46 619 contractions after ovariectomy. In conclusion, ovariectomy redirects endothelial responses from relaxation to contraction by reducing vascular

  8. Proliferating cells in psoriatic dermis are comprised primarily of T cells, endothelial cells, and factor XIIIa+ perivascular dendritic cells

    SciTech Connect

    Morganroth, G.S.; Chan, L.S.; Weinstein, G.D.; Voorhees, J.J.; Cooper, K.D. )

    1991-03-01

    Determination of the cell types proliferating in the dermis of patients with psoriasis should identify those cells experiencing activation or responding to growth factors in the psoriatic dermal milieu. Toward that end, sections of formalin-fixed biopsies obtained from 3H-deoxyuridine (3H-dU)-injected skin of eight psoriatic patients were immunostained, followed by autoradiography. Proliferating dermal cells exhibit silver grains from tritium emissions. The identity of the proliferating cells could then be determined by simultaneous visualization with antibodies specific for various cell types. UCHL1+ (CD45RO+) T cells (recall antigen-reactive helper T-cell subset) constituted 36.6 +/- 3.1% (mean +/- SEM, n = 6) of the proliferating dermal cells in involved skin, whereas Leu 18+ (CD45RA+) T cells (recall antigen naive T-cell subsets) comprised only 8.7 +/- 1.5% (n = 6). The Factor XIIIa+ dermal perivascular dendritic cell subset (24.9 +/- 1.5% of proliferating dermal cells, n = 6) and Factor VIII+ endothelial cells represented the two other major proliferating populations in lesional psoriatic dermis. Differentiated tissue macrophages, identified by phase microscopy as melanophages or by immunostaining with antibodies to Leu M1 (CD15) or myeloid histiocyte antigen, comprised less than 5% of the proliferating population in either skin type. In addition to calculating the relative proportions of these cells to each other as percent, we also determined the density of cells, in cells/mm2 of tissue. The density of proliferating cells within these populations was increased in involved versus uninvolved skin: UCHL1+, 9.0 +/- 1.7 cells/mm2 versus 1.8 +/- 0.6 cells/mm2, p less than 0.01; Factor XIIIa+, 6.0 +/- 0.7 cells/mm2 versus 1.5 +/- 0.5 cells/mm2, p less than 0.01; Factor VIII+, 5.5 +/- 1.4 cells/mm2 versus 0.0 cells/mm2, p less than 0.05.

  9. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): A lymphocytic reactive response of the central nervous system? A case report.

    PubMed

    Wang, Xiaolin; Huang, Dehui; Huang, Xusheng; Zhang, Jiatang; Ran, Ye; Lou, Xin; Gui, Qiuping; Yu, Shengyuan

    2017-04-15

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroid (CLIPPERS) was first described in 2010. The characteristic clinical picture, radiological distribution and steroid response have been well-described in previous reports. However, the underlying pathogenesis and nosological position of CLIPPERS in the CNS require further investigation for the primary CNS lymphoma have been identified by autopsy subsequently. Here, we report a 51-year-old woman who was diagnosed with CLIPPERS but progressed to primary CNS lymphomatoid granulomatosis, which supports that CLIPPERS is not just an inflammatory CNS disorder.

  10. Antioxidative response in variegated Pelargonium zonale leaves and generation of extracellular H2O2 in (peri)vascular tissue induced by sunlight and paraquat.

    PubMed

    Vidović, Marija; Morina, Filis; Prokić, Ljiljana; Milić-Komić, Sonja; Živanović, Bojana; Jovanović, Sonja Veljović

    2016-11-01

    In this study we exposed variegated leaves of Pelargonium zonale to strong sunlight (>1100μmolm(-2)s(-1) of photosynthetically active radiation) with and without paraquat (Pq), with the aim to elucidate the mechanisms of H2O2 regulation in green and white tissues with respect to the photosynthetically-dependent generation of reactive oxygen species (ROS). Sunlight induced marked accumulation of H2O2 in the apoplast of vascular and (peri)vascular tissues only in green sectors. This effect was enhanced by the addition of Pq. In the presence of diphenyl iodide, an NADPH oxidase inhibitor, H2O2 accumulation was abolished. Distinct light-induced responses were observed: in photosynthetic cells, sunlight rapidly provoked ascorbate (Asc) biosynthesis and an increase of glutathione reductase (GR) and catalase activities, while in non-photosynthetic cells, early up-regulation of soluble ascorbate peroxidase, dehydroascorbate reductase (DHAR) and GR activities was observed. Paraquat addition stimulated DHAR and GR activities in green sectors, while in white sectors activities of monodehydroascorbate reductase, DHAR and class III peroxidases, as well as Asc content rapidly increased. Differential antioxidative responses in the two tissues in the frame of their contrasting metabolisms, and the possible role of (peri)vascular H2O2 in signaling were discussed.

  11. Atypical chronic lymphocytic inflammation with pontocerebellar perivascular enhancement responsive to steroids (CLIPPERS), primary angiitis of the CNS mimicking CLIPPERS or overlap syndrome? A case report.

    PubMed

    Buttmann, Mathias; Metz, Imke; Brecht, Isabel; Brück, Wolfgang; Warmuth-Metz, Monika

    2013-01-15

    A novel type of encephalomyelitis was first described as chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) in 2010 and few additional patients were reported since then. Partially due to its unknown aetiology and a lack of pathognomonic features some have suggested that CLIPPERS may not represent a distinct disease, but rather a syndrome with different underlying aetiologies. Here we report a 49-year-old German female who presented with a number of clinical and paraclinical features described as typical for CLIPPERS, while additionally showing symptoms and findings compatible with primary angiitis of the CNS (PACNS). This case may establish a previously unnoted link between two poorly understood autoimmune conditions of the CNS.

  12. PDGFR-β (+) perivascular cells from infantile hemangioma display the features of mesenchymal stem cells and show stronger adipogenic potential in vitro and in vivo.

    PubMed

    Yuan, Si-Ming; Guo, Yao; Zhou, Xiao-Jun; Shen, Wei-Min; Chen, Hai-Ni

    2014-01-01

    Infantile hemangioma, a common benign tumor of infancy, grows quickly in the first year of life, and then regresses slowly to fibrofatty tissue in childhood. The accumulation of fibrofatty tissue in hemangioma involution indicates adipogenesis during this period. Perivascular cells (PCs) from multiple organs display multi-lineage differentiation, including adipogenesis. So we supposed that PCs in hemangioma may contribute to the adipogenesis in the involution. In this study, PDGFR-β (+) PCs was isolated from hemangioma tissue (hemangioma-derived perivascular cells, Hem-PCs) by fluorescence-activated cell sorter. In vitro, Hem-PCs showed fibroblast-like morphology. Immunofluorescence staining and flow cytometry showed Hem-PCs expressed MSCs markers CD105, CD90, CD29 and vimentin, pericyte markers α-SMA and PDGFR-β, stem cell marker CD133, and the adipogenic transcription factor PPAR-γ, but not hematopoietic/endothelial markers CD45, CD34, CD31, and flt-1. In vitro inductions confirmed multi-lineage differentiation of Hem-PCs, especially strong adipogenic potential. Then a murine model was established to observe in vivo differentiation of Hem-PCs by subcutaneous injection of cells/Matrigel compound into nude mice. The results showed Hem-PCs differentiated into adipocytes in vivo. To the best of our knowledge, this is the first study reporting the isolation of multipotential PDGFR-β (+) PCs from hemangioma, and observing their adipogenic differentiation in vivo. PCs may be the cellular basis of adipogenesis in hemangioma involution, and may be the target cells of adipogenic induction to promote hemangioma involution.

  13. CLIPPERS: chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. Review of an increasingly recognized entity within the spectrum of inflammatory central nervous system disorders

    PubMed Central

    Dudesek, A; Rimmele, F; Tesar, S; Kolbaske, S; Rommer, P S; Benecke, R; Zettl, U K

    2014-01-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently defined inflammatory central nervous system (CNS) disorder, prominently involving the brainstem and in particular the pons. The condition features a combination of clinical symptoms essentially referable to brainstem pathology and a characteristic magnetic resonance imaging (MRI) appearance with punctate and curvilinear gadolinium enhancement ‘peppering’ the pons. The radiological distribution is focused in the pons and adjacent rhombencephalic structures such as the cerebellar peduncles, cerebellum, medulla and the midbrain. While the lesion burden with a perivascular pattern is typically most dense in these pontine and peripontine regions, enhancing lesions may additionally extend into the spinal cord and supratentorial structures such as the thalamus, basal ganglia, capsula interna, corpus callosum and the cerebral white matter. Another core feature is clinical and radiological responsiveness to glucocorticosteroid (GCS)-based immunosuppression. As withdrawal of GCS treatment results commonly in disease exacerbation, long-term immunosuppressive therapy appears to be mandatory for sustained improvement. Diagnosis of CLIPPERS is challenging, and requires careful exclusion of alternative diagnoses. A specific serum or cerebrospinal fluid (CSF) biomarker for the disorder is currently not known. Pathogenesis of CLIPPERS remains poorly understood, and the nosological position of CLIPPERS has still to be established. Whether CLIPPERS represents an independent, actual new disorder or a syndrome that includes aetiologically heterogeneous diseases and/or their prestages remains a debated and not finally clarified issue. Clinicians and radiologists should be aware of this condition and its differential diagnoses, given that CLIPPERS constitutes a treatable condition and that patients may benefit from an early introduction of GCS ensued by long

  14. CLIPPERS: chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. Review of an increasingly recognized entity within the spectrum of inflammatory central nervous system disorders.

    PubMed

    Dudesek, A; Rimmele, F; Tesar, S; Kolbaske, S; Rommer, P S; Benecke, R; Zettl, U K

    2014-03-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently defined inflammatory central nervous system (CNS) disorder, prominently involving the brainstem and in particular the pons. The condition features a combination of clinical symptoms essentially referable to brainstem pathology and a characteristic magnetic resonance imaging (MRI) appearance with punctate and curvilinear gadolinium enhancement 'peppering' the pons. The radiological distribution is focused in the pons and adjacent rhombencephalic structures such as the cerebellar peduncles, cerebellum, medulla and the midbrain. While the lesion burden with a perivascular pattern is typically most dense in these pontine and peripontine regions, enhancing lesions may additionally extend into the spinal cord and supratentorial structures such as the thalamus, basal ganglia, capsula interna, corpus callosum and the cerebral white matter. Another core feature is clinical and radiological responsiveness to glucocorticosteroid (GCS)-based immunosuppression. As withdrawal of GCS treatment results commonly in disease exacerbation, long-term immunosuppressive therapy appears to be mandatory for sustained improvement. Diagnosis of CLIPPERS is challenging, and requires careful exclusion of alternative diagnoses. A specific serum or cerebrospinal fluid (CSF) biomarker for the disorder is currently not known. Pathogenesis of CLIPPERS remains poorly understood, and the nosological position of CLIPPERS has still to be established. Whether CLIPPERS represents an independent, actual new disorder or a syndrome that includes aetiologically heterogeneous diseases and/or their prestages remains a debated and not finally clarified issue. Clinicians and radiologists should be aware of this condition and its differential diagnoses, given that CLIPPERS constitutes a treatable condition and that patients may benefit from an early introduction of GCS ensued by long

  15. The “Perivascular Pump” Driven by Arterial Pulsation is a Powerful Mechanism for the Distribution of Therapeutic Molecules within the Brain

    PubMed Central

    Hadaczek, Piotr; Yamashita, Yoji; Mirek, Hanna; Tamas, Laszlo; Bohn, Martha C.; Noble, Charles; Park, John W.; Bankiewicz, Krystof

    2009-01-01

    We investigated the movement of interstitially infused macromolecules within the central nervous system (CNS) in rats with high and low blood pressure (BP)/heart rate and in rats euthanized immediately before infusion (no heart action). Adeno-associated virus 2 (AAV2), fluorescent liposomes, or bovine serum albumin was infused into rat striatum (six hemispheres per group) by convection-enhanced delivery (CED). After infusion, distribution volumes were evaluated. The rats with high BP/heart rate displayed a significantly larger distribution of the infused molecules within the injected site and more extensive transport of those molecules to the globus pallidus. This difference was particularly apparent for AAV2, for which a 16.5-fold greater distribution of viral capsids was observed in the rats with high BP/heart rate than in the rats with no heartbeat. Similar results were observed for liposomes, despite their larger diameter. The distribution of all infused molecules in all rats that had low or no blood flow was confined to the space around brain blood vessels. These findings show that fluid circulation within the CNS through the perivascular space is the primary mechanism by which viral particles and other therapeutic agents administered by CED are spread within the brain and that cardiac contractions power this process. PMID:16650807

  16. Deposition of amyloid β in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy☆

    PubMed Central

    Keable, Abby; Fenna, Kate; Yuen, Ho Ming; Johnston, David A.; Smyth, Neil R.; Smith, Colin; Salman, Rustam Al-Shahi; Samarasekera, Neshika; Nicoll, James A.R.; Attems, Johannes; Kalaria, Rajesh N.; Weller, Roy O.; Carare, Roxana O.

    2016-01-01

    Deposition of amyloid β (Aβ) in the walls of cerebral arteries as cerebral amyloid angiopathy (CAA) suggests an age-related failure of perivascular drainage of soluble Aβ from the brain. As CAA is associated with Alzheimer's disease and with intracerebral haemorrhage, the present study determines the unique sequence of changes that occur as Aβ accumulates in artery walls. Paraffin sections of post-mortem human occipital cortex were immunostained for collagen IV, fibronectin, nidogen 2, Aβ and smooth muscle actin and the immunostaining was analysed using Image J and confocal microscopy. Results showed that nidogen 2 (entactin) increases with age and decreases in CAA. Confocal microscopy revealed stages in the progression of CAA: Aβ initially deposits in basement membranes in the tunica media, replaces first the smooth muscle cells and then the connective tissue elements to leave artery walls completely or focally replaced by Aβ. The pattern of development of CAA in the human brain suggests expansion of Aβ from the basement membranes to progressively replace all tissue elements in the artery wall. Establishing this full picture of the development of CAA is pivotal in understanding the clinical presentation of CAA and for developing therapies to prevent accumulation of Aβ in artery walls. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26327684

  17. OxLDL-targeted iron oxide nanoparticles for in vivo MRI detection of perivascular carotid collar induced atherosclerotic lesions in ApoE-deficient mice

    PubMed Central

    Wen, Song; Liu, Dong-Fang; Liu, Zhen; Harris, Steven; Yao, Yu-Yu; Ding, Qi; Nie, Fang; Lu, Tong; Chen, Hua-Jun; An, Yan-Li; Zang, Feng-Chao; Teng, Gao-Jun

    2012-01-01

    Atherosclerotic disease is a leading cause of morbidity and mortality in developed countries, and oxidized LDL (OxLDL) plays a key role in the formation, rupture, and subsequent thrombus formation in atherosclerotic plaques. In the current study, anti-mouse OxLDL polyclonal antibody and nonspecific IgG antibody were conjugated to polyethylene glycol-coated ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, and a carotid perivascular collar model in apolipoprotein E-deficient mice was imaged at 7.0 Tesla MRI before contrast administration and at 8 h and 24 h after injection of 30 mg Fe/kg. The results showed MRI signal loss in the carotid atherosclerotic lesions after administration of targeted anti-OxLDL-USPIO at 8 h and 24 h, which is consistent with the presence of the nanoparticles in the lesions. Immunohistochemistry confirmed the colocalization of the OxLDL/macrophages and iron oxide nanoparticles. The nonspecific IgG-USPIO, unconjugated USPIO nanoparticles, and competitive inhibition groups had limited signal changes (p < 0.05). This report shows that anti-OxLDL-USPIO nanoparticles can be used to directly detect OxLDL and image atherosclerotic lesions within 24 h of nanoparticle administration and suggests a strategy for the therapeutic evaluation of atherosclerotic plaques in vivo. PMID:22393161

  18. Increased expression of ICAM-1, VCAM-1, MCP-1, and MIP-1α by spinal perivascular macrophages during experimental allergic encephalomyelitis in rats

    PubMed Central

    Hofmann, Nils; Lachnit, Nina; Streppel, Michael; Witter, Brigitte; Neiss, Wolfram F; Guntinas-Lichius, Orlando; Angelov, Doychin N

    2002-01-01

    Background T-cells extravasation and CNS parenchyma infiltration during autoimmune neurodegenerative disease can be evoked by local antigen presenting cells. Studying the chemoattracting potential of spinal perivascular macrophages (SPM) during experimental allergic encephalomyelitis (EAE), we observed numerous infiltrates of densely-packed mononuclear cells. Apart from the poor spatial and optical resolution, no differentiation between the resident SPM (mabs ED1+, ED2+) and the just recruited monocytes/macrophages (mab ED1+) was possible. Results This is why we labeled SPM by injections of different fluoresecent dyes into the lateral cerebral ventricle before induction of active EAE. Within an additional experimental set EAE was induced by an intraperitoneal injection of T-cells specifically sensitized to myelin basic protein (MBP) and engineered to express the green fluorescent protein (GFP). In both experiments we observed a strong activation of SPM (mabs OX6+, SILK6+, CD40+, CD80+, CD86+) which was accompanied by a consistently increased expression of ICAM-1, VCAM-1, and the chemokines MCP-1 and MIP-1α. Conclusion These observations indicate that SPM play a role in promoting lymphocyte extravasation. PMID:12196270

  19. Non-enzymatic isolation followed by supplementation of basic fibroblast growth factor improves proliferation, clonogenic capacity and SSEA-4 expression of perivascular cells from human umbilical cord.

    PubMed

    An, Borim; Na, Sunghun; Lee, Sungeun; Kim, Woo Jin; Yang, Se-Ran; Woo, Heung-Myong; Kook, Songyi; Hong, Yoonki; Song, Haengseok; Hong, Seok-Ho

    2015-03-01

    Multipotent perivascular cells (PVCs) have recently gained attention as an alternative source for cell-based regenerative medicine. Because of their rarity in human tissues, the development of efficient methods to isolate and expand PVCs from various fetal and adult tissues is necessary to obtain a clinically relevant number of cells that maintain progenitor potency. We report a simple non-enzymatic isolation (NE) method of PVCs from human umbilical cord (HUC) and compare its efficiency with the conventional collagenase treatment method (CT) in terms of proliferation, immunophenotype, clonogenic capacity, and differentiation potential. Cells isolated by NE expressed the accepted surface marker profile of PVCs and possessed multilineage differentiation potential. Whereas both methods provided similar patterns or levels of immunophenotypes and proliferation, PVCs obtained by NE maintained a higher level of CD146(+) frequency compared with that of CT over passages and displayed greater in vitro osteogenic differentiation potential and clonogenic capacity than CT-PVCs. We assess the potential of various exogenous factors to boost the proliferation of NE- and CT-PVCs in vitro. Supplementation of basic fibroblast growth factor (bFGF) provided optimal conditions that significantly enhanced their proliferation rate. This treatment drove the cells into S phase and increased the proportion of stage-specific antigen-4-positive population without altering other immunophenotypes. Thus, the NE method with bFGF supplementation offers an alternative way for obtaining sufficient numbers of HUCPVCs that have good clonogenic and differentiation potential and that are applicable at therapeutic doses for regenerative medicine.

  20. Human umbilical cord perivascular cells exhibited enhanced migration capacity towards hepatocellular carcinoma in comparison with bone marrow mesenchymal stromal cells: a role for autocrine motility factor receptor.

    PubMed

    Bayo, Juan; Fiore, Esteban; Aquino, Jorge B; Malvicini, Mariana; Rizzo, Manglio; Peixoto, Estanislao; Alaniz, Laura; Piccioni, Flavia; Bolontrade, Marcela; Podhajcer, Osvaldo; Garcia, Mariana G; Mazzolini, Guillermo

    2014-01-01

    Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Unfortunately, the incidence and mortality associated with HCC are increasing. Therefore, new therapeutic strategies are urgently needed and the use of mesenchymal stromal cells (MSCs) as carrier of therapeutic genes is emerging as a promising option. Different sources of MSCs are being studied for cell therapy and bone marrow-derived cells are the most extensively explored; however, birth associated-tissues represent a very promising source. The aim of this work was to compare the in vitro and in vivo migration capacity between bone marrow MSCs (BM-MSCs) and human umbilical cord perivascular cells (HUCPVCs) towards HCC. We observed that HUCPVCs presented higher in vitro and in vivo migration towards factors released by HCC. The expression of autocrine motility factor (AMF) receptor, genes related with the availability of the receptor on the cell surface (caveolin-1 and -2) and metalloproteinase 3, induced by the receptor activation and important for cell migration, was increased in HUCPVCs. The chemotactic response towards recombinant AMF was increased in HUCPVCs compared to BM-MSCs, and its inhibition in the conditioned medium from HCC induced higher decrease in HUCPVC migration than in BM-MSC. Our results indicate that HUCPVCs could be a useful cellular source to deliver therapeutic genes to HCC.

  1. Human Umbilical Cord Perivascular Cells Exhibited Enhanced Migration Capacity towards Hepatocellular Carcinoma in Comparison with Bone Marrow Mesenchymal Stromal Cells: A Role for Autocrine Motility Factor Receptor

    PubMed Central

    Aquino, Jorge B.; Malvicini, Mariana; Bolontrade, Marcela; Podhajcer, Osvaldo; Garcia, Mariana G.; Mazzolini, Guillermo

    2014-01-01

    Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Unfortunately, the incidence and mortality associated with HCC are increasing. Therefore, new therapeutic strategies are urgently needed and the use of mesenchymal stromal cells (MSCs) as carrier of therapeutic genes is emerging as a promising option. Different sources of MSCs are being studied for cell therapy and bone marrow-derived cells are the most extensively explored; however, birth associated-tissues represent a very promising source. The aim of this work was to compare the in vitro and in vivo migration capacity between bone marrow MSCs (BM-MSCs) and human umbilical cord perivascular cells (HUCPVCs) towards HCC. We observed that HUCPVCs presented higher in vitro and in vivo migration towards factors released by HCC. The expression of autocrine motility factor (AMF) receptor, genes related with the availability of the receptor on the cell surface (caveolin-1 and -2) and metalloproteinase 3, induced by the receptor activation and important for cell migration, was increased in HUCPVCs. The chemotactic response towards recombinant AMF was increased in HUCPVCs compared to BM-MSCs, and its inhibition in the conditioned medium from HCC induced higher decrease in HUCPVC migration than in BM-MSC. Our results indicate that HUCPVCs could be a useful cellular source to deliver therapeutic genes to HCC. PMID:25147818

  2. Clinical outcome and microvascular blood flow in VAC® - and Sorbalgon® -treated peri-vascular infected wounds in the groin after vascular surgery - an early interim analysis.

    PubMed

    Acosta, Stefan; Monsen, Christina; Dencker, Magnus

    2013-08-01

    Vacuum-assisted wound closure (VAC(®)) therapy is considered to be superior to conventional dressings in the treatment of peri-vascular groin infections after vascular surgery at our department. Therefore, we performed an early interim analysis of the clinical outcomes in these seriously ill patients at risk of amputation and death. Patients were randomised to either VAC(®) (n = 5) or Sorbalgon(®) (n = 5; best alternative treatment) therapy after surgical debridement. Non-invasive, laser Doppler perfusion imaging (LDPI) studies of the skin adjacent to the undressed wound were performed after 14 days of wound treatment. There was no difference in LDPI values in VAC(®) versus Sorbalgon(®) treated patients (P = 0·46). One patient in the VAC(®) group suffered from two re-bleeding episodes, leading to vascular resection and transfemoral amputation and in the Sorbalgon(®) group two had a complete wound healing time of more than 4 months and one had a visible interposition bypass graft in the groin after 1 month of treatment. No patient died of the groin infection. Although not statistically proven, fewer wound treatment failures were recorded in the VAC(®) group, justifying this early interim analysis. LDPI studies were feasible.

  3. "Malignant" uterine perivascular epithelioid cell tumor, pelvic lymph node lymphangioleiomyomatosis, and gynecological pecomatosis in a patient with tuberous sclerosis: a case report and review of the literature.

    PubMed

    Liang, Sharon X; Pearl, Michael; Liu, Jingxuan; Hwang, Sonia; Tornos, Carmen

    2008-01-01

    We report a case of uterine perivascular epithelioid cell tumor (PEComa) with malignant histological features in a 59-year-old woman with tuberous sclerosis (TBS). The patient also had extrapulmonary lymphangioleiomyomatosis involving pelvic lymph nodes, myometrium, cervix, and ovary ("pecomatosis"). The uterine tumor measured 2.6 cm and had marked nuclear pleomorphism, necrosis, and 2 mitoses per 50 high-powered field, with an occasional atypical mitosis and infiltrative borders. The nonneoplastic myometrium, the cervical wall, and the hilum of the ovary had multiple clusters of bland-looking epithelioid clear cells that ranged from 1 to 5 mm (pecomatosis). The uterine tumor cells were positive for HMB-45 (90%), Melan-A (70%), smooth muscle actin (50%), and estrogen receptor (30%). Of the 16 pelvic lymph nodes excised, 3 were involved with lymphangioleiomyomatosis that was positive for HMB-45 and estrogen receptor. This is only the second reported PEComa associated with pecomatosis and the fourth PEComa described in a patient with TBS. The clinical significance of pecomatosis is still uncertain but seems to be seen only in patients with TBS.

  4. H2O2 generated from mitochondrial electron transport chain in thoracic perivascular adipose tissue is crucial for modulation of vascular smooth muscle contraction.

    PubMed

    Costa, Rafael M; Filgueira, Fernando P; Tostes, Rita C; Carvalho, Maria Helena C; Akamine, Eliana H; Lobato, Nubia S

    2016-09-01

    The perivascular adipose tissue (PVAT) releases a variety of factors that affect vascular function. PVAT in the thoracic aorta shares characteristics with the brown adipose tissue, including a large amount of mitochondria. PVAT-derived factors influence both endothelial and smooth muscle function via several signaling mechanisms including the release/generation of reactive nitrogen and oxygen species. Considering the importance of reactive oxygen species (ROS) on vascular function and that mitochondria are an important source of ROS, we hypothesized that mitochondria-derived ROS in the PVAT modulates vascular reactivity. Vascular reactivity to norephinephrine (NE) was evaluated in thoracic aortic rings, with or without endothelium and/or PVAT, from male Wistar rats. Mitochondrial uncoupling, as well as hydrogen peroxide (H2O2) removal, increased the contraction in vessels surrounded by PVAT. PVAT stimulated with NE exhibited increased protein expression, determined by Western blot analysis, of manganese superoxide dismutase (Mn-SOD) and decreased protein expression of catalase. Ultimately, NE increased superoxide anion (O2(-)) generation in PVAT via increases in intracellular calcium. These results clearly demonstrate that mitochondrial electron transport chain (mETC) in PVAT contributes to modulation of aortic muscle contraction by generating higher amounts of O2(-) that is, in turn, dismutated to hydrogen peroxide, which then acts as a pivotal signaling molecule regulating vascular smooth muscle contraction.

  5. Lineage tracing and genetic ablation of ADAM12(+) perivascular cells identify a major source of profibrotic cells during acute tissue injury.

    PubMed

    Dulauroy, Sophie; Di Carlo, Selene E; Langa, Francina; Eberl, Gérard; Peduto, Lucie

    2012-08-01

    Profibrotic cells that develop upon injury generate permanent scar tissue and impair organ recovery, though their origin and fate are unclear. Here we show that transient expression of ADAM12 (a disintegrin and metalloprotease 12) identifies a distinct proinflammatory subset of platelet-derived growth factor receptor-α-positive stromal cells that are activated upon acute injury in the muscle and dermis. By inducible genetic fate mapping, we demonstrate in vivo that injury-induced ADAM12(+) cells are specific progenitors of a major fraction of collagen-overproducing cells generated during scarring, which are progressively eliminated during healing. Genetic ablation of ADAM12(+) cells, or knockdown of ADAM12, is sufficient to limit generation of profibrotic cells and interstitial collagen accumulation. ADAM12(+) cells induced upon injury are developmentally distinct from muscle and skin lineage cells and are derived from fetal ADAM12(+) cells programmed during vascular wall development. Thus, our data identify injury-activated profibrotic progenitors residing in the perivascular space that can be targeted through ADAM12 to limit tissue scarring.

  6. Transmission and scanning electron microscopy study of the characteristics and morphology of pericytes and novel desmin-immunopositive perivascular cells before and after castration in rat anterior pituitary gland.

    PubMed

    Jindatip, Depicha; Fujiwara, Ken; Kouki, Tom; Yashiro, Takashi

    2012-09-01

    Pericytes are perivascular cells associated with microcirculation. Typically, they are localized close to the capillary wall, underneath the basement membrane, and have sparse cytoplasm and poorly developed cell organelles. However, the specific properties of pericytes vary by organ and the conditions within organs. We recently demonstrated that pericytes in rat anterior pituitary gland produce type I and III collagens. The present study attempted to determine the morphological characteristics of these pituitary pericytes. Castrated rats were used as a model of hormonal and vascular changes in the gland. Pericytes, as determined by desmin immunohistochemistry, were more numerous and stained more intensely in castrated rats. Transmission electron microscopy revealed that pituitary pericytes displayed the typical characteristics of pericytes. In pituitary sections from castrated rats, the Golgi apparatus of pericytes was well developed and the rough endoplasmic reticulum was elongated. Additionally, scanning electron microscopy revealed four pericyte shapes: oval, elongate, triangular, and multiangular. As compared with normal rats, the proportion of oval pericytes was lower, and the proportions of the other three shapes were higher, in castrated rats. These results suggest that pericytes change their fine structure and cell shape in response to hormonal and vascular changes in the anterior pituitary gland. In addition, a novel type of perivascular cell was found by desmin immunoelectron microscopy. The morphological properties of these cells were dissimilar to those of pericytes. The cells were localized in the perivascular space, had no basement membrane, and contained dilated rough endoplasmic reticulum. This new cell type will require further study of its origin and characteristics.

  7. Inhibitory effect of sustained perivascular delivery of paclitaxel on neointimal hyperplasia in the jugular vein after open cutdown central venous catheter placement in rats

    PubMed Central

    Kim, Seongyup; Kim, Younglim; Hwang, Ji Woong

    2017-01-01

    Purpose Inhibitory effect of paclitaxel on neointimal hyperplasia after open cutdown has not been elucidated. Methods For the control group (n = 16), silicone 2.7-Fr catheters were placed via the right external jugular vein with the cutdown method. For the treatment group (n = 16), a mixture of 0.65 mg of paclitaxel and 1 mL of fibrin glue was infiltrated around the exposed vein after cutdown. After scheduled intervals (1, 2, 4, and 8 weeks), the vein segment was harvested and morphometric analysis was performed on cross-sections. Results Proliferation of smooth muscle cell (SMC) was strongly suppressed in the treatment group, and the ratio of neointima to vein wall was significantly reduced in the treatment group (8 weeks; 0.63 ± 0.08 vs. 0.2 ± 0.08, P < 0.05). Luminal patency was significantly more preserved in the treatment group, and the luminal area was significantly wider in the paclitaxel-treated group compared to the control group (8 weeks; 1.91 ± 0.43 mm2 vs. 5.1 ± 0.43 mm2, P < 0.05). Mean SMC counts measured at 1 and 2 weeks after cutdown were significantly lower in the treatment group (2 weeks; 115 ± 22 vs. 62 ± 22). Paclitaxel was undetectable in systemic circulation (<10 ng/mL). Conclusion Sustained perivascular delivery of paclitaxel with fibrin glue was effective in inhibiting neointimal hyperplasia in rat jugular vein after open cutdown. PMID:28203557

  8. Culture media-based selection of endothelial cells, pericytes, and perivascular-resident macrophage-like melanocytes from the young mouse vestibular system.

    PubMed

    Zhang, Jinhui; Chen, Songlin; Cai, Jing; Hou, Zhiqiang; Wang, Xiaohan; Kachelmeier, Allan; Shi, Xiaorui

    2017-03-01

    The vestibular blood-labyrinth barrier (BLB) is comprised of perivascular-resident macrophage-like melanocytes (PVM/Ms) and pericytes (PCs), in addition to endothelial cells (ECs) and basement membrane (BM), and bears strong resemblance to the cochlear BLB in the stria vascularis. Over the past few decades, in vitro cell-based models have been widely used in blood-brain barrier (BBB) and blood-retina barrier (BRB) research, and have proved to be powerful tools for studying cell-cell interactions in their respective organs. Study of both the vestibular and strial BLB has been limited by the unavailability of primary culture cells from these barriers. To better understand how barrier component cells interact in the vestibular system to control BLB function, we developed a novel culture medium-based method for obtaining EC, PC, and PVM/M primary cells from tiny explants of the semicircular canal, sacculus, utriculus, and ampullae tissue of young mouse ears at post-natal age 8-12 d. Each phenotype is grown in a specific culture medium which selectively supports the phenotype in a mixed population of vestibular cell types. The unwanted phenotypes do not survive passaging. The protocol does not require additional equipment or special enzyme treatment. The harvesting process takes less than 2 h. Primary cell types are generated within 7-10 d. The primary culture ECs, PCs, and PVM/M shave consistent phenotypes more than 90% pure after two passages (∼ 3 weeks). The highly purified primary cell lines can be used for studying cell-cell interactions, barrier permeability, and angiogenesis.

  9. A new model of multi-visceral and bone metastatic prostate cancer with perivascular niche targeting by a novel endothelial specific adenoviral vector.

    PubMed

    Lu, Zhi Hong; Kaliberov, Sergey; Sohn, Rebecca E; Kaliberova, Lyudmila; Du, Yingqiu; Prior, Julie L; Leib, Daniel J; Chauchereau, Anne; Sehn, Jennifer K; Curiel, David T; Arbeit, Jeffrey M

    2017-01-17

    While modern therapies for metastatic prostate cancer (PCa) have improved survival they are associated with an increasingly prevalent entity, aggressive variant PCa (AVPCa), lacking androgen receptor (AR) expression, enriched for cancer stem cells (CSCs), and evidencing epithelial-mesenchymal plasticity with a varying extent of neuroendocrine transdifferentiation. Parallel work revealed that endothelial cells (ECs) create a perivascular CSC niche mediated by juxtacrine and membrane tethered signaling. There is increasing interest in pharmacological metastatic niche targeting, however, targeted access has been impossible. Here, we discovered that the Gleason 7 derived, androgen receptor negative, IGR-CaP1 cell line possessed some but not all of the molecular features of AVPCa. Intracardiac injection into NOD/SCID/IL2Rg -/- (NSG) mice produced a completely penetrant bone, liver, adrenal, and brain metastatic phenotype; noninvasively and histologically detectable at 2 weeks, and necessitating sacrifice 4-5 weeks post injection. Bone metastases were osteoblastic, and osteolytic. IGR-CaP1 cells expressed the neuroendocrine marker synaptophysin, near equivalent levels of vimentin and e-cadherin, all of the EMT transcription factors, and activation of NOTCH and WNT pathways. In parallel, we created a new triple-targeted adenoviral vector containing a fiber knob RGD peptide, a hexon mutation, and an EC specific ROBO4 promoter (Ad.RGD.H5/3.ROBO4). This vector was expressed in metastatic microvessels tightly juxtaposed to IGR-CaP1 cells in bone and visceral niches. Thus, the combination of IGR-CaP1 cells and NSG mice produces a completely penetrant metastatic PCa model emulating end-stage human disease. In addition, the metastatic niche access provided by our novel Ad vector could be therapeutically leveraged for future disease control or cure.

  10. Severe microvascular injury induced by lysosomal releasates of human polymorphonuclear leukocytes. Increase in vasopermeability, hemorrhage, and microthrombosis due to degradation of subendothelial and perivascular matrices.

    PubMed Central

    Movat, H. Z.; Wasi, S.

    1985-01-01

    The purpose of this study was to assess the nature of the lesions in the microcirculation of the dermis of rabbits induced with lysosomal releasates of human polymorphonuclear leukocytes (PMNs). No attempt was made in the studies presented in this publication to deal with the offending agent in the releasate. Four parameters of microvascular injury were quantitated: increase in vascular permeability with 125I-labeled serum albumin, hemorrhage with 59Fe-labeled erythrocytes, accumulation (aggregation) of platelets with 111In-labeled platelets. In one experiment accumulation of 51Cr-PMNs was investigated. The lysosomal releasate induced a rapid increase in vasopermeability, but both hemorrhage and exudate formation peaked 1 hour after intradermal injection. Platelet accumulation was also demonstrable in these lesions, and microthrombosis was a very prominent feature. The microvascular injury, including microthrombosis, could be elicited also in animals rendered leukopenic with nitrogen mustard. Simultaneous injection of prostaglandin E2 with the releasate enhanced the microvascular injury. The morphologic changes in the microcirculation of the rabbit's dermis were assessed in lesions 5 minutes to 5 hours old. Several changes were encountered, primarily in the wall of venules and small veins and to a lesser degree in small arteries and capillaries. Ultrastructurally very early lesions (up to 15 minutes) had gaps or spaces in the endothelium, resembling those induced by mediators such as histamine or bradykinin. Older lesions were different, quite characteristic, and represent the hallmark of these lesions. Lysis and disappearance of vascular basement membrane, of perivascular collagen, and of the internal elastic lamina were a frequent finding, best demonstrable when microthrombi did not abut on vessel walls. Cellular components of vessels (endothelium, pericytes, smooth muscle) showed fragmentation, leading to complete disappearance of cellular elements. These

  11. Permission Forms

    ERIC Educational Resources Information Center

    Zirkel, Perry A.

    2005-01-01

    The prevailing practice in public schools is to routinely require permission or release forms for field trips and other activities that pose potential for liability. The legal status of such forms varies, but they are generally considered to be neither rock-solid protection nor legally valueless in terms of immunity. The following case and the…

  12. Densified waste form and method for forming

    DOEpatents

    Garino, Terry J.; Nenoff, Tina M.; Sava Gallis, Dorina Florentina

    2016-05-17

    Materials and methods of making densified waste forms for temperature sensitive waste material, such as nuclear waste, formed with low temperature processing using metallic powder that forms the matrix that encapsulates the temperature sensitive waste material. The densified waste form includes a temperature sensitive waste material in a physically densified matrix, the matrix is a compacted metallic powder. The method for forming the densified waste form includes mixing a metallic powder and a temperature sensitive waste material to form a waste form precursor. The waste form precursor is compacted with sufficient pressure to densify the waste precursor and encapsulate the temperature sensitive waste material in a physically densified matrix.

  13. Densified waste form and method for forming

    SciTech Connect

    Garino, Terry J.; Nenoff, Tina M.; Sava Gallis, Dorina Florentina

    2015-08-25

    Materials and methods of making densified waste forms for temperature sensitive waste material, such as nuclear waste, formed with low temperature processing using metallic powder that forms the matrix that encapsulates the temperature sensitive waste material. The densified waste form includes a temperature sensitive waste material in a physically densified matrix, the matrix is a compacted metallic powder. The method for forming the densified waste form includes mixing a metallic powder and a temperature sensitive waste material to form a waste form precursor. The waste form precursor is compacted with sufficient pressure to densify the waste precursor and encapsulate the temperature sensitive waste material in a physically densified matrix.

  14. Epsilon toxin: a fascinating pore-forming toxin.

    PubMed

    Popoff, Michel R

    2011-12-01

    Epsilon toxin (ETX) is produced by strains of Clostridium perfringens classified as type B or type D. ETX belongs to the heptameric β-pore-forming toxins including aerolysin and Clostridium septicum alpha toxin, which are characterized by the formation of a pore through the plasma membrane of eukaryotic cells consisting in a β-barrel of 14 amphipatic β strands. By contrast to aerolysin and C. septicum alpha toxin, ETX is a much more potent toxin and is responsible for enterotoxemia in animals, mainly sheep. ETX induces perivascular edema in various tissues and accumulates in particular in the kidneys and brain, where it causes edema and necrotic lesions. ETX is able to pass through the blood-brain barrier and stimulate the release of glutamate, which accounts for the symptoms of nervous excitation observed in animal enterotoxemia. At the cellular level, ETX causes rapid swelling followed by cell death involving necrosis. The precise mode of action of ETX remains to be determined. ETX is a powerful toxin, however, it also represents a unique tool with which to vehicle drugs into the central nervous system or target glutamatergic neurons.

  15. The effects of tumor location on diagnostic criteria for canine malignant peripheral nerve sheath tumors (MPNSTs) and the markers for distinction between canine MPNSTs and canine perivascular wall tumors.

    PubMed

    Suzuki, S; Uchida, K; Nakayama, H

    2014-07-01

    Canine malignant peripheral nerve sheath tumors (MPNSTs) occur not only in the peripheral nervous system (PNS) but also in soft tissue and various organs (non-PNS). The most important diagnostic criterion is proof of peripheral nerve sheath origin. This is difficult in non-PNS MPNSTs, and its differential diagnosis is challenging. Canine perivascular wall tumors (PWTs) also commonly arise in soft tissue. Their histopathological features are quite similar to those of canine MPNSTs, making their differential diagnosis challenging. To elucidate whether the morphological features are applicable to diagnose non-PNS MPNSTs and to demonstrate useful markers for distinction between canine MPNSTs and PWTs, the authors examined 30 canine MPNSTs and 31 PWTs immunohistochemically for S100, nestin, NGFR, Olig2, claudin-1, CD57, PRX, α-SMA, desmin, and calponin. Among canine MPNSTs, the PNS tumors displayed significantly higher S100 and Olig2 expression than the non-PNS tumors. The expression levels of the other markers did not differ significantly, suggesting that the same morphological diagnostic criteria are applicable regardless of their location. The PWT cells displayed significantly weaker immunoreactivity than MPNSTs to markers used except α-SMA and desmin. Cluster analysis sorted most canine MPNSTs and PWTs into 2 distinctly different clusters, whereas 3 MPNSTs and 6 PWTs were assigned to the opposing cluster. These 3 MPNSTs were negative for almost all markers, while these 6 PWTs were positive for only neuronal markers. In particular, NGFR and Olig2 were almost negative in the rest of PWT cases. These findings suggest that NGFR and Olig2 are useful to distinguish these 2 tumors.

  16. Careers (A Course of Study). Unit V: Forms, Forms, Forms.

    ERIC Educational Resources Information Center

    Turley, Kay

    Designed to enable special needs students to understand and complete various job-related forms, this set of activities devoted to forms encountered before and after one obtains a job is the fifth in a nine-unit secondary level careers course intended to provide handicapped students with the knowledge and tools necessary to succeed in the world of…

  17. The perivascular niche regulates breast tumor dormancy

    PubMed Central

    Peinado, Héctor; Mori, Hidetoshi; Matei, Irina R.; Evason, Kimberley J.; Brazier, Hélène; Almeida, Dena; Koller, Antonius; Hajjar, Katherine A.; Stainier, Didier Y.R.; Chen, Emily I.; Lyden, David

    2013-01-01

    In a significant fraction of breast cancer patients, distant metastases emerge after years or even decades of latency. How disseminated tumor cells (DTCs) are kept dormant, and what ‘wakes them up’, are fundamental problems in tumor biology. To address these questions, we utilized metastasis assays in mice to show that dormant DTCs reside upon microvasculature of lung, bone marrow and brain. We then engineered organotypic microvascular niches to determine whether endothelial cells directly influence breast cancer cell (BCC) growth. These models demonstrated that endothelial-derived thrombospondin-1 induces sustained BCC quiescence. This suppressive cue was lost in sprouting neovasculature; time-lapse analysis showed that sprouting vessels not only permit, but accelerate BCC outgrowth. We confirmed this surprising result in dormancy models and in zebrafish, and identified active TGF-β1 and periostin as tumor-promoting, endothelial tip cell-derived factors. Our work reveals that stable microvasculature constitutes a ‘dormant niche,’ whereas sprouting neovasculature sparks micrometastatic outgrowth. PMID:23728425

  18. Involvement of IGF-1 and MEOX2 in PI3K/Akt1/2 and ERK1/2 pathways mediated proliferation and differentiation of perivascular adipocytes

    SciTech Connect

    Liu, Ping; Kong, Feng; Wang, Jue; Lu, Qinghua; Xu, Haijia; Qi, Tonggang; Meng, Juan

    2015-02-01

    Perivascular adipocyte (PVAC) proliferation and differentiation were closely involved in cardiovascular disease. We aimed to investigate whether phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways enhance PVAC functions activated by insulin-like growth factor 1(IGF-1) and suppressed by mesenchyme homeobox 2 (MEOX2). In this study, PVACs from primary culture were cultured and induced to differentiate. Cell viability assays demonstrated that IGF-1 promoted PVAC proliferation and differentiation. However MEOX2 counteracted these IGF-1-mediated actions. Flow Cytometry revealed that IGF-1 increased S phase cells and decreased apoptosis; however, MEOX2 decreased S phase cells, increased G0–G1 phase cells, and promoted apoptosis. During PVAC proliferation and differentiation, IGF-1 activated PI3K/Akt1/2 and ERK1/2 signaling pathways, upregulated the expression of these signaling proteins and FAS, and increased PVAC lipid content. In contrast, MEOX2 constrained the phosphorylation of ERK1/2 and Akt1/2 protein, down-regulated these signaling molecules and FAS, and decreased PVAC lipid content. Instead, MEOX2 knockdown enhanced the ERK1/2 and Akt1/2 phosphorylation, augmented the expression of these signaling molecules and FAS, and increased PVAC lipid content. Our findings suggested that PI3K/Akt1/2 and ERK1/2 activation mediated by IGF-1 is essential for PVAC proliferation and differentiation, and MEOX2 is a promising therapeutic gene to intervene in the signaling pathways and inhibit PVAC functions. - Highlights: • IGF-1 activated PI3K/Akt2 and ERK1/2 pathways to mediate PVAC proliferation and differentiation. • The expression of ERK1, ERK 2, PI3K, Akt1 and Akt2 showed different change trends between PVAC proliferation and differentiation. • MEOX2 effectively expressed in PVAC, increased early and late cellular apoptosis, and inhibited its proliferation. • MEOX2 depressed PVAC differentiation and FAS expression

  19. PSF/SFPQ is a very common gene fusion partner in TFE3 rearrangement-associated perivascular epithelioid cell tumors (PEComas) and melanotic Xp11 translocation renal cancers: clinicopathologic, immunohistochemical, and molecular characteristics suggesting classification as a distinct entity.

    PubMed

    Rao, Qiu; Shen, Qin; Xia, Qiu-yuan; Wang, Zi-yu; Liu, Biao; Shi, Shan-shan; Shi, Qun-li; Yin, Hong-lin; Wu, Bo; Ye, Sheng-bing; Li, Li; Chen, Jie-Yu; Pan, Min-hong; Li, Qing; Li, Rui; Wang, Xuan; Zhang, Ru-song; Yu, Bo; Ma, Heng-hui; Lu, Zhen-feng; Zhou, Xiao-jun

    2015-09-01

    An increasing number of TFE3 rearrangement-associated tumors, such as TFE3 rearrangement-associated perivascular epithelioid cell tumors (PEComas), melanotic Xp11 translocation renal cancers, and melanotic Xp11 neoplasms, have recently been reported. We examined 12 such cases, including 5 TFE3 rearrangement-associated PEComas located in the pancreas, cervix, or pelvis and 7 melanotic Xp11 translocation renal cancers, using clinicopathologic, immunohistochemical, and molecular analyses. All the tumors shared a similar morphology, including a purely nested or sheet-like architecture separated by a delicate vascular network, purely epithelioid cells displaying a clear or granular eosinophilic cytoplasm, a lack of papillary structures and spindle cell or fat components, uniform round or oval nuclei containing small visible nucleoli, and, in most cases (11/12), melanin pigmentation. The levels of mitotic activity and necrosis varied. All 12 cases displayed moderately (2+) or strongly (3+) positive immunoreactivity for TFE3 and cathepsin K. One case labeled focally for HMB45 and Melan-A, whereas the others typically labeled moderately (2+) or strongly (3+) for 1 of these markers. None of the cases were immunoreactive for smooth muscle actin, desmin, CKpan, S100, or PAX8. PSF-TFE3 fusion genes were confirmed by reverse transcription polymerase chain reaction in cases (7/7) in which a novel PSF-TFE3 fusion point was identified. All of the cases displayed TFE3 rearrangement associated with Xp11 translocation. Furthermore, we developed a PSF-TFE3 fusion fluorescence in situ hybridization assay for the detection of the PSF-TFE3 fusion gene and detected it in all 12 cases. Clinical follow-up data were available for 7 patients. Three patients died, and 2 patients (cases 1 and 3) remained alive with no evidence of disease after initial resection. Case 2 experienced recurrence and remained alive with disease. Case 5, a recent case, remained alive with extensive abdominal cavity

  20. Elevated temperature envelope forming

    NASA Technical Reports Server (NTRS)

    Burg, Bruce M. (Inventor); Gane, David H. (Inventor); Starowski, Robert M. (Inventor)

    1992-01-01

    Elevated temperature envelope forming includes enclosing a part blank and form tool within an envelope sealed against the atmosphere, heat treating the combination while forming pressure holds the envelope and part against the form tool, and allowing part cool down to occur in an inert atmosphere with forming pressure removed. The forming pressure is provided by evacuating the envelope and may be aided by differential force applied between the envelope and the form tool.

  1. Form 5-Mining venture agreement model form

    SciTech Connect

    Not Available

    1984-01-01

    This text acts as a reference of the basic terms and conditions for a negotiated mining venture agreement. Alternative clauses and provisions, along with extensive commentary, are supplied. The model form contains many articles which define and detail the process.

  2. Bacteria form tellurium nanocrystals

    USGS Publications Warehouse

    Oremland, R.S.

    2007-01-01

    A team of researchers have found two bacterial species that produce tellurium oxyanions as respiratory electron acceptors for growth, leaving elemental tellurium in the form of nanoparticles. The crystals from the two organisms exhibit distinctively different structures. Bacillus selenitireducens initially forms nanorods that cluster together to form rosettes. Sulfurospirillum barnesii forms irregularly-shaped nanospheres that coalesce into larger composite aggregates.

  3. Handbook of Poetic Forms.

    ERIC Educational Resources Information Center

    Padgett, Ron, Ed.

    Intended for secondary teachers and student writers but useful for anyone interested in poetic forms, this book defines 74 basic poetic forms, summarizes their histories, quotes examples from noted poets, and offers professional tricks of the trade on how to use each form. The book covers the following poetic forms: abstract poem, acrostic,…

  4. RY 2004 Reporting Forms

    EPA Pesticide Factsheets

    The TRI reporting forms on this page are for reference only. Do not submit these forms to EPA. All facilities are required to submit their TRI data electronically using the TRI-MEweb application, per the TRI Electronic Reporting Rule.

  5. RY 2009 Reporting Forms

    EPA Pesticide Factsheets

    The TRI reporting forms on this page are for reference only. Do not submit these forms to EPA. All facilities are required to submit their TRI data electronically using the TRI-MEweb application, per the TRI Electronic Reporting Rule.

  6. RY 2003 Reporting Forms

    EPA Pesticide Factsheets

    The TRI reporting forms on this page are for reference only. Do not submit these forms to EPA. All facilities are required to submit their TRI data electronically using the TRI-MEweb application, per the TRI Electronic Reporting Rule.

  7. Forms of Arthritis

    MedlinePlus

    ... stiffness, inflammation, swelling and, sometimes, destruction of joints. Gout — a form of arthritis that occurs when uric ... the joints. Some 2.1 million Americans have gout. Lupus — a form of arthritis, like rheumatoid arthritis, ...

  8. Method for forming ammonia

    DOEpatents

    Kong, Peter C.; Pink, Robert J.; Zuck, Larry D.

    2008-08-19

    A method for forming ammonia is disclosed and which includes the steps of forming a plasma; providing a source of metal particles, and supplying the metal particles to the plasma to form metal nitride particles; and providing a substance, and reacting the metal nitride particles with the substance to produce ammonia, and an oxide byproduct.

  9. Forms in Space.

    ERIC Educational Resources Information Center

    Moore, Paula

    1998-01-01

    Uses the work of M. C. Escher to instruct upper elementary students in the transformation of flat shape into three-dimensional form. Outlines the lesson as a series of sections: (1) reviewing form drawing; (2) creating three-dimensional effects; (3) imagining the forms in an inhabited world; and (4) using color and shading. (DSK)

  10. Methods of forming steel

    DOEpatents

    Branagan, Daniel J.; Burch, Joseph V.

    2001-01-01

    In one aspect, the invention encompasses a method of forming a steel. A metallic glass is formed and at least a portion of the glass is converted to a crystalline steel material having a nanocrystalline scale grain size. In another aspect, the invention encompasses another method of forming a steel. A molten alloy is formed and cooled the alloy at a rate which forms a metallic glass. The metallic glass is devitrified to convert the glass to a crystalline steel material having a nanocrystalline scale grain size. In yet another aspect, the invention encompasses another method of forming a steel. A first metallic glass steel substrate is provided, and a molten alloy is formed over the first metallic glass steel substrate to heat and devitrify at least some of the underlying metallic glass of the substrate.

  11. Crystal forms of naproxen.

    PubMed

    Song, Jung-Soon; Sohn, Young-Taek

    2011-01-01

    The objective of this work was to investigate the existence of polymorphs and pseudopolymorphs of naproxen and the transformation of crystal forms. Four crystal forms of naproxen have been isolated by recrystallization and characterized by differential scanning calorimetry, powder X-ray diffractometry and thermogravimetric analysis. The differential scanning calorimetry and powder X-ray diffractometry patterns of the four crystal forms were different respectively. In the dissolution studies in pH 6.8 ± 0.05 buffer equilibrated at 37 ± 0.5°C, the solubility of four crystal forms was similar (within the error range). After storage of 1 month at 0% RH (silica gel, 20°C), 52% RH (saturated solution of Na(2)Cr(2)O(7.2)H(2)O/20°C) and 95% RH (saturated solution of Na(2)HPO(4)/20°C), Form 2 and Form 4 were transformed to Form 1, but Form 3 and Form 1 were not transformed and they were shown to have a good physical stability at room temperature for 1 month.

  12. Method of forming nanodielectrics

    DOEpatents

    Tuncer, Enis [Knoxville, TN; Polyzos, Georgios [Oak Ridge, TN

    2014-01-07

    A method of making a nanoparticle filled dielectric material. The method includes mixing nanoparticle precursors with a polymer material and reacting the nanoparticle mixed with the polymer material to form nanoparticles dispersed within the polymer material to form a dielectric composite.

  13. The "Energy" of Form.

    ERIC Educational Resources Information Center

    Blankenship, Jane; Sweeney, Barbara

    1980-01-01

    Examines three types of "energy" of form as form relates to content: "dynamos," potential energy; "energeia," that energy which sustains movement toward an end; and "ergon," that energy which is associated with perfected habit. Uses some examples from contemporary political rhetoric to illustrate this analysis. (JMF)

  14. Method for forming materials

    DOEpatents

    Tolle, Charles R.; Clark, Denis E.; Smartt, Herschel B.; Miller, Karen S.

    2009-10-06

    A material-forming tool and a method for forming a material are described including a shank portion; a shoulder portion that releasably engages the shank portion; a pin that releasably engages the shoulder portion, wherein the pin defines a passageway; and a source of a material coupled in material flowing relation relative to the pin and wherein the material-forming tool is utilized in methodology that includes providing a first material; providing a second material, and placing the second material into contact with the first material; and locally plastically deforming the first material with the material-forming tool so as mix the first material and second material together to form a resulting material having characteristics different from the respective first and second materials.

  15. Spin forming development

    SciTech Connect

    Gates, W.G.

    1982-05-01

    Bendix product applications require the capability of fabricating heavy gage, high strength materials. Five commercial sources have been identified that have the capability of spin forming metal thicknesses greater than 9.5 mm and four equiment manufacturers produce machines with this capability. Twelve assemblies selected as candidates for spin forming applications require spin forming of titanium, 250 maraging steel, 17-4 pH stainless steel, Nitronic 40 steel, 304 L stainless steel, and 6061 aluminum. Twelve parts have been cold spin formed from a 250 maraging steel 8.1 mm wall thickness machine preform, and six have been hot spin formed directly from 31.8-mm-thick flat plate. Thirty-three Ti-6Al-4V titanium alloy parts and 26 17-4 pH stainless steel parts have been hot spin formed directly from 31.8-mm-thick plate. Hot spin forming directly from plate has demonstrated the feasibility and favorable economics of this fabrication technique for Bendix applications.

  16. Nestin+cells forming spheroids aggregates resembling tumorspheres in experimental ENU-induced gliomas.

    PubMed

    García-Blanco, Alvaro; Bulnes, Susana; Pomposo, Iñigo; Carrasco, Alex; Lafuente, José Vicente

    2016-12-01

    Nestin+cells from spheroid aggregates display typical histopathological features compatible with cell stemness. Nestin and CD133+cells found in glioblastomas, distributed frequently around aberrant vessels, are considered as potential cancer stem cells. They are possible targets for antitumoral therapy because they lead the tumorigenesis, invasiveness and angiogenesis. However, little is known about their role and presence in low-grade gliomas. The aim of this work is to localize and characterize the distribution of these cells inside tumors during the development of experimental endogenous glioma. For this study, a single dose of Ethyl-nitrosourea was injected into pregnant rats. Double immunofluorescences were performed in order to identify stem-like and differentiated cells. Low-grade gliomas display Nestin+cells distributed throughout the tumor. More malignant gliomas show, in addition to that, a perivascular location with some Nestin+cells co-expressing CD133 or VEGF, and the intratumoral spheroid aggregates of Nestin/CD133+cells. These structures are encapsulated by well-differentiated VEGF/GFAP+cells. Spheroid aggregates increase in size in the most malignant stages. Spheroid aggregates have morphological and phenotypic similarities to in vitro neurospheres and could be an in vivo analogue of them. These arrangements could be a reservoir of undifferentiated cells formed to escape adverse microenvironments.

  17. Pulmonary capillaritis: a possible histologic form of acute pulmonary allograft rejection.

    PubMed

    Badesch, D B; Zamora, M; Fullerton, D; Weill, D; Tuder, R; Grover, F; Schwarz, M I

    1998-04-01

    Acute rejection after lung transplantation occurs commonly and is usually characterized histologically by a perivascular mononuclear infiltrate. We report five cases of pulmonary capillaritis with a histologic appearance distinct from typical rejection, occurring in patients ranging in age from 18 to 45 years, with a variety of underlying diseases including alpha1 antitrypsin deficiency, pulmonary hypertension, cystic fibrosis, and rheumatoid arthritis. Four of the five patients had alveolar hemorrhage histologically, and two had frank hemoptysis. Time of onset ranged from 3 weeks to many months after transplantation. Three cases were fulminant, and there were two deaths. In only one case, with methicillin-resistant Staphylococcus aureus bronchitis, could infection be established. All were treated with intensification of immunosuppressive therapy. Plasmapheresis was carried out in two cases and coincided with temporary improvement, but its efficacy was questionable because of concurrent immunosuppressive therapy. Two had recurrent biopsy-proven acute rejection within 6 weeks of treatment, and one had recurrent severe pulmonary hemorrhage that abated with total lymphoid irradiation. Our experience suggests that pulmonary capillaritis in lung transplant recipients can be an acute, fatal illness with the potential for recurrence in the survivors. We speculate that it represents a form of acute vascular rejection. Early pathologic diagnosis and aggressive immunosuppressive therapy are recommended. Although a humoral component was not documented, the possible response to plasmapheresis requires continued evaluation.

  18. Advanced Electrochemical Waste Forms

    SciTech Connect

    Riley, Brian J.; Crum, Jarrod V.; McCloy, John S.; Matyas, Josef

    2011-12-01

    This is a brief description of PNNL's efforts in FY2011 towards developing advanced electrochemical waste forms. This is a short section that will become part of a larger document being put together by INL.

  19. Handprinted Forms and Characters

    National Institute of Standards and Technology Data Gateway

    NIST Handprinted Forms and Characters (PC database for purchase)   NIST Special Database 19 contains NIST's entire corpus of training materials for handprinted document and character recognition. It supersedes NIST Special Databases 3 and 7.

  20. Image forming apparatus

    DOEpatents

    Satoh, Hisao; Haneda, Satoshi; Ikeda, Tadayoshi; Morita, Shizuo; Fukuchi, Masakazu

    1996-01-01

    In an image forming apparatus having a detachable process cartridge in which an image carrier on which an electrostatic latent image is formed, and a developing unit which develops the electrostatic latent image so that a toner image can be formed, both integrally formed into one unit. There is provided a developer container including a discharge section which can be inserted into a supply opening of the developing unit, and a container in which a predetermined amount of developer is contained, wherein the developer container is provided to the toner supply opening of the developing unit and the developer is supplied into the developing unit housing when a toner stirring screw of the developing unit is rotated.

  1. Electromagnetic nucleon form factors

    SciTech Connect

    Bender, A.; Roberts, C.D.; Frank, M.R.

    1995-08-01

    The Dyson-Schwinger equation framework is employed to obtain expressions for the electromagnetic nucleon form factor. In generalized impulse approximation the form factor depends on the dressed quark propagator, the dressed quark-photon vertex, which is crucial to ensuring current conservation, and the nucleon Faddeev amplitude. The approach manifestly incorporates the large space-like-q{sup 2} renormalization group properties of QCD and allows a realistic extrapolation to small space-like-q{sup 2}. This extrapolation allows one to relate experimental data to the form of the quark-quark interaction at small space-like-q{sup 2}, which is presently unknown. The approach provides a means of unifying, within a single framework, the treatment of the perturbative and nonperturbative regimes of QCD. The wealth of experimental nucleon form factor data, over a large range of q{sup 2}, ensures that this application will provide an excellent environment to test, improve and extend our approach.

  2. Forming techniques and procedures

    NASA Astrophysics Data System (ADS)

    Ronde-Oustau, F.

    1980-09-01

    Several forming techniques are discussed including: (1) cooling stamping and swaging tools by the "Caloduc' methods; (2) non-burr stamping (stamping in a closed die); (3) continuous casting; (4) orbital forging; and (5) plastic deformation and spheroidal graphite iron. In addition, the subject of superplasticity is discussed in some detail, and brief consideration is given to precision forging, forging die castings, sintered forging, squeeze casting, ausforming, magnetoforming, and ultrasonic forming.

  3. Shell forming system

    NASA Technical Reports Server (NTRS)

    Kendall, Jr., James M. (Inventor); Wang, Taylor G. (Inventor); Elleman, Daniel D. (Inventor)

    1990-01-01

    Hollow shells of high uniformity are formed by emitting liquid through an outer nozzle and gas through an inner nozzle, to form a hollow extrusion, by flowing the gas at a velocity between about 1.3 and 10 times the liquid velocity. The natural breakup rate of the extrusion can be increased to decrease shell size by applying periodic perturbations to one of the materials prior to exiting the nozzles, to a nozzle, or to the extrusion.

  4. UltraForm finishing

    NASA Astrophysics Data System (ADS)

    Fess, E.; Schoen, J.; Bechtold, M.; Mohring, D.

    2005-05-01

    A new compliant sub-aperture optical finishing technique is being investigated for the removal of mid-spatial frequency artifacts and smoothing of hard polycrystalline infrared ceramics for aspheric applications and conformal shaped optics. The UltraForm concept was developed by OptiPro Systems, Ontario, NY, and is a joint process development effort with the Center for Optics manufacturing (COM). The UltraForm tool is a pressurized, elastomeric bladder in the shape of a toroid. Finishing pads are attached to the periphery, allowing the use of a wide variety of pad materials and abrasive selections. Experimentation has been conducted using both slurry mixes and fixed abrasive pads. The toroidal tool is rotated while the compliant tool is compressed into contact with the surface. Currently this process has specific interest for the finishing of conformal ALON Domes. Also to be discussed will be new versions of the UltraForm Tools which are currently be developed and tested.

  5. Microbicide dosage forms.

    PubMed

    Rohan, L C; Devlin, B; Yang, H

    2014-01-01

    Microbicides are topically applied, user controlled dosage forms that are being developed to prevent the transmission of HIV during coitus. Early candidates focused on coitally dependent dosage forms such as gels and creams. More recent development has focused on broadening the coitally dependent options through the introduction of films and fast dissolving tablets. Additionally, it has become important to have longer acting products to minimize the burden of user compliance and thus vaginal rings have been developed providing sustained delivery of antiretroviral drugs. This chapter discusses the history of microbicides along with a detailed description of coitally dependent products, gels, films, tablets diaphragms, as well as coitally independent dosage forms such as vaginal rings and the introduction of a new technology, electrospun fibers.

  6. Physical forms of MIPs.

    PubMed

    Biffis, Andrea; Dvorakova, Gita; Falcimaigne-Cordin, Aude

    2012-01-01

    The current state of the art in the development of methodologies for the preparation of MIPs in predetermined physical forms is critically reviewed, with particular attention being paid to the forms most widely employed in practical applications, such as spherical beads in the micro- to nanometer range, microgels, monoliths, membranes. Although applications of the various MIP physical forms are mentioned, the focus of the paper is mainly on the description of the various preparative methods. The aim is to provide the reader with an overview of the latest achievements in the field, as well as with a mean for critically evaluating the various proposed methodologies towards an envisaged application. The review covers the literature up to early 2010, with special emphasis on the developments of the last 10 years.

  7. Hydrogen forming reaction process

    SciTech Connect

    Marianowski, L.G.; Fleming, D.K.

    1989-03-07

    A hydrogen forming process is described, comprising: conducting in a hydrogen production zone a chemical reaction forming mixed gases comprising molecular hydrogen; contacting one side of a hydrogen ion porous and molecular gas nonporous metallic foil with the mixed gases in the hydrogen production zone; dissociating the molecular hydrogen to ionic hydrogen on the one side of the metallic foil; passing the ionic hydrogen through the metallic foil to its other side; and withdrawing hydrogen from the other side of the metallic foil, thereby removing hydrogen from the hydrogen production zone.

  8. Emotions: form follows function.

    PubMed

    Farb, Norman A S; Chapman, Hanah A; Anderson, Adam K

    2013-06-01

    Emotion research has been divided by debate as to whether emotions are universal in form or cognitively constructed. We review an emerging approach that focuses on function rather than form. Functional affective science suggests that the particular origin of an emotion is relatively unimportant; instead, emotions can be understood in terms of a rapidly deployed set of mechanisms that structure perception, cognition and behavior to facilitate goal fulfillment. Evidence from this approach suggests at least three major functions of emotion: sensory gating, embodying affect, and integrating knowledge toward goal resolution. These functions appear to be universal and automatically activated, yet also moderated by conscious representation and regulatory efforts.

  9. Sixth Form Examining Methods.

    ERIC Educational Resources Information Center

    Schools Council, London (England).

    The methods of examining in the sixth form of secondary education in England and Wales is the basis for discussion by subject committees of the Schools Council. Special reference is made to internal examinations, oral assessments, teacher's assessments, the relaxing of the time limits for examination, and the use of aids during examinations. The…

  10. Many Forms of Culture

    ERIC Educational Resources Information Center

    Cohen, Adam B.

    2009-01-01

    Psychologists interested in culture have focused primarily on East-West differences in individualism-collectivism, or independent-interdependent self-construal. As important as this dimension is, there are many other forms of culture with many dimensions of cultural variability. Selecting from among the many understudied cultures in psychology,…

  11. Geodiversity and land form

    NASA Astrophysics Data System (ADS)

    Gray, Murray

    2014-05-01

    The Earth's surface has a dynamic and topographically varied natural landscape. In some cases the resulting landforms are given generic names reflecting their form and/or origin, (e.g. sand dunes, eskers, ox-bow lakes) but in many cases the land surface has a more amorphous form and is less easily categorized other than at a landscape scale (e.g. dissected plateau, Chalk downland). Across much of Europe, while the natural vegetation has been removed or radically modified, the natural land form/topography remains in tact. In this context and in terms of geoconservation we ought to be: • allowing the dynamic natural processes that create, carve and modify landscapes to continue to operate; and • retaining natural topographic character and geomorphological authenticity in the face of human actions seeking to remodel the land surface. In this presentation examples of this approach to geoconservation of land form will be given from the UK and other parts of the world. This will include examples of both appropriate and inappropriate topographic modifications.

  12. Literature: Internal Forms.

    ERIC Educational Resources Information Center

    Regional Curriculum Project, Atlanta, GA.

    This curriculum guide in literature, developed as part of a total English curriculum for pre-kindergarten through grade 10, suggests that students can best understand literature by recognizing its internal forms (i.e., characteristics that recur in settings, characters, and narrative patterns). Materials cover (1) an overview for teachers on the…

  13. Bristol Stool Form Scale

    MedlinePlus

    ... Stool Form Scale Type Description Type 1 Separate hard lumps, like nuts Image Type 2 Sausage-shaped but lumpy Type 3 Like a sausage or snake but with cracks on its surface Type 4 Like a sausage or snake, smooth and soft ...

  14. Forms of Soft Sculpture

    ERIC Educational Resources Information Center

    Tucker, Dorothy

    1978-01-01

    For the past several years, students at Madison Senior High School in San Diego have responded to the tactile texture and draping quality of soft materials. They experimented enthusiastically with three-dimensional forms made out of foam rubber. Here is the result of their efforts and experimentation. (Author/RK)

  15. Apparatus for forming targets

    DOEpatents

    Woerner, Robert L.

    1980-01-01

    Apparatus and method for cryoinduced uniform deposition of cryogenic materials, such as deuterium-tritium (DT) mixtures, on the inner surface of hollow spherical members, such as inertially imploded targets. By vaporizing and quickly refreezing cryogenic materials contained within a hollow spherical member, a uniform layer of the materials is formed on the inner surface of the spherical member. Heating of the cryogenic material, located within a non-isothermal compact freezing cell, is accomplished by an electrical heat pulse, whereafter the material is quickly frozen forming a uniform layer on the inner surface of the spherical member. The method is not restricted to producing a frozen layer on only the inner surface of the innermost hollow member, but where multiple concentric hollow spheres are involved, such as in multiple shell targets for lasers, electron beams, etc., layers of cryogenic material may also be formed on the inner surface of intermediate or outer spherical members, thus providing the capability of forming targets having multiple concentric layers or shells of frozen DT.

  16. Method for forming targets

    DOEpatents

    Woerner, Robert L.

    1979-01-01

    Method for cryoinduced uniform deposition of cryogenic materials, such as deuterium-tritium (DT) mixtures, on the inner surface of hollow spherical members, such as inertially imploded targets. By vaporizing and quickly refreezing cryogenic materials contained within a hollow spherical member, a uniform layer of the materials is formed on the inner surface of the spherical member. Heating of the cryogenic material, located within a non-isothermal compact freezing cell, is accomplished by an electrical heat pulse, whereafter the material is quickly frozen forming a uniform layer on the inner surface of the spherical member. The method is not restricted to producing a frozen layer on only the inner surface of the innermost hollow member, but where multiple concentric hollow spheres are involved, such as in multiple shell targets for lasers, electron beams, etc., layers of cryogenic material may also be formed on the inner surface of intermediate or outer spherical members, thus providing the capability of forming targets having multiple concentric layers or shells of frozen DT.

  17. High energy forming facility

    NASA Technical Reports Server (NTRS)

    Ciurlionis, B.

    1967-01-01

    Watertight, high-explosive forming facility, 25 feet in diameter and 15 feet deep, withstands repeated explosions of 10 pounds of TNT equivalent. The shell is fabricated of high strength steel and allows various structural elements to deform or move elastically and independently while retaining structural integrity.

  18. Nucleon electromagnetic form factors

    SciTech Connect

    Kees de Jager

    2000-01-01

    A review of data on the nucleon electromagnetic form factors in the space-like region is presented. Recent results from experiments using polarized beams and polarized targets or nucleon recoil polarimeters have yielded a significant improvement on the precision of the data obtained with the traditional Rosenbluth separation. Future plans for extended measurements are outlined.

  19. Nucleon Magnetic Form Factors

    SciTech Connect

    Kees de Jager

    2001-12-01

    A review of data on the nucleon electromagnetic form factors in the space-like region is presented. Recent results from experiments using polarized beams and polarized targets or nucleon recoil polarimeters have yielded a significant improvement on the precision of the data obtained with the traditional Rosenbluth separation. Future plans for extended measurements are outlined.

  20. Nucleon Form Factors

    SciTech Connect

    Kees de Jager

    2002-10-01

    A review of data on the nucleon electro-weak form factors in the space-like region is presented. Recent results from experiments using polarized beams and either polarized targets or nucleon recoil polarimeters have yielded a significant improvement on the precision of the electromagnetic data obtained with the traditional Rosenbluth separation. An outlook is presented of planned experiments.

  1. Formed photovoltaic module busbars

    DOEpatents

    Rose, Douglas; Daroczi, Shan; Phu, Thomas

    2015-11-10

    A cell connection piece for a photovoltaic module is disclosed herein. The cell connection piece includes an interconnect bus, a plurality of bus tabs unitarily formed with the interconnect bus, and a terminal bus coupled with the interconnect bus. The plurality of bus tabs extend from the interconnect bus. The terminal bus includes a non-linear portion.

  2. Gnatophyma - A rare form of rosacea*

    PubMed Central

    de Macedo, Ana Carolina Lisboa; Sakai, Fernanda Dias Pacheco; de Vasconcelos, Rossana Cantanhede Farias; Duarte, Artur Antonio

    2012-01-01

    Phyma is the last stage of rosacea and is due to chronic inflammation and edema. It can affect nose (rhinophyma), chin (gnatophyma), forehead (metophyma), ears (otophyma) and eyelids (blepharophyma). Rhinophyma is the most frequent location and there are few reports about gnatophyma. We report the case of a female patient, 41 years old, who had an infiltrated, erythematous, edematous plaque around the chin and lower lip for two years. Histopathology showed perivascular lymphocytic infiltrate, hypertrophied follicles and sebaceous glands, dilated vessels and fibrosis. She was treated with oral tetracycline, oral ivermectin and metronidazole cream with a satisfactory response. The clinical, histopathological and therapeutic response correlation confirmed the diagnosis of gnatophyma, a rare variant of phyma. PMID:23197212

  3. Familial Chilblain Lupus, a Monogenic Form of Cutaneous Lupus Erythematosus, Maps to Chromosome 3p

    PubMed Central

    Lee-Kirsch, Min Ae; Gong, Maolian; Schulz, Herbert; Rüschendorf, Franz; Stein, Annette; Pfeiffer, Christiane; Ballarini, Annalisa; Gahr, Manfred; Hubner, Norbert; Linné, Maja

    2006-01-01

    Systemic lupus erythematosus is a prototypic autoimmune disease. Apart from rare monogenic deficiencies of complement factors, where lupuslike disease may occur in association with other autoimmune diseases or high susceptibility to bacterial infections, its etiology is multifactorial in nature. Cutaneous findings are a hallmark of the disease and manifest either alone or in association with internal-organ disease. We describe a novel genodermatosis characterized by painful bluish-red inflammatory papular or nodular lesions in acral locations such as fingers, toes, nose, cheeks, and ears. The lesions sometimes appear plaquelike and tend to ulcerate. Manifestation usually begins in early childhood and is precipitated by cold and wet exposure. Apart from arthralgias, there is no evidence for internal-organ disease or an increased susceptibility to infection. Histological findings include a deep inflammatory infiltrate with perivascular distribution and granular deposits of immunoglobulins and complement along the basement membrane. Some affected individuals show antinuclear antibodies or immune complex formation, whereas cryoglobulins or cold agglutinins are absent. Thus, the findings are consistent with chilblain lupus, a rare form of cutaneous lupus erythematosus. Investigation of a large German kindred with 18 affected members suggests a highly penetrant trait with autosomal dominant inheritance. By single-nucleotide-polymorphism–based genomewide linkage analysis, the locus was mapped to chromosome 3p. Haplotype analysis defined the locus to a 13.8-cM interval with a LOD score of 5.04. This is the first description of a monogenic form of cutaneous lupus erythematosus. Identification of the gene responsible for familial chilblain lupus may shed light on the pathogenesis of common forms of connective-tissue disease such as systemic lupus erythematosus. PMID:16960810

  4. Major trends in stem anatomy and growth forms in the perianth-bearing Piperales, with special focus on Aristolochia

    PubMed Central

    Wagner, Sarah T.; Hesse, Linnea; Isnard, Sandrine; Samain, Marie-Stéphanie; Bolin, Jay; Maass, Erika; Neinhuis, Christoph; Rowe, Nick P.; Wanke, Stefan

    2014-01-01

    Background and Aims The order Piperales has the highest diversity of growth forms among the earliest angiosperm lineages, including trees, shrubs, climbers and herbs. However, within the perianth-bearing Piperales (Asarum, Saruma, Lactoris, Hydnora, Prosopanche, Thottea and Aristolochia), climbing species only occur in the most species-rich genus Aristolochia. This study traces anatomical and morphological traits among these lineages, to detect trends in growth form evolution and developmental processes. Methods Transverse stem sections of different developmental stages of representatives of Asarum, Saruma, Lactoris, Hydnora, Thottea and Aristolochia were compared and anatomical traits were linked to growth form evolution. Biomechanical properties of representative climbers were determined in three-point bending tests and are discussed based on the anatomical observations. Growth form evolution of the perianth-bearing Piperales was reconstructed by ancestral character state reconstruction using Mesquite. Key Results While species of Asarum and Saruma are exclusively herbaceous, species of the remaining genera show a higher diversity of growth habit and anatomy. This growth form diversity is accompanied by a more complex stem anatomy and appropriate biomechanical properties. The ancestral growth form of the perianth-bearing Piperales is reconstructed with either a shrub-like or herbaceous character state, while the following three backbone nodes in the reconstruction show a shrub-like character state. Accordingly, the climbing habit most probably evolved in the ancestor of Aristolochia. Conclusions Since the ancestor of the perianth-bearing Piperales has been reconstructed with a herb- or shrub-like habit, it is proposed that the climbing habit is a derived growth form, which evolved with the diversification of Aristolochia, and might have been a key feature for its diversification. Observed anatomical synapomorphies, such as the perivascular fibres in Lactoris

  5. Analytic pion form factor

    NASA Astrophysics Data System (ADS)

    Lomon, Earle L.; Pacetti, Simone

    2016-09-01

    The pion electromagnetic form factor and two-pion production in electron-positron collisions are simultaneously fitted by a vector dominance model evolving to perturbative QCD at large momentum transfer. This model was previously successful in simultaneously fitting the nucleon electromagnetic form factors (spacelike region) and the electromagnetic production of nucleon-antinucleon pairs (timelike region). For this pion case dispersion relations are used to produce the analytic connection of the spacelike and timelike regions. The fit to all the data is good, especially for the newer sets of timelike data. The description of high-q2 data, in the timelike region, requires one more meson with ρ quantum numbers than listed in the 2014 Particle Data Group review.

  6. Waste-form development

    SciTech Connect

    Neilson, R.M. Jr.; Colombo, P.

    1982-01-01

    Contemporary solidification agents are being investigated relative to their applications to major fuel cycle and non-fuel cycle low-level waste (LLW) streams. Work is being conducted to determine the range of conditions under which these solidification agents can be applied to specific LLW streams. These studies are directed primarily towards defining operating parameters for both improved solidification of problem wastes and solidification of new LLW streams generated from advanced volume reduction technologies. Work is being conducted to measure relevant waste form properties. These data will be compiled and evaluated to demonstrate compliance with waste form performance and shallow land burial acceptance criteria and transportation requirements (both as they exist and as they are modified with time).

  7. Formed HIP Can Processing

    SciTech Connect

    Clarke, Kester Diederik

    2015-07-27

    The intent of this report is to document a procedure used at LANL for HIP bonding aluminum cladding to U-10Mo fuel foils using a formed HIP can for the Domestic Reactor Conversion program in the NNSA Office of Material, Management and Minimization, and provide some details that may not have been published elsewhere. The HIP process is based on the procedures that have been used to develop the formed HIP can process, including the baseline process developed at Idaho National Laboratory (INL). The HIP bonding cladding process development is summarized in the listed references. Further iterations with Babcock & Wilcox (B&W) to refine the process to meet production and facility requirements is expected.

  8. How Stars Form

    NASA Astrophysics Data System (ADS)

    McKee, Christopher F.

    2017-01-01

    Stars are the atoms of the universe. The process by which stars form is at the nexus of astrophysics since they are believed to be responsible for the re-ionization of the universe, they created the heavy elements, they play a central role in the formation and evolution of galaxies, and their formation naturally leads to the formation of planets. Whereas early work on star formation was based on the assumption that it is a quiescent process, it is now believed that turbulence plays a dominant role. In this overview, I shall discuss the evolution of our understanding of how stars form and current ideas about the stellar initial mass function and the rate of star formation.

  9. Tube-Forming Assays.

    PubMed

    Brown, Ryan M; Meah, Christopher J; Heath, Victoria L; Styles, Iain B; Bicknell, Roy

    2016-01-01

    Angiogenesis involves the generation of new blood vessels from the existing vasculature and is dependent on many growth factors and signaling events. In vivo angiogenesis is dynamic and complex, meaning assays are commonly utilized to explore specific targets for research into this area. Tube-forming assays offer an excellent overview of the molecular processes in angiogenesis. The Matrigel tube forming assay is a simple-to-implement but powerful tool for identifying biomolecules involved in angiogenesis. A detailed experimental protocol on the implementation of the assay is described in conjunction with an in-depth review of methods that can be applied to the analysis of the tube formation. In addition, an ImageJ plug-in is presented which allows automatic quantification of tube images reducing analysis times while removing user bias and subjectivity.

  10. Evoked Cultural Forms

    DTIC Science & Technology

    2013-12-01

    individual (1) pathological behaviors (such as those exhibited by Obsessive Compulsive Disorder (OCD) patients) and (2) non-pathological precautionary...McClelland, J., et al. (2001). Compulsive Checking Behavior of Quinpirole-Sensitized Rats as an Animal Model of Obsessive - Compulsive Disorder (OCD...Form and Control. BMC Neuroscience, 2(1), 4. Szechtman, H., & Woody, E. (2004). Obsessive - Compulsive disorder as a disturbance of security Motivation

  11. GlassForm

    SciTech Connect

    2011-09-16

    GlassForm is a software tool for generating preliminary waste glass formulas for a given waste stream. The software is useful because it reduces the number of verification melts required to develop a suitable additive composition. The software includes property models that calculate glass properties of interest from the chemical composition of the waste glass. The software includes property models for glass viscosity, electrical conductivity, glass transition temperature, and leach resistance as measured by the 7-day product consistency test (PCT).

  12. Nucleon Electromagnetic Form Factors

    SciTech Connect

    Kees de Jager

    2004-08-01

    Although nucleons account for nearly all the visible mass in the universe, they have a complicated structure that is still incompletely understood. The first indication that nucleons have an internal structure, was the measurement of the proton magnetic moment by Frisch and Stern (1933) which revealed a large deviation from the value expected for a point-like Dirac particle. The investigation of the spatial structure of the nucleon, resulting in the first quantitative measurement of the proton charge radius, was initiated by the HEPL (Stanford) experiments in the 1950s, for which Hofstadter was awarded the 1961 Nobel prize. The first indication of a non-zero neutron charge distribution was obtained by scattering thermal neutrons off atomic electrons. The recent revival of its experimental study through the operational implementation of novel instrumentation has instigated a strong theoretical interest. Nucleon electro-magnetic form factors (EMFFs) are optimally studied through the exchange of a virtual photon, in elastic electron-nucleon scattering. The momentum transferred to the nucleon by the virtual photon can be selected to probe different scales of the nucleon, from integral properties such as the charge radius to scaling properties of its internal constituents. Polarization instrumentation, polarized beams and targets, and the measurement of the polarization of the recoiling nucleon have been essential in the accurate separation of the charge and magnetic form factors and in studies of the elusive neutron charge form factor.

  13. Electromagnetic pion form factor

    SciTech Connect

    Roberts, C.D.

    1995-08-01

    A phenomenological Dyson-Schwinger/Bethe-Salpeter equation approach to QCD, formalized in terms of a QCD-based model field theory, the Global Color-symmetry Model (GCM), was used to calculate the generalized impulse approximation contribution to the electromagnetic pion form factor at space-like q{sup 2} on the domain [0,10] GeV{sup 2}. In effective field theories this form factor is sometimes understood as simply being due to Vector Meson Dominance (VMD) but this does not allow for a simple connection with QCD where the VMD contribution is of higher order than that of the quark core. In the GCM the pion is treated as a composite bound state of a confined quark and antiquark interacting via the exchange of colored vector-bosons. A direct study of the quark core contribution is made, using a quark propagator that manifests the large space-like-q{sup 2} properties of QCD, parameterizes the infrared behavior and incorporates confinement. It is shown that the few parameters which characterize the infrared form of the quark propagator may be chosen so as to yield excellent agreement with the available data. In doing this one directly relates experimental observables to properties of QCD at small space-like-q{sup 2}. The incorporation of confinement eliminates endpoint and pinch singularities in the calculation of F{sub {pi}}(q{sup 2}). With asymptotic freedom manifest in the dressed quark propagator the calculation yields q{sup 4}F{sub {pi}}(q{sup 2}) = constant, up to [q{sup 2}]- corrections, for space-like-q{sup 2} {approx_gt} 35 GeV{sup 2}, which indicates that soft, nonperturbative contributions dominate the form factor at presently accessible q{sup 2}. This means that the often-used factorization Ansatz fails in this exclusive process. A paper describing this work was submitted for publication. In addition, these results formed the basis for an invited presentation at a workshop on chiral dynamics and will be published in the proceedings.

  14. Bipolar pulse forming line

    DOEpatents

    Rhodes, Mark A.

    2008-10-21

    A bipolar pulse forming transmission line module for linear induction accelerators having first, second, third, fourth, and fifth planar conductors which form an interleaved stack with dielectric layers between the conductors. Each conductor has a first end, and a second end adjacent an acceleration axis. The first and second planar conductors are connected to each other at the second ends, the fourth and fifth planar conductors are connected to each other at the second ends, and the first and fifth planar conductors are connected to each other at the first ends via a shorting plate adjacent the first ends. The third planar conductor is electrically connectable to a high voltage source, and an internal switch functions to short a high voltage from the first end of the third planar conductor to the first end of the fourth planar conductor to produce a bipolar pulse at the acceleration axis with a zero net time integral. Improved access to the switch is enabled by an aperture through the shorting plate and the proximity of the aperture to the switch.

  15. Nucleon form factors '99

    SciTech Connect

    Kees de Jager; B. Pire

    1999-06-01

    The authors review recent progress in the experimental knowledge of and theoretical speculations about nucleon form factors, with special emphasis on the large Q{sup 2} region. There is now a long history of continuous progress in the understanding of electromagnetic form factors at large momentum transfer. After the pioneering works leading to the celebrated quark counting rules, the understanding of hard scattering exclusive processes has been solidly founded. A perturbative QCD subprocess is factorized from a wave function-like distribution amplitude {var_phi}(x{sub i},Q{sup 2}) (x{sub i} being the light cone fractions of momentum carried by valence quarks), the Q{sup 2} dependence of which is analyzed in the renormalization group approach. Although an asymptotic expression emerges from this analysis for the x dependence of the distribution, it was quickly understood that the evolution to the asymptotic Q{sub 2} is very slow and that indeed some non perturbative input is required to get reliable estimates of this distribution amplitude at measurable Q{sup 2}.

  16. Pion form factor

    SciTech Connect

    Ryong Ji, C.; Pang, A.; Szczepaniak, A.

    1994-04-01

    It is pointed out that the correct criterion to define the legal PQCD contribution to the exclusive processes in the lightcone perturbative expansion should be based on the large off-shellness of the lightcone energy in the intermediate states. In the lightcone perturbative QCD calculation of the pion form factor, the authors find that the legal PQCD contribution defined by the lightcone energy cut saturates in the smaller Q{sup 2} region compared to that defined by the gluon four-momentum square cut. This is due to the contribution by the highly off-energy-shell gluons in the end point regions of the phase space, indicating that the gluon four-momentum-square cut may have cut too much to define the legal PQCD.

  17. Nucleon Electromagnetic Form Factors

    SciTech Connect

    Marc Vanderhaeghen; Charles Perdrisat; Vina Punjabi

    2007-10-01

    There has been much activity in the measurement of the elastic electromagnetic proton and neutron form factors in the last decade, and the quality of the data has greatly improved by performing double polarization experiments, in comparison with previous unpolarized data. Here we review the experimental data base in view of the new results for the proton, and neutron, obtained at JLab, MAMI, and MIT-Bates. The rapid evolution of phenomenological models triggered by these high-precision experiments will be discussed, including the recent progress in the determination of the valence quark generalized parton distributions of the nucleon, as well as the steady rate of improvements made in the lattice QCD calculations.

  18. Shell forming apparatus

    NASA Technical Reports Server (NTRS)

    Wang, Taylor G. (Inventor); Granett, Dan (Inventor); Akutagawa, Wesley M. (Inventor)

    1987-01-01

    A nozzle assembly is described for use in a system that forms small gas-filled shells, which avoids the need for holding a miniature inner nozzle precisely concentric with a miniature outer nozzle. The outer nozzle has a diameter which is less than about 0.7 millimeter, which results in fluid passing through the nozzle having a progressively greater velocity at locations progressively further from the walls of the outer nozzle across most of the nozzle. This highly variable velocity profile automatically forces gas to the center of the outer nozzle. The end of the inner nozzle, which emits gas, is spaced upstream from the tip of the outer nozzle, to provide a distance along which to center the gas. This self-centering characteristic permits the inner nozzle to be positioned so its axis is not concentric with the axis of the outer nozzle.

  19. Shell forming system

    NASA Technical Reports Server (NTRS)

    Kendall, Jr., James M. (Inventor); Wang, Taylor G. (Inventor); Elleman, Daniel D. (Inventor)

    1987-01-01

    An apparatus is provided for forming gas-filled spheres of metal, glass or other material, which produces spheres (12) of uniform size and wall thickness in a relatively simple system. The system includes concentric nozzles, including an inner nozzle (18) through which gas flows and and an outer nozzle (20), which jointly define an annular passageway (50) through which a liquid flows. The flow rates are adjusted so that the gas flows at greater velocity than does the liquid, out of their respective nozzles, e.g. three times as great, in order to produce an extrusion (30) which undergoes axisymmetric oscillations resulting in the pinch off into hollow spheres with very uniform spacing. The system is useful not only where gas-filled spheres are required, but also is useful to accurately control the dispensing of solid, liquid, or gaseous materials.

  20. 78 FR 58605 - Proposed Collection; Comment Request for Form 8453-EMP, Form 8453-F, Form 8453-FE, Form 8879-F...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-24

    ... Internal Revenue Service Proposed Collection; Comment Request for Form 8453-EMP, Form 8453-F, Form 8453-FE, Form 8879-F, and 8879-EMP. AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request... comments concerning Form 8453-F, U.S. Estate of Trust Income Tax Declaration and Signature for...

  1. Forming Spirals From Shadows

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-07-01

    What causes the large-scale spiral structures found in some protoplanetary disks? Most models assume theyre created by newly-forming planets, but a new study suggests that planets might have nothing to do with it.Perturbations from Planets?In some transition disks protoplanetary disks with gaps in their inner regions weve directly imaged large-scale spiral arms. Many theories currently attribute the formation of these structures to young planets: either the direct perturbations of a planet embedded in the disk cause the spirals, or theyre indirectly caused by the orbit of a planetary body outside of the arms.Another example of spiral arms detected in a protoplanetary disk, MWC 758. [NASA/ESA/ESO/M. Benisty et al.]But what if you could get spirals without any planets? A team of scientists led by Matas Montesinos (University of Chile) have recently published a study in which they examine what happens to a shadowed protoplanetary disk.Casting Shadows with WarpsIn the teams setup, they envision a protoplanetary disk that is warped: the inner region is slightly tilted relative to the outer region. As the central star casts light out over its protoplanetary disk, this disk warping would cause some regions of the disk to be shaded in a way that isnt axially symmetric with potentially interesting implications.Montesinos and collaborators ran 2D hydrodynamics simulations to determine what happens to the motion of particles within the disk when they pass in and out of the shadowed regions. Since the shadowed regions are significantly colder than the illuminated disk, the pressure in these regions is much lower. Particles are therefore accelerated and decelerated as they pass through these regions, and the lack of axial symmetry causes spiral density waves to form in the disk as a result.Initial profile for the stellar heating rate per unit area for one of the authors simulations. The regions shadowed as a result of the disk warp subtend 0.5 radians each (shown on the left

  2. Moon (Form-Origin)

    NASA Astrophysics Data System (ADS)

    Tsiapas, Elias

    2016-04-01

    When the Earth was formed, it was in a state of burning heat. As time went by, temperature on the planet's surface was falling due to radiation and heat transfer, and various components (crusts) began taking solid form at the Earth's poles. The formation of crusts took place at the Earth's poles, because the stirring of burning and fluid masses on the surface of the Earth was significantly slighter there than it was on the equator. Due to centrifugal force and Coriolis Effect, these solid masses headed towards the equator; those originating from the North Pole followed a south-western course, while those originating from the South Pole followed a north-western course and there they rotated from west to east at a lower speed than the underlying burning and liquid earth, because of their lower initial linear velocity, their solid state and inertia. Because inertia is proportional to mass, the initially larger solid body swept all new solid ones, incorporating them to its western side. The density of the new solid masses was higher, because the components on the surface would freeze and solidify first, before the underlying thicker components. As a result, the western side of the initial islet of solid rocks submerged, while the east side elevated. . As a result of the above, this initial islet began to spin in reverse, and after taking on the shape of a sphere, it formed the "heart" of the Moon. The Moon-sphere, rolling on the equator, would sink the solid rocks that continued to descend from the Earth's poles. The sinking rocks partially melted because of higher temperatures in the greater depths that the Moon descended to, while part of the rocks' mass bonded with the Moon and also served as a heat-insulating material, preventing the descended side of the sphere from melting. Combined with the Earth's liquid mass that covered its emerging eastern surface, new sphere-shaped shells were created, with increased density and very powerful structural cohesion. During the

  3. Moon (Form-Origin)

    NASA Astrophysics Data System (ADS)

    Tsiapas, Elias

    2014-05-01

    When the Earth was formed, it was in a state of burning heat. As time went by, temperature on the planet's surface was falling due to radiation and heat transfer, and various components (crusts) began taking solid form at the Earth's poles. The formation of crusts took place at the Earth's poles, because the stirring of burning and fluid masses on the surface of the Earth was significantly slighter there than it was on the equator. Due to centrifugal force and Coriolis Effect, these solid masses headed towards the equator; those originating from the North Pole followed a south-western course, while those originating from the South Pole followed a north-western course and there they rotated from west to east at a lower speed than the underlying burning and liquid earth, because of their lower initial linear velocity, their solid state and inertia. Because inertia is proportional to mass, the initially larger solid body swept all new solid ones, incorporating them to its western side. The density of the new solid masses was higher, because the components on the surface would freeze and solidify first, before the underlying thicker components. As a result, the western side of the initial islet of solid rocks submerged, while the east side elevated. . As a result of the above, this initial islet began to spin in reverse, and after taking on the shape of a sphere, it formed the "heart" of the Moon. The Moon-sphere, rolling on the equator, would sink the solid rocks that continued to descend from the Earth's poles. The sinking rocks partially melted because of higher temperatures in the greater depths that the Moon descended to, while part of the rocks' mass bonded with the Moon and also served as a heat-insulating material, preventing the descended side of the sphere from melting. Combined with the Earth's liquid mass that covered its emerging eastern surface, new sphere-shaped shells were created, with increased density and very powerful structural cohesion. During the

  4. Moon (Form-Origin)

    NASA Astrophysics Data System (ADS)

    Tsiapas, Elias

    2015-04-01

    When the Earth was formed, it was in a state of burning heat. As time went by, temperature on the planet's surface was falling due to radiation and heat transfer, and various components (crusts) began taking solid form at the Earth's poles. The formation of crusts took place at the Earth's poles, because the stirring of burning and fluid masses on the surface of the Earth was significantly slighter there than it was on the equator. Due to centrifugal force and Coriolis Effect, these solid masses headed towards the equator; those originating from the North Pole followed a south-western course, while those originating from the South Pole followed a north-western course and there they rotated from west to east at a lower speed than the underlying burning and liquid earth, because of their lower initial linear velocity, their solid state and inertia. Because inertia is proportional to mass, the initially larger solid body swept all new solid ones, incorporating them to its western side. The density of the new solid masses was higher, because the components on the surface would freeze and solidify first, before the underlying thicker components. As a result, the western side of the initial islet of solid rocks submerged, while the east side elevated. . As a result of the above, this initial islet began to spin in reverse, and after taking on the shape of a sphere, it formed the "heart" of the Moon. The Moon-sphere, rolling on the equator, would sink the solid rocks that continued to descend from the Earth's poles. The sinking rocks partially melted because of higher temperatures in the greater depths that the Moon descended to, while part of the rocks' mass bonded with the Moon and also served as a heat-insulating material, preventing the descended side of the sphere from melting. Combined with the Earth's liquid mass that covered its emerging eastern surface, new sphere-shaped shells were created, with increased density and very powerful structural cohesion. During the

  5. Moon (Form-Origin)

    NASA Astrophysics Data System (ADS)

    Tsiapas, Elias

    2013-04-01

    When the Earth was formed, it was in a state of burning heat. As time went by, temperature on the planet's surface was falling due to radiation and heat transfer, and various components (crusts) began taking solid form at the Earth's poles. The formation of crusts took place at the Earth's poles, because the stirring of burning and fluid masses on the surface of the Earth was significantly slighter there than it was on the equator. Due to centrifugal force and Coriolis Effect, these solid masses headed towards the equator; those originating from the North Pole followed a south-western course, while those originating from the South Pole followed a north-western course and there they rotated from west to east at a lower speed than the underlying burning and liquid earth, because of their lower initial linear velocity, their solid state and inertia. Because inertia is proportional to mass, the initially larger solid body swept all new solid ones, incorporating them to its western side. The density of the new solid masses was higher, because the components on the surface would freeze and solidify first, before the underlying thicker components. As a result, the western side of the initial islet of solid rocks submerged, while the east side elevated. As a result of the above, this initial islet began to spin in reverse, and after taking on the shape of a sphere, it formed the "heart" of the Moon. The Moon-sphere, rolling on the equator, would sink the solid rocks that continued to descend from the Earth's poles. The sinking rocks partially melted because of higher temperatures in the greater depths that the Moon descended to, while part of the rocks' mass bonded with the Moon and also served as a heat-insulating material, preventing the descended side of the sphere from melting. Combined with the Earth's liquid mass that covered its emerging eastern surface, new sphere-shaped shells were created, with increased density and very powerful structural cohesion. During the

  6. Gas Giants Form Quickly

    NASA Technical Reports Server (NTRS)

    2007-01-01

    This is an artist's concept of a hypothetical 10-million-year-old star system. The bright blur at the center is a star much like our sun. The other orb in the image is a gas-giant planet like Jupiter. Wisps of white throughout the image represent traces of gas.

    Astronomers using NASA's Spitzer Space Telescope have found evidence showing that gas-giant planets either form within the first 10 million years of a sun-like star's life, or not at all. The lifespan for sun-like stars is about 10 billion years.

    The scientists came to this conclusion after searching for traces of gas around 15 different sun-like stars, most with ages ranging from 3 million to 30 million years. With the help of Spitzer's Infrared Spectrometer instrument, they were able to search for relatively warm gas in the inner regions of these star systems, an area comparable to the zone between Earth and Jupiter in our own solar system. They also used ground-based radio telescopes to search for cooler gas in the outer regions of these systems, an area comparable to the zone around Saturn and beyond.

  7. Case Report: A Rosette-forming Glioneuronal Tumor in the Tectal Plate in a Patient with Neurofibromatosis Type I

    PubMed Central

    Payne, Russell; Langan, Sara; Specht, Charles S

    2016-01-01

    We report the case of a 41–year-old female with neurofibromatosis Type 1 (NF1) who developed a rosette-forming glioneuronal tumor (RGNT) in the tectal plate. This tumor was diagnosed in 2002 when the patient presented with obstructive hydrocephalus, which was subsequently treated with a ventriculoperitoneal shunt and then an endoscopic third ventriculostomy. Initially thought to be a pilocytic astrocytoma, it was followed with serial magnetic resonance imaging (MRI) until tumor progression and development of a large fourth ventricular cystic component prompted resection via suboccipital craniotomy. Histological examination demonstrated an RGNT, a WHO Grade 1 tumor, with neurocytic rosettes, perivascular pseudorosettes, and elements resembling a pilocytic astrocytoma. Initially, the patient did well after her craniotomy, but postoperative complications set in that eventually led to her death. In this case report, we describe a relatively rare tumor that, despite its benign nature, leads to frequent complications and deficits due to its surgically challenging location. Along with previously reported examples, this cases raises the possibility of a causal relationship between NF1 and RGNT.  PMID:27917325

  8. Waste form product characteristics

    SciTech Connect

    Taylor, L.L.; Shikashio, R.

    1995-01-01

    The Department of Energy has operated nuclear facilities at the Idaho National Engineering Laboratory (INEL) to support national interests for several decades. Since 1953, it has supported the development of technologies for the storage and reprocessing of spent nuclear fuels (SNF) and the resultant wastes. However, the 1992 decision to discontinue reprocessing of SNF has left nearly 768 MT of SNF in storage at the INEL with unspecified plans for future dispositioning. Past reprocessing of these fuels for uranium and other resource recovery has resulted in the production of 3800 M{sup 3} calcine and a total inventory of 7600 M{sup 3} of radioactive liquids (1900 M{sup 3} destined for immediate calcination and the remaining sodium-bearing waste requiring further treatment before calcination). These issues, along with increased environmental compliance within DOE and its contractors, mandate operation of current and future facilities in an environmentally responsible manner. This will require satisfactory resolution of spent fuel and waste disposal issues resulting from the past activities. A national policy which identifies requirements for the disposal of SNF and high level wastes (HLW) has been established by the Nuclear Waste Policy Act (NWPA) Sec.8,(b) para(3)) [1982]. The materials have to be conditioned or treated, then packaged for disposal while meeting US Environmental Protection Agency (EPA) and Nuclear Regulatory Commission (NRC) regulations. The spent fuel and HLW located at the INEL will have to be put into a form and package that meets these regulatory criteria. The emphasis of Idaho Chemical Processing Plant (ICPP) future operations has shifted toward investigating, testing, and selecting technologies to prepare current and future spent fuels and waste for final disposal. This preparation for disposal may include mechanical, physical and/or chemical processes, and may differ for each of the various fuels and wastes.

  9. Science Grade 7, Long Form.

    ERIC Educational Resources Information Center

    New York City Board of Education, Brooklyn, NY. Bureau of Curriculum Development.

    The Grade 7 Science course of study was prepared in two parallel forms. A short form designed for students who had achieved a high measure of success in previous science courses; the long form for those who have not been able to maintain the pace. Both forms contain similar content. The Grade 7 guide is the first in a three-year sequence for…

  10. 10. VIEW SHOWING THE ARCH FORMS. THE INTRADOS FORM IS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. VIEW SHOWING THE ARCH FORMS. THE INTRADOS FORM IS COMMONLY LIFTED 3 TO 4 DAYS AFTER POURING. REINFORCING STEEL IS THEN PLACED AND THE EXTRADOS FORM RAISED TO POSITION. THE OPERATING OF MOVING FORMS, PLACING STEEL AND CONCRETE FOR EACH ARCH LIFT REQUIRES, ON AVERAGE, EIGHT DAYS. NOTE THE TWO LINES OF WATER PIPE ON THE EXTRADOS FORM. THESE PIPES ARE FILLED WITH SPRAY NOZZLES WHICH ARE IN PRACTICALLY CONTINUOUS OPERATION EXCEPT WHEN WORK IS BEING DONE ON THE FORMS. August 9, 1938 - Bartlett Dam, Verde River, Phoenix, Maricopa County, AZ

  11. Electrochemical form grinding. Fnal report

    SciTech Connect

    Stiles, R.W.

    1980-06-01

    Electrochemical form grinding cutting tests were performed on 25 17-4 PH stainless steel bars by a copper resin aluminum oxide wheel formed from a diamond form block. Tests investigated methods of dressing a form into a grinding wheel, nozzle design, optimum machine settings, and tolerance capabilities. The electrolyte was distributed evenly onto the wheel by a form-fitting nozzle, and a minimum of two passes, rough and finish, were made because of current density variations throughout the cut. Tolerance held on the form test samples was +- 0.12 mm on the contour, with an average 0.12 mm overcut.

  12. Heated die facilitates tungsten forming

    NASA Technical Reports Server (NTRS)

    Chattin, J. H.; Haystrick, J. E.; Laughlin, J. C.; Leidy, R. A.

    1966-01-01

    Tungsten forming in a press brake employs a bottom die assembly with a heating manifold between two water-cooled die sections. The manifold has hydrogen-oxygen burners spaced along its length for even heat during forming.

  13. Superplastic Forming of Titanium Structures

    DTIC Science & Technology

    1975-04-01

    configurations. These configurations included rectangular and circular pan sections, stepped side walls, beads, joggles , and multiple parts formed at one...capability of being formed to a complex configuration with well-formed beads and Joggles , tight bend radii, and 90-degree return flanges. Since titanium...Coming operation. The configuration consists of joggles and steps positioned into the basic forming box to produce a four-cavity tool symmetrical about

  14. Warm Forming of Mg Sheets: From Incremental to Electromagnetic Forming

    NASA Astrophysics Data System (ADS)

    Ulacia, Ibai; Galdos, Lander; Esnaola, Jon Ander; Larrañaga, Jon; Arruebarrena, Gurutze; de Argandoña, Eneko Saenz; Hurtado, Iñaki

    2014-07-01

    Magnesium alloys are generating interest in the automotive and aeronautic industries due to their low density and potential to reduce gross vehicular weight. However, the formability of these alloys is poor and they are very difficult to be formed at room temperature due to their strong basal texture in rolled form. In this paper, the potential of magnesium alloy sheets to be processed at warm conditions is studied for four different forming technologies: incremental forming (IF), deep drawing (DD), hydroforming (HF), and electromagnetic forming (EMF). Forming mechanisms and process window are experimentally characterized by monitoring different process parameters. Special focus is made on the influence of the forming temperature and the strain rate. Thus, experiments at temperatures from room to 523 K (250 °C) and a wide range of strain rates, between 10-3 up to 103 s-1 according to each process nature and scope, are conducted. It is observed that, even the inherent forming rate range of each process vary considerably, increasing forming temperature increases formability for all of these forming processes. In the other hand, an opposing effect of the strain rate is observed between the quasi-static processes (IF, DD, and HF) and the high speed process (EMF). Thus, a detrimental effect on formability is observed when increasing strain rate for quasi-static processes, while a mild increase is observed for EMF.

  15. Index of NASA prefixed forms

    NASA Technical Reports Server (NTRS)

    1992-01-01

    This Handbook sets forth information for the guidance of all users of the NASA Forms Management Program System. It is issued in accordance with the Federal Information Resources Management Regulation (FIRMR), Subpart 201-9.1. This Handbook sets forth an alpha-functional index of NASA-prefixed forms by title, identifying number, and unit of issue. The automated processing two-letter code (NF) has been substituted for the spelling out of the NASA form-prefix preceding the form number. To indicate a description in lieu of a distinct title, the entire reference under the Form Title/Description column has been enclosed in parentheses. A list of current forms, shown by number and page, is included for cross-reference and to preclude the ordering of those forms which have been deleted from the system. This Handbook will be updated, as appropriate. NHB 1420.2H dated July 1986, is cancelled.

  16. 76 FR 61725 - Agency Information Collection Activities: Case Submission Form, Case Assistance Form; (Form DHS...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-05

    ... SECURITY Agency Information Collection Activities: Case Submission Form, Case Assistance Form; (Form DHS... CIS Ombudsman to identify the issue such as: (1) A case problem which is a request for information.... SUMMARY: The Department of Homeland Security, Office of the Citizenship and Immigration Service...

  17. Undercuts by Laser Shock Forming

    SciTech Connect

    Wielage, Hanna; Vollertsen, Frank

    2011-05-04

    In laser shock forming TEA-CO{sub 2}-laser induced shock waves are used to form metal foils, such as aluminum or copper. The process utilizes an initiated plasma shock wave on the target surface, which leads to a forming of the foil. A challenge in forming technologies is the manufacturing of undercuts. By conventional forming methods these special forms are not feasible. In this article, it is presented that undercuts in the micro range can be produced by laser shock deep drawing. Different drawing die diameters, drawing die depths and the material aluminum in the thicknesses 20 and 50 {mu}m were investigated. It will be presented that smaller die diameters facilitate undercuts compared to bigger die diameters. The phenomena can be explained by Barlow's formula. Furthermore, it is shown which maximum undercut depth at different die diameters can be reached. To this end, cross-sections of the different parameter combinations are displayed.

  18. Seal for fluid forming tools

    DOEpatents

    Golovashchenko, Sergey Fedorovich [Beverly Hills, MI; Bonnen, John Joseph Francis [Milford, MI

    2012-03-20

    An electro-hydraulic forming tool for forming a sheet metal blank in a one-sided die has first and second rigid rings that engage opposite sides of a sheet metal blank. The rigid rings are contained within slots on a die portion and a hydraulic force applicator portion of the forming tool. The seals are either resiliently biased by an elastomeric member or inherently resiliently biased into contact with the blank.

  19. Metallurgical Characterization of Superplastic Forming

    DTIC Science & Technology

    1980-09-01

    PANEL J (GRAIN SIZE - 4.4 pm, VOLUME % PRIMARY ALPHA - 47). Alpha pain size Beta Wain size Final alpha Forming cycle Total stmain, at forming at forming...12.2 j ro, (b) groi %= size -7.7 /jm, and Wc grain size SA gm.8 ro 248 6 /NJ • " ’••• - , • •,• • , • "• •’ W " l! •r ,p • P

  20. Solid form additives and method of forming same

    SciTech Connect

    Schuettenberg, A.D.; Gragson, J.T.

    1987-01-27

    This patent describes a solid form additive comprising: a normally liquid fuel additive selected from carburetor detergent additives, antiknock additives, deposit-control additives, and mixtures thereof, suitable for use in fuel comprising gasoline for internal combustion engines; and a structural agent for containing the fuel additive and for providing dimensional stability to the solid form additive, the structural agent being soluble and dispersible in the fuel; wherein the fuel additive comprises between about 25% and about 75% by weight of the solid form additive; and wherein the solid form additive is a pellet having structural agent and fuel additive essentially homogeneously dispersed throughout the solid form additive; and wherein the pellet is coated with a sealing agent.

  1. Improving the forming capability of laser dynamic forming by using rubber as a forming medium

    NASA Astrophysics Data System (ADS)

    Shen, Zongbao; Liu, Huixia; Wang, Xiao; Wang, Cuntang

    2016-04-01

    Laser dynamic forming (LDF) is a novel high velocity forming technique, which employs laser-generated shock wave to load the sample. The forming velocity induced by the high energy laser pulse may exceed the critical forming velocity, resulting in the occurrence of premature fracture. To avoid the above premature fracture, rubber is introduced in LDF as a forming medium to prolong the loading duration in this paper. Laser induced shock wave energy is transferred to the sample in different forming stages, so the forming velocity can be kept below the critical forming velocity when the initial laser energy is high for fracture. Bulge forming experiments with and without rubber were performed to study the effect of rubber on loading duration. The experimental results show that, the shock wave energy attenuates during the propagation through the rubber layer, the rubber can avoid the premature fracture. So the plastic deformation can continue, the forming capability of LDF is improved. Due to the severe plastic deformation under rubber compression, adiabatic shear bands (ASB) occur in LDF with rubber. The material softening in ASB leads to the irregular fracture, which is different from the premature fracture pattern (regular fracture) in LDF without rubber. To better understand this deformation behavior, Johnson-Cook model is used to simulate the dynamic response and the evolution of ASB of copper sample. The simulation results also indicate the rubber can prolong the loading duration.

  2. Method of forming ceramic bricks

    DOEpatents

    Poeppel, Roger B.; Claar, Terry D.; Silkowski, Peter

    1988-09-06

    A method for forming free standing ceramic bricks for use as tritium breeder material is disclosed. Aqueous solutions of sodium carbonate and potassium carbonate are mixed with an organic hydrocolloid dispersion and powdered lithium carbonate, spray dried, and ceramic bricks formed by molding in a die and firing.

  3. Method of forming ceramic bricks

    DOEpatents

    Poeppel, R.B.; Claar, T.D.; Silkowski, P.

    1987-04-22

    A method for forming free standing ceramic bricks for use as tritium breeder material is disclosed. Aqueous solutions of sodium carbonate and potassium carbonate are mixed with an organic hydrocolloid dispersion and powdered lithium carbonate, spray dried, and ceramic bricks formed by molding in a die and firing.

  4. The Using Evaluation Data Form.

    ERIC Educational Resources Information Center

    Roecks, Alan L.; Casper, Paul

    The Using Evaluation Data Form (UEDF) represents a psychological lever for getting a program's decision maker to consider major evaluation findings. The form may be used at any point of the evaluation process when sufficient data exist to support a finding deserving of action or reaction by the project staff. By local policy, it is required for…

  5. Method of forming ceramic bricks

    DOEpatents

    Poeppel, Roger B.; Claar, Terry D.; Silkowski, Peter

    1988-01-01

    A method for forming free standing ceramic bricks for use as tritium breeder material is disclosed. Aqueous solutions of sodium carbonate and potassium carbonate are mixed with an organic hydrocolloid dispersion and powdered lithium carbonate, spray dried, and ceramic bricks formed by molding in a die and firing.

  6. When Permission Forms Work Best

    ERIC Educational Resources Information Center

    Zirkel, Perry A.

    2005-01-01

    Public schools routinely require permission or release forms for field trips and other activities of potential liability. The legal status of such forms varies, but they are generally considered neither rock-solid protection nor legally valueless in terms of immunity. This article presents a case involving a student who sustained bicycle injuries…

  7. Benchmark 3 - Incremental sheet forming

    NASA Astrophysics Data System (ADS)

    Elford, Michael; Saha, Pradip; Seong, Daeyong; Haque, MD Ziaul; Yoon, Jeong Whan

    2013-12-01

    Benchmark-3 is designed to predict strains, punch load and deformed profile after spring-back during single tool incremental sheet forming. AA 7075-O material has been selected. A corn shape is formed to 45 mm depth with an angle of 45°. Problem description, material properties, and simulation reports with experimental data are summarized.

  8. Degeneration and regeneration of perivascular innervation in arterial grafts.

    PubMed

    Heikki, Penttilä; Timo, Waris; Nureddin, Ashammakhi; Sampsa, Vanhatalo

    2004-07-01

    Because the understanding of postoperative changes in arterial graft innervation is limited, this study was performed to characterize neuronal degeneration and regeneration events immunohistochemically in femoral arterial grafts transplanted to carotid arteries in rats. Specimens taken 1 day, 3 days, 7 days, 1 month, 3 months, and 5 months after surgery were assessed for vasoactive intestinal peptide, neurofilaments, growth-associated protein 43, tyrosine hydroxylase, and nitric oxide synthase isoenzymes. During neuronal degeneration, vasoactive intestinal peptide disappeared within 1 day, transmitter-synthesizing enzymes (nitric oxide synthase and tyrosine hydroxylase) had vanished by day 7, and neurofilaments (cytoskeletal markers) had essentially disappeared after 1 week. In the regeneration phase, the most robust axonal growth, as visualized by growth-associated protein 43, was observed at 1 month, followed by a gradual increase in neurotransmitter markers at 1 and 3 months, whereas the neurofilaments increased gradually up to the end of the 5-month observation period. Reinnervation proceeded from the proximal carotid (host) trunk distally to the graft. Axonal re-growth occurred mainly in arterial adventitia. Innervation density, as visually assessed, was denser in the graft than in the host. These findings suggest that 1) the main sequence of degeneration and regeneration follows that reported in other models of neuronal degeneration; 2) reinnervation of the arterial grafts comes mainly from the host arteries; and 3) the innervation density in the graft may differ from that in the host, which may suggest target-derived regulation of innervation. The latter finding may have clinical implications. It suggests that for a good outcome it would be beneficial to choose a sparsely innervated graft rather than a densely innervated one.

  9. Laminin isoforms in endothelial and perivascular basement membranes.

    PubMed

    Yousif, Lema F; Di Russo, Jacopo; Sorokin, Lydia

    2013-01-01

    Laminins, one of the major functional components of basement membranes, are found underlying endothelium, and encasing pericytes and smooth muscle cells in the vessel wall. Depending on the type of blood vessel (capillary, venule, postcapillary venule, vein or artery) and their maturation state, both the endothelial and mural cell phenotype vary, with associated changes in laminin isoform expression. Laminins containing the α4 and α5 chains are the major isoforms found in the vessel wall, with the added contribution of laminin α2 in larger vessels. We here summarize current data on the precise localization of these laminin isoforms and their receptors in the different layers of the vessel wall, and their potential contribution to vascular homeostasis.

  10. Multiplicative form of the Lagrangian

    NASA Astrophysics Data System (ADS)

    Surawuttinack, K.; Yoo-Kong, S.; Tanasittikosol, M.

    2016-12-01

    We obtain an alternative class of Lagrangians in the so-called the multiplicative form for a system with one degree of freedom in the nonrelativistic and the relativistic cases. This new form of the Lagrangian can be regarded as a one-parameter class with the parameter λ obtained using an extension of the standard additive form of the Lagrangian because both forms yield the same equation of motion. We note that the multiplicative form of the Lagrangian can be regarded as a generating function for obtaining an infinite hierarchy of Lagrangians that yield the same equation of motion. This nontrivial set of Lagrangians confirms that the Lagrange function is in fact nonunique.

  11. Quantum modular forms, mock modular forms, and partial theta functions

    NASA Astrophysics Data System (ADS)

    Kimport, Susanna

    Defined by Zagier in 2010, quantum modular forms have been the subject of an explosion of recent research. Many of these results are aimed at discovering examples of these functions, which are defined on the rational numbers and have "nice" modularity properties. Though the subject is in its early stages, numerous results (including Zagier's original examples) show these objects naturally arising from many areas of mathematics as limits of other modular-like functions. One such family of examples is due to Folsom, Ono, and Rhoades, who connected these new objects to partial theta functions (introduced by Rogers in 1917) and mock modular forms (about which there is a rich theory, whose origins date back to Ramanujan in 1920). In this thesis, we build off of the work of Folsom, Ono, and Rhoades by providing an infinite family of quantum modular forms of arbitrary positive half-integral weight. Further, this family of quantum modular forms "glues" mock modular forms to partial theta functions and is constructed from a so-called "universal" mock theta function by extending a method of Eichler and Zagier (originally defined for holomorphic Jacobi forms) into a non-holomorphic setting. In addition to the infinite family, we explore the weight 1/2 and 3/2 functions in more depth. For both of these weights, we are able to explicitly write down the quantum modular form, as well as the corresponding "errors to modularity," which can be shown to be Mordell integrals of specific theta functions and, as a consequence, are real-analytic functions. Finally, we turn our attention to the partial theta functions associated with these low weight examples. Berndt and Kim provide asymptotic expansions for a certain class of partial theta functions as q approaches 1 radially within the unit disk. Here, we extend this work to not only obtain asymptotic expansions for this class of functions as q approaches any root of unity, but also for a certain class of derivatives of these functions

  12. Supergravity actions with integral forms

    NASA Astrophysics Data System (ADS)

    Castellani, L.; Catenacci, R.; Grassi, P. A.

    2014-12-01

    Integral forms provide a natural and powerful tool for the construction of supergravity actions. They are generalizations of usual differential forms and are needed for a consistent theory of integration on supermanifolds. The group geometrical approach to supergravity and its variational principle are reformulated and clarified in this language. Central in our analysis is the Poincaré dual of a bosonic manifold embedded into a supermanifold. Finally, using integral forms we provide a proof of Gates' so-called "Ectoplasmic Integration Theorem", relating superfield actions to component actions.

  13. Process to form mesostructured films

    DOEpatents

    Brinker, C.J.; Anderson, M.T.; Ganguli, R.; Lu, Y.F.

    1999-01-12

    This invention comprises a method to form a family of supported films with pore size in the approximate range 0.8-20 nm exhibiting highly ordered microstructures and porosity derived from an ordered micellar or liquid-crystalline organic-inorganic precursor structure that forms during film deposition. Optically transparent, 100-500-nm thick films exhibiting a unique range of microstructures and uni-modal pore sizes are formed in seconds in a continuous coating operation. Applications of these films include sensors, membranes, low dielectric constant interlayers, anti-reflective coatings, and optical hosts. 12 figs.

  14. Process to form mesostructured films

    DOEpatents

    Brinker, C. Jeffrey; Anderson, Mark T.; Ganguli, Rahul; Lu, Yunfeng

    1999-01-01

    This invention comprises a method to form a family of supported films film with pore size in the approximate range 0.8-20 nm exhibiting highly ordered microstructures and porosity derived from an ordered micellar or liquid-crystalline organic-inorganic precursor structure that forms during film deposition. Optically transparent, 100-500-nm thick films exhibiting a unique range of microstructures and uni-modal pore sizes are formed in seconds in a continuous coating operation. Applications of these films include sensors, membranes, low dielectric constant interlayers, anti-reflective coatings, and optical hosts.

  15. Multiple forming tools in incremental forming - Influence of the forming strategies on sheet contour

    NASA Astrophysics Data System (ADS)

    Dang, T.; Tebaay, L. M.; Gies, S.; Tekkaya, A. E.

    2016-10-01

    Single point incremental forming (SPIF) is a well known process which is used for rapid prototyping or for small-quantity production. The feature of this process is the flexible manufacturing of complex hollow shapes with the use of basic equipments. However, this forming process takes very long time. To speed up the process time, multiple forming tools can be used simultaneously. This paper presents the influence of the multiple tools in SPIF on the formed shape. The conventional SPIF with a single tool is taken into account for a comparative analysis. The results in this study showed that the tool arrangements and its distance have a significant effect on the geometrical accuracy. Moreover, it is shown the influence between the vertical step size of the tool and the strain distributions. This knowledge can be used for generation of new forming strategies.

  16. Wind-formed gravel bed forms, Wright Valley, Antarctica

    NASA Astrophysics Data System (ADS)

    Gillies, John A.; Nickling, William G.; Tilson, Michael; Furtak-Cole, Eden

    2012-12-01

    Bed forms composed of gravel size particles (≈50% of particles >4 mm) are observed in the Wright Valley of the McMurdo Dry Valley system in Antarctica. These bed forms are characterized by a very asymmetrical shape with a mean aspect ratio of 0.025 (standard deviation 0.005), mean wavelength of 2.7 m (±0.49 m), and a mean height of 0.06 m (±0.01 m). Particle size analysis of the bed form sediments shows bimodality with a peak near 9 mm and another between 0.5 mm and 0.25 mm. Time-integrated sediment trap samples of horizontal saltation and creep flux indicate the flux of particles ≥4 mm during the two-year monitoring period was extremely low. Measurements of the horizontal displacement of tracer particles (14 mm, 12 mm, 10 mm, 8 mm, and 6 mm diameter) placed onto the bed forms corroborate the low particle flux measurements and limited movement of particles. The bed forms share form and grain size characteristics with both ripples and mega-ripples, showing poor sorting of particles across a single wavelength except for a slight coarsening at the crest similar to ripples, but their sinuosity suggest that transverse instabilities affect their formation similar to mega-ripples. Based on the data for the prevailing environmental conditions it can be argued that the Wright Valley form is an expression of gravel particles moved solely by highly intermittent creep processes. This also argues for the need for a very long period of time for their evolution, on the order of centuries.

  17. Triggered pore-forming agents

    DOEpatents

    Bayley, Hagan; Walker, Barbara J.; Chang, Chung-yu; Niblack, Brett; Panchal, Rekha

    1998-01-01

    An inactive pore-forming agent which is activated to lytic function by a condition such as pH, light, heat, reducing potential, or metal ion concentration, or substance such as a protease, at the surface of a cell.

  18. [Aspergillosis. Clinical forms and treatment].

    PubMed

    Fortún, Jesús; Meije, Yolanda; Fresco, Gema; Moreno, Santiago

    2012-04-01

    Invasive aspergillosis, chronic pulmonary aspergillosis and allergic bronchopulmonary aspergillosis are the clinical forms of aspergillosis. Although there is a great number of Aspergillus species, Aspergillus fumigatus-complex is the more frequent aetiological agent, regardless of clinical form or baseline condition. The increase in immunosuppressive agents and the higher use of corticosteroids in chronic obstructive pulmonary disease have led to aspergillosis becoming more prominent in recent years. Galactomannan detection and radiological diagnostic images complement the limitations of microbiology cultures in these patients. Voriconazole and liposomal amphotericin B are the gold standard in patients requiring therapy, and posaconazole, itraconazole, caspofungin and other echinocandins are effective alternatives. The prognosis depends of clinical forms and characteristics of the host, but it is particularly poor in the disseminated invasive forms.

  19. INDIPAY Financial Data Request Forms

    EPA Pesticide Factsheets

    The INDIPAY financial data request form requires the individual to provide financial information to support its claim of inability to pay the civil penalty. Both an English and Spanish version are provided.

  20. Method for forming metal contacts

    DOEpatents

    Reddington, Erik; Sutter, Thomas C; Bu, Lujia; Cannon, Alexandra; Habas, Susan E; Curtis, Calvin J; Miedaner, Alexander; Ginley, David S; Van Hest, Marinus Franciscus Antonius Maria

    2013-09-17

    Methods of forming metal contacts with metal inks in the manufacture of photovoltaic devices are disclosed. The metal inks are selectively deposited on semiconductor coatings by inkjet and aerosol apparatus. The composite is heated to selective temperatures where the metal inks burn through the coating to form an electrical contact with the semiconductor. Metal layers are then deposited on the electrical contacts by light induced or light assisted plating.

  1. Method of forming pointed structures

    NASA Technical Reports Server (NTRS)

    Pugel, Diane E. (Inventor)

    2011-01-01

    A method of forming an array of pointed structures comprises depositing a ferrofluid on a substrate, applying a magnetic field to the ferrofluid to generate an array of surface protrusions, and solidifying the surface protrusions to form the array of pointed structures. The pointed structures may have a tip radius ranging from approximately 10 nm to approximately 25 micron. Solidifying the surface protrusions may be carried out at a temperature ranging from approximately 10 degrees C. to approximately 30 degrees C.

  2. Roll formed pan solar module

    SciTech Connect

    Jester, T.L.; Bottenberg, W.R.; Gay, C.F.; Yerkes, J.W.

    1984-02-21

    A solar module comprising a solar cell string laminated between layers of pottant material and a transparent superstrate and a steel substrate. The steel substrate is roll formed to provide stiffening flanges on its edges while simultaneously forming a pan-shaped structure to hold other portions of the laminate in position during the laminating process. An improved terminal provides high voltage protection and improved mechanical strength. A conduit element provides protected raceways for external wires connected to module terminals.

  3. Star-forming Filament Models

    NASA Astrophysics Data System (ADS)

    Myers, Philip C.

    2017-03-01

    New models of star-forming filamentary clouds are presented in order to quantify their properties and to predict their evolution. These 2D axisymmetric models describe filaments that have no core, one low-mass core, and one cluster-forming core. They are based on Plummer-like cylinders and spheroids that are bounded by a constant-density surface of finite extent. In contrast to 1D Plummer-like models, they have specific values of length and mass, they approximate observed column density maps, and their distributions of column density (N-pdfs) are pole-free. Each model can estimate the star-forming potential of a core-filament system by identifying the zone of gas dense enough to form low-mass stars and by counting the number of enclosed thermal Jeans masses. This analysis suggests that the Musca central filament may be near the start of its star-forming life, with enough dense gas to make its first ∼3 protostars, while the Coronet filament is near the midpoint of its star formation, with enough dense gas to add ∼8 protostars to its ∼20 known stars. In contrast, L43 appears to be near the end of its star-forming life, since it lacks enough dense gas to add any new protostars to the two young stellar objectsalready known.

  4. Superplastic forming of ceramic insulation

    NASA Technical Reports Server (NTRS)

    Nieh, T. G.; Wittenauer, J. P.; Wadsworth, J.

    1992-01-01

    Superplasticity has been demonstrated in many fine-grained structural ceramics and ceramic composites, including yttria-stabilized tetragonal zirconia polycrystal (YTZP), alumina, and Al2O3-reinforced zirconia (Al2O3/YTZ) duplex composites and SiC-reinforced Si3N4. These superplastic ceramics obviously offer the potential benefit of forming net shape or near net shape parts. This could be particularly useful for forming complicated shapes that are difficult to achieve using conventional forming techniques, or require elaborate, subsequent machining. In the present study, we successfully demonstrated the following: (1) superplastic 3Y-TXP and 20 percent Al2O3/YTZ composite have for the first time been successfully deformed into hemispherical caps via a biaxial gas-pressure forming technique; (2) no experimental difficulty was encountered in applying the required gas pressures and temperatures to achieve the results, thus, it is certain that higher rates of deformation than those presented in this study will be possible by using the current test apparatus at higher temperatures and pressures; and (3) an analytical model incorporating material parameters, such as variations during forming in the strain rate sensitivity exponent and grain growth-induced strain hardening, is needed to model accurately and therefore precisely control the biaxial gas-pressure forming of superplastic ceramics. Based on the results of this study, we propose to fabricate zirconia insulation tubes by superplastic extrusion of zirconia polycrystal. This would not only reduce the cost, but also improve the reliability of the tube products.

  5. INEL Spray-forming Research

    NASA Technical Reports Server (NTRS)

    Mchugh, Kevin M.; Key, James F.

    1993-01-01

    Spray forming is a near-net-shape fabrication technology in which a spray of finely atomized liquid droplets is deposited onto a suitably shaped substrate or mold to produce a coherent solid. The technology offers unique opportunities for simplifying materials processing without sacrificing, and oftentimes substantially improving, product quality. Spray forming can be performed with a wide range of metals and nonmetals, and offers property improvements resulting from rapid solidification (e.g., refined microstructures, extended solid solubilities and reduced segregation). Economic benefits result from process simplification and the elimination of unit operations. Researchers at the Idaho National Engineering Laboratory (INEL) are developing spray-forming technology for producing near-net-shape solids and coatings of a variety of metals, polymers, and composite materials. Results from several spray forming programs are presented to illustrate the range of capabilities of the technique as well as the accompanying technical and economic benefits. Low-carbon steel strip greater than 0.75 mm thick and polymer membranes for gas/gas and liquid/liquid separations that were spray formed are discussed; recent advances in spray forming molds, dies, and other tooling using low-melting-point metals are described.

  6. Form 6 - gas balancing agreement

    SciTech Connect

    Not Available

    1990-01-01

    In 1988, a special Committee of the Rocky Mountain Mineral Law Foundation undertook a project to draft a model from gas balancing agreement. This project was initiated at the request of a number of Foundation members who felt that a model form gas balancing agreement would facilitate the negotiation of operating agreement, since gas balancing issues had become sticking points in the process. The Committee was composed of attorneys representing a wide cross-section of the oil and gas industry including both major and independent oil companies, production companies with interstate pipeline affiliates, and private practitioners. The Committee attempted to address the more controversial issues in gas balancing with optional provisions in the Form. To facilitate the negotiation process, the number of optional provisions was minimized. This form may be used as an Appendix to the new A.A.P.L. Form 610-1989 Model Form Operating Agreement. This book includes provision of this Form which are: Ownership of gas production; Balancing of production accounts; Cash balancing upon depletion; Deliverability tests; Nominations; Statements; Payment of taxes; Operating expenses; Overproducing allowable; Payment of leasehold burdens; Operator's liability; Successors and assigns; Audits; Arbitration; and Operator's fees.

  7. Conjoint Forming - Technologies for Simultaneous Forming and Joining

    NASA Astrophysics Data System (ADS)

    Groche, P.; Wohletz, S.; Mann, A.; Krech, M.; Monnerjahn, V.

    2016-03-01

    The market demand for new products optimized for e. g. lightweight applications or smart components leads to new challenges in production engineering. Hybrid structures represent one promising approach. They aim at higher product performance by using a suitable combination of different materials. The developments of hybrid structures stimulate the research on joining of dissimilar materials. Since they allow for joining dissimilar materials without external heating technologies based on joining by plastic deformation seem to be of special attractiveness. The paper at hand discusses the conjoint forming approach. This approach combines forming and joining in one process. Two or more workpieces are joined while at least one workpiece is plastically deformed. After presenting the fundamental joining mechanisms, the conjoint forming approach is discussed comprehensively. Examples of conjoint processes demonstrate the effectiveness and reveal the underlying phenomena.

  8. Electromagnetic nucleon form factors in instant and point form

    SciTech Connect

    Melde, T.; Berger, K.; Plessas, W.; Wagenbrunn, R. F.; Canton, L.

    2007-10-01

    We present a study of the electromagnetic structure of the nucleons with constituent quark models in the framework of relativistic quantum mechanics. In particular, we address the construction of spectator-model currents in the instant and point forms. Corresponding results for the elastic nucleon electromagnetic form factors as well as charge radii and magnetic moments are presented. We also compare results obtained by different realistic nucleon wave functions stemming from alternative constituent quark models. Finally, we discuss the theoretical uncertainties that reside in the construction of spectator-model transition operators.

  9. Characterization of polymorphic ampicillin forms.

    PubMed

    Baraldi, C; Tinti, A; Ottani, S; Gamberini, M C

    2014-11-01

    In this work polymorphs of α-aminobenzylpenicillin (ampicillin), a β-lactamic antibiotic, were prepared and investigated by several experimental and theoretical methods. Amorphous monohydrate and three crystalline forms, the trihydrate, the crystal form I and the crystal form II, were investigated by FT-IR and micro-Raman. Also data obtained by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray powder diffraction (XRPD) and hot-stage Raman spectroscopy are reported. Finally, quantum mechanical calculations were performed by density functional theory (DFT) to assist the assignment of spectroscopic experimental bands. For the first time, the ampicillin molecule in its zwitterionic form was studied at the B3LYP/aug-cc-pVDZ level and the corresponding theoretical vibrational spectra were computed. In fact, ampicillin in the crystal is in zwitterionic form and concentrations of this same form are quite relevant in solutions at physiological pH. Experimental and theoretical results allowed identification of specific features for polymorph characterization. Bands typical of the different polymorphs are identified both in IR and Raman spectra: in particular in the NH stretching region (IR), in the amide I+δNH region (both techniques), in the 1520-1490cm(-1) region (IR), in the 1320-1300cm(-1) and 1280-1220cm(-1) (IR), in the 1200-1170cm(-1) (Raman), in the amide V region (IR), and, finally, in the 715-640cm(-1) and 220-200cm(-1) (Raman). Interconversion among different polymorphs was investigated by hot-stage Raman spectroscopy and thermal analysis, clarifying the complex pattern of transformations undergone as a function of temperature and heating rate. In particular, DSC scans show how the trihydrate crystals transform into anhydrous forms on heating. Finally, stability tests demonstrated, after a two years period, that no transformation or degradation of the polymorphs occurred.

  10. The discovery of structural form

    PubMed Central

    Kemp, Charles; Tenenbaum, Joshua B.

    2008-01-01

    Algorithms for finding structure in data have become increasingly important both as tools for scientific data analysis and as models of human learning, yet they suffer from a critical limitation. Scientists discover qualitatively new forms of structure in observed data: For instance, Linnaeus recognized the hierarchical organization of biological species, and Mendeleev recognized the periodic structure of the chemical elements. Analogous insights play a pivotal role in cognitive development: Children discover that object category labels can be organized into hierarchies, friendship networks are organized into cliques, and comparative relations (e.g., “bigger than” or “better than”) respect a transitive order. Standard algorithms, however, can only learn structures of a single form that must be specified in advance: For instance, algorithms for hierarchical clustering create tree structures, whereas algorithms for dimensionality-reduction create low-dimensional spaces. Here, we present a computational model that learns structures of many different forms and that discovers which form is best for a given dataset. The model makes probabilistic inferences over a space of graph grammars representing trees, linear orders, multidimensional spaces, rings, dominance hierarchies, cliques, and other forms and successfully discovers the underlying structure of a variety of physical, biological, and social domains. Our approach brings structure learning methods closer to human abilities and may lead to a deeper computational understanding of cognitive development. PMID:18669663

  11. The discovery of structural form.

    PubMed

    Kemp, Charles; Tenenbaum, Joshua B

    2008-08-05

    Algorithms for finding structure in data have become increasingly important both as tools for scientific data analysis and as models of human learning, yet they suffer from a critical limitation. Scientists discover qualitatively new forms of structure in observed data: For instance, Linnaeus recognized the hierarchical organization of biological species, and Mendeleev recognized the periodic structure of the chemical elements. Analogous insights play a pivotal role in cognitive development: Children discover that object category labels can be organized into hierarchies, friendship networks are organized into cliques, and comparative relations (e.g., "bigger than" or "better than") respect a transitive order. Standard algorithms, however, can only learn structures of a single form that must be specified in advance: For instance, algorithms for hierarchical clustering create tree structures, whereas algorithms for dimensionality-reduction create low-dimensional spaces. Here, we present a computational model that learns structures of many different forms and that discovers which form is best for a given dataset. The model makes probabilistic inferences over a space of graph grammars representing trees, linear orders, multidimensional spaces, rings, dominance hierarchies, cliques, and other forms and successfully discovers the underlying structure of a variety of physical, biological, and social domains. Our approach brings structure learning methods closer to human abilities and may lead to a deeper computational understanding of cognitive development.

  12. Form und Sinn: Sprachwissenschaftliche Betrachtungen (Form and Meaning: Linguistic Observations).

    ERIC Educational Resources Information Center

    Jakobson, Roman

    This collection of 14 papers and articles by Roman Jakobson contains works written and published between 1931 and 1970 which deal either with global aspects of language or with specific grammatical issues. The collection emphasizes Jakobson's concern for finding the links between form and meaning in language. The text is entirely in German with…

  13. A Notional Matrix for Grammatical Forms: Teaching Question Forms.

    ERIC Educational Resources Information Center

    Shields, Carolyn L.

    This paper proposes a matrix of notional categories for classifying grammatical structures. The use of the matrix is illustrated through question forms. Communicative competence in a language presupposes mastery of the grammatical system of that language. Therefore, in adopting a communicatively appropriate syllabus, containing varieties of…

  14. Sixth-Form Colleges: An Endangered Organisational Form?

    ERIC Educational Resources Information Center

    Stoten, David William

    2014-01-01

    The sixth-form college sector is often marginalised in policy and academic discourse, where the much larger school and further education sectors dominate. This paper sets out to describe the sector's key features, assess its position within the wider education system and consider its future in an increasingly competitive education market. The…

  15. Two forms of reactive arthritis?

    PubMed Central

    Toivanen, P.; Toivanen, A.

    1999-01-01

    Inflammatory arthritides developing after a distant infection have so far been called reactive or postinfectious, quite often depending on the microbial trigger and/or HLA-B27 status of the patient. For clarity, it is proposed that they all should be called reactive arthritis, which, according to the trigger, occurs as an HLA-B27 associated or non-associated form. In addition to the causative agents and HLA-B27, these two categories are also distinguished by other characteristics. Most important, HLA-B27 associated arthritis may occur identical to the Reiter's syndrome with accompanying uretheritis and/or conjunctivitis, whereas in the B27 non-associated form this has not been clearly described. Likewise, only the B27 associated form belongs to the group of spondyloarthropathies.

 PMID:10577958

  16. Method of forming structural heliostat

    DOEpatents

    Anderson, Alfred J.

    1984-06-26

    In forming a heliostat having a main support structure and pivoting and tilting motors and gears and a mirror module for reflecting solar energy onto a collector, the improvement characterized by a method of forming the mirror module in which the mirror is laid upon a solid rigid supporting bed in one or more sections, with or without focusing; a mirror backing sheet is applied by first applying respective thin layers of silicone grease and, thereafter, progressively rolling application to eliminate air bubbles; followed by affixing of a substrate assembly to the mirror backing sheet to form a mirror module that does not curve because of thermally induced stresses and differential thermal expansion or contraction effects. The silicone grease also serves to dampen fluttering of the mirror and protect the mirror backside against adverse effects of the weather. Also disclosed are specific details of preferred embodiments.

  17. PROCESS OF FORMING POWDERED MATERIAL

    DOEpatents

    Glatter, J.; Schaner, B.E.

    1961-07-14

    A process of forming high-density compacts of a powdered ceramic material is described by agglomerating the powdered ceramic material with a heat- decompossble binder, adding a heat-decompossble lubricant to the agglomerated material, placing a quantity of the material into a die cavity, pressing the material to form a compact, pretreating the compacts in a nonoxidizing atmosphere to remove the binder and lubricant, and sintering the compacts. When this process is used for making nuclear reactor fuel elements, the ceramic material is an oxide powder of a fissionsble material and after forming, the compacts are placed in a cladding tube which is closed at its ends by vapor tight end caps, so that the sintered compacts are held in close contact with each other and with the interior wall of the cladding tube.

  18. Methods of forming boron nitride

    DOEpatents

    Trowbridge, Tammy L; Wertsching, Alan K; Pinhero, Patrick J; Crandall, David L

    2015-03-03

    A method of forming a boron nitride. The method comprises contacting a metal article with a monomeric boron-nitrogen compound and converting the monomeric boron-nitrogen compound to a boron nitride. The boron nitride is formed on the same or a different metal article. The monomeric boron-nitrogen compound is borazine, cycloborazane, trimethylcycloborazane, polyborazylene, B-vinylborazine, poly(B-vinylborazine), or combinations thereof. The monomeric boron-nitrogen compound is polymerized to form the boron nitride by exposure to a temperature greater than approximately 100.degree. C. The boron nitride is amorphous boron nitride, hexagonal boron nitride, rhombohedral boron nitride, turbostratic boron nitride, wurzite boron nitride, combinations thereof, or boron nitride and carbon. A method of conditioning a ballistic weapon and a metal article coated with the monomeric boron-nitrogen compound are also disclosed.

  19. Substrate system for spray forming

    DOEpatents

    Chu, Men G.; Chernicoff, William P.

    2002-01-01

    A substrate system for receiving a deposit of sprayed metal droplets including a movable outer substrate on which the sprayed metal droplets are deposited. The substrate system also includes an inner substrate disposed adjacent the outer substrate where the sprayed metal droplets are deposited on the outer substrate. The inner substrate includes zones of differing thermal conductivity to resist substrate layer porosity and to resist formation of large grains and coarse constituent particles in a bulk layer of the metal droplets which have accumulated on the outer substrate. A spray forming apparatus and associated method of spray forming a molten metal to form a metal product using the substrate system of the invention is also provided.

  20. Substrate system for spray forming

    DOEpatents

    Chu, Men G.; Chernicoff, William P.

    2000-01-01

    A substrate system for receiving a deposit of sprayed metal droplets including a movable outer substrate on which the sprayed metal droplets are deposited. The substrate system also includes an inner substrate disposed adjacent the outer substrate where the sprayed metal droplets are deposited on the outer substrate. The inner substrate includes zones of differing thermal conductivity to resist substrate layer porosity and to resist formation of large grains and coarse constituent particles in a bulk layer of the metal droplets which have accumulated on the outer substrate. A spray forming apparatus and associated method of spray forming a molten metal to form a metal product using the substrate system of the invention is also provided.

  1. Canonical form of Hamiltonian matrices

    NASA Astrophysics Data System (ADS)

    Zuker, A. P.; Waha Ndeuna, L.; Nowacki, F.; Caurier, E.

    2001-08-01

    On the basis of shell model simulations, it is conjectured that the Lanczos construction at fixed quantum numbers defines-within fluctuations and behavior very near the origin-smooth canonical matrices whose forms depend on the rank of the Hamiltonian, dimensionality of the vector space, and second and third moments. A framework emerges that amounts to a general Anderson model capable of dealing with ground state properties and strength functions. The smooth forms imply binomial level densities. A simplified approach to canonical thermodynamics is proposed.

  2. FORM version 4.0

    NASA Astrophysics Data System (ADS)

    Kuipers, J.; Ueda, T.; Vermaseren, J. A. M.; Vollinga, J.

    2013-05-01

    We present version 4.0 of the symbolic manipulation system FORM. The most important new features are manipulation of rational polynomials and the factorization of expressions. Many other new functions and commands are also added; some of them are very general, while others are designed for building specific high level packages, such as one for Gröbner bases. New is also the checkpoint facility, that allows for periodic backups during long calculations. Finally, FORM 4.0 has become available as open source under the GNU General Public License version 3. Program summaryProgram title: FORM. Catalogue identifier: AEOT_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEOT_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU General Public License, version 3 No. of lines in distributed program, including test data, etc.: 151599 No. of bytes in distributed program, including test data, etc.: 1 078 748 Distribution format: tar.gz Programming language: The FORM language. FORM itself is programmed in a mixture of C and C++. Computer: All. Operating system: UNIX, LINUX, Mac OS, Windows. Classification: 5. Nature of problem: FORM defines a symbolic manipulation language in which the emphasis lies on fast processing of very large formulas. It has been used successfully for many calculations in Quantum Field Theory and mathematics. In speed and size of formulas that can be handled it outperforms other systems typically by an order of magnitude. Special in this version: The version 4.0 contains many new features. Most important are factorization and rational arithmetic. The program has also become open source under the GPL. The code in CPC is for reference. You are encouraged to upload the most recent sources from www.nikhef.nl/form/formcvs.php because of frequent bug fixes. Solution method: See "Nature of Problem", above. Additional comments: NOTE: The code in CPC is for reference. You are encouraged

  3. Auxin biosynthesis and storage forms.

    PubMed

    Korasick, David A; Enders, Tara A; Strader, Lucia C

    2013-06-01

    The plant hormone auxin drives plant growth and morphogenesis. The levels and distribution of the active auxin indole-3-acetic acid (IAA) are tightly controlled through synthesis, inactivation, and transport. Many auxin precursors and modified auxin forms, used to regulate auxin homeostasis, have been identified; however, very little is known about the integration of multiple auxin biosynthesis and inactivation pathways. This review discusses the many ways auxin levels are regulated through biosynthesis, storage forms, and inactivation, and the potential roles modified auxins play in regulating the bioactive pool of auxin to affect plant growth and development.

  4. Auxin biosynthesis and storage forms

    PubMed Central

    Strader, Lucia C.

    2013-01-01

    The plant hormone auxin drives plant growth and morphogenesis. The levels and distribution of the active auxin indole-3-acetic acid (IAA) are tightly controlled through synthesis, inactivation, and transport. Many auxin precursors and modified auxin forms, used to regulate auxin homeostasis, have been identified; however, very little is known about the integration of multiple auxin biosynthesis and inactivation pathways. This review discusses the many ways auxin levels are regulated through biosynthesis, storage forms, and inactivation, and the potential roles modified auxins play in regulating the bioactive pool of auxin to affect plant growth and development. PMID:23580748

  5. Exploring Novel Forms of Superconductivity

    DTIC Science & Technology

    2012-10-19

    REPORT FINALPROJECT REPORT: W911NF-08-1-0196 “EXPLORING NOVEL FORMS OF SUPERCONDUCTIVITY ....” 14. ABSTRACT 16. SECURITY CLASSIFICATION OF: Novel...Rev 8/98) Prescribed by ANSI Std. Z39.18 - 30-Jun-2011 FINALPROJECT REPORT: W911NF-08-1-0196 “EXPLORING NOVEL FORMS OF SUPERCONDUCTIVITY ...publications (other than abstracts): Received Paper 12/24/2009 1.00 Jian Liu, M. Kareev, S. Prosandeev, B. Gray, P. Ryan, J.W. Freeland, J. Chakhalian. Effect

  6. 48 CFR Appendix - List of IAAR Forms

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true List of IAAR Forms Federal Acquisition Regulations System BROADCASTING BOARD OF GOVERNORS CLAUSES AND FORMS FORMS Illustrations of Forms The Broadcasting Board of Governors forms. List of IAAR Forms 1953.370-21The Broadcasting Board of Governors Form IA-21, Abstract...

  7. Process for forming sulfuric acid

    DOEpatents

    Lu, Wen-Tong P.

    1981-01-01

    An improved electrode is disclosed for the anode in a sulfur cycle hydrogen generation process where sulfur dioxie is oxidized to form sulfuric acid at the anode. The active compound in the electrode is palladium, palladium oxide, an alloy of palladium, or a mixture thereof. The active compound may be deposited on a porous, stable, conductive substrate.

  8. Assessing "Combining Forms" in Science.

    ERIC Educational Resources Information Center

    Floriani, Bernard P.; Cairns, Jack C.

    1982-01-01

    Since there appears to be a direct relationship between reading comprehension and vocabulary, an inventory is offered which assesses students' knowledge of the meaning of "combining forms" (automobile, aero-dynamics, etc.) and not words themselves. The inventory can serve as a model to develop additional inventories for Latin/Greek roots.…

  9. Cheaper Hydride-Forming Cathodes

    NASA Technical Reports Server (NTRS)

    Jones, Jack A.; Blue, Gary

    1990-01-01

    Hydride-forming cathodes for electrochemical experiments made of materials or combinations of materials cheaper and more abundant than pure palladium, according to proposal. Concept prompted by needs of experimenters in now-discredited concept of electrochemical nuclear fusion, cathodes useful in other electrochemical applications involving generation or storage of hydrogen, deuterium, or tritium.

  10. Collaborating with Forms in Nature

    ERIC Educational Resources Information Center

    Castro, Aileen Pugliese

    2011-01-01

    Taking students outside is a great opportunity to make art. In this article, the author describes how her students collaborated with forms in nature to create their own visual structures to communicate ideas. This lesson can be done on the beach, in a sand box on the school playground, in grassy areas, or nature can even be brought into the…

  11. PIC Reading Readiness Test Form.

    ERIC Educational Resources Information Center

    Short, N. J.

    This rating form concerns the measurement of basic skills in connection with assessing reading readiness. Motor skills, ability to adjust to learning situations, familiarity with the alphabet, and general knowledge are assessed. See TM 001 111 for details of the Regional PIC program in which it is used. (DLG)

  12. Technetium Immobilization Forms Literature Survey

    SciTech Connect

    Westsik, Joseph H.; Cantrell, Kirk J.; Serne, R. Jeffrey; Qafoku, Nikolla

    2014-05-01

    Of the many radionuclides and contaminants in the tank wastes stored at the Hanford site, technetium-99 (99Tc) is one of the most challenging to effectively immobilize in a waste form for ultimate disposal. Within the Hanford Tank Waste Treatment and Immobilization Plant (WTP), the Tc will partition between both the high-level waste (HLW) and low-activity waste (LAW) fractions of the tank waste. The HLW fraction will be converted to a glass waste form in the HLW vitrification facility and the LAW fraction will be converted to another glass waste form in the LAW vitrification facility. In both vitrification facilities, the Tc is incorporated into the glass waste form but a significant fraction of the Tc volatilizes at the high glass-melting temperatures and is captured in the off-gas treatment systems at both facilities. The aqueous off-gas condensate solution containing the volatilized Tc is recycled and is added to the LAW glass melter feed. This recycle process is effective in increasing the loading of Tc in the LAW glass but it also disproportionally increases the sulfur and halides in the LAW melter feed which increases both the amount of LAW glass and either the duration of the LAW vitrification mission or the required supplemental LAW treatment capacity.

  13. Spin-forming Project Report

    SciTech Connect

    Switzner, Nathan; Henry, Dick

    2009-03-20

    In a second development order, spin-forming equipment was again evaluated using the test shape, a hemispherical shell. In this second development order, pure vanadium and alloy titanium (Ti-6Al-4V) were spin-formed, as well as additional copper and 21-6-9 stainless. In the first development order the following materials had been spin-formed: copper (alloy C11000 ETP), 6061 aluminum, 304L stainless steel, 21-6-9 stainless steel, and tantalum-2.5% tungsten. Significant challenges included properly adjusting the rotations-per-minute (RPM), cracking at un-beveled edges and laser marks, redressing of notches, surface cracking, non-uniform temperature evolution in the titanium, and cracking of the tailstock. Lessons learned were that 300 RPM worked better than 600 RPM for most materials (at the feed rate of 800 mm/min); beveling the edges to lower the stress reduces edge cracking; notches, laser marks, or edge defects in the preform doom the process to cracking and failure; coolant is required for vanadium spin-forming; increasing the number of passes to nine or more eliminates surface cracking for vanadium; titanium develops a hot zone in front of the rollers; and the tailstock should be redesigned to eliminate the cylindrical stress concentrator in the center.

  14. Triggered pore-forming agents

    DOEpatents

    Bayley, H.; Walker, B.J.; Chang, C.Y.; Niblack, B.; Panchal, R.

    1998-07-07

    An inactive pore-forming agent is revealed which is activated to lytic function by a condition such as pH, light, heat, reducing potential, or metal ion concentration, or substance such as a protease, at the surface of a cell. 30 figs.

  15. Electro-Hydraulic Forming of Sheet Metals: Free-forming vs. Conical-die Forming

    SciTech Connect

    Rohatgi, Aashish; Stephens, Elizabeth V.; Davies, Richard W.; Smith, Mark T.; Soulami, Ayoub; Ahzi, Said

    2012-05-01

    This work builds upon our recent advances in quantifying high-rate deformation behavior of sheet metals, during electro-hydraulic forming (EHF), using high-speed imaging and digital image correlation techniques. Following recent publication of an earlier manuscript, resulting from this project, in the Journal of Materials Processing Technology, this manuscript further details our results and compares forming behavior when the process is carried out inside an open-die or a conical die. It is anticipated that quantitative information of the sheet deformation history, made possible by the experimental technique developed in this work, will improve our understanding on the roles of strain-rate and sheet-die interactions in enhancing the sheet metal formability during high-rate forming. This knowledge will be beneficial to the automotive industry and enable them to fabricate light-weight sheet parts out of Al and advanced high strength steels.

  16. Cyclodextrin Inclusion Polymers Forming Hydrogels

    NASA Astrophysics Data System (ADS)

    Li, Jun

    This chapter reviews the advances in the developments of supramolecular hydrogels based on the polypseudorotaxanes and polyrotaxanes formed by inclusion complexes of cyclodextrins threading onto polymer chains. Both physical and chemical supramolecular hydrogels of many different types are discussed with respect to their preparation, structure, property, and gelation mechanism. A large number of physical supramolecular hydrogels were formed induced by self-assembly of densely packed cyclodextrin rings threaded on polymer or copolymer chains acting as physical crosslinking points. The thermo-reversible and thixotropic properties of these physical supramolecular hydrogels have inspired their applications as injectable drug delivery systems. Chemical supramolecular hydrogels synthesized from polypseudorotaxanes and polyrotaxanes were based on the chemical crosslinking of either the cyclodextrin molecules or the included polymer chains. The chemical supramolecular hydrogels were often made biodegradable through incorporation of hydrolyzable threading polymers, end caps, or crosslinkers, for their potential applications as biomaterials.

  17. Method of forming clathrate ice

    DOEpatents

    Hino, Toshiyuki; Gorski, Anthony J.

    1987-01-01

    A method of forming clathrate ice in a supercooled water-based liquid contained in a vessel is disclosed. Initially, an oscillator device is located in the liquid in the vessel. The oscillator device is then oscillated ultrasonically so that small crystals are formed in the liquid. These small crystals serve as seed crystals for ice formation in the liquid and thereby prevent supercooling of the liquid. Preferably, the oscillating device is controlled by a thermostat which initiates operation of the oscillator device when the temperature of the liquid is lowered to the freezing point. Thereafter, the operation of the oscillator device is terminated when ice is sensed in the liquid by an ice sensor.

  18. Method of forming calthrate ice

    DOEpatents

    Hino, T.; Gorski, A.J.

    1985-09-30

    A method of forming clathrate ice in a supercooled water-based liquid contained in a vessel is disclosed. Initially, an oscillator device is located in the liquid in the vessel. The oscillator device is then oscillated ultransonically so that small crystals are formed in the liquid. Thes small crystals serve as seed crystals for ice formation in the liquid and thereby prevent supercooling of the liquid. Preferably, the oscillating device is controlled by a thermostat which initiates operation of the oscillator device when the temperature of the liquid is lowered to the freezing point. Thereafter, the operation of the oscillator device is terminated when ice is sensed in the liquid by an ice sensor.

  19. Sphere forming method and apparatus

    NASA Technical Reports Server (NTRS)

    Youngberg, C. L.; Miller, C. G.; Stephens, J. B.; Finnerty, A. A. (Inventor)

    1983-01-01

    A system is provided for forming small accurately spherical objects. Preformed largely spherical objects are supported at the opening of a conduit on the update of hot gas emitted from the opening, so the object is in a molten state. The conduit is suddenly jerked away at a downward incline, to allow the molten object to drop in free fall, so that surface tension forms a precise sphere. The conduit portion that has the opening, lies in a moderate vacuum chamber, and the falling sphere passes through the chamber and through a briefly opened valve into a tall drop tower that contains a lower pressure, to allow the sphere to cool without deformation caused by falling through air.

  20. Automatic recognition of auroral forms

    NASA Astrophysics Data System (ADS)

    Pudovkin, Mikhail I.; Steen, Ake; Nikolaev, N. V.; Kornilov, O. I.; Brandstrom, Urban; Gustavsson, Bjorn; Rydesater, Peter

    1999-03-01

    A method for recognition of geometrical shapes in auroral forms is presented. The method is based on the analysis of isolines of auroral luminosity shapes. The basic variables used are the angle, (phi) (s), between the tangent of the contour and the x-axis of an arbitrary coordinate system, and the differential, d(phi) (s), as a function of the distance, s, along the contour. The analysis also includes Fourier transformation of the experimental function d(phi) (s) obtained for the observed auroral forms, and the comparison of the power spectrum, F(k), with those for a series of model contours. Some dynamical characteristics of the aurora are also discussed.

  1. Method of forming a joint

    DOEpatents

    Butt, Darryl Paul; Cutler, Raymond Ashton; Rynders, Steven Walton; Carolan, Michael Francis

    2006-08-22

    A method of joining at least two sintered bodies to form a composite structure, including providing a first multicomponent metallic oxide having a perovskitic or fluorite crystal structure; providing a second sintered body including a second multicomponent metallic oxide having a crystal structure of the same type as the first; and providing at an interface a joint material containing at least one metal oxide containing at least one metal identically contained in at least one of the first and second multicomponent metallic oxides. The joint material is free of cations of Si, Ge, Sn, Pb, P and Te and has a melting point below the sintering temperatures of both sintered bodies. The joint material is heated to a temperature above the melting point of the metal oxide(s) and below the sintering temperatures of the sintered bodies to form the joint. Structures containing such joints are also disclosed.

  2. Free-form illumination optics

    NASA Astrophysics Data System (ADS)

    Mohedano, Rubén; Chaves, Julio; Hernández, Maikel

    2016-04-01

    In many illumination problems, the beam pattern needed and/or some geometrical constraints lead to very asymmetric design conditions. These asymmetries have been solved in the past by means of arrangements of rotationally symmetric or linear lamps aimed in different directions whose patterns overlap to provide the asymmetric prescriptions or by splitting one single lamp into several sections, each one providing a part of the pattern. The development of new design methods yielding smooth continuous free-form optical surfaces to solve these challenging design problems, combined with the proper CAD modeling tools plus the development of multiple axes diamond turn machines, give birth to a new generation of optics. These are able to offer the performance and other advanced features, such as efficiency, compactness, or aesthetical advantages, and can be manufactured at low cost by injection molding. This paper presents two examples of devices with free-form optical surfaces, a camera flash, and a car headlamp.

  3. Unsplit bipolar pulse forming line

    DOEpatents

    Rhodes, Mark A.

    2011-05-24

    A bipolar pulse forming transmission line module and system for linear induction accelerators having first, second, third, and fourth planar conductors which form a sequentially arranged interleaved stack having opposing first and second ends, with dielectric layers between the conductors. The first and second planar conductors are connected to each other at the first end, and the first and fourth planar conductors are connected to each other at the second end via a shorting plate. The third planar conductor is electrically connectable to a high voltage source, and an internal switch functions to short at the first end a high voltage from the third planar conductor to the fourth planar conductor to produce a bipolar pulse at the acceleration axis with a zero net time integral. Improved access to the switch is enabled by an aperture through the shorting plate and the proximity of the aperture to the switch.

  4. Terra firma-forme dermatosis.

    PubMed

    Erkek, Emel; Sahin, Sedef; Çetin, Emel Dikicioglu; Sezer, Engin

    2012-01-01

    Terra firma-forme dermatosis is characterized by 'dirty' brown-grey cutaneous patches and plaques that can simply be eradicated by forceful swabbing with alcohol pads. The pathogenesis has been attributed to abnormal and delayed keratinization. Although affected patients present with typical lesions, the disorder is not well-known by dermatologists. In this report, we describe two patients with terra firma-forme dermatosis in the setting of xerosis cutis and atopic dermatitis. From a clinical point of view, we lay emphasis on its unique expression and diagnosis/treatment. From a histological perspective, we highlight its resemblance to dermatosis neglecta and speculate on the role of 'neglect' in a patient with seemingly adequate hygiene. The role of urea containing emollients in the development of this disorder remains to be determined.

  5. Method for forming hermetic seals

    NASA Technical Reports Server (NTRS)

    Gallagher, Brian D.

    1987-01-01

    The firmly adherent film of bondable metal, such as silver, is applied to the surface of glass or other substrate by decomposing a layer of solution of a thermally decomposable metallo-organic deposition (MOD) compound such as silver neodecanoate in xylene. The MOD compound thermally decomposes into metal and gaseous by-products. Sealing is accomplished by depositing a layer of bonding metal, such as solder or a brazing alloy, on the metal film and then forming an assembly with another high melting point metal surface such as a layer of Kovar. When the assembly is heated above the temperature of the solder, the solder flows, wets the adjacent surfaces and forms a hermetic seal between the metal film and metal surface when the assembly cools.

  6. Studying how protein crystals form

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Watching molecules of the iron-storing protein apoferritin come together to form a nucleus reveals some interesting behavior. In this series of images, researchers observed clusters of four molecules at the corners of a diamond shape (top). As more molecules attach to the cluster, they arrange themselves into rods (second from top), and a raft-like configuration of molecules forms the critical nucleus (third from top), suggesting that crystal growth is much slower than it could be were the molecules arranged in a more compact formation. In the final image, a crystallite consisting of three layers containing approximately 60 to 70 molecules each is formed. Atomic force microscopy made visualizing the process of nucleation possible for the first time. The principal investigator is Peter Vekilov, of the University of Alabama in Huntsville. Vekilov's team at UAH studies protein solutions as they change phases from liquids to crystalline solids. They want to know if the molecules in the solution interact with one another, and if so, how, from the perspectives of thermodynamics and kinetics. They want to understand which forces -- electrical, electrostatic, hydrodynamic, or other kinds of forces -- are responsible for the interactions. They also study nucleation, the begirning stage of crystallization. This process is important to understand because it sets the stage for crystal growth in all kinds of solutions and liquid melts that are important in such diverse fields as agriculture, medicine, and the fabrication of metal components. Nucleation can determine the rate of crystal growth, the number of crystals that will be formed, and the quality and size of the crystals.

  7. Old and New Insurgency Forms

    DTIC Science & Technology

    2016-03-01

    The use of violence on its own, espe - cially that which is conventional military in nature, is more indicative of warfare waged by states. This...be based on other forms of crime, espe - cially smuggling. The defining feature is expansion of the criminal activity into a security threat, espe ...Agencies - Legal and Economic Focus -Federal Law Enforcement Blood Cultist EmergentLimited to Moderate Implications Federal Law Enforcement and/or

  8. Dynamic Forms. Part 1: Functions

    NASA Technical Reports Server (NTRS)

    Meyer, George; Smith, G. Allan

    1993-01-01

    The formalism of dynamic forms is developed as a means for organizing and systematizing the design control systems. The formalism allows the designer to easily compute derivatives to various orders of large composite functions that occur in flight-control design. Such functions involve many function-of-a-function calls that may be nested to many levels. The component functions may be multiaxis, nonlinear, and they may include rotation transformations. A dynamic form is defined as a variable together with its time derivatives up to some fixed but arbitrary order. The variable may be a scalar, a vector, a matrix, a direction cosine matrix, Euler angles, or Euler parameters. Algorithms for standard elementary functions and operations of scalar dynamic forms are developed first. Then vector and matrix operations and transformations between parameterization of rotations are developed in the next level in the hierarchy. Commonly occurring algorithms in control-system design, including inversion of pure feedback systems, are developed in the third level. A large-angle, three-axis attitude servo and other examples are included to illustrate the effectiveness of the developed formalism. All algorithms were implemented in FORTRAN code. Practical experience shows that the proposed formalism may significantly improve the productivity of the design and coding process.

  9. Coated particle waste form development

    SciTech Connect

    Oma, K.H.; Buckwalter, C.Q.; Chick, L.A.

    1981-12-01

    Coated particle waste forms have been developed as part of the multibarrier concept at Pacific Northwest Laboratory under the Alternative Waste Forms Program for the Department of Energy. Primary efforts were to coat simulated nuclear waste glass marbles and ceramic pellets with low-temperature pyrolytic carbon (LT-PyC) coatings via the process of chemical vapor deposition (CVD). Fluidized bed (FB) coaters, screw agitated coaters (SAC), and rotating tube coaters were used. Coating temperatures were reduced by using catalysts and plasma activation. In general, the LT-PyC coatings did not provide the expected high leach resistance as previously measured for carbon alone. The coatings were friable and often spalled off the substrate. A totally different concept, thermal spray coating, was investigated at PNL as an alternative to CVD coating. Flame spray, wire gun, and plasma gun systems were evaluated using glass, ceramic, and metallic coating materials. Metal plasma spray coatings (Al, Sn, Zn, Pb) provided a two to three orders-of-magnitude increase in chemical durability. Because the aluminum coatings were porous, the superior leach resistance must be due to either a chemical interaction or to a pH buffer effect. Because they are complex, coated waste form processes rank low in process feasibility. Of all the possible coated particle processes, plasma sprayed marbles have the best rating. Carbon coating of pellets by CVD ranked ninth when compared with ten other processes. The plasma-spray-coated marble process ranked sixth out of eleven processes.

  10. Rib forming tool for tubing

    DOEpatents

    Rowley, James P.; Lewandowski, Edward F.; Groh, Edward F.

    1976-01-01

    Three cylindrical rollers are rotatably mounted equidistant from the center of a hollow tool head on radii spaced 120.degree. apart. Each roller has a thin flange; the three flanges lie in a single plane to form an internal circumferential rib in a rotating tubular workpiece. The tool head has two complementary parts with two rollers in one part of the head and one roller in the other part; the two parts are joined by a hinge. A second hinge, located so the rollers are between the two hinges, connects one of the parts to a tool bar mounted in a lathe tool holder. The axes of rotation of both hinges and all three rollers are parallel. A hole exposing equal portions of the three roller flanges is located in the center of the tool head. The two hinges permit the tool head to be opened and rotated slightly downward, taking the roller flanges out of the path of the workpiece which is supported on both ends and rotated by the lathe. The parts of the tool head are then closed on the workpiece so that the flanges are applied to the workpiece and form the rib. The tool is then relocated for forming of the next rib.

  11. 48 CFR 53.303 - Agency forms.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Agency forms. 53.303 Section 53.303 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.303 Agency forms. This section illustrates agency forms...

  12. 48 CFR 53.303 - Agency forms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 2 2012-10-01 2012-10-01 false Agency forms. 53.303 Section 53.303 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.303 Agency forms. This section illustrates agency forms...

  13. 48 CFR 53.303 - Agency forms.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 2 2014-10-01 2014-10-01 false Agency forms. 53.303 Section 53.303 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.303 Agency forms. This section illustrates agency forms...

  14. 48 CFR Appendix - List of IAAR Forms

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false List of IAAR Forms Federal Acquisition Regulations System BROADCASTING BOARD OF GOVERNORS CLAUSES AND FORMS FORMS Illustrations of Forms The Broadcasting Board of Governors forms. List of IAAR Forms 1953.370-21The Broadcasting Board...

  15. 48 CFR 53.303 - Agency forms.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 2 2013-10-01 2013-10-01 false Agency forms. 53.303 Section 53.303 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.303 Agency forms. This section illustrates agency forms...

  16. 48 CFR 53.303 - Agency forms.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false Agency forms. 53.303 Section 53.303 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.303 Agency forms. This section illustrates agency forms...

  17. Weak Energy: Form and Function

    NASA Astrophysics Data System (ADS)

    Parks, Allen D.

    The equation of motion for a time-dependent weak value of a quantum mechanical observable contains a complex valued energy factor—the weak energy of evolution. This quantity is defined by the dynamics of the pre-selected and post-selected states which specify the observable's weak value. It is shown that this energy: (i) is manifested as dynamical and geometric phases that govern the evolution of the weak value during the measurement process; (ii) satisfies the Euler-Lagrange equations when expressed in terms of Pancharatnam (P) phase and Fubini-Study (FS) metric distance; (iii) provides for a PFS stationary action principle for quantum state evolution; (iv) time translates correlation amplitudes; (v) generalizes the temporal persistence of state normalization; and (vi) obeys a time-energy uncertainty relation. A similar complex valued quantity—the pointed weak energy of an evolving quantum state—is also defined and several of its properties in PFS coordinates are discussed. It is shown that the imaginary part of the pointed weak energy governs the state's survival probability and its real part is—to within a sign—the Mukunda-Simon geometric phase for arbitrary evolutions or the Aharonov-Anandan (AA) geometric phase for cyclic evolutions. Pointed weak energy gauge transformations and the PFS 1-form are defined and discussed and the relationship between the PFS 1-form and the AA connection 1-form is established. [Editors note: for a video of the talk given by Prof. Parks at the Aharonov-80 conference in 2012 at Chapman University, see http://quantum.chapman.edu/talk-25.

  18. CERAMIC WASTE FORM DATA PACKAGE

    SciTech Connect

    Amoroso, J.; Marra, J.

    2014-06-13

    The purpose of this data package is to provide information about simulated crystalline waste forms that can be used to select an appropriate composition for a Cold Crucible Induction Melter (CCIM) proof of principle demonstration. Melt processing, viscosity, electrical conductivity, and thermal analysis information was collected to assess the ability of two potential candidate ceramic compositions to be processed in the Idaho National Laboratory (INL) CCIM and to guide processing parameters for the CCIM operation. Given uncertainties in the CCIM capabilities to reach certain temperatures throughout the system, one waste form designated 'Fe-MP' was designed towards enabling processing and another, designated 'CAF-5%TM-MP' was designed towards optimized microstructure. Melt processing studies confirmed both compositions could be poured from a crucible at 1600{degrees}C although the CAF-5%TM-MP composition froze before pouring was complete due to rapid crystallization (upon cooling). X-ray diffraction measurements confirmed the crystalline nature and phase assemblages of the compositions. The kinetics of melting and crystallization appeared to vary significantly between the compositions. Impedance spectroscopy results indicated the electrical conductivity is acceptable with respect to processing in the CCIM. The success of processing either ceramic composition will depend on the thermal profiles throughout the CCIM. In particular, the working temperature of the pour spout relative to the bulk melter which can approach 1700{degrees}C. The Fe-MP composition is recommended to demonstrate proof of principle for crystalline simulated waste forms considering the current configuration of INL's CCIM. If proposed modifications to the CCIM can maintain a nominal temperature of 1600{degrees}C throughout the melter, drain, and pour spout, then the CAF-5%TM-MP composition should be considered for a proof of principle demonstration.

  19. Nuclear waste forms for actinides.

    PubMed

    Ewing, R C

    1999-03-30

    The disposition of actinides, most recently 239Pu from dismantled nuclear weapons, requires effective containment of waste generated by the nuclear fuel cycle. Because actinides (e.g., 239Pu and 237Np) are long-lived, they have a major impact on risk assessments of geologic repositories. Thus, demonstrable, long-term chemical and mechanical durability are essential properties of waste forms for the immobilization of actinides. Mineralogic and geologic studies provide excellent candidate phases for immobilization and a unique database that cannot be duplicated by a purely materials science approach. The "mineralogic approach" is illustrated by a discussion of zircon as a phase for the immobilization of excess weapons plutonium.

  20. Export of newly formed LSW

    NASA Astrophysics Data System (ADS)

    Müller, Katharina; Klein, Birgit; Karstensen, Johannes; Fischer, Jürgen; Baumann, Till; Kanzow, Torsten

    2015-04-01

    The Atlantic meridional overturning circulation represents the strongest mechanism for oceanic northward heat transport. This is accomplished by moving warm water northward in the upper ocean compensated by a deep return flow of cold and dense North Atlantic Deep Water (NADW). Labrador Sea Water (LSW) constitutes the shallowest component of NADW. Since LSW is also supposed to be the most sensitive NADW component to climate change it is of particular interest. LSW is formed by deep convection not only in the centre of the Labrador Sea but also near its western boundary. Recent studies have suggested that LSW formed in the boundary region enters its export route from the Labrador Sea, the Deep Western Boundary Current, faster than LSW originating from the central Labrador Sea. In this study the spatial and temporal evolution of the export of newly formed LSW is investigated. For this purpose hydrographic mooring data from an array located at the western bounndary at 53°N starting in the late 1990s until 2014 and data from the Argo float network is used. The averaged seasonal salinity cycle at the array, particularly at the moorings further onshore, shows a pronounced freshwater signal in May indicating the arrival of newly formed LSW in the boundary current. In order to learn more about its preceding pathway and the corresponding export timescale the mooring data is complemented by data from Argo floats. Besides the annual cycles of LSW formation and export, their interannual variations are important aspects affecting the large-scale circulation. For instance, in years of relatively strong convection, as in 2008 and 2012, LSW is observed to pass the boundary current array at 53°N earlier, i.e. in February and March, respectively, than in years with weak convection, as in 2007 or 2010. Besides seasonal variations in the boundary current, a possible explanation for the earlier freshwater signal in years of enhanced convection might be a shift in convection sites

  1. FORMING PROTECTIVE FILMS ON METAL

    DOEpatents

    Gurinsky, D.H.; Kammerer, O.F.; Sadofsky, J.; Weeks, J.R.

    1958-12-16

    Methods are described of inhibiting the corrosion of ferrous metal by contact with heavy liquid metals such as bismuth and gallium at temperatures above 500 icient laborato C generally by bringing nltrogen and either the metal zirconium, hafnium, or titanium into reactlve contact with the ferrous metal to form a thin adherent layer of the nitride of the metal and thereafter maintaining a fractional percentage of the metal absorbed in the heavy liquid metal in contact with the ferrous metal container. The general purpose for uslng such high boiling liquid metals in ferrous contalners would be as heat transfer agents in liquid-metal-fueled nuclear reactors.

  2. Integrally formed radio frequency quadrupole

    DOEpatents

    Abbott, Steven R.

    1989-01-01

    An improved radio frequency quadrupole (10) is provided having an elongate housing (11) with an elongate central axis (12) and top, bottom and two side walls (13a-d) symmetrically disposed about the axis, and vanes (14a-d) formed integrally with the walls (13a-d), the vanes (14a-d) each having a cross-section at right angles to the central axis (12) which tapers inwardly toward the axis to form electrode tips (15a-d) spaced from each other by predetermined distances. Each of the four walls (13a-d), and the vanes (14a-d) integral therewith, is a separate structural element having a central lengthwise plane (16) passing through the tip of the vane, the walls (13a-d) having flat mounting surfaces (17, 18) at right angles to and parallel to the control plane (16), respectively, which are butted together to position the walls and vane tips relative to each other.

  3. Gravity, light and plant form.

    PubMed

    Hangarter, R P

    1997-06-01

    Plants have evolved highly sensitive and selective mechanisms that detect and respond to various aspects of their environment. As a plant develops, it integrates the environmental information perceived by all of its sensory systems and adapts its growth to the prevailing environmental conditions. Light is of critical importance because plants depend on it for energy and, thus, survival. The quantity, quality and direction of light are perceived by several different photosensory systems that together regulate nearly all stages of plant development, presumably in order to maintain photosynthetic efficiency. Gravity provides an almost constant stimulus that is the source of critical spatial information about its surroundings and provides important cues for orientating plant growth. Gravity plays a particularly important role during the early stages of seedling growth by stimulating a negative gravitropic response in the primary shoot that orientates it towards the source of light, and a positive gravitropic response in the primary root that causes it to grow down into the soil, providing support and nutrient acquisition. Gravity also influences plant form during later stages of development through its effect on lateral organs and supporting structures. Thus, the final form of a plant depends on the cumulative effects of light, gravity and other environmental sensory inputs on endogenous developmental programs. This article is focused on developmental interactions modulated by light and gravity.

  4. Gravity, light and plant form

    NASA Technical Reports Server (NTRS)

    Hangarter, R. P.

    1997-01-01

    Plants have evolved highly sensitive and selective mechanisms that detect and respond to various aspects of their environment. As a plant develops, it integrates the environmental information perceived by all of its sensory systems and adapts its growth to the prevailing environmental conditions. Light is of critical importance because plants depend on it for energy and, thus, survival. The quantity, quality and direction of light are perceived by several different photosensory systems that together regulate nearly all stages of plant development, presumably in order to maintain photosynthetic efficiency. Gravity provides an almost constant stimulus that is the source of critical spatial information about its surroundings and provides important cues for orientating plant growth. Gravity plays a particularly important role during the early stages of seedling growth by stimulating a negative gravitropic response in the primary shoot that orientates it towards the source of light, and a positive gravitropic response in the primary root that causes it to grow down into the soil, providing support and nutrient acquisition. Gravity also influences plant form during later stages of development through its effect on lateral organs and supporting structures. Thus, the final form of a plant depends on the cumulative effects of light, gravity and other environmental sensory inputs on endogenous developmental programs. This article is focused on developmental interactions modulated by light and gravity.

  5. Preventing Ice Before it Forms

    NASA Technical Reports Server (NTRS)

    2006-01-01

    In the late 1990s, a team of engineers at Ames Research Center invented an anti-icing fluid to keep ice from building up on airplane wings. Ice on wings can be a serious safety hazard, especially during takeoff, when a sheet of ice the thickness of a compact disc can reduce lift by 25 percent or more. The typical approach to clearing off the ice is to use a deicing solution once the ice has built up. The fluid created by the Ames team, though, when applied to a dry surface, prevents the ice from even forming a surface bond, which saves deicing time and money, while also preventing excessive use of chemical solvents. If, however, the solution is not applied before ice forms, it also serves as a traditional deicing formula. The formula contains propylene glycol, which has a very low freezing point, and a thickener, which helps the fluid adhere to the surface. Ice gathers on top of the formula, and then it can be wiped off with little effort. This thickening agent, a pseudo-plastic, sprays on as a liquid, like lemonade, gels like a lemon sherbet, turns back to a liquid when wiped, and then gels again into its sherbet consistency when left to solidify. The sherbet-gel stage is especially important when the formula is sprayed onto a vertical or steeped surface, as it clings better than a liquid would.

  6. Nuclear waste forms for actinides

    PubMed Central

    Ewing, Rodney C.

    1999-01-01

    The disposition of actinides, most recently 239Pu from dismantled nuclear weapons, requires effective containment of waste generated by the nuclear fuel cycle. Because actinides (e.g., 239Pu and 237Np) are long-lived, they have a major impact on risk assessments of geologic repositories. Thus, demonstrable, long-term chemical and mechanical durability are essential properties of waste forms for the immobilization of actinides. Mineralogic and geologic studies provide excellent candidate phases for immobilization and a unique database that cannot be duplicated by a purely materials science approach. The “mineralogic approach” is illustrated by a discussion of zircon as a phase for the immobilization of excess weapons plutonium. PMID:10097054

  7. Alumina forming iron base superalloy

    DOEpatents

    Yamamoto, Yukinori; Muralidharan, Govindarajan; Brady, Michael P.

    2014-08-26

    An austenitic stainless steel alloy, consists essentially of, in weight percent 2.5 to 4 Al; 25 to 35 Ni; 12 to 19 Cr; at least 1, up to 4 total of at least one element selected from the group consisting of Nb and Ta; 0.5 to 3 Ti; less than 0.5 V; 0.1 to 1 of at least on element selected from the group consisting of Zr and Hf; 0.03 to 0.2 C; 0.005 to 0.1 B; and base Fe. The weight percent Fe is greater than the weight percent Ni. The alloy forms an external continuous scale including alumina, and contains coherent precipitates of .gamma.'-Ni.sub.3Al, and a stable essentially single phase FCC austenitic matrix microstructure. The austenitic matrix is essentially delta-ferrite-free and essentially BCC-phase-free.

  8. Miscellaneous Waste-Form FEPs

    SciTech Connect

    A. Schenker

    2000-12-08

    The US DOE must provide a reasonable assurance that the performance objectives for the Yucca Mountain Project (YMP) potential radioactive-waste repository can be achieved for a 10,000-year post-closure period. The guidance that mandates this direction is under the provisions of 10 CFR Part 63 and the US Department of Energy's ''Revised Interim Guidance Pending Issuance of New US Nuclear Regulatory Commission (NRC) Regulations (Revision 01, July 22, 1999), for Yucca Mountain, Nevada'' (Dyer 1999 and herein referred to as DOE's Interim Guidance). This assurance must be demonstrated in the form of a performance assessment that: (1) identifies the features, events, and processes (FEPs) that might affect the performance of the potential geologic repository; (2) examines the effects of such FEPs on the performance of the potential geologic repository; (3) estimates the expected annual dose to a specified receptor group; and (4) provides the technical basis for inclusion or exclusion of specific FEPs.

  9. Hereditary forms of colorectal cancer.

    PubMed

    Castells, Antoni

    2016-09-01

    Colorectal cancer is one of the most frequent neoplasms in western countries; it is the third most common cancer in men after prostate and lung cancer and the second most common in women after breast cancer. Colorectal cancer is usually sporadic but in a small proportion is hereditary. The genetic cause is well established, allowing pre-symptomatic diagnosis in at-risk relatives. The present article reviews the most novel findings presented at the latest meeting of the American Gastroenterological Association on hereditary forms of colorectal cancer, especially Lynch syndrome and MUTYH-associated polyposis, as well as diverse organisational aspects that can favour the correct management of these patients and their relatives.

  10. New marine science organization formed

    NASA Astrophysics Data System (ADS)

    Wooster, Warren S.

    A new international organization, the North Pacific Marine Science Organization (PICES) will be established to promote and coordinate marine scientific research in the northern North Pacific Ocean and the Berlin Sea. This was decided in Ottawa on December 12, 1990, when a draft convention was approved by representatives of Canada, China, Japan, the United States, and the Soviet Union. PICES will focus on research on the ocean environment and its interactions with land and atmosphere, its role and response to global weather and climate change, its flora, fauna and ecosystems, its uses and resources, and impacts upon it from human activities. Such studies relate not only to the effects of fishing and environmental change on fish stocks but also to such issues as the impacts of oil spills and other forms of pollution and the eventual consequences of climate change for uses of the ocean and its resources.

  11. Method for forming energetic nanopowders

    DOEpatents

    Lee, Kien-Yin; Asay, Blaine W.; Kennedy, James E.

    2013-10-15

    A method for the preparation of neat energetic powders, having nanometer dimensions, is described herein. For these neat powder, a solution of a chosen energetic material is prepared in an aprotic solvent and later combined with liquid hexane that is miscible with such solvent. The energetic material chosen is less soluble in the liquid hexane than in the aprotic solvent and the liquid hexane is cooled to a temperature that is below that of the solvent solution. In order to form a precipitate of said neat powders, the solvent solution is rapidly combined with the liquid hexane. When the resulting precipitate is collected, it may be dried and filtered to yield an energetic nanopowder material.

  12. Form factors from lattice QCD

    SciTech Connect

    Dru Renner

    2012-04-01

    Precision computation of hadronic physics with lattice QCD is becoming feasible. The last decade has seen precent-level calculations of many simple properties of mesons, and the last few years have seen calculations of baryon masses, including the nucleon mass, accurate to a few percent. As computational power increases and algorithms advance, the precise calculation of a variety of more demanding hadronic properties will become realistic. With this in mind, I discuss the current lattice QCD calculations of generalized parton distributions with an emphasis on the prospects for well-controlled calculations for these observables as well. I will do this by way of several examples: the pion and nucleon form factors and moments of the nucleon parton and generalized-parton distributions.

  13. An arthroscopic hip documentation form.

    PubMed

    Gokhale, Satesh; Khan, Munir; Kuiper, Jan-Herman; Richardson, James B; Davies, Jonathan P

    2008-07-01

    Hip arthroscopy is becoming increasingly popular. A simple, precise, and practical means of recording arthroscopic findings will be useful for diagnostic, research, and audit purposes. Basic principles of cartography exist to produce two-dimensional paper representations of our spherical planet. We used the same principles to produce a two-dimensional map of the acetabulum and femoral head. The resulting hip diagram shows the acetabulum as viewed from the side and the femoral head as viewed from above. The ligamentum teres is attached to the medial margin of the head. The head-neck junction and part of the femoral neck is shown at the opposite margin of the ligamentum teres. The hip documentation form is simple, precise, and accurate. We use it to record our findings at hip arthroscopy, which we have used to assist us in our practice.

  14. [Dosage forms of phytogenic drugs].

    PubMed

    Luftensteiner, C P; Viernstein, H

    1999-01-01

    Herbal drug formulation is a challenge in pharmaceutical technology due to the complex physicochemical properties of these multicomponent materials. Potential instabilities of the pharmacologically active and coactive substances as well as incompatibilities and interactions of the extracted compounds and excipients have to be considered. Microbial contamination of the applied plant material might limit the shelf life of the products. Using state of the art methods in formulation stable preparations are obtained; additionally compliance of drugs might be enhanced due to simplified application or better sensorial quality. Nowadays, besides traditional pharmacopoeial aqueous, ethanolic, or (partially) dried extracts fluid, semisolid, or solid dosage forms of these extracts are in use, for example syrups, juices, drops, liniments, gels, ointments, creams, suppositories, tablets, coated tablets (dragees) as well as soft and hard gelatine capsules.

  15. Eight salt forms of sulfadiazine.

    PubMed

    Buist, Amanda R; Dennany, Lynn; Kennedy, Alan R; Manzie, Craig; McPhie, Katherine; Walker, Brandon

    2014-09-01

    Proton transfer to the sulfa drug sulfadiazine [systematic name: 4-amino-N-(pyrimidin-2-yl)benzenesulfonamide] gave eight salt forms. These are the monohydrate and methanol hemisolvate forms of the chloride (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium chloride monohydrate, C(10)H(11)N(4)O(2)S(+) · Cl(-) · H2O, (I), and 2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium chloride methanol hemisolvate, C(10)H(11)N(4)O(2)S(+) · Cl(-) · (0.5)CH(3)OH, (II)); a bromide monohydrate (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium bromide monohydrate, C(10)H(11)N(4)O(2)S(+) · Br(-) · H2O, (III)), which has a disordered water channel; a species containing the unusual tetraiodide dianion [bis(2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium) tetraiodide, 2C(10)H(11)N(4)O(2)S(+) · I4(2-), (IV)], where the [I4](2-) ion is located at a crystallographic inversion centre; a tetrafluoroborate monohydrate (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium tetrafluoroborate monohydrate, C(10)H(11)N(4)O(2)S(+) · BF(4)(-) · H2O, (V)); a nitrate (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium nitrate, C(10)H(11)N(4)O(2)S(+) · NO(3)(-), (VI)); an ethanesulfonate {4-[(pyrimidin-2-yl)sulfamoyl]anilinium ethanesulfonate, C(10)H(11)N(4)O(2)S(+) · C(2)H(5)SO(3)(-), (VII)}; and a dihydrate of the 4-hydroxybenzenesulfonate {4-[(pyrimidin-2-yl)sulfamoyl]anilinium 4-hydroxybenzenesulfonate dihydrate, C(10)H(11)N(4)O(2)S(+) · HOC(6)H(4)SO(3)(-) · 2H2O, (VIII)}. All these structures feature alternate layers of cations and of anions where any solvent is associated with the anion layers. The two sulfonate salts are protonated at the aniline N atom and the amide N atom of sulfadiazine, a tautomeric form of the sulfadiazine cation that has not been crystallographically described before. All the other salt forms are instead protonated at the aniline group and on one N atom of the pyrimidine ring. Whilst all eight species are based upon

  16. Forming parts over small radii

    NASA Astrophysics Data System (ADS)

    Hazra, S. K.; Hughes, D. J.; Pereira, M. P.; Rolfe, B. F.

    2016-08-01

    Stamping simulations usually make the plane stress simplifying assumption. However, this becomes less valid when material draws around features with radius to sheet thickness ratios less than 20. Pereira, Yan & Rolfe (Wear, Vol.265, p.1687 (2008)) predicted that out-of-plane stress equivalent to material yield can occur because a line contact forms briefly at the start of the draw process. The high transient stress can cause high rates of tool wear and may cause the ‘die impact line’ cosmetic defect. In this work, we present residual strain results of a channel section that was drawn over a small radius. Using the neutron source at the Institut Laue-Langevin, in-plane and out-of-plane strains were measured in the channel part to show some support for the conclusions of Pereira et. al.

  17. Forming impressions from incongruent traits.

    PubMed

    Casselden, P A; Hampson, S E

    1990-08-01

    The factors that affect the ease with which impressions are formed from incongruent trait pairs are investigated. In Experiments 1 and 2, trait pairs that were both descriptively and evaluatively congruent, as well as ones that were only evaluatively congruent, were found to be more imaginable and to be perceived as more frequently co-occurring than incongruent trait pairs. In Experiment 3, response latency provided a converging measure of ease of imaginability. Experiment 4 examined written descriptions of targets described by these trait pairs, and found more attempts to integrate the congruent than the incongruent pairs. These findings are discussed in terms of the relation between laypersons' impressions of personality and formal personality assessment.

  18. 48 CFR 53.302 - Optional forms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 2 2012-10-01 2012-10-01 false Optional forms. 53.302 Section 53.302 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.302 Optional forms. This section illustrates the...

  19. 48 CFR 53.301 - Standard forms.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 2 2013-10-01 2013-10-01 false Standard forms. 53.301 Section 53.301 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.301 Standard forms. This section illustrates the...

  20. 48 CFR 1253.303 - Agency forms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Agency forms. 1253.303 Section 1253.303 Federal Acquisition Regulations System DEPARTMENT OF TRANSPORTATION CLAUSES AND FORMS FORMS Illustration of Forms 1253.303 Agency forms. This subpart contains illustrations of DOT and...

  1. 48 CFR 53.301 - Standard forms.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Standard forms. 53.301 Section 53.301 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.301 Standard forms. This section illustrates the...

  2. 48 CFR 453.303 - Agency forms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Agency forms. 453.303 Section 453.303 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE CLAUSES AND FORMS FORMS Illustrations of Forms 453.303 Agency forms....

  3. 48 CFR 53.302 - Optional forms.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 2 2014-10-01 2014-10-01 false Optional forms. 53.302 Section 53.302 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.302 Optional forms. This section illustrates the...

  4. 48 CFR 453.303 - Agency forms.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Agency forms. 453.303 Section 453.303 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE CLAUSES AND FORMS FORMS Illustrations of Forms 453.303 Agency forms....

  5. 48 CFR 53.301 - Standard forms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 2 2012-10-01 2012-10-01 false Standard forms. 53.301 Section 53.301 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.301 Standard forms. This section illustrates the...

  6. 48 CFR 1253.303 - Agency forms.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Agency forms. 1253.303 Section 1253.303 Federal Acquisition Regulations System DEPARTMENT OF TRANSPORTATION CLAUSES AND FORMS FORMS Illustration of Forms 1253.303 Agency forms. This subpart contains illustrations of DOT and...

  7. 48 CFR 453.303 - Agency forms.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Agency forms. 453.303 Section 453.303 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE CLAUSES AND FORMS FORMS Illustrations of Forms 453.303 Agency forms....

  8. 48 CFR 1253.303 - Agency forms.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Agency forms. 1253.303 Section 1253.303 Federal Acquisition Regulations System DEPARTMENT OF TRANSPORTATION CLAUSES AND FORMS FORMS Illustration of Forms 1253.303 Agency forms. This subpart contains illustrations of DOT and...

  9. 48 CFR 53.301 - Standard forms.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false Standard forms. 53.301 Section 53.301 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.301 Standard forms. This section illustrates the...

  10. 48 CFR 1253.303 - Agency forms.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Agency forms. 1253.303 Section 1253.303 Federal Acquisition Regulations System DEPARTMENT OF TRANSPORTATION CLAUSES AND FORMS FORMS Illustration of Forms 1253.303 Agency forms. This subpart contains illustrations of DOT and...

  11. 48 CFR 53.302 - Optional forms.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 2 2013-10-01 2013-10-01 false Optional forms. 53.302 Section 53.302 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.302 Optional forms. This section illustrates the...

  12. 48 CFR 53.301 - Standard forms.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 2 2014-10-01 2014-10-01 false Standard forms. 53.301 Section 53.301 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.301 Standard forms. This section illustrates the...

  13. 48 CFR 53.302 - Optional forms.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Optional forms. 53.302 Section 53.302 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.302 Optional forms. This section illustrates the...

  14. 48 CFR 53.302 - Optional forms.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false Optional forms. 53.302 Section 53.302 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.302 Optional forms. This section illustrates the...

  15. 48 CFR 3053.303 - Agency forms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Refunds, Rebates, Credits and Other Amounts DHS Form 700-2. Contractor's Release DHS Form 700-3. Employee... section illustrates agency-specified forms. To access these forms go to: http://www.dhs.gov (under “Business, Acquisition Information”) or https://dhsonline.dhs.gov/portal/jhtml/general/forms.jhtml....

  16. 48 CFR 3053.303 - Agency forms.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Refunds, Rebates, Credits and Other Amounts DHS Form 700-2. Contractor's Release DHS Form 700-3. Employee... section illustrates agency-specified forms. To access these forms go to: http://www.dhs.gov (under “Business, Acquisition Information”) or https://dhsonline.dhs.gov/portal/jhtml/general/forms.jhtml....

  17. 48 CFR 3053.303 - Agency forms.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Refunds, Rebates, Credits and Other Amounts DHS Form 700-2. Contractor's Release DHS Form 700-3. Employee... section illustrates agency-specified forms. To access these forms go to: http://www.dhs.gov (under “Business, Acquisition Information”) or https://dhsonline.dhs.gov/portal/jhtml/general/forms.jhtml....

  18. 16 CFR 455.3 - Window form.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Window form. 455.3 Section 455.3 Commercial... Window form. (a) Form given to buyer. Give the buyer of a used vehicle sold by you the window form...) Incorporated into contract. The information on the final version of the window form is incorporated into...

  19. Growth and form of spherulites

    NASA Astrophysics Data System (ADS)

    Gránásy, László; Pusztai, Tamás; Tegze, György; Warren, James A.; Douglas, Jack F.

    2005-07-01

    Many structural materials (metal alloys, polymers, minerals, etc.) are formed by quenching liquids into crystalline solids. This highly nonequilibrium process often leads to polycrystalline growth patterns that are broadly termed “spherulites” because of their large-scale average spherical shape. Despite the prevalence and practical importance of spherulite formation, only rather qualitative concepts of this phenomenon exist. It is established that phase field methods naturally account for diffusional instabilities that are responsible for dendritic single-crystal growth. However, a generalization of this model is required to describe spherulitic growth patterns, and in the present paper we propose a minimal model of this fundamental crystal growth process. Our calculations indicate that the diversity of spherulitic growth morphologies arises from a competition between the ordering effect of discrete local crystallographic symmetries and the randomization of the local crystallographic orientation that accompanies crystal grain nucleation at the growth front [growth front nucleation (GFN)]. This randomization in the orientation accounts for the isotropy of spherulitic growth at large length scales and long times. In practice, many mechanisms can give rise to GFN, and the present work describes and explores three physically prevalent sources of disorder that lead to this kind of growth. While previous phase field modeling elucidated two of these mechanisms—disorder created by particulate impurities or other static disorder or by the dynamic heterogeneities that spontaneously form in supercooled liquids (even pure ones)—the present paper considers an additional mechanism, crystalline branching induced by a misorientation-dependent grain boundary energy, which can significantly affect spherulite morphology. We find the entire range of observed spherulite morphologies can be reproduced by this generalized phase field model of polycrystalline growth.

  20. 48 CFR 3053.303 - Agency forms.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... section illustrates agency-specified forms. To access these forms go to: http://www.dhs.gov (under “Business, Acquisition Information”) or https://dhsonline.dhs.gov/portal/jhtml/general/forms.jhtml....

  1. 16 CFR 455.3 - Window form.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Window form. (a) Form given to buyer. Give the buyer of a used vehicle sold by you the window form... coverage agreed upon. If you prefer, you may give the buyer a copy of the original, so long as that...

  2. 16 CFR 455.3 - Window form.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Window form. (a) Form given to buyer. Give the buyer of a used vehicle sold by you the window form... coverage agreed upon. If you prefer, you may give the buyer a copy of the original, so long as that...

  3. 16 CFR 455.3 - Window form.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Window form. (a) Form given to buyer. Give the buyer of a used vehicle sold by you the window form... coverage agreed upon. If you prefer, you may give the buyer a copy of the original, so long as that...

  4. 16 CFR 455.3 - Window form.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Window form. (a) Form given to buyer. Give the buyer of a used vehicle sold by you the window form... coverage agreed upon. If you prefer, you may give the buyer a copy of the original, so long as that...

  5. Dyadosphere formed in gravitational collapse

    SciTech Connect

    Ruffini, Remo; Xue Shesheng

    2008-10-10

    We first recall the concept of Dyadosphere (electron-positron-photon plasma around a formed black holes) and its motivation, and recall on (i) the Dirac process: annihilation of electron-positron pairs to photons; (ii) the Breit-Wheeler process: production of electron-positron pairs by photons with the energy larger than electron-positron mass threshold; the Sauter-Euler-Heisenberg effective Lagrangian and rate for the process of electron-positron production in a constant electric field. We present a general formula for the pair-production rate in the semi-classical treatment of quantum mechanical tunneling. We also present in the Quantum Electro-Dynamics framework, the calculations of the Schwinger rate and effective Lagrangian for constant electromagnetic fields. We give a review on the electron-positron plasma oscillation in constant electric fields, and its interaction with photons leading to energy and number equipartition of photons, electrons and positrons. The possibility of creating an overcritical field in astrophysical condition is pointed out. We present the discussions and calculations on (i) energy extraction from gravitational collapse; (ii) the formation of Dyadosphere in gravitational collapsing process, and (iii) its hydrodynamical expansion in Reissner Nordstroem geometry. We calculate the spectrum and flux of photon radiation at the point of transparency, and make predictions for short Gamma-Ray Bursts.

  6. Filtrating forms of soil bacteria

    NASA Astrophysics Data System (ADS)

    Van'kova, A. A.; Ivanov, P. I.; Emtsev, V. T.

    2013-03-01

    Filtrating (ultramicroscopic) forms (FF) of bacteria were studied in a soddy-podzolic soil and the root zone of alfalfa plants as part of populations of the most widespread physiological groups of soil bacteria. FF were obtained by filtering soil solutions through membrane filters with a pore diameter of 0.22 μm. It was established that the greater part of the bacteria in the soil and in the root zone of the plants has an ultramicroscopic size: the average diameter of the cells is 0.3 μm, and their length is 0.6 μm, which is significantly less than the cell size of banal bacteria. The number of FF varies within a wide range depending on the physicochemical conditions of the habitat. The FF number's dynamics in the soil is of a seasonal nature; i.e., the number of bacteria found increases in the summer and fall and decreases in the winter-spring period. In the rhizosphere of the alfalfa, over the vegetation period, the number of FF and their fraction in the total mass of the bacteria increase. A reverse tendency is observed in the rhizoplane. The morphological particularities (identified by an electron microscopy) and the nature of the FF indicate their physiological activity.

  7. [Severe form of herpes gestationis].

    PubMed

    Orsini, G; Loizzi, P; Morelli, L; Chiechi, L M; Sabatini, R; Distante, G

    2003-06-01

    We report a very severe form of herpers gestationis that arose at the 26(th) week of pregnancy and reached us for observation at the 30(th) week. Herpes gestationis in an autoimmune vesicobullous dermatosis characterised by skin eruptions, intense itching and consequent increase in fetal morbility, with delayed intrauterine growth and prematurity. Owing to its particular severity (involvement of the entire body surface including the face), between the 30th and the 32(nd) weeks we had to address a severe clinical condition characterised by anaemia, marked hypoproteinaemia, hypoalbuminaemia, hupertension and hyperglycaemia which led us to resort to the maximum dose of oral corticotherapy in association with topical therapy using clobetasol propionate. In our opinion the results obtained were highly statisfactory with the result that at the end of the 37(th) week, in consideration of the patient's obstetric history, podalic presentation and parity, we performed a Caesarean delivering a newborn of 3000 g in excellent condition. The patient was discharged symptom-free on the 6(th) day and the newborn was in full healt.

  8. Interactions of form and orientation

    NASA Technical Reports Server (NTRS)

    Mittelstaedt, Horst

    1989-01-01

    It is well known that the orientation of an optical pattern relative to egocentric or extraneous references affects its figural quality, that is, alters its perceived form and concomitantly delays or quickens its identification (Rock 1973). A square presented in the frontal plane to an upright person (S), for instance, changes from a box to a diamond when it is rotated with respect to the S's median plane by 45 deg. This angle, that is, the angle between the orientations of the pattern in which the two apparent figures (Gestalten) attain a summit of purity and distinctness, will be called the figural disparity of the pattern. If, as in this case, the S is upright, the retinal meridian and the subjective vertical (SV) are both in the viewer's median plane. The question arises with respect to which of these orientation references the two figures are identified. The answer may be found when the pattern and the S are oriented in such a way that the projections of the retinal meridian and the SV into the plane of the pattern diverge by the pattern's figural disparity or its periodic multiples: that is, in this case of a square by 45 or 135 deg, respectively. Similarly, which reference determines whether an equilateral triangle is seen as a pyramid or a traffic warning sign may be revealed at a divergence of SV and retinal meridian of 60 or 180 deg, respectively. It is generally found that for head roll tilts (Rho) and figural disparities of up to 90 deg, the figure whose axis coincides with the SV is seen. At head tilts of Rho=180 deg, however, the retinal reference dominates, as a rule independently of the figural disparity.

  9. Uniform-droplet spray forming

    SciTech Connect

    Blue, C.A.; Sikka, V.K.; Chun, Jung-Hoon; Ando, T.

    1997-04-01

    The uniform-droplet process is a new method of liquid-metal atomization that results in single droplets that can be used to produce mono-size powders or sprayed-on to substrates to produce near-net shapes with tailored microstructure. The mono-sized powder-production capability of the uniform-droplet process also has the potential of permitting engineered powder blends to produce components of controlled porosity. Metal and alloy powders are commercially produced by at least three different methods: gas atomization, water atomization, and rotating disk. All three methods produce powders of a broad range in size with a very small yield of fine powders with single-sized droplets that can be used to produce mono-size powders or sprayed-on substrates to produce near-net shapes with tailored microstructures. The economical analysis has shown the process to have the potential of reducing capital cost by 50% and operating cost by 37.5% when applied to powder making. For the spray-forming process, a 25% savings is expected in both the capital and operating costs. The project is jointly carried out at Massachusetts Institute of Technology (MIT), Tuffs University, and Oak Ridge National Laboratory (ORNL). Preliminary interactions with both finished parts and powder producers have shown a strong interest in the uniform-droplet process. Systematic studies are being conducted to optimize the process parameters, understand the solidification of droplets and spray deposits, and develop a uniform-droplet-system (UDS) apparatus appropriate for processing engineering alloys.

  10. 8 CFR 103.32 - Information forms.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...; AVAILABILITY OF RECORDS § 103.32 Information forms. (a) Review of forms. The Service shall be responsible for the review of forms it uses to collect information from and about individuals. (b) Scope of review... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Information forms. 103.32 Section...

  11. Completing cremation forms: a practical guide.

    PubMed

    Proctor, Ian; Winstanley, Alison

    2013-07-01

    Before a body can be cremated doctors must complete a series of lengthy forms better known as 'crem forms'. One doctor first completes a medical certificate (Cremation Form 4, previously known as 'Part B') while a second must complete a confirmatory medical certificate (Cremation Form 5, previously 'Part C').

  12. 12 CFR 262.6 - Forms.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... PROCEDURE § 262.6 Forms. Necessary forms to be used in connection with applications and other matters are available at the Federal Reserve Banks. A list of all such forms, which is reviewed and revised periodically... 12 Banks and Banking 4 2013-01-01 2013-01-01 false Forms. 262.6 Section 262.6 Banks and...

  13. 46 CFR 535.503 - Information Form.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 9 2014-10-01 2014-10-01 false Information Form. 535.503 Section 535.503 Shipping... AND MARINE TERMINAL OPERATOR AGREEMENTS SUBJECT TO THE SHIPPING ACT OF 1984 Information Form Requirements § 535.503 Information Form. (a) The Information Form, with instructions, for agreements...

  14. 12 CFR 262.6 - Forms.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... § 262.6 Forms. Necessary forms to be used in connection with applications and other matters are available at the Federal Reserve Banks. A list of all such forms, which is reviewed and revised periodically... 12 Banks and Banking 3 2011-01-01 2011-01-01 false Forms. 262.6 Section 262.6 Banks and...

  15. 46 CFR 535.503 - Information Form.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 9 2011-10-01 2011-10-01 false Information Form. 535.503 Section 535.503 Shipping... AND MARINE TERMINAL OPERATOR AGREEMENTS SUBJECT TO THE SHIPPING ACT OF 1984 Information Form Requirements § 535.503 Information Form. (a) The Information Form, with instructions, for agreements...

  16. 7 CFR 51.1317 - Well formed.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Well formed. 51.1317 Section 51.1317 Agriculture... Standards for Winter Pears 1 Definitions § 51.1317 Well formed. Well formed means having the shape... general appearance of the fruit shall be considered well formed....

  17. 7 CFR 51.1354 - Well formed.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Well formed. 51.1354 Section 51.1354 Agriculture... Standards for Pears for Canning Definitions § 51.1354 Well formed. Well formed means that the pear has the... the pear shall be well formed. Bartlett pears shall have at least a fairly well developed neck....

  18. 7 CFR 51.1354 - Well formed.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Well formed. 51.1354 Section 51.1354 Agriculture... Standards for Pears for Canning Definitions § 51.1354 Well formed. Well formed means that the pear has the... the pear shall be well formed. Bartlett pears shall have at least a fairly well developed neck....

  19. 7 CFR 51.1317 - Well formed.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Well formed. 51.1317 Section 51.1317 Agriculture... Standards for Winter Pears 1 Definitions § 51.1317 Well formed. Well formed means having the shape... general appearance of the fruit shall be considered well formed....

  20. 7 CFR 51.1354 - Well formed.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Well formed. 51.1354 Section 51.1354 Agriculture... Standards for Pears for Canning Definitions § 51.1354 Well formed. Well formed means that the pear has the... the pear shall be well formed. Bartlett pears shall have at least a fairly well developed neck....

  1. 7 CFR 51.1317 - Well formed.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Well formed. 51.1317 Section 51.1317 Agriculture... Standards for Winter Pears 1 Definitions § 51.1317 Well formed. Well formed means having the shape... general appearance of the fruit shall be considered well formed....

  2. Extension of Chern-Simons forms

    SciTech Connect

    Konitopoulos, Spyros; Savvidy, George

    2014-06-15

    We investigate metric independent, gauge invariant, and closed forms in the generalized Yang-Mills (YM) theory. These forms are polynomial on the corresponding fields strength tensors – curvature forms and are analogous to the Pontryagin-Chern densities in the YM gauge theory. The corresponding secondary characteristic classes have been expressed in integral form in analogy with the Chern-Simons form. Because they are not unique, the secondary forms can be dramatically simplified by the addition of properly chosen differentials of one-step-lower-order forms. Their gauge variation can also be found yielding the potential anomalies in the gauge field theory.

  3. Pre-form ceramic matrix composite cavity and method of forming and method of forming a ceramic matrix composite component

    DOEpatents

    Monaghan, Philip Harold; Delvaux, John McConnell; Taxacher, Glenn Curtis

    2015-06-09

    A pre-form CMC cavity and method of forming pre-form CMC cavity for a ceramic matrix component includes providing a mandrel, applying a base ply to the mandrel, laying-up at least one CMC ply on the base ply, removing the mandrel, and densifying the base ply and the at least one CMC ply. The remaining densified base ply and at least one CMC ply form a ceramic matrix component having a desired geometry and a cavity formed therein. Also provided is a method of forming a CMC component.

  4. 78 FR 38341 - Federal Acquisition Regulation; Information Collection; Preaward Survey Forms (Standard Forms...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-26

    ... Regulation; Information Collection; Preaward Survey Forms (Standard Forms 1403, 1404, 1405, 1406, 1407, and... preaward survey forms (Standard Forms 1403, 1404, 1405, 1406, 1407, and 1408). DATES: Submit comments on or..., Preaward Survey Forms, (Standard Forms 1403, 1404, 1405, 1406, 1407, and 1408) by any of the...

  5. Green Supplier Network Manufacturer Commitment Form

    EPA Pesticide Factsheets

    Online form expressing interest in committing to be a Green Supplier; this form expresses your intent to participate in a confidential Green Suppliers Network assessment, implement recommended environmental improvements and complete a NIST MEP follow-up.

  6. 7 CFR 51.3747 - Well formed.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., CERTIFICATION, AND STANDARDS) United States Standards for Grades of Honey Dew and Honey Ball Type Melons Definitions § 51.3747 Well formed. Well formed means that the melon has the normal shape characteristic of...

  7. 7 CFR 51.3747 - Well formed.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., CERTIFICATION, AND STANDARDS) United States Standards for Grades of Honey Dew and Honey Ball Type Melons Definitions § 51.3747 Well formed. Well formed means that the melon has the normal shape characteristic of...

  8. Linearized gravity in terms of differential forms

    NASA Astrophysics Data System (ADS)

    Baykal, Ahmet; Dereli, Tekin

    2017-01-01

    A technique to linearize gravitational field equations is developed in which the perturbation metric coefficients are treated as second rank, symmetric, 1-form fields belonging to the Minkowski background spacetime by using the exterior algebra of differential forms.

  9. 48 CFR Appendix - List of IAAR Forms

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 1953.370-21The Broadcasting Board of Governors Form IA-21, Abstract of Quotations. 1953.370-44The Broadcasting Board of Governors Form IA-44, Requisition-Purchase—Order-Invoice for Professional Services....

  10. Pancreastatin molecular forms in normal human plasma.

    PubMed

    Kitayama, N; Tateishi, K; Funakoshi, A; Miyasaka, K; Shimazoe, T; Kono, A; Iwamoto, N; Matsuoka, Y

    1994-01-01

    Circulating molecular forms with pancreastatin (PST)-like immunoreactivity in plasma from normal subjects were examined. An immunoreactive form corresponding to a human PST-like sequence [human chromogranin-A-(250-301)] (hPST-52) and a larger form (mol wt 15-21 kDa) were detected by gel filtration of plasma from normal subjects. On high performance liquid chromatography, predominant immunoreactive forms coeluted with the three larger forms which were purified from the xenograft of human pancreatic islet cell carcinoma cell line QGP-1N cells and with synthetic hPST-52. The fraction containing larger forms purified from xenograft of QGP-1N cells had biological activity equivalent to that of hPST-52 on the inhibition of pancreatic exocrine secretion. These results suggest that the larger molecular forms as well as hPST-52 may be physiologically important circulating forms of PST in human.

  11. 32 CFR 94.5 - Forms required.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...). (c) G-325 Biographic Information (Submit original and duplicate of multileaf form). (d) G-325B Biographic Information (Submit original form only). (e) FD-258 Applicant Fingerprint Card (Submit...

  12. 32 CFR 94.5 - Forms required.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...). (c) G-325 Biographic Information (Submit original and duplicate of multileaf form). (d) G-325B Biographic Information (Submit original form only). (e) FD-258 Applicant Fingerprint Card (Submit...

  13. 7 CFR 51.2653 - Well formed.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., CERTIFICATION, AND STANDARDS) United States Standards for Grades for Sweet Cherries 1 Definitions § 51.2653 Well formed. Well formed means that the cherry has the normal shape characteristic of the variety, except...

  14. 7 CFR 51.2653 - Well formed.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Standards for Grades for Sweet Cherries 1 Definitions § 51.2653 Well formed. Well formed means that the cherry has the normal shape characteristic of the variety, except that mature well developed...

  15. Forming Refractory Insulation On Copper Wire

    NASA Technical Reports Server (NTRS)

    Setlock, J.; Roberts, G.

    1995-01-01

    Alternative insulating process forms flexible coat of uncured refractory insulating material on copper wire. Coated wire formed into coil or other complex shape. Wire-coating apparatus forms "green" coat on copper wire. After wire coiled, heating converts "green" coat to refractory electrical insulator. When cured to final brittle form, insulating material withstands temperatures above melting temperature of wire. Process used to make coils for motors, solenoids, and other electrical devices to be operated at high temperatures.

  16. 15 CFR 908.21 - Report form.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... SUBMITTING REPORTS ON WEATHER MODIFICATION ACTIVITIES § 908.21 Report form. Public Law 92-205 and these rules... 15 Commerce and Foreign Trade 3 2014-01-01 2014-01-01 false Report form. 908.21 Section 908.21... forms obtainable on request from the Administrator, or on an equivalent format. 1 In special...

  17. 7 CFR 3201.46 - Forming lubricants.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 15 2012-01-01 2012-01-01 false Forming lubricants. 3201.46 Section 3201.46... Designated Items § 3201.46 Forming lubricants. (a) Definition. Products designed to provide lubrication... preference for qualifying biobased forming lubricants. By that date, Federal agencies that have...

  18. 7 CFR 3201.46 - Forming lubricants.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 15 2013-01-01 2013-01-01 false Forming lubricants. 3201.46 Section 3201.46... Designated Items § 3201.46 Forming lubricants. (a) Definition. Products designed to provide lubrication... preference for qualifying biobased forming lubricants. By that date, Federal agencies that have...

  19. 7 CFR 3201.46 - Forming lubricants.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 15 2014-01-01 2014-01-01 false Forming lubricants. 3201.46 Section 3201.46... Designated Items § 3201.46 Forming lubricants. (a) Definition. Products designed to provide lubrication... preference for qualifying biobased forming lubricants. By that date, Federal agencies that have...

  20. 7 CFR 2902.46 - Forming lubricants.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 15 2011-01-01 2011-01-01 false Forming lubricants. 2902.46 Section 2902.46... Items § 2902.46 Forming lubricants. (a) Definition. Products designed to provide lubrication during... forming lubricants. By that date, Federal agencies that have the responsibility for drafting or...

  1. 30 CFR 256.49 - Lease form.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Lease form. 256.49 Section 256.49 Mineral... IN THE OUTER CONTINENTAL SHELF Issuance of Leases § 256.49 Lease form. Oil and gas leases and leases for sulphur shall be issued on forms approved by the Director. Other mineral leases shall be issued...

  2. Simultaneous Assembly of Multiple Test Forms.

    ERIC Educational Resources Information Center

    van der Linden, Wim J.; Adema, Jos J.

    1998-01-01

    Proposes an algorithm for the assembly of multiple test forms in which the multiple-form problem is reduced to a series of computationally less intensive two-form problems. Illustrates how the method can be implemented using 0-1 linear programming and gives two examples. (SLD)

  3. 47 CFR 3.20 - Application form.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... AUTHORITIES IN MARITIME AND MARITIME MOBILE-SATELLITE RADIO SERVICES Application Procedures § 3.20 Application form. Written application must be made to the Federal Communications Commission on FCC Form 44... 47 Telecommunication 1 2011-10-01 2011-10-01 false Application form. 3.20 Section...

  4. 47 CFR 3.20 - Application form.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... AUTHORITIES IN MARITIME AND MARITIME MOBILE-SATELLITE RADIO SERVICES Application Procedures § 3.20 Application form. Written application must be made to the Federal Communications Commission on FCC Form 44... 47 Telecommunication 1 2010-10-01 2010-10-01 false Application form. 3.20 Section...

  5. 48 CFR 413.307 - Forms.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Forms. 413.307 Section 413.307 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE CONTRACTING METHODS AND CONTRACT TYPES SIMPLIFIED ACQUISITION PROCEDURES Simplified Acquisition Methods 413.307 Forms. Form...

  6. Focus on Form: A Critical Review

    ERIC Educational Resources Information Center

    Ellis, Rod

    2016-01-01

    "Focus on form" (FonF) is a central construct in task-based language teaching. The term was first introduced by Michael Long to refer to an approach where learners' attention is attracted to linguistic forms as they engage in the performance of tasks. It contrasts with a structure-based approach--"focus on forms" (FonFs)--where…

  7. Utilize Vacuum Forming to Make Interdisciplinary Connections

    ERIC Educational Resources Information Center

    Love, Tyler S.; Valenza, Frank

    2011-01-01

    The concept of vacuum forming has been around since the 19th century, despite not being fully utilized in industry until the 1950s. In the past, industrial arts classes have used vacuum-forming projects to concentrate solely on the manufacturing process and the final product. However, vacuum forming is not just an old industrial arts activity; it…

  8. 46 CFR 252.11 - Application forms.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 8 2011-10-01 2011-10-01 false Application forms. 252.11 Section 252.11 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS AFFECTING SUBSIDIZED VESSELS AND... and Agreement § 252.11 Application forms. Application forms may be obtained from the...

  9. 48 CFR 913.307 - Forms.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Forms. 913.307 Section 913.307 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CONTRACTING METHODS AND CONTRACT TYPES SIMPLIFIED ACQUISITION PROCEDURES Simplified Acquisition Methods 913.307 Forms. (b) Optional Forms 347...

  10. 48 CFR 913.307 - Forms.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Forms. 913.307 Section 913.307 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CONTRACTING METHODS AND CONTRACT TYPES SIMPLIFIED ACQUISITION PROCEDURES Simplified Acquisition Methods 913.307 Forms. (b) Optional Forms 347...

  11. 48 CFR 913.307 - Forms.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Forms. 913.307 Section 913.307 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CONTRACTING METHODS AND CONTRACT TYPES SIMPLIFIED ACQUISITION PROCEDURES Simplified Acquisition Methods 913.307 Forms. (b) Optional Forms 347...

  12. 48 CFR 913.307 - Forms.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Forms. 913.307 Section 913.307 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CONTRACTING METHODS AND CONTRACT TYPES SIMPLIFIED ACQUISITION PROCEDURES Simplified Acquisition Methods 913.307 Forms. (b) Optional Forms 347...

  13. 48 CFR 913.307 - Forms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Forms. 913.307 Section 913.307 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CONTRACTING METHODS AND CONTRACT TYPES SIMPLIFIED ACQUISITION PROCEDURES Simplified Acquisition Methods 913.307 Forms. (b) Optional Forms 347...

  14. 7 CFR 51.1157 - Well formed.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Well formed. 51.1157 Section 51.1157 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Grades of Florida Oranges and Tangelos Definitions § 51.1157 Well formed. Well formed...

  15. 7 CFR 51.1825 - Well formed.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false Well formed. 51.1825 Section 51.1825 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Well formed. Well formed means that the fruit has the characteristic tangerine shape and is...

  16. 7 CFR 51.697 - Well formed.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Well formed. 51.697 Section 51.697 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing..., California, and Arizona) Definitions § 51.697 Well formed. Well formed means that the fruit has the...

  17. 7 CFR 51.1999 - Well formed.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false Well formed. 51.1999 Section 51.1999 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing....1999 Well formed. Well formed means that the filbert shell is not materially misshapen....

  18. 7 CFR 51.3060 - Well formed.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Well formed. 51.3060 Section 51.3060 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Florida Avocados Definitions § 51.3060 Well formed. Well formed means that the avocado has...

  19. 7 CFR 51.1825 - Well formed.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Well formed. 51.1825 Section 51.1825 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Grades of Florida Tangerines Definitions § 51.1825 Well formed. Well formed means that...

  20. 7 CFR 51.3060 - Well formed.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Well formed. 51.3060 Section 51.3060 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Florida Avocados Definitions § 51.3060 Well formed. Well formed means that the avocado has...

  1. 7 CFR 51.1825 - Well formed.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Well formed. 51.1825 Section 51.1825 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Grades of Florida Tangerines Definitions § 51.1825 Well formed. Well formed means that...

  2. 7 CFR 51.1157 - Well formed.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Well formed. 51.1157 Section 51.1157 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Grades of Florida Oranges and Tangelos Definitions § 51.1157 Well formed. Well formed...

  3. 7 CFR 51.1157 - Well formed.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Well formed. 51.1157 Section 51.1157 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Grades of Florida Oranges and Tangelos Definitions § 51.1157 Well formed. Well formed...

  4. 7 CFR 51.635 - Well formed.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Well formed. 51.635 Section 51.635 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Florida, California, and Arizona) Definitions § 51.635 Well formed. Well formed means that the fruit...

  5. 7 CFR 51.697 - Well formed.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Well formed. 51.697 Section 51.697 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... § 51.697 Well formed. Well formed means that the fruit has the shape characteristic of the variety....

  6. 7 CFR 51.635 - Well formed.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false Well formed. 51.635 Section 51.635 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Florida, California, and Arizona) Definitions § 51.635 Well formed. Well formed means that the fruit...

  7. 7 CFR 51.3060 - Well formed.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Well formed. 51.3060 Section 51.3060 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Florida Avocados Definitions § 51.3060 Well formed. Well formed means that the avocado has...

  8. 7 CFR 51.697 - Well formed.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Well formed. 51.697 Section 51.697 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... § 51.697 Well formed. Well formed means that the fruit has the shape characteristic of the variety....

  9. 7 CFR 51.697 - Well formed.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false Well formed. 51.697 Section 51.697 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing..., California, and Arizona) Definitions § 51.697 Well formed. Well formed means that the fruit has the...

  10. 7 CFR 51.488 - Well formed.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Well formed. 51.488 Section 51.488 Agriculture..., CERTIFICATION, AND STANDARDS) United States Standards for Grades of Cantaloups 1 Definitions § 51.488 Well formed. Well formed means that the cantaloup has the normal shape characteristic of the variety....

  11. 7 CFR 51.766 - Well formed.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Well formed. 51.766 Section 51.766 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Grades of Florida Grapefruit Definitions § 51.766 Well formed. Well formed means that...

  12. 7 CFR 51.2653 - Well formed.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Well formed. 51.2653 Section 51.2653 Agriculture... Standards for Grades for Sweet Cherries 1 Definitions § 51.2653 Well formed. Well formed means that the cherry has the normal shape characteristic of the variety, except that mature well developed...

  13. 7 CFR 51.1825 - Well formed.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Well formed. 51.1825 Section 51.1825 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Well formed. Well formed means that the fruit has the characteristic tangerine shape and is...

  14. 7 CFR 51.1157 - Well formed.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false Well formed. 51.1157 Section 51.1157 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... § 51.1157 Well formed. Well formed means that the fruit has the shape characteristic of the variety....

  15. 7 CFR 51.1999 - Well formed.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Well formed. 51.1999 Section 51.1999 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Grades of Filberts in the Shell 1 Definitions § 51.1999 Well formed. Well formed means...

  16. 7 CFR 51.488 - Well formed.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Well formed. 51.488 Section 51.488 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Grades of Cantaloups 1 Definitions § 51.488 Well formed. Well formed means that the...

  17. 7 CFR 51.635 - Well formed.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Well formed. 51.635 Section 51.635 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing...) Definitions § 51.635 Well formed. Well formed means that the fruit has the shape characteristic of the variety....

  18. 7 CFR 51.1528 - Well formed.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Well formed. 51.1528 Section 51.1528 Agriculture... Standards for Grades of Fresh Plums and Prunes Definitions § 51.1528 Well formed. “Well formed” means that the fruit has the shape characteristic of the variety. Doubles shall not be considered well formed....

  19. 7 CFR 51.2653 - Well formed.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Well formed. 51.2653 Section 51.2653 Agriculture... Standards for Grades for Sweet Cherries 1 Definitions § 51.2653 Well formed. Well formed means that the cherry has the normal shape characteristic of the variety, except that mature well developed...

  20. 7 CFR 51.1528 - Well formed.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Well formed. 51.1528 Section 51.1528 Agriculture... Standards for Grades of Fresh Plums and Prunes Definitions § 51.1528 Well formed. “Well formed” means that the fruit has the shape characteristic of the variety. Doubles shall not be considered well formed....

  1. 7 CFR 51.488 - Well formed.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false Well formed. 51.488 Section 51.488 Agriculture..., CERTIFICATION, AND STANDARDS) United States Standards for Grades of Cantaloups 1 Definitions § 51.488 Well formed. Well formed means that the cantaloup has the normal shape characteristic of the variety....

  2. 7 CFR 51.697 - Well formed.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Well formed. 51.697 Section 51.697 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... § 51.697 Well formed. Well formed means that the fruit has the shape characteristic of the variety....

  3. 7 CFR 51.2653 - Well formed.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Well formed. 51.2653 Section 51.2653 Agriculture..., CERTIFICATION, AND STANDARDS) United States Standards for Grades for Sweet Cherries 1 Definitions § 51.2653 Well formed. Well formed means that the cherry has the normal shape characteristic of the variety, except...

  4. 7 CFR 51.635 - Well formed.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Well formed. 51.635 Section 51.635 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing...) Definitions § 51.635 Well formed. Well formed means that the fruit has the shape characteristic of the variety....

  5. 7 CFR 51.766 - Well formed.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Well formed. 51.766 Section 51.766 Agriculture..., CERTIFICATION, AND STANDARDS) United States Standards for Grades of Florida Grapefruit Definitions § 51.766 Well formed. Well formed means that the fruit has the shape characteristic of the variety....

  6. 7 CFR 51.1999 - Well formed.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Well formed. 51.1999 Section 51.1999 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Grades of Filberts in the Shell 1 Definitions § 51.1999 Well formed. Well formed means...

  7. 7 CFR 51.1157 - Well formed.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Well formed. 51.1157 Section 51.1157 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... § 51.1157 Well formed. Well formed means that the fruit has the shape characteristic of the variety....

  8. 7 CFR 51.569 - Well formed.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Well formed. 51.569 Section 51.569 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Celery Definitions § 51.569 Well formed. Well formed means that the branches are...

  9. 7 CFR 51.1825 - Well formed.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Well formed. 51.1825 Section 51.1825 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Grades of Florida Tangerines Definitions § 51.1825 Well formed. Well formed means that...

  10. 7 CFR 51.766 - Well formed.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Well formed. 51.766 Section 51.766 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Grades of Florida Grapefruit Definitions § 51.766 Well formed. Well formed means that...

  11. 7 CFR 51.1999 - Well formed.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Well formed. 51.1999 Section 51.1999 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing....1999 Well formed. Well formed means that the filbert shell is not materially misshapen....

  12. 7 CFR 51.3060 - Well formed.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Well formed. 51.3060 Section 51.3060 Agriculture..., CERTIFICATION, AND STANDARDS) United States Standards for Florida Avocados Definitions § 51.3060 Well formed. Well formed means that the avocado has the normal shape characteristic of the variety....

  13. 7 CFR 51.3060 - Well formed.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false Well formed. 51.3060 Section 51.3060 Agriculture..., CERTIFICATION, AND STANDARDS) United States Standards for Florida Avocados Definitions § 51.3060 Well formed. Well formed means that the avocado has the normal shape characteristic of the variety....

  14. 7 CFR 51.569 - Well formed.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Well formed. 51.569 Section 51.569 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Celery Definitions § 51.569 Well formed. Well formed means that the branches are...

  15. 7 CFR 51.1354 - Well formed.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Well formed. 51.1354 Section 51.1354 Agriculture..., CERTIFICATION, AND STANDARDS) United States Standards for Pears for Canning Definitions § 51.1354 Well formed. Well formed means that the pear has the shape characteristic of the variety, so that after...

  16. 7 CFR 51.1528 - Well formed.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Well formed. 51.1528 Section 51.1528 Agriculture... Standards for Grades of Fresh Plums and Prunes Definitions § 51.1528 Well formed. “Well formed” means that the fruit has the shape characteristic of the variety. Doubles shall not be considered well formed....

  17. 7 CFR 51.766 - Well formed.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false Well formed. 51.766 Section 51.766 Agriculture..., CERTIFICATION, AND STANDARDS) United States Standards for Grades of Florida Grapefruit Definitions § 51.766 Well formed. Well formed means that the fruit has the shape characteristic of the variety....

  18. 7 CFR 51.488 - Well formed.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Well formed. 51.488 Section 51.488 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Grades of Cantaloups 1 Definitions § 51.488 Well formed. Well formed means that the...

  19. 7 CFR 51.635 - Well formed.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Well formed. 51.635 Section 51.635 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing...) Definitions § 51.635 Well formed. Well formed means that the fruit has the shape characteristic of the variety....

  20. 7 CFR 51.1354 - Well formed.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false Well formed. 51.1354 Section 51.1354 Agriculture..., CERTIFICATION, AND STANDARDS) United States Standards for Pears for Canning Definitions § 51.1354 Well formed. Well formed means that the pear has the shape characteristic of the variety, so that after...

  1. 7 CFR 51.1528 - Well formed.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Well formed. 51.1528 Section 51.1528 Agriculture... Well formed. “Well formed” means that the fruit has the shape characteristic of the variety. Doubles shall not be considered well formed....

  2. 7 CFR 51.1999 - Well formed.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Well formed. 51.1999 Section 51.1999 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Grades of Filberts in the Shell 1 Definitions § 51.1999 Well formed. Well formed means...

  3. 7 CFR 51.1528 - Well formed.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false Well formed. 51.1528 Section 51.1528 Agriculture... Well formed. “Well formed” means that the fruit has the shape characteristic of the variety. Doubles shall not be considered well formed....

  4. Method of forming composite fiber blends

    NASA Technical Reports Server (NTRS)

    McMahon, Paul E. (Inventor); Chung, Tai-Shung (Inventor); Ying, Lincoln (Inventor)

    1989-01-01

    The instant invention involves a process used in preparing fibrous tows which may be formed into polymeric plastic composites. The process involves the steps of (a) forming a tow of strong filamentary materials; (b) forming a thermoplastic polymeric fiber; (c) intermixing the two tows; and (d) withdrawing the intermixed tow for further use.

  5. 12 CFR 905.25 - Forms.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION AND OPERATIONS DESCRIPTION OF ORGANIZATION AND FUNCTIONS Miscellaneous § 905.25 Forms. The following forms are available at the Finance Board...—Appointive Director Candidates—Personal Certification and Disclosure Form. E-1—Elective Director...

  6. FormEd: An X Window System application for managing first-order formulas

    SciTech Connect

    Henry, T.L.; McCune, W.W.

    1990-11-01

    FormEd is a window-based program for constructing, displaying, and managing first-order logic formulas. The main motivation for constructing FormEd was the desire to have formulas displayed in a readable, two-dimensional format. Users of FormEd can make two kinds of transformation on formulas: logic transformations, such as negation normal form translation, which preserve the meaning of a formula, and edit transformations, which can be used to make arbitrary changes, such as adding a hypothesis to a subformula. FormEd was written by using the X Window System, Version 11, and code from the theorem prover OTTER. 4 refs.

  7. 75 FR 5867 - Proposed Collection; Comment Request for Form 8879-C and Form 8879-I

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-04

    ... Internal Revenue Service Proposed Collection; Comment Request for Form 8879-C and Form 8879-I AGENCY... U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 8879-C, IRS e-file... Number: 8879-C; 8879-I. Abstract: The Form 8879-C, IRS e-file Signature Authorization for Form 1120,...

  8. 78 FR 23979 - Proposed Collection; Comment Request for Form 8610 and Schedule A (Form 8610)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-23

    ..., Annual Low-Income Housing Credit Agencies Report, and Schedule A (Form 8610), Carryover Allocation of Low...: Form 8610, Annual Low-Income Housing Credit Agencies Report, and Schedule A (Form 8610), Carryover Allocation of Low-Income Housing Credit. OMB Number: 1545-0990. Form Number: Form 8610 and Schedule A...

  9. Experimental investigation of braided fabric forming

    NASA Astrophysics Data System (ADS)

    Wang, Peng; Soulat, Damien; Legrand, Xavier; Zemni, Lilia; Jacquot, Pierre-Baptiste

    2016-10-01

    Woven and braided textile structures are largely used as the composite reinforcements. Forming of the continuous fibre reinforcements and thermoplastic resin commingled yarns can be performed at room temperature. The "cool" forming stage is well-controlled and more economical compared to thermoforming. Many studies have been addressed for carbon and glass fibres / thermoplastic commingled yarns reinforced composite forming for woven structure. On the contrary, few research works has deal with the natural fibre reinforced textile forming and none concerns the braided fabrics forming. In this present work, the Flax/Polyamide 12 commingled yarns are used to produce braided fabric and then to analyze their deformability behaviour.

  10. New Forming Technologies for Autobody at POSCO

    NASA Astrophysics Data System (ADS)

    Lee, Hong-Woo; Cha, Myung-Hwan; Choi, Byung-Keun; Kim, Gyo-Sung; Park, Sung-Ho

    2011-08-01

    As development of car body with light weight and enhanced safety became one of the hottest issues in the auto industry, the advanced high strength steels have been broadly applied to various automotive parts over the last few years. Corresponding to this trend, POSCO has developed various types of cold and hot rolled AHSSs such as DP, TRIP, CP and FB, and continues to develop new types of steel in order to satisfy the requirement of OEMs more extensively. To provide optimal technical supports to customers, POSCO has developed more advanced EVI concept, which includes the concept of CE/SE, VA/VE, VI and PP as well as the conventional EVI strategy. To realize this concept, POSCO not only supports customers with material data, process guideline, and evaluation of formability, weld-ability, paint-ability and performance but also provides parts or sub-assemblies which demand highly advanced technologies. Especially, to accelerate adoption of AHSS in autobody, POSCO has tried to come up with optimal solutions to AHSS forming. Application of conventional forming technologies has been restricted more and more by relatively low formability of AHSS with high tensile-strength. To overcome the limitation in the forming, POSCO has recently developed new forming technologies such as hydro-forming, hot press forming, roll forming and form forming. In this paper, tailored strength HPF, hydroformed torsion beam axle and multi-directional roll forming are introduced as examples of new forming technologies.

  11. Performance Test on Polymer Waste Form - 12137

    SciTech Connect

    Lee, Se Yup

    2012-07-01

    Polymer solidification was attempted to produce stable waste form for the boric acid concentrates and the dewatered spent resins. The polymer mixture was directly injected into the mold or drum which was packed with the boric acid concentrates and the dewatered spent resins, respectively. The waste form was produced by entirely curing the polymer mixture. A series of performance tests was conducted including compressive strength test, water immersion test, leach test, thermal stability test, irradiation stability test and biodegradation stability test for the polymer waste forms. From the results of the performance tests for the polymer waste forms, it is believed that the polymer waste form is very stable and can satisfy the acceptance criteria for permanent disposal. At present, performance tests with full scale polymer waste forms are being carried out in order to obtain qualification certificate by the regulatory institute in Korea. Polymer waste forms were prepared with the surrogate of boric acid concentrates and the surrogate of spent ion exchange resins respectively. Waste forms were also made in lab scale and in full scale. Lab. scale waste forms were directly subjected to a series of the performance tests. In the case of full scale waste form, the test specimens for the performance test were taken from a part of waste form by coring. A series of performance tests was conducted including compressive strength test, thermal stability test, irradiation stability test and biodegradation stability test, water immersion test, leach test, and free standing water for the polymer waste forms. In addition, a fire resistance test was performed on the waste forms by the requirement of the regulatory institute in Korea. Every polymer waste forms containing the boric acid concentrates and the spent ion exchange resins had exhibited excellent structural integrity of more than 27.58 MPa (4,000 psi) of compressive strength. On thermal stability testing, biodegradation

  12. 2 CFR Appendix X to Part 200 - Data Collection Form (Form SF-SAC)

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... PRINCIPLES, AND AUDIT REQUIREMENTS FOR FEDERAL AWARDS Pt. 200, App. X Appendix X to Part 200—Data Collection Form (Form SF-SAC) The Data Collection Form SF-SAC is available on the FAC Web site....

  13. Geometrical and FEA study on Millipede Forming

    NASA Astrophysics Data System (ADS)

    Kong, Lingran; Tang, Di; Ding, Shichao; Zhang, Yuankun

    2013-12-01

    Millipede Forming is an innovative sheet metal forming approach that has been proposed and developed in Australia. U-channels, Z-channels or tubular products can be made by Millipede Forming. While a strip moves through an optimal transitional surface between the entry to exit of a forming stand, the redundant longitudinal membrane strain can be significantly reduced compared to the conventional roll forming, which is the essential principle to obtaining high quality products. The incremental forming process studied has demonstrated major advantages on space efficiency, power consumption and materials sensitivities. The purpose of this study is to investigate the effects of main geometrical parameters and their optimization, in order to minimize the redundant longitudinal strains into elastic to avoid the redundant plastic deformations at flange during forming. In this study, a mild-steel U-channel sample with 10 mm flange width, fabricated by Millipede Forming in a forming length of 200 mm has been studied. Theoretical longitudinal membrane strains at profile's edge of different transitional surfaces and downhill pass are also analyzed. The results showed that obtaining an optimal transitional surface is essential and necessary in controlling the peak longitudinal strain to an acceptable amount and that by increasing downhill pass, longitudinal strain can be significantly reduced. The optimized transitional surface and downhill pass flow were simulated by Abaqus, and the peak longitudinal strain was finally less than 0.2% through a very short forming length of 200 mm. The results prove that Millipede Forming can achieve a better product quality in a much shorter forming distance than conventional roll forming.

  14. A generalized definition for waste form durability.

    SciTech Connect

    Fanning, T. H.; Bauer, T. H.; Morris, E. E.; Wigeland, R. A.

    2002-06-26

    When evaluating waste form performance, the term ''durability'' often appears in casual discourse, but in the technical literature, the focus is often on waste form ''degradation'' in terms of mass lost per unit area per unit time. Waste form degradation plays a key role in developing models of the long-term performance in a repository environment, but other factors also influence waste form performance. These include waste form geometry; density, porosity, and cracking; the presence of cladding; in-package chemistry feedback; etc. The paper proposes a formal definition of waste form ''durability'' which accounts for these effects. Examples from simple systems as well as from complex models used in the Total System Performance Assessment of Yucca Mountain are provided. The application of ''durability'' in the selection of bounding models is also discussed.

  15. Adult-onset cerebello-brainstem dominant form of X-linked adrenoleukodystrophy presenting as multiple system atrophy: Case report and literature review

    PubMed Central

    Ogaki, Kotaro; Koga, Shunsuke; Aoki, Naoya; Lin, Wenlang; Suzuki, Kinuko; Ross, Owen A.; Dickson, Dennis W.

    2015-01-01

    X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder and is caused by ABCD1 mutations. A cerebello-brainstem dominant form that mainly involves the cerebellum and brainstem is summarized in a review of the literature, with autopsy confirmed cases exceedingly rare. We report a 69-year-old white man who was diagnosed with this rare disorder and describe neuropathologic, ultrastructural and genetic analyses. He did not have adrenal insufficiency or a family history of X-ALD or Addison’s disease. His initial symptom was temporary loss of eyesight at age 34 years. His major symptoms were chronic and progressive gait disorder, weakness in his lower extremities, and spasticity, as well as autonomic failure and cerebellar ataxia suggesting possible multiple system atrophy (MSA). He also had seizures, hearing loss, and sensory disturbances. His brain MRI showed no obvious atrophy or significant white matter pathology in cerebrum, brainstem or cerebellum. He died at age 69 years with a diagnosis of multiple system atrophy. Microscopic analysis showed mild, patchy myelin rarefaction with perivascular clusters of PAS-positive, CD68-positive macrophages in the white matter most prominent in the cerebellum and occipital lobe, but also affecting optic tract and internal capsule. Electron microscopy of cerebellar white matter showed cleft-like trilamellar cytoplasmic inclusions in macrophages typical of X-ALD, which prompted genetic analysis that revealed a novel ABCD1 mutation, p.R163G. Given the relatively mild pathological findings and long disease duration, it is likely that the observed pathology was the result of a slow and indolent disease process. We described a patient who had sporadic cerebello-brainstem dominant form of X-ALD with long clinical course, mild pathological findings, and an ABCD1 p.R163G substitution. We also review a total of 34 cases of adult-onset cerebello-brainstem dominant form of X-ALD. Although rare, X-ALD should be

  16. Social control of form diversity and the emergence of new forms in children's blockbuilding1

    PubMed Central

    Goetz, Elizabeth M.; Baer, Donald M.

    1973-01-01

    The blockbuilding behavior of three preschool girls was analyzed in terms of the forms manifest in any completed block construction, and found to contain few different forms in baseline sessions. Social reinforcement, given contingent on the production of any form not previously constructed within the current session (i.e., every first appearance of any form within a session was reinforced but no subsequent appearances of that form within that session were), increased the number of different forms built per sessions. Social reinforcement, given for all second and later appearances within the session, decreased the number of different forms built per session. Furthermore, it was found that new forms (forms never seen before in the child's total prior sequence of blockbuilding sessions) emerged at higher rates during periods of reinforcement of different forms (first appearances) than during periods of baseline or reinforcement of same forms (second and later appearances). PMID:16795402

  17. Ladder Forms in Estimation and System Identification.

    DTIC Science & Technology

    1977-01-01

    system identification . Many record applications, such as in geophysical signal processing, high resolution (’maximum entropy’) spectral estimation and speech encoding, justify the interest in these forms. They appear in many contexts, such as scattering and network theory and the theory of orthogonal polynomials. The state-space model ladder realizations are very closely related in (block) Schwarz matrix canonical forms, which generally appear in the context of stability analysis. In fact they are the natural ’stability canonical form’ for

  18. Mechanisms in Thermal Mechanical Forming of Plates.

    DTIC Science & Technology

    1987-05-01

    specific locations within the plate is discussed, and recommendations for further research are made. Keywords: Metal plates; Ship plates; Material forming; Thermomechanics; Edge effect ; Laser line heating.

  19. Review on cold-formed steel connections.

    PubMed

    Lee, Yeong Huei; Tan, Cher Siang; Mohammad, Shahrin; Tahir, Mahmood Md; Shek, Poi Ngian

    2014-01-01

    The concept of cold-formed light steel framing construction has been widespread after understanding its structural characteristics with massive research works over the years. Connection serves as one of the important elements for light steel framing in order to achieve its structural stability. Compared to hot-rolled steel sections, cold-formed steel connections perform dissimilarity due to the thin-walled behaviour. This paper aims to review current researches on cold-formed steel connections, particularly for screw connections, storage rack connections, welded connections, and bolted connections. The performance of these connections in the design of cold-formed steel structures is discussed.

  20. 24 CFR 200.80 - Mortgage form.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... DEVELOPMENT GENERAL INTRODUCTION TO FHA PROGRAMS Requirements for Application, Commitment, and Endorsement... Eligibility Requirements for Existing Projects Mortgage Provisions § 200.80 Mortgage form. The mortgage...

  1. 24 CFR 200.80 - Mortgage form.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... DEVELOPMENT GENERAL INTRODUCTION TO FHA PROGRAMS Requirements for Application, Commitment, and Endorsement... Eligibility Requirements for Existing Projects Mortgage Provisions § 200.80 Mortgage form. The mortgage...

  2. The canonical forms of a lattice rule

    SciTech Connect

    Lyness, J.N.

    1992-12-31

    Much of the elementary theory of lattice rules may, be presented as an elegant application of classical results. These include Kronecker group representation theorem and the Hermite and Smith normal forms of integer matrices. The theory of the canonical form is a case in point. In this paper, some of this theory is treated in a constructive rather than abstract manner. A step-by-step approach that parallels the group theory is described, leading to an algorithm to obtain a canonical form of a rule of prime power order. The number of possible distinct canonical forms is derived, and this is used to determine the number of integration lattices having specified invariants.

  3. The canonical forms of a lattice rule

    SciTech Connect

    Lyness, J.N.

    1992-01-01

    Much of the elementary theory of lattice rules may, be presented as an elegant application of classical results. These include Kronecker group representation theorem and the Hermite and Smith normal forms of integer matrices. The theory of the canonical form is a case in point. In this paper, some of this theory is treated in a constructive rather than abstract manner. A step-by-step approach that parallels the group theory is described, leading to an algorithm to obtain a canonical form of a rule of prime power order. The number of possible distinct canonical forms is derived, and this is used to determine the number of integration lattices having specified invariants.

  4. Review on Cold-Formed Steel Connections

    PubMed Central

    Tan, Cher Siang; Mohammad, Shahrin; Md Tahir, Mahmood; Shek, Poi Ngian

    2014-01-01

    The concept of cold-formed light steel framing construction has been widespread after understanding its structural characteristics with massive research works over the years. Connection serves as one of the important elements for light steel framing in order to achieve its structural stability. Compared to hot-rolled steel sections, cold-formed steel connections perform dissimilarity due to the thin-walled behaviour. This paper aims to review current researches on cold-formed steel connections, particularly for screw connections, storage rack connections, welded connections, and bolted connections. The performance of these connections in the design of cold-formed steel structures is discussed. PMID:24688448

  5. Method for hot press forming articles

    DOEpatents

    Baker, Robert R.; Hartsock, Dale L.

    1982-01-01

    This disclosure relates to an improved method for achieving the best bond strength and for minimizing distortion and cracking of hot pressed articles. In particular, in a method for hot press forming both an outer facing circumferential surface of and an inner portion of a hub, and of bonding that so-formed outer facing circumferential surface to an inner facing circumferential surface of a pre-formed ring thereby to form an article, the following improvement is made. Normally, in this method, the outside ring is restrained by a restraining sleeve of ring-shaped cross-section having an inside diameter. A die member, used to hot press form the hub, is so-formed as to have an outside diameter sized to engage the inside diameter of the restraining sleeve in a manner permitting relative movement therebetween. The improved method is one in which several pairs of matched restraining sleeve and die member are formed with each matched pair having a predetermined diameter. The predetermined diameter of each matched pair is different from another matched pair by stepped increments. The largest inside diameter of a restraining sleeve is equal to the diameter of the outer facing circumferential surface of the hub. Each pair of the matched restraining sleeve and die member is used to form an article in which an inside hub is bonded to an outside ring. The several samples so-formed are evaluated to determine which sample has the best bond formed between the hub and the ring with the least or no cracking or distortion in the ring portion of the article. Thereafter, the matched restraining sleeve and die member which form the article having the best bonding characteristics and least distortion cracking is then used for repeated formations of articles.

  6. 76 FR 36582 - Submission for Review: Standard Form 2809, Health Benefits Election Form

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-22

    ... MANAGEMENT Submission for Review: Standard Form 2809, Health Benefits Election Form AGENCY: U.S. Office of... to comment on a revised information collection request (ICR) 3206-0160, Health Benefits Election Form... collection techniques or other forms of information technology, e.g., permitting electronic submissions...

  7. 38 CFR Appendix A to Part 41 - Data Collection Form (Form SF-SAC)

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (Form SF-SAC) A Appendix A to Part 41 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) AUDITS OF STATES, LOCAL GOVERNMENTS, AND NON-PROFIT ORGANIZATIONS Pt. 41, App. A, Nt. Appendix A to Part 41—Data Collection Form (Form SF-SAC) Note: Data Collection Form SF-SAC and...

  8. 75 FR 4564 - Federal Acquisition Regulation; Information Collection; Preaward Survey Forms (Standard Forms...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-28

    ... Regulation; Information Collection; Preaward Survey Forms (Standard Forms 1403, 1404, 1405, 1406, 1407, and... requirement concerning preaward survey forms (Standard Forms 1403, 1404, 1405, 1406, 1407, and 1408.) Public... eligible to receive an award under appropriate laws and regulations. If such information is not in...

  9. 76 FR 36620 - Proposed Collection; Comment Request for Form 8453-F and Form 8879-F

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-22

    ... Internal Revenue Service Proposed Collection; Comment Request for Form 8453-F and Form 8879-F AGENCY... U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning Form 8453-F, U.S. Estate of Trust Income Tax Declaration and Signature for Electronic and Magnetic Made Filing and Form...

  10. RASD's New Interlibrary Reference Request Form.

    ERIC Educational Resources Information Center

    American Libraries, 1985

    1985-01-01

    Introduces information request form developed by Cooperative Reference Services Committee of American Library Association's Reference and Adult Services Division to be used whenever a library cannot supply information requested by a patron and would like to ask another library for assistance. Front of proposed form with sample question is shown.…

  11. 27 CFR 4.3 - Forms prescribed.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Forms prescribed. 4.3 Section 4.3 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE Scope § 4.3 Forms prescribed. (a)...

  12. Exploring Quality Assurance in Sixth Form Colleges

    ERIC Educational Resources Information Center

    Stoten, David William

    2012-01-01

    Purpose: This paper aims to focus on the changing nature of quality assurance systems within the sixth form college sector. Design/methodology/approach: Ten sixth form colleges were surveyed across England and staff from varying levels within college hierarchies questioned about how quality assurance systems were implemented. Research involved…

  13. 20 CFR 702.121 - Forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Forms. 702.121 Section 702.121 Employees' Benefits EMPLOYMENT STANDARDS ADMINISTRATION, DEPARTMENT OF LABOR LONGSHOREMEN'S AND HARBOR WORKERS' COMPENSATION ACT AND RELATED STATUTES ADMINISTRATION AND PROCEDURE General Provisions Forms § 702.121...

  14. 20 CFR 702.121 - Forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Forms. 702.121 Section 702.121 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR LONGSHOREMEN'S AND HARBOR WORKERS' COMPENSATION ACT AND RELATED STATUTES ADMINISTRATION AND PROCEDURE General Provisions Forms § 702.121...

  15. 20 CFR 702.121 - Forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 4 2012-04-01 2012-04-01 false Forms. 702.121 Section 702.121 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR LONGSHOREMEN'S AND HARBOR WORKERS' COMPENSATION ACT AND RELATED STATUTES ADMINISTRATION AND PROCEDURE General Provisions Forms § 702.121...

  16. 20 CFR 702.121 - Forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 4 2013-04-01 2013-04-01 false Forms. 702.121 Section 702.121 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR LONGSHOREMEN'S AND HARBOR WORKERS' COMPENSATION ACT AND RELATED STATUTES ADMINISTRATION AND PROCEDURE General Provisions Forms § 702.121...

  17. 20 CFR 702.121 - Forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 4 2014-04-01 2014-04-01 false Forms. 702.121 Section 702.121 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR LONGSHOREMEN'S AND HARBOR WORKERS' COMPENSATION ACT AND RELATED STATUTES ADMINISTRATION AND PROCEDURE General Provisions Forms § 702.121...

  18. 25 CFR 227.30 - Forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Forms. 227.30 Section 227.30 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF CERTAIN LANDS IN WIND RIVER INDIAN RESERVATION, WYOMING, FOR OIL AND GAS MINING Operations § 227.30 Forms. The provisions of § 211.30 of...

  19. 25 CFR 227.30 - Forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Forms. 227.30 Section 227.30 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF CERTAIN LANDS IN WIND RIVER INDIAN RESERVATION, WYOMING, FOR OIL AND GAS MINING Operations § 227.30 Forms. The provisions of § 211.30 of...

  20. 25 CFR 227.30 - Forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Forms. 227.30 Section 227.30 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF CERTAIN LANDS IN WIND RIVER INDIAN RESERVATION, WYOMING, FOR OIL AND GAS MINING Operations § 227.30 Forms. The provisions of § 211.30 of...