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Sample records for a-type nuclear lamins

  1. Proteasome-mediated degradation of integral inner nuclear membrane protein emerin in fibroblasts lacking A-type lamins

    SciTech Connect

    Muchir, Antoine; Massart, Catherine; Engelen, Baziel G. van; Lammens, Martin; Bonne, Gisele; Worman, Howard J. . E-mail: hjw14@columbia.edu

    2006-12-29

    We previously identified and characterized a homozygous LMNA nonsense mutation leading to the absence of A-type lamins in a premature neonate who died at birth. We show here that the absence of A-type lamins is due to degradation of the aberrant mRNA transcript with a premature termination codon. In cultured fibroblasts from the subject with the homozygous LMNA nonsense mutation, there was a decreased steady-state expression of the integral inner nuclear membrane proteins emerin and nesprin-1{alpha} associated with their mislocalization to the bulk endoplasmic reticulum and a hyperphosphorylation of emerin. To determine if decreased emerin expression occurred post-translationally, we treated cells with a selective proteasome inhibitor and observed an increase in expression. Our results show that mislocalization of integral inner nuclear membrane proteins to the endoplasmic reticulum in human cells lacking A-type lamins leads to their degradation and provides the first evidence that their degradation is mediated by the proteasome.

  2. A-type and B-type lamins initiate layer assembly at distinct areas of the nuclear envelope in living cells

    SciTech Connect

    Furukawa, Kazuhiro; Ishida, Kazuya; Tsunoyama, Taka-aki; Toda, Suguru; Osoda, Shinichi; Horigome, Tsuneyoshi; Fisher, Paul A.; Sugiyama, Shin

    2009-04-15

    To investigate nuclear lamina re-assembly in vivo, Drosophila A-type and B-type lamins were artificially expressed in Drosophila lamin Dm{sub 0}null mutant brain cells. Both exogenous lamin C (A-type) and Dm{sub 0} (B-type) formed sub-layers at the nuclear periphery, and efficiently reverted the abnormal clustering of the NPC. Lamin C initially appeared where NPCs were clustered, and subsequently extended along the nuclear periphery accompanied by the recovery of the regular distribution of NPCs. In contrast, lamin Dm{sub 0} did not show association with the clustered NPCs during lamina formation and NPC spacing recovered only after completion of a closed lamin Dm{sub 0} layer. Further, when lamin Dm{sub 0} and C were both expressed, they did not co-polymerize, initiating layer formation in separate regions. Thus, A and B-type lamins reveal differing properties during lamina assembly, with A-type having the primary role in organizing NPC distribution. This previously unknown complexity in the assembly of the nuclear lamina could be the basis for intricate nuclear envelope functions.

  3. Directed targeting of chromatin to the nuclear lamina is mediated by chromatin state and A-type lamins

    PubMed Central

    Harr, Jennifer C.; Luperchio, Teresa Romeo; Wong, Xianrong; Cohen, Erez; Wheelan, Sarah J.

    2015-01-01

    Nuclear organization has been implicated in regulating gene activity. Recently, large developmentally regulated regions of the genome dynamically associated with the nuclear lamina have been identified. However, little is known about how these lamina-associated domains (LADs) are directed to the nuclear lamina. We use our tagged chromosomal insertion site system to identify small sequences from borders of fibroblast-specific variable LADs that are sufficient to target these ectopic sites to the nuclear periphery. We identify YY1 (Ying-Yang1) binding sites as enriched in relocating sequences. Knockdown of YY1 or lamin A/C, but not lamin A, led to a loss of lamina association. In addition, targeted recruitment of YY1 proteins facilitated ectopic LAD formation dependent on histone H3 lysine 27 trimethylation and histone H3 lysine di- and trimethylation. Our results also reveal that endogenous loci appear to be dependent on lamin A/C, YY1, H3K27me3, and H3K9me2/3 for maintenance of lamina-proximal positioning. PMID:25559185

  4. Both lamin A and lamin C mutations cause lamina instability as well as loss of internal nuclear lamin organization

    SciTech Connect

    Broers, Jos L.V. . E-mail: jos.broers@molcelb.unimaas.nl; Kuijpers, H.J.H.; Oestlund, C.; Worman, H.J.; Endert, J.; Ramaekers, F.C.S.

    2005-04-01

    We have applied the fluorescence loss of intensity after photobleaching (FLIP) technique to study the molecular dynamics and organization of nuclear lamin proteins in cell lines stably transfected with green fluorescent protein (GFP)-tagged A-type lamin cDNA. Normal lamin A and C proteins show abundant decoration of the inner layer of the nuclear membrane, the nuclear lamina, and a generally diffuse localization in the nuclear interior. Bleaching studies revealed that, while the GFP-tagged lamins in the lamina were virtually immobile, the intranuclear fraction of these molecules was partially mobile. Intranuclear lamin C was significantly more mobile than intranuclear lamina A. In search of a structural cause for the variety of inherited diseases caused by A-type lamin mutations, we have studied the molecular organization of GFP-tagged lamin A and lamin C mutants R453W and R386K, found in Emery-Dreifuss muscular dystrophy (EDMD), and lamin A and lamin C mutant R482W, found in patients with Dunnigan-type familial partial lipodystrophy (FPLD). In all mutants, a prominent increase in lamin mobility was observed, indicating loss of structural stability of lamin polymers, both at the perinuclear lamina and in the intranuclear lamin organization. While the lamin rod domain mutant showed overall increased mobility, the tail domain mutants showed mainly intranuclear destabilization, possibly as a result of loss of interaction with chromatin. Decreased stability of lamin mutant polymers was confirmed by flow cytometric analyses and immunoblotting of nuclear extracts. Our findings suggest a loss of function of A-type lamin mutant proteins in the organization of intranuclear chromatin and predict the loss of gene regulatory function in laminopathies.

  5. Altering lamina assembly reveals lamina-dependent and -independent functions for A-type lamins.

    PubMed

    Zwerger, Monika; Roschitzki-Voser, Heidi; Zbinden, Reto; Denais, Celine; Herrmann, Harald; Lammerding, Jan; Grütter, Markus G; Medalia, Ohad

    2015-10-01

    Lamins are intermediate filament proteins that form a fibrous meshwork, called the nuclear lamina, between the inner nuclear membrane and peripheral heterochromatin of metazoan cells. The assembly and incorporation of lamin A/C into the lamina, as well as their various functions, are still not well understood. Here, we employed designed ankyrin repeat proteins (DARPins) as new experimental tools for lamin research. We screened for DARPins that specifically bound to lamin A/C, and interfered with lamin assembly in vitro and with incorporation of lamin A/C into the native lamina in living cells. The selected DARPins inhibited lamin assembly and delocalized A-type lamins to the nucleoplasm without modifying lamin expression levels or the amino acid sequence. Using these lamin binders, we demonstrate the importance of proper integration of lamin A/C into the lamina for nuclear mechanical properties and nuclear envelope integrity. Finally, our study provides evidence for cell-type-specific differences in lamin functions. PMID:26275827

  6. A-type lamin complexes and regenerative potential: a step towards understanding laminopathic diseases?

    PubMed

    Gotzmann, Josef; Foisner, Roland

    2006-01-01

    The lamins are nuclear intermediate filament-type proteins forming the nuclear lamina meshwork at the inner nuclear membrane as well as complexes in the nucleoplasm. The recent discoveries that mutated A-type lamins and lamin-binding nuclear membrane proteins can be linked to numerous rare human diseases (laminopathies) affecting a multitude of tissues has changed the cell biologist's view of lamins as mere structural nuclear scaffold proteins. It is still unclear how mutations in these ubiquitously expressed proteins give rise to tissue-restricted pathological phenotypes. Potential disease models include mutation-caused defects in lamin structure and stability, the deregulation of gene expression, and impaired cell cycle control. This review brings together various previously proposed ideas and suggests a novel, more general, disease model based on an impairment of adult stem cell function and thus compromised tissue regeneration in laminopathic diseases. PMID:16142451

  7. Mechanical model of blebbing in nuclear lamin meshworks

    PubMed Central

    Funkhouser, Chloe M.; Sknepnek, Rastko; Shimi, Takeshi; Goldman, Anne E.; Goldman, Robert D.; Olvera de la Cruz, Monica

    2013-01-01

    Much of the structural stability of the nucleus comes from meshworks of intermediate filament proteins known as lamins forming the inner layer of the nuclear envelope called the nuclear lamina. These lamin meshworks additionally play a role in gene expression. Abnormalities in nuclear shape are associated with a variety of pathologies, including some forms of cancer and Hutchinson–Gilford Progeria Syndrome, and often include protruding structures termed nuclear blebs. These nuclear blebs are thought to be related to pathological gene expression; however, little is known about how and why blebs form. We have developed a minimal continuum elastic model of a lamin meshwork that we use to investigate which aspects of the meshwork could be responsible for bleb formation. Mammalian lamin meshworks consist of two types of lamin proteins, A type and B type, and it has been reported that nuclear blebs are enriched in A-type lamins. Our model treats each lamin type separately and thus, can assign them different properties. Nuclear blebs have been reported to be located in regions where the fibers in the lamin meshwork have a greater separation, and we find that this greater separation of fibers is an essential characteristic for generating nuclear blebs. The model produces structures with comparable morphologies and distributions of lamin types as real pathological nuclei. Thus, preventing this opening of the meshwork could be a route to prevent bleb formation, which could be used as a potential therapy for the pathologies associated with nuclear blebs. PMID:23401537

  8. A-type lamins regulate retinoblastoma protein function by promoting subnuclear localization and preventing proteasomal degradation.

    PubMed

    Johnson, Brett R; Nitta, Ryan T; Frock, Richard L; Mounkes, Leslie; Barbie, David A; Stewart, Colin L; Harlow, Ed; Kennedy, Brian K

    2004-06-29

    The retinoblastoma protein (pRB) is a critical regulator of cell proliferation and differentiation and an important tumor suppressor. In the G(1) phase of the cell cycle, pRB localizes to perinucleolar sites associated with lamin A/C intranuclear foci. Here, we examine pRB function in cells lacking lamin A/C, finding that pRB levels are dramatically decreased and that the remaining pRB is mislocalized. We demonstrate that A-type lamins protect pRB from proteasomal degradation. Both pRB levels and localization are restored upon reintroduction of lamin A. Lmna(-/-) cells resemble Rb(-/-) cells, exhibiting altered cell-cycle properties and reduced capacity to undergo cell-cycle arrest in response to DNA damage. These findings establish a functional link between a core nuclear structural component and an important cell-cycle regulator. They further raise the possibility that altered pRB function may be a contributing factor in dystrophic syndromes arising from LMNA mutation. PMID:15210943

  9. Subcellular localization of SREBP1 depends on its interaction with the C-terminal region of wild-type and disease related A-type lamins

    PubMed Central

    Duband-Goulet, Isabelle; Woerner, Stephanie; Gasparini, Sylvaine; Attanda, Wikayatou; Kondé, Emilie; Tellier-Lebègue, Carine; Craescu, Constantin T.; Gombault, Aurélie; Roussel, Pascal; Vadrot, Nathalie; Vicart, Patrick; Östlund, Cecilia; Worman, Howard J.; Zinn-Justin, Sophie; Buendia, Brigitte

    2011-01-01

    Lamins A and C are nuclear intermediate filament proteins expressed in most differentiated somatic cells. Previous data suggested that prelamin A, the lamin A precursor, accumulates in some lipodystrophy syndromes caused by mutations in the lamin A/C gene, and binds and inactivates the sterol regulatory element binding protein 1 (SREBP1). Here we show that, in vitro, the tail regions of prelamin A, lamin A and lamin C bind a polypeptide of SREBP1. Such interactions also occur in HeLa cells, since expression of lamin tail regions impedes nucleolar accumulation of the SREBP1 polypeptide fused to a nucleolar localization signal sequence. In addition, the tail regions of A-type lamin variants that occur in Dunnigan-type familial partial lipodystrophy of (R482W) and Hutchison Gilford progeria syndrome (Δ607–656) bind to the SREBP1 polypeptide in vitro, and the corresponding FLAG-tagged full-length lamin variants co-immunoprecipitate the SREBP1 polypeptide in cells. Overexpression of wild-type A-type lamins and variants favors SREBP1 polypeptide localization at the intranuclear periphery, suggesting its sequestration. Our data support the hypothesis that variation of A-type lamin protein level and spatial organization, in particular due to disease-linked mutations, influences the sequestration of SREBP1 at the nuclear envelope and thus contributes to the regulation of SREBP1 function. PMID:21993218

  10. Subcellular localization of SREBP1 depends on its interaction with the C-terminal region of wild-type and disease related A-type lamins

    SciTech Connect

    Duband-Goulet, Isabelle; Woerner, Stephanie; Gasparini, Sylvaine; Attanda, Wikayatou; Konde, Emilie; Tellier-Lebegue, Carine; Craescu, Constantin T.; Roussel, Pascal; Vadrot, Nathalie; Vicart, Patrick; Oestlund, Cecilia; Worman, Howard J.; and others

    2011-12-10

    Lamins A and C are nuclear intermediate filament proteins expressed in most differentiated somatic cells. Previous data suggested that prelamin A, the lamin A precursor, accumulates in some lipodystrophy syndromes caused by mutations in the lamin A/C gene, and binds and inactivates the sterol regulatory element binding protein 1 (SREBP1). Here we show that, in vitro, the tail regions of prelamin A, lamin A and lamin C bind a polypeptide of SREBP1. Such interactions also occur in HeLa cells, since expression of lamin tail regions impedes nucleolar accumulation of the SREBP1 polypeptide fused to a nucleolar localization signal sequence. In addition, the tail regions of A-type lamin variants that occur in Dunnigan-type familial partial lipodystrophy of (R482W) and Hutchison Gilford progeria syndrome ( Increment 607-656) bind to the SREBP1 polypeptide in vitro, and the corresponding FLAG-tagged full-length lamin variants co-immunoprecipitate the SREBP1 polypeptide in cells. Overexpression of wild-type A-type lamins and variants favors SREBP1 polypeptide localization at the intranuclear periphery, suggesting its sequestration. Our data support the hypothesis that variation of A-type lamin protein level and spatial organization, in particular due to disease-linked mutations, influences the sequestration of SREBP1 at the nuclear envelope and thus contributes to the regulation of SREBP1 function.

  11. Blocking farnesylation of the prelamin A variant in Hutchinson-Gilford progeria syndrome alters the distribution of A-type lamins.

    PubMed

    Wang, Yuexia; Ostlund, Cecilia; Choi, Jason C; Swayne, Theresa C; Gundersen, Gregg G; Worman, Howard J

    2012-01-01

    Mutations in the lamin A/C gene that cause Hutchinson-Gilford progeria syndrome lead to expression of a truncated, permanently farnesylated prelamin A variant called progerin. Blocking farnesylation leads to an improvement in the abnormal nuclear morphology observed in cells expressing progerin, which is associated with a re-localization of the variant protein from the nuclear envelope to the nuclear interior. We now show that a progerin construct that cannot be farnesylated is localized primarily in intranuclear foci and that its diffusional mobility is significantly greater than that of farnesylated progerin localized predominantly at the nuclear envelope. Expression of non-farnesylated progerin in transfected cells leads to a redistribution of lamin A and lamin C away from the nuclear envelope into intranuclear foci but does not significantly affect the localization of endogenous lamin B1 at nuclear envelope. There is a similar redistribution of lamin A and lamin C into intranuclear foci in transfected cells expressing progerin in which protein farnesylation is blocked by treatment with a protein farnesyltransferase inhibitor. Blocking farnesylation of progerin can lead to a redistribution of normal A-type lamins away from the inner nuclear envelope. This may have implications for using drugs that block protein prenylation to treat children with Hutchinson-Gilford progeria syndrome. These findings also provide additional evidence that A-type and B-type lamins can form separate microdomains within the nucleus. PMID:22895092

  12. Nuclear Envelope Lamin-A Couples Actin Dynamics with Immunological Synapse Architecture and T Cell Activation

    PubMed Central

    González-Granado, José María; Trigueros-Motos, Laia; Cibrián, Danay; Morlino, Giulia; Blanco-Berrocal, Marta; Osorio, Fernando Garcia; Freije, José María Pérez; López-Otín, Carlos; Sánchez-Madrid, Francisco; Andrés, Vicente

    2014-01-01

    In many cell types, nuclear A-type lamins have been implicated in structural and functional activities, including higher-order genome organization, DNA replication and repair, gene transcription, and signal transduction. However, their role in specialized immune cells remains largely unexplored. Here, we showed that the abundance of A-type lamins is almost negligible in resting naïve T lymphocytes, but that it is substantially increased upon activation of the T cell receptor (TCR), and is an early event that accelerates formation of the immunological synapse between T cells and antigen-presenting cells. We found that lamin-A enhanced the polymerization of F-actin in T cells, a critical step for immunological synapse formation, by physically connecting the nucleus to the plasma membrane through the linker of nucleoskeleton and cytoskeleton (LINC) complex. We also showed that lamin-A played a key role in other membrane, cytoplasmic, and nuclear events related to TCR activation, including receptor-clustering, downstream signaling, and target gene expression. Notably, the presence of lamin-A was associated with enhanced extracellular signal–regulated kinase 1/2 signaling, and pharmacological inhibition of this pathway reduced the extent of lamin-A–dependent T cell activation. Moreover, mice deficient in lamin-A exhibited impaired T cell responses in vivo. These findings underscore the importance of A-type lamins for TCR activation, and identify lamin-A as a previously unappreciated regulator of the immune response. PMID:24757177

  13. Nuclear protein import is reduced in cells expressing nuclear envelopathy-causing lamin A mutants

    SciTech Connect

    Busch, Albert; Kiel, Tilman; Heupel, Wolfgang-M.; Wehnert, Manfred; Huebner, Stefan

    2009-08-15

    Lamins, which form the nuclear lamina, not only constitute an important determinant of nuclear architecture, but additionally play essential roles in many nuclear functions. Mutations in A-type lamins cause a wide range of human genetic disorders (laminopathies). The importance of lamin A (LaA) in the spatial arrangement of nuclear pore complexes (NPCs) prompted us to study the role of LaA mutants in nuclear protein transport. Two mutants, causing prenatal skin disease restrictive dermopathy (RD) and the premature aging disease Hutchinson Gilford progeria syndrome, were used for expression in HeLa cells to investigate their impact on the subcellular localization of NPC-associated proteins and nuclear protein import. Furthermore, dynamics of the LaA mutants within the nuclear lamina were studied. We observed affected localization of NPC-associated proteins, diminished lamina dynamics for both LaA mutants and reduced nuclear import of representative cargo molecules. Intriguingly, both LaA mutants displayed similar effects on nuclear morphology and functions, despite their differences in disease severity. Reduced nuclear protein import was also seen in RD fibroblasts and impaired lamina dynamics for the nucleoporin Nup153. Our data thus represent the first study of a direct link between LaA mutant expression and reduced nuclear protein import.

  14. The truncated prelamin A in Hutchinson-Gilford progeria syndrome alters segregation of A-type and B-type lamin homopolymers.

    PubMed

    Delbarre, Erwan; Tramier, Marc; Coppey-Moisan, Maïté; Gaillard, Claire; Courvalin, Jean-Claude; Buendia, Brigitte

    2006-04-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a dominant autosomal premature aging syndrome caused by the expression of a truncated prelamin A designated progerin (Pgn). A-type and B-type lamins are intermediate filament proteins that polymerize to form the nuclear lamina network apposed to the inner nuclear membrane of vertebrate somatic cells. It is not known if in vivo both type of lamins assemble independently or co-assemble. The blebbing and disorganization of the nuclear envelope and adjacent heterochromatin in cells from patients with HGPS is a hallmark of the disease, and the ex vivo reversal of this phenotype is considered important for the development of therapeutic strategies. Here, we investigated the alterations in the lamina structure that may underlie the disorganization caused in nuclei by Pgn expression. We studied the polymerization of enhanced green fluorescent protein- and red fluorescent protein-tagged wild-type and mutated lamins in the nuclear envelope of living cells by measuring fluorescence resonance energy transfer (FRET) that occurs between the two fluorophores when tagged lamins interact. Using time domain fluorescence lifetime imaging microscopy that allows a quantitative analysis of FRET signals, we show that wild-type lamins A and B1 polymerize in distinct homopolymers that further interact in the lamina. In contrast, expressed Pgn co-assembles with lamin B1 and lamin A to form a mixed heteropolymer in which A-type and B-type lamin segregation is lost. We propose that such structural lamina alterations may be part of the primary mechanisms leading to HGPS, possibly by impairing functions specific for each lamin type such as nuclear membrane biogenesis, signal transduction, nuclear compartmentalization and gene regulation. PMID:16481358

  15. Dynamic properties of meiosis-specific lamin C2 and its impact on nuclear envelope integrity

    PubMed Central

    Jahn, Daniel; Schramm, Sabine; Benavente, Ricardo

    2010-01-01

    A hallmark of meiosis is the precise pairing and the stable physical connection (synapsis) of the homologous chromosomes. These processes are essential prerequisite for their proper segregation. Pairing of the homologs during meiotic prophase I critically depends on characteristic movements of chromosomes. These movements, in turn, require attachment of meiotic telomeres to the nuclear envelope and their subsequent dynamic repositioning. Dynamic repositioning of meiotic telomeres goes along with profound structural reorganization of the nuclear envelope. The short A-type lamin C2 is thought to play a critical role in this process due to its specific expression during meiotic prophase I and the unique localization surrounding telomere attachments. Consistent with this notion, here we provide compelling evidence that meiosis-specific lamin C2 features a significantly increased mobility compared to somatic lamins as revealed by photobleaching techniques. We show that this property can be clearly ascribed to the lack of the N-terminal head and the significantly shorter α-helical coil domain. Moreover, expression of lamin C2 in somatic cells induces nuclear deformations and alters the distribution of the endogenous nuclear envelope proteins lamin B1, LAP2, SUN1 and SUN2. Together, our data define lamin C2 as a “natural lamin deletion mutant” that confers unique properties to the nuclear envelope which would be essential for dynamic telomere repositioning during meiotic prophase I. PMID:21327075

  16. Lamins position the nuclear pores and centrosomes by modulating dynein

    PubMed Central

    Guo, Yuxuan; Zheng, Yixian

    2015-01-01

    Lamins, the type V nuclear intermediate filament proteins, are reported to function in both interphase and mitosis. For example, lamin deletion in various cell types can lead to an uneven distribution of the nuclear pore complexes (NPCs) in the interphase nuclear envelope, whereas deletion of B-type lamins results in spindle orientation defects in mitotic neural progenitor cells. How lamins regulate these functions is unknown. Using mouse cells deleted of different combinations or all lamins, we show that lamins are required to prevent the aggregation of NPCs in the nuclear envelope near centrosomes in late G2 and prophase. This asymmetric NPC distribution in the absence of lamins is caused by dynein forces acting on NPCs via the dynein adaptor BICD2. We further show that asymmetric NPC distribution upon lamin depletion disrupts the distribution of BICD2 and p150 dynactin on the nuclear envelope at prophase, which results in inefficient dynein-driven centrosome separation during prophase. Therefore lamins regulate microtubule-based motor forces in vivo to ensure proper NPC distribution in interphase and centrosome separation in the mitotic prophase. PMID:26246603

  17. Roles of endothelial A-type lamins in migration of T cells on and under endothelial layers.

    PubMed

    Song, Kwang Hoon; Lee, Jaehyun; Park, HyoungJun; Kim, Hye Mi; Park, Jeehun; Kwon, Keon Woo; Doh, Junsang

    2016-01-01

    Stiff nuclei in cell-dense microenvironments may serve as distinct biomechanical cues for cell migration, but such a possibility has not been tested experimentally. As a first step addressing this question, we altered nuclear stiffness of endothelial cells (ECs) by reducing the expression of A-type lamins using siRNA, and investigated the migration of T cells on and under EC layers. While most T cells crawling on control EC layers avoided crossing over EC nuclei, a significantly higher fraction of T cells on EC layers with reduced expression of A-type lamins crossed over EC nuclei. This result suggests that stiff EC nuclei underlying T cells may serve as "duro-repulsive" cues to direct T cell migration toward less stiff EC cytoplasm. During subendothelial migration under EC layers with reduced expression of A-type lamins, T cells made prolonged contact and substantially deformed EC nuclei, resulting in reduced speed and directional persistence. This result suggests that EC nuclear stiffness promotes fast and directionally persistent subendothelial migration of T cells by allowing minimum interaction between T cells and EC nuclei. PMID:26996137

  18. Roles of endothelial A-type lamins in migration of T cells on and under endothelial layers

    PubMed Central

    Song, Kwang Hoon; Lee, Jaehyun; Park, HyoungJun; Kim, Hye Mi; Park, Jeehun; Kwon, Keon Woo; Doh, Junsang

    2016-01-01

    Stiff nuclei in cell-dense microenvironments may serve as distinct biomechanical cues for cell migration, but such a possibility has not been tested experimentally. As a first step addressing this question, we altered nuclear stiffness of endothelial cells (ECs) by reducing the expression of A-type lamins using siRNA, and investigated the migration of T cells on and under EC layers. While most T cells crawling on control EC layers avoided crossing over EC nuclei, a significantly higher fraction of T cells on EC layers with reduced expression of A-type lamins crossed over EC nuclei. This result suggests that stiff EC nuclei underlying T cells may serve as “duro-repulsive” cues to direct T cell migration toward less stiff EC cytoplasm. During subendothelial migration under EC layers with reduced expression of A-type lamins, T cells made prolonged contact and substantially deformed EC nuclei, resulting in reduced speed and directional persistence. This result suggests that EC nuclear stiffness promotes fast and directionally persistent subendothelial migration of T cells by allowing minimum interaction between T cells and EC nuclei. PMID:26996137

  19. Roles of endothelial A-type lamins in migration of T cells on and under endothelial layers

    NASA Astrophysics Data System (ADS)

    Song, Kwang Hoon; Lee, Jaehyun; Park, Hyoungjun; Kim, Hye Mi; Park, Jeehun; Kwon, Keon Woo; Doh, Junsang

    2016-03-01

    Stiff nuclei in cell-dense microenvironments may serve as distinct biomechanical cues for cell migration, but such a possibility has not been tested experimentally. As a first step addressing this question, we altered nuclear stiffness of endothelial cells (ECs) by reducing the expression of A-type lamins using siRNA, and investigated the migration of T cells on and under EC layers. While most T cells crawling on control EC layers avoided crossing over EC nuclei, a significantly higher fraction of T cells on EC layers with reduced expression of A-type lamins crossed over EC nuclei. This result suggests that stiff EC nuclei underlying T cells may serve as “duro-repulsive” cues to direct T cell migration toward less stiff EC cytoplasm. During subendothelial migration under EC layers with reduced expression of A-type lamins, T cells made prolonged contact and substantially deformed EC nuclei, resulting in reduced speed and directional persistence. This result suggests that EC nuclear stiffness promotes fast and directionally persistent subendothelial migration of T cells by allowing minimum interaction between T cells and EC nuclei.

  20. A progeria mutation reveals functions for lamin A in nuclear assembly, architecture, and chromosome organization.

    PubMed

    Taimen, Pekka; Pfleghaar, Katrin; Shimi, Takeshi; Möller, Dorothee; Ben-Harush, Kfir; Erdos, Michael R; Adam, Stephen A; Herrmann, Harald; Medalia, Ohad; Collins, Francis S; Goldman, Anne E; Goldman, Robert D

    2009-12-01

    Numerous mutations in the human A-type lamin gene (LMNA) cause the premature aging disease, progeria. Some of these are located in the alpha-helical central rod domain required for the polymerization of the nuclear lamins into higher order structures. Patient cells with a mutation in this domain, 433G>A (E145K) show severely lobulated nuclei, a separation of the A- and B-type lamins, alterations in pericentric heterochromatin, abnormally clustered centromeres, and mislocalized telomeres. The induction of lobulations and the clustering of centromeres originate during postmitotic nuclear assembly in daughter cells and this early G1 configuration of chromosomes is retained throughout interphase. In vitro analyses of E145K-lamin A show severe defects in the assembly of protofilaments into higher order lamin structures. The results show that this central rod domain mutation affects nuclear architecture in a fashion distinctly different from the changes found in the most common form of progeria caused by the expression of LADelta50/progerin. The study also emphasizes the importance of lamins in nuclear assembly and chromatin organization. PMID:19926845

  1. Nuclear lamins during gametogenesis, fertilization and early development

    NASA Technical Reports Server (NTRS)

    Maul, G. G.; Schatten, G.

    1986-01-01

    The distribution of lamins (described by Gerace, 1978, as major proteins of nuclear envelope) during gametogenesis, fertilization, and early development was investigated in germ cells of a mouse (Mus musculus), an echinoderm (Lytechinus variegatus), and the surf clam (Spisula solidissima) was investigated in order to determine whether the differences detected could be correlated with differences in the function of cells in these stages of the germ cells. In order to monitor the behavior of lamins, the gametes and embryos were labeled with antibodies to lamins A, C, and B extracted from autoimmune sera of patients with scleroderma and Lupus erythematosus. Results indicated that lamin B could be identified in nuclear envelopes on only those nuclei where chromatin is attached and where RNA synthesis takes place.

  2. Nuclear lamins and peripheral nuclear antigens during fertilization and embryogenesis in mice and sea urchins

    SciTech Connect

    Schatten, G.; Schatten, H.; Simerly, C.; Maul, G.G.; Chaly, N.

    1985-07-01

    Nuclear structural changes during fertilization and embryogenesis in mice and sea urchins are traced using four antibodies. The oocytes from virgin female mice, morulae and blastocytes from mated females, and gametes from the sea urchin Lytechnius variegatis are studied using mouse monoclonal antibodies to nuclear lamin A/C, monoclonal antibody to P1, human autoimmune antibodies to lamin A/C, and to lamin B. The mouse fertilization data reveal no lamins on the oocyte; however, lamins are present on the pronuclei, and chromosomes are found on the oocytes and pronuclei. It is detected that on the sea urchin sperm the lamins are reduced to acrosomal and centriolar fossae and peripheral antigens are around the sperm nucleus. The mouse sperm bind lamin antibodies regionally and do not contain antigens. Lamins and antigens are observed on both pronuclei and chromosomes during sea urchin fertilization. Mouse embryogenesis reveals that lamin A/C is not recognized at morula and blastocyst stages; however, lamin B stains are retained. In sea urchin embryogenesis lamin recognition is lost at the blastrula, gastrula, and plutei stages. It is noted that nuclear lamins lost during spermatogenesis are restored at fertilization and peripheral antigens are associated with the surface of chromosomes during meiosis and mitosis and with the periphery of the pronuclei and nuclei during interphase. 32 references.

  3. Nuclear lamins and peripheral nuclear antigens during fertilization and embryogenesis in mice and sea urchins

    NASA Technical Reports Server (NTRS)

    Schatten, G.; Schatten, H.; Simerly, C.; Maul, G. G.; Chaly, N.

    1985-01-01

    Nuclear structural changes during fertilization and embryogenesis in mice and sea urchins are traced using four antibodies. The oocytes from virgin female mice, morulae and blastocytes from mated females, and gametes from the sea urchin Lytechnius variegatis are studied using mouse monoclonal antibodies to nuclear lamin A/C, monoclonal antibody to P1, human autoimmune antibodies to lamin A/C, and to lamin B. The mouse fertilization data reveal no lamins on the oocyte; however, lamins are present on the pronuclei, and chromosomes are found on the oocytes and pronuclei. It is detected that on the sea urchin sperm the lamins are reduced to acrosomal and centriolar fossae and peripheral antigens are around the sperm nucleus. The mouse sperm bind lamin antibodies regionally and do not contain antigens. Lamins and antigens are observed on both pronuclei and chromosomes during sea urchin fertilization. Mouse embryogenesis reveals that lamin A/C is not recognized at morula and blastocyst stages; however, lamin B stains are retained. In sea urchin embryogenesis lamin recognition is lost at the blastrula, gastrula, and plutei stages. It is noted that nuclear lamins lost during spermatogenesis are restored at fertilization and peripheral antigens are associated with the surface of chromosomes during meiosis and mitosis and with the periphery of the pronuclei and nuclei during interphase.

  4. A-type lamins bind both hetero- and euchromatin, the latter being regulated by lamina-associated polypeptide 2 alpha

    PubMed Central

    Gesson, Kevin; Rescheneder, Philipp; Skoruppa, Michael P.; von Haeseler, Arndt; Dechat, Thomas

    2016-01-01

    Lamins are components of the peripheral nuclear lamina and interact with heterochromatic genomic regions, termed lamina-associated domains (LADs). In contrast to lamin B1 being primarily present at the nuclear periphery, lamin A/C also localizes throughout the nucleus, where it associates with the chromatin-binding protein lamina-associated polypeptide (LAP) 2 alpha. Here, we show that lamin A/C also interacts with euchromatin, as determined by chromatin immunoprecipitation of euchromatin- and heterochromatin-enriched samples. By way of contrast, lamin B1 was only found associated with heterochromatin. Euchromatic regions occupied by lamin A/C overlap with those bound by LAP2alpha, and lack of LAP2alpha in LAP2alpha-deficient cells shifts binding of lamin A/C toward more heterochromatic regions. These alterations in lamin A/C-chromatin interactions correlate with changes in epigenetic histone marks in euchromatin but do not significantly affect gene expression. Loss of lamin A/C in heterochromatic regions in LAP2alpha-deficient cells, however, correlated with increased gene expression. Our data show a novel role of nucleoplasmic lamin A/C and LAP2alpha in regulating euchromatin. PMID:26798136

  5. Deficiencies in lamin B1 and lamin B2 cause neurodevelopmental defects and distinct nuclear shape abnormalities in neurons

    PubMed Central

    Coffinier, Catherine; Jung, Hea-Jin; Nobumori, Chika; Chang, Sandy; Tu, Yiping; Barnes, Richard H.; Yoshinaga, Yuko; de Jong, Pieter J.; Vergnes, Laurent; Reue, Karen; Fong, Loren G.; Young, Stephen G.

    2011-01-01

    Neuronal migration is essential for the development of the mammalian brain. Here, we document severe defects in neuronal migration and reduced numbers of neurons in lamin B1–deficient mice. Lamin B1 deficiency resulted in striking abnormalities in the nuclear shape of cortical neurons; many neurons contained a solitary nuclear bleb and exhibited an asymmetric distribution of lamin B2. In contrast, lamin B2 deficiency led to increased numbers of neurons with elongated nuclei. We used conditional alleles for Lmnb1 and Lmnb2 to create forebrain-specific knockout mice. The forebrain-specific Lmnb1- and Lmnb2-knockout models had a small forebrain with disorganized layering of neurons and nuclear shape abnormalities, similar to abnormalities identified in the conventional knockout mice. A more severe phenotype, complete atrophy of the cortex, was observed in forebrain-specific Lmnb1/Lmnb2 double-knockout mice. This study demonstrates that both lamin B1 and lamin B2 are essential for brain development, with lamin B1 being required for the integrity of the nuclear lamina, and lamin B2 being important for resistance to nuclear elongation in neurons. PMID:21976703

  6. Nuclear localization signal deletion mutants of lamin A and progerin reveal insights into lamin A processing and emerin targeting.

    PubMed

    Wu, Di; Flannery, Andrew R; Cai, Helen; Ko, Eunae; Cao, Kan

    2014-01-01

    Lamin A is a major component of the lamina, which creates a dynamic network underneath the nuclear envelope. Mutations in the lamin A gene (LMNA) cause severe genetic disorders, one of which is Hutchinson-Gilford progeria syndrome (HGPS), a disease triggered by a dominant mutant named progerin. Unlike the wild-type lamin A, whose farnesylated C-terminus is excised during post-translational processing, progerin retains its farnesyl tail and accumulates on the nuclear membrane, resulting in abnormal nuclear morphology during interphase. In addition, membrane-associated progerin forms visible cytoplasmic aggregates in mitosis. To examine the potential effects of cytoplasmic progerin, nuclear localization signal (NLS) deleted progerin and lamin A (PGΔNLS and LAΔNLS, respectively) have been constructed. We find that both ΔNLS mutants are farnesylated in the cytosol and associate with a sub-domain of the ER via their farnesyl tails. While the farnesylation on LAΔNLS can be gradually removed, which leads to its subsequent release from the ER into the cytoplasm, PGΔNLS remains permanently farnesylated and membrane-bounded. Moreover, both ΔNLS mutants dominantly affect emerin's nuclear localization. These results reveal new insights into lamin A biogenesis and lamin A-emerin interaction. PMID:24637396

  7. Nuclear localization signal deletion mutants of lamin A and progerin reveal insights into lamin A processing and emerin targeting

    PubMed Central

    Wu, Di; Flannery, Andrew R; Cai, Helen; Ko, Eunae; Cao, Kan

    2014-01-01

    Lamin A is a major component of the lamina, which creates a dynamic network underneath the nuclear envelope. Mutations in the lamin A gene (LMNA) cause severe genetic disorders, one of which is Hutchinson-Gilford progeria syndrome (HGPS), a disease triggered by a dominant mutant named progerin. Unlike the wild-type lamin A, whose farnesylated C-terminus is excised during post-translational processing, progerin retains its farnesyl tail and accumulates on the nuclear membrane, resulting in abnormal nuclear morphology during interphase. In addition, membrane-associated progerin forms visible cytoplasmic aggregates in mitosis. To examine the potential effects of cytoplasmic progerin, nuclear localization signal (NLS) deleted progerin and lamin A (PGΔNLS and LAΔNLS, respectively) have been constructed. We find that both ΔNLS mutants are farnesylated in the cytosol and associate with a sub-domain of the ER via their farnesyl tails. While the farnesylation on LAΔNLS can be gradually removed, which leads to its subsequent release from the ER into the cytoplasm, PGΔNLS remains permanently farnesylated and membrane-bounded. Moreover, both ΔNLS mutants dominantly affect emerin’s nuclear localization. These results reveal new insights into lamin A biogenesis and lamin A-emerin interaction. PMID:24637396

  8. Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin

    PubMed Central

    Dechat, Thomas; Pfleghaar, Katrin; Sengupta, Kaushik; Shimi, Takeshi; Shumaker, Dale K.; Solimando, Liliana; Goldman, Robert D.

    2008-01-01

    Over the past few years it has become evident that the intermediate filament proteins, the types A and B nuclear lamins, not only provide a structural framework for the nucleus, but are also essential for many aspects of normal nuclear function. Insights into lamin-related functions have been derived from studies of the remarkably large number of disease-causing mutations in the human lamin A gene. This review provides an up-to-date overview of the functions of nuclear lamins, emphasizing their roles in epigenetics, chromatin organization, DNA replication, transcription, and DNA repair. In addition, we discuss recent evidence supporting the importance of lamins in viral infections. PMID:18381888

  9. Prelamin A and lamin A appear to be dispensable in the nuclear lamina.

    PubMed

    Fong, Loren G; Ng, Jennifer K; Lammerding, Jan; Vickers, Timothy A; Meta, Margarita; Coté, Nathan; Gavino, Bryant; Qiao, Xin; Chang, Sandy Y; Young, Stephanie R; Yang, Shao H; Stewart, Colin L; Lee, Richard T; Bennett, C Frank; Bergo, Martin O; Young, Stephen G

    2006-03-01

    Lamin A and lamin C, both products of Lmna, are key components of the nuclear lamina. In the mouse, a deficiency in both lamin A and lamin C leads to slow growth, muscle weakness, and death by 6 weeks of age. Fibroblasts deficient in lamins A and C contain misshapen and structurally weakened nuclei, and emerin is mislocalized away from the nuclear envelope. The physiologic rationale for the existence of the 2 different Lmna products lamin A and lamin C is unclear, although several reports have suggested that lamin A may have particularly important functions, for example in the targeting of emerin and lamin C to the nuclear envelope. Here we report the development of lamin C-only mice (Lmna(LCO/LCO)), which produce lamin C but no lamin A or prelamin A (the precursor to lamin A). Lmna(LCO/LCO) mice were entirely healthy, and Lmna(LCO/LCO) cells displayed normal emerin targeting and exhibited only very minimal alterations in nuclear shape and nuclear deformability. Thus, at least in the mouse, prelamin A and lamin A appear to be dispensable. Nevertheless, an accumulation of farnesyl-prelamin A (as occurs with a deficiency in the prelamin A processing enzyme Zmpste24) caused dramatically misshapen nuclei and progeria-like disease phenotypes. The apparent dispensability of prelamin A suggested that lamin A-related progeroid syndromes might be treated with impunity by reducing prelamin A synthesis. Remarkably, the presence of a single Lmna(LCO) allele eliminated the nuclear shape abnormalities and progeria-like disease phenotypes in Zmpste24-/- mice. Moreover, treating Zmpste24-/- cells with a prelamin A-specific antisense oligonucleotide reduced prelamin A levels and significantly reduced the frequency of misshapen nuclei. These studies suggest a new therapeutic strategy for treating progeria and other lamin A diseases. PMID:16511604

  10. Nuclear envelope remodeling during mouse spermiogenesis: Postmeiotic expression and redistribution of germline lamin B3

    SciTech Connect

    Schuetz, Wolfgang; Alsheimer, Manfred; Oellinger, Rupert; Benavente, Ricardo . E-mail: benavente@biozentrum.uni-wuerzburg.de

    2005-07-15

    Lamins are members of a multigene family of structural nuclear envelope (NE) proteins. Differentiated mammalian somatic cells express lamins A, C, B1, and B2. The composition and organization of the nuclear lamina of mammalian spermatogenic cells differ significantly from that of somatic cells as they express lamin B1 as well as two short germ line-specific isoforms, namely lamins B3 and C2. Here we describe in detail the expression pattern and localization of lamin B3 during mouse spermatogenesis. By combining RT-PCR, immunoblotting, and immunofluorescence microscopy, we show that lamin B3 is selectively expressed during spermiogenesis (i.e., postmeiotic stages of spermatogenesis). In round spermatids, lamin B3 is distributed in the nuclear periphery and, notably, also in the nucleoplasm. In the course of spermiogenesis, lamin B3 becomes redistributed as it concentrates progressively to the posterior pole of spermatid nuclei. Our results show that during mammalian spermiogenesis the nuclear lamina is composed of B-type isoforms only, namely the ubiquitous lamin B1 and the germline-specific lamin B3. Lamin B3 is the first example of a mammalian lamin that is selectively expressed during postmeiotic stages of spermatogenesis.

  11. Differential basal-to-apical accessibility of lamin A/C epitopes in the nuclear lamina regulated by changes in cytoskeletal tension

    PubMed Central

    Herzog, Florian A.; Schwartlander, Ruth; Moeller, Jens; Vogel, Viola

    2015-01-01

    Nuclear lamins play central roles at the intersection between cytoplasmic signalling and nuclear events. Here, we show that at least two N- and C-terminal lamin epitopes are not accessible at the basal side of the nuclear envelope under environmental conditions known to upregulate cell contractility. The conformational epitope on the Ig-domain of A-type lamins is more buried in the basal than apical nuclear envelope of human mesenchymal stem cells undergoing osteogenesis (but not adipogenesis), and in fibroblasts adhering to rigid (but not soft) polyacrylamide hydrogels. This structural polarization of the lamina is promoted by compressive forces, emerges during cell spreading, and requires lamin A/C multimerization, intact nucleoskeleton-cytoskeleton linkages (LINC), and apical-actin stress-fibre assembly. Notably, the identified Igepitope overlaps with emerin, DNA and histone binding sites, and comprises various laminopathy mutation sites. Our findings should help deciphering how the physical properties of cellular microenvironments regulate nuclear events. PMID:26301768

  12. Differential basal-to-apical accessibility of lamin A/C epitopes in the nuclear lamina regulated by changes in cytoskeletal tension

    NASA Astrophysics Data System (ADS)

    Ihalainen, Teemu O.; Aires, Lina; Herzog, Florian A.; Schwartlander, Ruth; Moeller, Jens; Vogel, Viola

    2015-12-01

    Nuclear lamins play central roles at the intersection between cytoplasmic signalling and nuclear events. Here, we show that at least two N- and C-terminal lamin epitopes are not accessible at the basal side of the nuclear envelope under environmental conditions known to upregulate cell contractility. The conformational epitope on the Ig-domain of A-type lamins is more buried in the basal than apical nuclear envelope of human mesenchymal stem cells undergoing osteogenesis (but not adipogenesis), and in fibroblasts adhering to rigid (but not soft) polyacrylamide hydrogels. This structural polarization of the lamina is promoted by compressive forces, emerges during cell spreading, and requires lamin A/C multimerization, intact nucleoskeleton-cytoskeleton linkages (LINC), and apical-actin stress-fibre assembly. Notably, the identified Ig-epitope overlaps with emerin, DNA and histone binding sites, and comprises various laminopathy mutation sites. Our findings should help decipher how the physical properties of cellular microenvironments regulate nuclear events.

  13. Gene-rich chromosomal regions are preferentially localized in the lamin B deficient nuclear blebs of atypical progeria cells

    PubMed Central

    Bercht Pfleghaar, Katrin; Taimen, Pekka; Butin-Israeli, Veronika; Shimi, Takeshi; Langer-Freitag, Sabine; Markaki, Yolanda; Goldman, Anne E; Wehnert, Manfred; Goldman, Robert D

    2015-01-01

    More than 20 mutations in the gene encoding A-type lamins (LMNA) cause progeria, a rare premature aging disorder. The major pathognomonic hallmarks of progeria cells are seen as nuclear deformations or blebs that are related to the redistribution of A- and B-type lamins within the nuclear lamina. However, the functional significance of these progeria-associated blebs remains unknown. We have carried out an analysis of the structural and functional consequences of progeria-associated nuclear blebs in dermal fibroblasts from a progeria patient carrying a rare point mutation p.S143F (C428T) in lamin A/C. These blebs form microdomains that are devoid of major structural components of the nuclear envelope (NE)/lamina including B-type lamins and nuclear pore complexes (NPCs) and are enriched in A-type lamins. Using laser capture microdissection and comparative genomic hybridization (CGH) analyses, we show that, while these domains are devoid of centromeric heterochromatin and gene-poor regions of chromosomes, they are enriched in gene-rich chromosomal regions. The active form of RNA polymerase II is also greatly enriched in blebs as well as nascent RNA but the nuclear co-activator SKIP is significantly reduced in blebs compared to other transcription factors. Our results suggest that the p.S143F progeria mutation has a severe impact not only on the structure of the lamina but also on the organization of interphase chromatin domains and transcription. These structural defects are likely to contribute to gene expression changes reported in progeria and other types of laminopathies. PMID:25738644

  14. Differential expression of A-type and B-type lamins during hair cycling.

    PubMed

    Hanif, Mubashir; Rosengardten, Ylva; Sagelius, Hanna; Rozell, Björn; Eriksson, Maria

    2009-01-01

    Multiple genetic disorders caused by mutations that affect the proteins lamin A and C show strong skin phenotypes. These disorders include the premature aging disorders Hutchinson-Gilford progeria syndrome and mandibuloacral dysplasia, as well as restrictive dermopathy. Prior studies have shown that the lamin A/C and B proteins are expressed in skin, but little is known about their normal expression in the different skin cell-types and during the hair cycle. Our immunohistochemical staining for lamins A/C and B in wild-type mice revealed strong expression in the basal cell layer of the epidermis, the outer root sheath, and the dermal papilla during all stages of the hair cycle. Lower expression of both lamins A/C and B was seen in suprabasal cells of the epidermis, in the hypodermis, and in the bulb of catagen follicles. In addition, we have utilized a previously described mouse model of Hutchinson-Gilford progeria syndrome and show here that the expression of progerin does not result in pronounced effects on hair cycling or the expression of lamin B. PMID:19122810

  15. Herpes simplex virus 2 UL13 protein kinase disrupts nuclear lamins

    SciTech Connect

    Cano-Monreal, Gina L.; Wylie, Kristine M.; Cao, Feng; Tavis, John E.; Morrison, Lynda A.

    2009-09-15

    Herpesviruses must cross the inner nuclear membrane and underlying lamina to exit the nucleus. HSV-1 US3 and PKC can phosphorylate lamins and induce their dispersion but do not elicit all of the phosphorylated lamin species produced during infection. UL13 is a serine threonine protein kinase conserved among many herpesviruses. HSV-1 UL13 phosphorylates US3 and thereby controls UL31 and UL34 nuclear rim localization, indicating a role in nuclear egress. Here, we report that HSV-2 UL13 alone induced conformational changes in lamins A and C and redistributed lamin B1 from the nuclear rim to intranuclear granular structures. HSV-2 UL13 directly phosphorylated lamins A, C, and B1 in vitro, and the lamin A1 tail domain. HSV-2 infection recapitulated the lamin alterations seen upon expression of UL13 alone, and other alterations were also observed, indicating that additional viral and/or cellular proteins cooperate with UL13 to alter lamins during HSV-2 infection to allow nuclear egress.

  16. Herpes simplex virus 2 UL13 protein kinase disrupts nuclear lamins

    PubMed Central

    Cano-Monreal, Gina L.; Wylie, Kristine M.; Cao, Feng; Tavis, John E.; Morrison, Lynda A.

    2009-01-01

    Herpesviruses must cross the inner nuclear membrane and underlying lamina to exit the nucleus. HSV-1 US3 and PKC can phosphorylate lamins and induce their dispersion but do not elicit all of the phosphorylated lamin species produced during infection. UL13 is a serine threonine protein kinase conserved among many herpesviruses. HSV-1 UL13 phosphorylates US3 and thereby controls UL31 and UL34 nuclear rim localization, indicating a role in nuclear egress. Here, we report that HSV-2 UL13 alone induced conformational changes in lamins A and C and redistributed lamin B1 from the nuclear rim to intranuclear granular structures. HSV-2 UL13 directly phosphorylated lamins A, C, and B1 in vitro, and the lamin A1 tail domain. HSV-2 infection recapitulated the lamin alterations seen upon expression of UL13 alone, and other alterations were also observed, indicating that additional viral and/or cellular proteins cooperate with UL13 to alter lamins during HSV-2 infection to allow nuclear egress. PMID:19640559

  17. Nuclear envelope lamin-A as a coordinator of T cell activation

    PubMed Central

    Rocha-Perugini, Vera; González-Granado, José M

    2014-01-01

    Nuclear lamins A/C control several critical cellular functions, e.g., chromatin organization, gene transcription, DNA replication, DNA damage responses, cell cycle progression, cell differentiation, and cell polarization during migration. However, few studies have addressed the role of lamins A/C in the control of the functions of immune cells. Recently, we have demonstrated that lamins A/C are induced in T cells upon antigen recognition. Lamins A/C enhance T cell responses by coupling the plasma membrane to the nucleus via the linker of nucleoskeleton and cytoskeleton (LINC) complex and the actin cytoskeleton. Here, we discuss the possible physiological relevance and functional context of lamin A/C in T cell activation and propose a model in which lamins A/C are key modulators of immune cell functions. PMID:25482193

  18. Nuclear lamin A inhibits adipocyte differentiation: implications for Dunnigan-type familial partial lipodystrophy.

    PubMed

    Boguslavsky, Revekka L; Stewart, Colin L; Worman, Howard J

    2006-02-15

    Mutations in the LMNA gene encoding A-type lamins cause several diseases, including Emery-Dreifuss muscular dystrophy and Dunnigan-type familial partial lipodystrophy (FPLD). We analyzed differentiation of 3T3-L1 preadipocytes to adipocytes in cells overexpressing wild-type lamin A as well as lamin A with amino acid substitutions at position 482 that cause FPLD. We also examined adipogenic conversion of mouse embryonic fibroblasts lacking A-type lamins. Overexpression of both wild-type and mutant lamin A inhibited lipid accumulation, triglyceride synthesis and expression of adipogenic markers. This was associated with inhibition of expression of peroxisome-proliferator-activated receptor gamma 2 (PPARgamma2) and Glut4. In contrast, embryonic fibroblasts lacking A-type lamins accumulated more intracellular lipid and exhibited elevated de novo triglyceride synthesis compared with wild-type fibroblasts. They also had increased basal phosphorylation of AKT1, a mediator of insulin signaling. We conclude that A-type lamins act as inhibitors of adipocyte differentiation, possibly by affecting PPARgamma2 and insulin signaling. PMID:16415042

  19. Structural organization of nuclear lamins A, C, B1, and B2 revealed by superresolution microscopy

    PubMed Central

    Shimi, Takeshi; Kittisopikul, Mark; Tran, Joseph; Goldman, Anne E.; Adam, Stephen A.; Zheng, Yixian; Jaqaman, Khuloud; Goldman, Robert D.

    2015-01-01

    The nuclear lamina is a key structural element of the metazoan nucleus. However, the structural organization of the major proteins composing the lamina is poorly defined. Using three-dimensional structured illumination microscopy and computational image analysis, we characterized the supramolecular structures of lamin A, C, B1, and B2 in mouse embryo fibroblast nuclei. Each isoform forms a distinct fiber meshwork, with comparable physical characteristics with respect to mesh edge length, mesh face area and shape, and edge connectivity to form faces. Some differences were found in face areas among isoforms due to variation in the edge lengths and number of edges per face, suggesting that each meshwork has somewhat unique assembly characteristics. In fibroblasts null for the expression of either lamins A/C or lamin B1, the remaining lamin meshworks are altered compared with the lamin meshworks in wild-type nuclei or nuclei lacking lamin B2. Nuclei lacking LA/C exhibit slightly enlarged meshwork faces and some shape changes, whereas LB1-deficient nuclei exhibit primarily a substantial increase in face area. These studies demonstrate that individual lamin isoforms assemble into complex networks within the nuclear lamina and that A- and B-type lamins have distinct roles in maintaining the organization of the nuclear lamina. PMID:26310440

  20. Oxydative stress alters nuclear shape through lamins dysregulation: a route to senescence.

    PubMed

    Barascu, Aurélia; Le Chalony, Catherine; Pennarun, Gaëlle; Genet, Diane; Zaarour, Nancy; Bertrand, Pascale

    2012-01-01

    Progeroid phenotypes are mainly encountered in 2 types of syndromes: in laminopathies, which are characterized by nuclear shape abnormalities due to lamin A alteration, and in DNA damage response defect syndromes. Because lamin A dysregulation leads to DNA damages, it has been proposed that senescence occurs in both types of syndromes through the accumulation of damages. We recently showed that elevated oxidative stress is responsible for lamin B1 accumulation, nuclear shape alteration and senescence in the DDR syndrome, ataxia telangiectasia (A-T). Interestingly, overexpression of lamin B1 in wild type cells is sufficient to induce senescence without the induction of DNA damages. Here, we will discuss the importance of controlling the lamins level in order for maintenance nuclear architecture and we will comment the relationships of lamins with other senescence mechanisms. Finally, we will describe emerging data reporting redox control by lamins, leading us to propose a general mechanism by which reactive oxygen species can induce senescence through lamin dysregulation and NSA. PMID:22895091

  1. Lamin Mutations Accelerate Aging via Defective Export of Mitochondrial mRNAs through Nuclear Envelope Budding.

    PubMed

    Li, Yihang; Hassinger, Linda; Thomson, Travis; Ding, Baojin; Ashley, James; Hassinger, William; Budnik, Vivian

    2016-08-01

    Defective RNA metabolism and transport are implicated in aging and degeneration [1, 2], but the underlying mechanisms remain poorly understood. A prevalent feature of aging is mitochondrial deterioration [3]. Here, we link a novel mechanism for RNA export through nuclear envelope (NE) budding [4, 5] that requires A-type lamin, an inner nuclear membrane-associated protein, to accelerated aging observed in Drosophila LaminC (LamC) mutations. These LamC mutations were modeled after A-lamin (LMNA) mutations causing progeroid syndromes (PSs) in humans. We identified mitochondrial assembly regulatory factor (Marf), a mitochondrial fusion factor (mitofusin), as well as other transcripts required for mitochondrial integrity and function, in a screen for RNAs that exit the nucleus through NE budding. PS-modeled LamC mutations induced premature aging in adult flight muscles, including decreased levels of specific mitochondrial protein transcripts (RNA) and progressive mitochondrial degradation. PS-modeled LamC mutations also induced the accelerated appearance of other phenotypes associated with aging, including a progressive accumulation of polyubiquitin aggregates [6, 7] and myofibril disorganization [8, 9]. Consistent with these observations, the mutants had progressive jumping and flight defects. Downregulating marf alone induced the above aging defects. Nevertheless, restoring marf was insufficient for rescuing the aging phenotypes in PS-modeled LamC mutations, as other mitochondrial RNAs are affected by inhibition of NE budding. Analysis of NE budding in dominant and recessive PS-modeled LamC mutations suggests a mechanism by which abnormal lamina organization prevents the egress of these RNAs via NE budding. These studies connect defects in RNA export through NE budding to progressive loss of mitochondrial integrity and premature aging. PMID:27451905

  2. Invertebrate lamins

    SciTech Connect

    Melcer, Shai; Gruenbaum, Yosef . E-mail: gru@vms.huji.ac.il; Krohne, Georg . E-mail: krohne@biozentrum.uni-wuerzburg.de

    2007-06-10

    Lamins are the main component of the nuclear lamina and considered to be the ancestors of all intermediate filament proteins. They are localized mainly at the nuclear periphery where they form protein complexes with integral proteins of the nuclear inner membrane, transcriptional regulators, histones and chromatin modifiers. Studying lamins in invertebrate species has unique advantages including the smaller number of lamin genes in the invertebrate genomes and powerful genetic analyses in Caenorhabditis elegans and Drosophila melanogaster. These simpler nuclear lamina systems allow direct analyses of their structure and functions. Here we give an overview of recent advances in the field of invertebrate nuclear lamins with special emphasis on their evolution, assembly and functions.

  3. Type B lamins remain associated with the integral nuclear envelope protein p58 during mitosis: implications for nuclear reassembly.

    PubMed Central

    Meier, J; Georgatos, S D

    1994-01-01

    p58 (also referred to as the lamin B receptor) is an integral membrane protein of the nuclear envelope known to form a multimeric complex with the lamins and other nuclear proteins during interphase. To examine the fate of this complex during mitosis, we have investigated the partitioning and the molecular interactions of p58 in dividing chicken hepatoma (DU249) cells. Using confocal microscopy and double immunolabelling, we show here that lamins B1 and B2 co-localize with p58 during all phases of mitosis and co-assemble around reforming nuclei. A close juxtaposition of p58/lamin B-containing vesicles and chromosomes is already detectable in metaphase; however, p58 and lamin reassembly proceeds slowly and is completed in late telophase--G1. Flotation of mitotic membranes in sucrose density gradients and analysis of mitotic vesicles by immunoelectron microscopy confirms that p58 and most of the type B lamins reside in the same compartment. Co-immunoprecipitation of both proteins by affinity-purified anti-p58 antibodies shows that they are physically associated in the context of a mitotic p58 'sub-complex'. This sub-assembly does not include the type A lamins which are fully solubilized during mitosis. Our data provide direct, in vivo and in vitro evidence that the majority of type B lamins remain connected to nuclear membrane 'receptors' during mitosis. The implications of these findings in nuclear envelope reassembly are discussed below. Images PMID:8168487

  4. Nuclear lamins are not required for lamina-associated domain organization in mouse embryonic stem cells

    PubMed Central

    Amendola, Mario; van Steensel, Bas

    2015-01-01

    In mammals, the nuclear lamina interacts with hundreds of large genomic regions, termed lamina-associated domains (LADs) that are generally in a transcriptionally repressed state. Lamins form the major structural component of the lamina and have been reported to bind DNA and chromatin. Here, we systematically evaluate whether lamins are necessary for the LAD organization in murine embryonic stem cells. Surprisingly, removal of essentially all lamins does not have any detectable effect on the genome-wide interaction pattern of chromatin with emerin, a marker of the inner nuclear membrane. This suggests that other components of the lamina mediate these interactions. PMID:25784758

  5. Mutations in the nuclear lamin proteins resulting in their aberrant assembly in the cytoplasm.

    PubMed Central

    Loewinger, L; McKeon, F

    1988-01-01

    We have constructed a series of mutations in the human A lamin cDNA to identify and alter the nuclear localization signal using an in vivo functional assay system. The nuclear localization signal in the lamin proteins has both structural and functional similarities with that of the SV40 large T-antigen. Mutations within this functional domain result in the assembly of cytoplasmic tubular structures, and the behavior of these mutants suggests a post-translational dimerization of the lamin proteins prior to their transport into the nucleus. In the course of this work other regions of the carboxy terminus of the A/C lamin proteins have been implicated in the proper assembly and structure of the nuclear envelope. Images PMID:3056713

  6. The A- and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription

    PubMed Central

    Shimi, Takeshi; Pfleghaar, Katrin; Kojima, Shin-ichiro; Pack, Chan-Gi; Solovei, Irina; Goldman, Anne E.; Adam, Stephen A.; Shumaker, Dale K.; Kinjo, Masataka; Cremer, Thomas; Goldman, Robert D.

    2008-01-01

    The nuclear lamins function in the regulation of replication, transcription, and epigenetic modifications of chromatin. However, the mechanisms responsible for these lamin functions are poorly understood. We demonstrate that A- and B-type lamins form separate, but interacting, stable meshworks in the lamina and have different mobilities in the nucleoplasm as determined by fluorescence correlation spectroscopy (FCS). Silencing lamin B1 (LB1) expression dramatically increases the lamina meshwork size and the mobility of nucleoplasmic lamin A (LA). The changes in lamina mesh size are coupled to the formation of LA/C-rich nuclear envelope blebs deficient in LB2. Comparative genomic hybridization (CGH) analyses of microdissected blebs, fluorescence in situ hybridization (FISH), and immunofluorescence localization of modified histones demonstrate that gene-rich euchromatin associates with the LA/C blebs. Enrichment of hyperphosphorylated RNA polymerase II (Pol II) and histone marks for active transcription suggest that blebs are transcriptionally active. However, in vivo labeling of RNA indicates that transcription is decreased, suggesting that the LA/C-rich microenvironment induces promoter proximal stalling of Pol II. We propose that different lamins are organized into separate, but interacting, microdomains and that LB1 is essential for their organization. Our evidence suggests that the organization and regulation of chromatin are influenced by interconnections between these lamin microdomains. PMID:19141474

  7. Analyses of the Dynamic Properties of Nuclear Lamins by Fluorescence Recovery After Photobleaching (FRAP) and Fluorescence Correlation Spectroscopy (FCS).

    PubMed

    Takeshi, Shimi; Pack, Chan-Gi; Goldman, Robert D

    2016-01-01

    The major structural components of the nuclear lamina are the A- and B-type nuclear lamin proteins which are also present in the nucleoplasm. Studies of molecular movements of the lamins in both the lamina and nucleoplasm of living cell nuclei have provided insights into their roles in maintaining nuclear architecture. In this chapter, we present protocols for quantitatively measuring the mobilities of lamin proteins by fluorescence recovery after photobleaching (FRAP) and fluorescence correlation spectroscopy (FCS) in mammalian cell nuclei. PMID:27147036

  8. Loss of lamin A function increases chromatin dynamics in the nuclear interior

    PubMed Central

    Bronshtein, I.; Kepten, E.; Kanter, I.; Berezin, S.; Lindner, M.; Redwood, Abena B.; Mai, S; Gonzalo, S.; Foisner, R.; Shav-Tal, Y.; Garini, Y.

    2015-01-01

    Chromatin is organized in a highly ordered yet dynamic manner in the cell nucleus, but the principles governing this organization remain unclear. Similarly, it is unknown whether, and how, various proteins regulate chromatin motion and as a result influence nuclear organization. Here by studying the dynamics of different genomic regions in the nucleus of live cells, we show that the genome has highly constrained dynamics. Interestingly, depletion of lamin A strikingly alters genome dynamics, inducing a dramatic transition from slow anomalous diffusion to fast and normal diffusion. In contrast, depletion of LAP2α, a protein that interacts with lamin A and chromatin, has no such effect on genome dynamics. We speculate that chromosomal inter-chain interactions formed by lamin A throughout the nucleus contribute to chromatin dynamics, and suggest that the molecular regulation of chromatin diffusion by lamin A in the nuclear interior is critical for the maintenance of genome organization. PMID:26299252

  9. Loss of lamin A function increases chromatin dynamics in the nuclear interior

    NASA Astrophysics Data System (ADS)

    Bronshtein, I.; Kepten, E.; Kanter, I.; Berezin, S.; Lindner, M.; Redwood, Abena B.; Mai, S.; Gonzalo, S.; Foisner, R.; Shav-Tal, Y.; Garini, Y.

    2015-08-01

    Chromatin is organized in a highly ordered yet dynamic manner in the cell nucleus, but the principles governing this organization remain unclear. Similarly, it is unknown whether, and how, various proteins regulate chromatin motion and as a result influence nuclear organization. Here by studying the dynamics of different genomic regions in the nucleus of live cells, we show that the genome has highly constrained dynamics. Interestingly, depletion of lamin A strikingly alters genome dynamics, inducing a dramatic transition from slow anomalous diffusion to fast and normal diffusion. In contrast, depletion of LAP2α, a protein that interacts with lamin A and chromatin, has no such effect on genome dynamics. We speculate that chromosomal inter-chain interactions formed by lamin A throughout the nucleus contribute to chromatin dynamics, and suggest that the molecular regulation of chromatin diffusion by lamin A in the nuclear interior is critical for the maintenance of genome organization.

  10. Nuclear lamin stiffness is a barrier to 3D migration, but softness can limit survival

    PubMed Central

    Harada, Takamasa; Swift, Joe; Irianto, Jerome; Shin, Jae-Won; Spinler, Kyle R.; Athirasala, Avathamsa; Diegmiller, Rocky; Dingal, P.C. Dave P.; Ivanovska, Irena L.

    2014-01-01

    Cell migration through solid tissue often involves large contortions of the nucleus, but biological significance is largely unclear. The nucleoskeletal protein lamin-A varies both within and between cell types and was shown here to contribute to cell sorting and survival in migration through constraining micropores. Lamin-A proved rate-limiting in 3D migration of diverse human cells that ranged from glioma and adenocarcinoma lines to primary mesenchymal stem cells (MSCs). Stoichiometry of A- to B-type lamins established an activation barrier, with high lamin-A:B producing extruded nuclear shapes after migration. Because the juxtaposed A and B polymer assemblies respectively conferred viscous and elastic stiffness to the nucleus, subpopulations with different A:B levels sorted in 3D migration. However, net migration was also biphasic in lamin-A, as wild-type lamin-A levels protected against stress-induced death, whereas deep knockdown caused broad defects in stress resistance. In vivo xenografts proved consistent with A:B-based cell sorting, and intermediate A:B-enhanced tumor growth. Lamins thus impede 3D migration but also promote survival against migration-induced stresses. PMID:24567359

  11. An absence of nuclear lamins in keratinocytes leads to ichthyosis, defective epidermal barrier function, and intrusion of nuclear membranes and endoplasmic reticulum into the nuclear chromatin.

    PubMed

    Jung, Hea-Jin; Tatar, Angelica; Tu, Yiping; Nobumori, Chika; Yang, Shao H; Goulbourne, Chris N; Herrmann, Harald; Fong, Loren G; Young, Stephen G

    2014-12-01

    B-type lamins (lamins B1 and B2) have been considered to be essential for many crucial functions in the cell nucleus (e.g., DNA replication and mitotic spindle formation). However, this view has been challenged by the observation that an absence of both B-type lamins in keratinocytes had no effect on cell proliferation or the development of skin and hair. The latter findings raised the possibility that the functions of B-type lamins are subserved by lamins A and C. To explore that idea, we created mice lacking all nuclear lamins in keratinocytes. Those mice developed ichthyosis and a skin barrier defect, which led to death from dehydration within a few days after birth. Microscopy of nuclear-lamin-deficient skin revealed hyperkeratosis and a disordered stratum corneum with an accumulation of neutral lipid droplets; however, BrdU incorporation into keratinocytes was normal. Skin grafting experiments confirmed the stratum corneum abnormalities and normal BrdU uptake. Interestingly, the absence of nuclear lamins in keratinocytes resulted in an interspersion of nuclear/endoplasmic reticulum membranes with the chromatin. Thus, a key function of the nuclear lamina is to serve as a "fence" and prevent the incursion of cytoplasmic organelles into the nuclear chromatin. PMID:25312645

  12. An Absence of Nuclear Lamins in Keratinocytes Leads to Ichthyosis, Defective Epidermal Barrier Function, and Intrusion of Nuclear Membranes and Endoplasmic Reticulum into the Nuclear Chromatin

    PubMed Central

    Jung, Hea-Jin; Tatar, Angelica; Tu, Yiping; Nobumori, Chika; Yang, Shao H.; Goulbourne, Chris N.; Herrmann, Harald

    2014-01-01

    B-type lamins (lamins B1 and B2) have been considered to be essential for many crucial functions in the cell nucleus (e.g., DNA replication and mitotic spindle formation). However, this view has been challenged by the observation that an absence of both B-type lamins in keratinocytes had no effect on cell proliferation or the development of skin and hair. The latter findings raised the possibility that the functions of B-type lamins are subserved by lamins A and C. To explore that idea, we created mice lacking all nuclear lamins in keratinocytes. Those mice developed ichthyosis and a skin barrier defect, which led to death from dehydration within a few days after birth. Microscopy of nuclear-lamin-deficient skin revealed hyperkeratosis and a disordered stratum corneum with an accumulation of neutral lipid droplets; however, BrdU incorporation into keratinocytes was normal. Skin grafting experiments confirmed the stratum corneum abnormalities and normal BrdU uptake. Interestingly, the absence of nuclear lamins in keratinocytes resulted in an interspersion of nuclear/endoplasmic reticulum membranes with the chromatin. Thus, a key function of the nuclear lamina is to serve as a “fence” and prevent the incursion of cytoplasmic organelles into the nuclear chromatin. PMID:25312645

  13. Organization of the lamin scaffold in the internal nuclear matrix of normal and transformed hepatocytes

    SciTech Connect

    Barboro, Paola; D'Arrigo, Cristina; Repaci, Erica; Patrone, Eligio; Balbi, Cecilia

    2010-04-01

    Nuclear lamins are among the more abundant proteins making up the internal nuclear matrix, but very little is known about their structure in the nucleoplasm. Using immunoelectron microscopy, we demonstrate the organization of lamins in the nuclear matrix isolated from rat hepatocytes for the first time. Lamin epitopes are arrayed both in locally ordered clusters and in quasi-regular rows. Fourier filtering of the images demonstrates that the epitopes are placed at the nodes and halfway between the nodes of square or rhombic lattices that are about 50 nm on each side, as well as along rows at regular {approx}25-nm intervals. In addition, we have compared this structure with that of the internal nuclear matrix isolated from persistent hepatocyte nodules. In transformed hepatocytes, the islands of lamin lattice are lost, and only a partial regularity in the rows of gold particles remains. We suggest that orthogonal lattice assembly might be an intrinsic property of lamin molecules, and that the disassembly may be triggered by simple molecular events such as phosphorylation.

  14. Adult stem cell maintenance and tissue regeneration in the ageing context: the role for A-type lamins as intrinsic modulators of ageing in adult stem cells and their niches

    PubMed Central

    Pekovic, Vanja; Hutchison, Christopher J

    2008-01-01

    Adult stem cells have been identified in most mammalian tissues of the adult body and are known to support the continuous repair and regeneration of tissues. A generalized decline in tissue regenerative responses associated with age is believed to result from a depletion and/or a loss of function of adult stem cells, which itself may be a driving cause of many age-related disease pathologies. Here we review the striking similarities between tissue phenotypes seen in many degenerative conditions associated with old age and those reported in age-related nuclear envelope disorders caused by mutations in the LMNA gene. The concept is beginning to emerge that nuclear filament proteins, A-type lamins, may act as signalling receptors in the nucleus required for receiving and/or transducing upstream cytosolic signals in a number of pathways central to adult stem cell maintenance as well as adaptive responses to stress. We propose that during ageing and in diseases caused by lamin A mutations, dysfunction of the A-type lamin stress-resistant signalling network in adult stem cells, their progenitors and/or stem cell niches leads to a loss of protection against growth-related stress. This in turn triggers an inappropriate activation or a complete failure of self-renewal pathways with the consequent initiation of stress-induced senescence. As such, A-type lamins should be regarded as intrinsic modulators of ageing within adult stem cells and their niches that are essential for survival to old age. PMID:18638067

  15. B-type nuclear lamin and the nuclear pore complex Nup107-160 influences maintenance of the spindle envelope required for cytokinesis in Drosophila male meiosis.

    PubMed

    Hayashi, Daisuke; Tanabe, Karin; Katsube, Hiroka; Inoue, Yoshihiro H

    2016-01-01

    In higher eukaryotes, nuclear envelope (NE) disassembly allows chromatin to condense and spindle microtubules to access kinetochores. The nuclear lamina, which strengthens the NE, is composed of a polymer meshwork made of A- and B-type lamins. We found that the B-type lamin (Lam) is not fully disassembled and continues to localize along the spindle envelope structure during Drosophila male meiosis I, while the A-type lamin (LamC) is completely dispersed throughout the cytoplasm. Among the nuclear pore complex proteins, Nup107 co-localized with Lam during this meiotic division. Surprisingly, Lam depletion resulted in a higher frequency of cytokinesis failure in male meiosis. We also observed the similar meiotic phenotype in Nup107-depleted cells. Abnormal localization of Lam was found in the Nup-depleted cells at premeiotic and meiotic stages. The central spindle microtubules became abnormal and recruitment of a contractile ring component to the cleavage sites was disrupted in Lam-depleted cells and Nup107-depleted cells. Therefore, we speculate that both proteins are required for a reinforcement of the spindle envelope, which supports the formation of central spindle microtubules essential for cytokinesis in Drosophila male meiosis. PMID:27402967

  16. B-type nuclear lamin and the nuclear pore complex Nup107-160 influences maintenance of the spindle envelope required for cytokinesis in Drosophila male meiosis

    PubMed Central

    Hayashi, Daisuke; Tanabe, Karin; Katsube, Hiroka

    2016-01-01

    ABSTRACT In higher eukaryotes, nuclear envelope (NE) disassembly allows chromatin to condense and spindle microtubules to access kinetochores. The nuclear lamina, which strengthens the NE, is composed of a polymer meshwork made of A- and B-type lamins. We found that the B-type lamin (Lam) is not fully disassembled and continues to localize along the spindle envelope structure during Drosophila male meiosis I, while the A-type lamin (LamC) is completely dispersed throughout the cytoplasm. Among the nuclear pore complex proteins, Nup107 co-localized with Lam during this meiotic division. Surprisingly, Lam depletion resulted in a higher frequency of cytokinesis failure in male meiosis. We also observed the similar meiotic phenotype in Nup107-depleted cells. Abnormal localization of Lam was found in the Nup-depleted cells at premeiotic and meiotic stages. The central spindle microtubules became abnormal and recruitment of a contractile ring component to the cleavage sites was disrupted in Lam-depleted cells and Nup107-depleted cells. Therefore, we speculate that both proteins are required for a reinforcement of the spindle envelope, which supports the formation of central spindle microtubules essential for cytokinesis in Drosophila male meiosis. PMID:27402967

  17. CTP:phosphocholine cytidylyltransferase α (CCTα) and lamins alter nuclear membrane structure without affecting phosphatidylcholine synthesis.

    PubMed

    Gehrig, Karsten; Ridgway, Neale D

    2011-06-01

    CTP:phosphocholine cytidylyltransferase α (CCTα) is a nuclear enzyme that catalyzes the rate-limiting step in the CDP-choline pathway for phosphatidylcholine (PC) synthesis. Lipid activation of CCTα results in its translocation to the nuclear envelope and expansion of an intranuclear membrane network termed the nucleoplasmic reticulum (NR) by a mechanism involving membrane deformation. Nuclear lamins are also required for stability and proliferation of the NR, but whether this unique structure, or the nuclear lamina in general, is required for PC synthesis is not known. To examine this relationship, the nuclear lamina was depleted by RNAi or disrupted by expression of the Hutchinson-Gilford progeria syndrome (HGPS) mutant lamin A (progerin), and the effect on CCTα and choline metabolism was analyzed. siRNA-mediated silencing of lamin A/C or lamin B1 in CHO cells to diminish the NR had no effect on PC synthesis, while double knockdown non-specifically inhibited the pathway. Confirming this minor role in PC synthesis, only 10% of transiently overexpressed choline/ethanolamine phosphotransferase was detected in the NR. In CHO cells, CCTα was nucleoplasmic and co-localized with GFP-progerin in nuclear folds and invaginations; however, HGPS fibroblasts displayed an abnormal distribution of CCTα in the cytoplasm and nuclear envelope that was accompanied by a 2-fold reduction in PC synthesis. In spite of its altered localization, choline-labeling experiments showed that CCT activity was unaffected, and inhibition of PC synthesis was traced to reduced activity of a hemicholinium-sensitive choline transporter. We conclude that CCTα and lamins specifically cooperate to form the NR, but the overall structure of the nuclear envelope has a minimal impact on CCT activity and PC synthesis. PMID:21504799

  18. Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C–deficient mice

    PubMed Central

    Nikolova, Vesna; Leimena, Christiana; McMahon, Aisling C.; Tan, Ju Chiat; Chandar, Suchitra; Jogia, Dilesh; Kesteven, Scott H.; Michalicek, Jan; Otway, Robyn; Verheyen, Fons; Rainer, Stephen; Stewart, Colin L.; Martin, David; Feneley, Michael P.; Fatkin, Diane

    2004-01-01

    Laminopathies are a group of disorders caused by mutations in the LMNA gene that encodes the nuclear lamina proteins, lamin A and lamin C; their pathophysiological basis is unknown. We report that lamin A/C–deficient (Lmna–/–) mice develop rapidly progressive dilated cardiomyopathy (DCM) characterized by left ventricular (LV) dilation and reduced systolic contraction. Isolated Lmna–/– myocytes show reduced shortening with normal baseline and peak amplitude of Ca2+ transients. Lmna–/– LV myocyte nuclei have marked alterations of shape and size with central displacement and fragmentation of heterochromatin; these changes are present but less severe in left atrial nuclei. Electron microscopy of Lmna–/– cardiomyocytes shows disorganization and detachment of desmin filaments from the nuclear surface with progressive disruption of the cytoskeletal desmin network. Alterations in nuclear architecture are associated with defective nuclear function evidenced by decreased SREBP1 import, reduced PPARγ expression, and a lack of hypertrophic gene activation. These findings suggest a model in which the primary pathophysiological mechanism in Lmna–/– mice is defective force transmission resulting from disruption of lamin interactions with the muscle-specific desmin network and loss of cytoskeletal tension. Despite severe DCM, defects in nuclear function prevent Lmna–/– cardiomyocytes from developing compensatory hypertrophy and accelerate disease progression. PMID:14755333

  19. Lamins at the crossroads of mechanosignaling

    PubMed Central

    Osmanagic-Myers, Selma; Dechat, Thomas

    2015-01-01

    The intermediate filament proteins, A- and B-type lamins, form the nuclear lamina scaffold adjacent to the inner nuclear membrane. B-type lamins confer elasticity, while A-type lamins lend viscosity and stiffness to nuclei. Lamins also contribute to chromatin regulation and various signaling pathways affecting gene expression. The mechanical roles of lamins and their functions in gene regulation are often viewed as independent activities, but recent findings suggest a highly cross-linked and interdependent regulation of these different functions, particularly in mechanosignaling. In this newly emerging concept, lamins act as a “mechanostat” that senses forces from outside and responds to tension by reinforcing the cytoskeleton and the extracellular matrix. A-type lamins, emerin, and the linker of the nucleoskeleton and cytoskeleton (LINC) complex directly transmit forces from the extracellular matrix into the nucleus. These mechanical forces lead to changes in the molecular structure, modification, and assembly state of A-type lamins. This in turn activates a tension-induced “inside-out signaling” through which the nucleus feeds back to the cytoskeleton and the extracellular matrix to balance outside and inside forces. These functions regulate differentiation and may be impaired in lamin-linked diseases, leading to cellular phenotypes, particularly in mechanical load-bearing tissues. PMID:25644599

  20. Structural organization of the human gene (LMNB1) encoding nuclear lamin B1

    SciTech Connect

    Lin, F.; Worman, H.J.

    1995-05-20

    The authors have determined the structural organization of the human gene (LMNB1) that encodes nuclear lamin B1, an intermediate filament protein of the nuclear envelope. The transcription unit spans more than 45 kb and the transcription start site is 348 nucleotides upstream from the translation initiation codon. Lamin B1 is encoded by 11 exons. Exon 1 codes for the amino-terminal head domain and the first portion of the central rod domain, exons 2 through 6 the central rod domain, and exons 7 through 11 the carboxyl-terminal tail domain of this intermediate filament protein. Intron positions are conserved in other lamin genes from frogs, mice, and humans but different in lamin genes from Drosophila melanogaster and Caenorhabditis elegans. In the region encoding the central rod domain, intron positions are also similar to those in the gene for an invertebrate nonneuronal cytoplasmic intermediate filament protein and the genes for most vertebrate cytoplasmic intermediate filament proteins except neurofilaments and nestin. 51 refs., 3 figs.

  1. Lamin A precursor induces barrier-to-autointegration factor nuclear localization.

    PubMed

    Capanni, Cristina; Cenni, Vittoria; Haraguchi, Tokuko; Squarzoni, Stefano; Schüchner, Stefan; Ogris, Egon; Novelli, Giuseppe; Maraldi, Nadir; Lattanzi, Giovanna

    2010-07-01

    Lamin A, a protein component of the nuclear lamina, is synthesized as a precursor named prelamin A, whose multi-step maturation process involves different protein intermediates. As demonstrated in laminopathies such as familial partial lipodystrophy, mandibuloacral dysplasia, Werner syndrome, Hutchinson-Gilford progeria syndrome and restrictive dermopathy, failure of prelamin A processing results in the accumulation of lamin A protein precursors inside the nucleus which dominantly produces aberrant chromatin structure. To understand if nuclear lamina components may be involved in prelamin A chromatin remodeling effects, we investigated barrier-to-autointegration factor (BAF) localization and expression in prelamin A accumulating cells. BAF is a DNA-binding protein that interacts directly with histones, lamins and LEM-domain proteins and has roles in chromatin structure, mitosis and gene regulation. In this study, we show that the BAF heterogeneous localization between nucleus and cytoplasm observed in HEK293 cycling cells changes in response to prelamin A accumulation. In particular, we observed that the accumulation of lamin A, non-farnesylated prelamin A and farnesylated carboxymethylated lamin A precursors induce BAF nuclear translocation. Moreover, we show that the treatment of human fibroblasts with prelamin A interfering drugs results in similar changes. Finally, we report that the accumulation of progerin, a truncated form of farnesylated and carboxymethylated prelamin A identified in Hutchinson-Gilford progeria syndrome cells, induces BAF recruitment in the nucleus. These findings are supported by coimmunoprecipitation of prelamin A or progerin with BAF in vivo and suggest that BAF could mediate prelamin A-induced chromatin effects. PMID:20581439

  2. The role of lamin B1 for the maintenance of nuclear structure and function

    PubMed Central

    Camps, Jordi; Erdos, Michael R; Ried, Thomas

    2015-01-01

    Abstract Lamins constitute an integral structural component of the nuclear lamina. However, their impact on the structure and stability of chromosome territories, and on the regulation of gene expression is explored to a lesser extent. By 3D-FISH, Camps and colleagues showed that lamin B1 (LMNB1) is required for proper chromosome condensation in interphase nuclei, and deficiency of LMNB1 triggers the relocation of the epigenetic mark of facultative heterochromatin, H3K27me3, toward the interior of the nucleus. Additionally, LMNB1 repression slowed cellular growth due to S-phase delays and increased genomic instability. Finally, silencing of LMNB1 resulted in enlarged nuclear speckles and in extensive changes in alternative splicing of multiple genes. Altogether, the data suggest a central role of LMNB1 for the condensation of chromosome territories, for the distribution of heterochromatin, and for the regulation of gene expression and splicing. PMID:25602590

  3. Expression of nuclear lamin A and muscle-specific proteins in differentiating muscle cells in ovo and in vitro

    PubMed Central

    1989-01-01

    Primary cultures and tissue samples of chicken embryonic muscle were immunologically probed for the expression of muscle-specific proteins, such as myosin heavy chain and the tropomyosins, as well as for the nuclear lamina protein, lamin A. As determined by quantitative immunoblotting, the expression of lamin A and the muscle-specific proteins were at low levels or absent in predifferentiation myoblasts both in vitro and in ovo. During differentiation, an increase of lamin A expression preceded the induction to high levels of expression of muscle-specific proteins. Immunofluorescence staining of chicken embryonic muscle cells in culture also indicates an accumulation of lamin A before the induction of muscle-specific proteins expression. Furthermore, the accumulation of lamin A reached a plateau before the muscle-specific proteins during muscle development. In two dimensional NEPHGE gel analysis of immunoprecipitated lamin A, no detectable change in the ratio of the acidic/basic isoelectric variants of lamin A was observed during myogenesis. A potential role for lamin A in the mechanisms which underlie the differential and coordinate expression of muscle-specific genes is proposed. PMID:2668298

  4. Phosphorylation of lamins determine their structural properties and signaling functions

    PubMed Central

    Torvaldson, Elin; Kochin, Vitaly; Eriksson, John E

    2015-01-01

    Lamin A/C is part of the nuclear lamina, a meshwork of intermediate filaments underlying the inner nuclear membrane. The lamin network is anchoring a complex set of structural and linker proteins and is either directly or through partner proteins also associated or interacting with a number of signaling protein and transcription factors. During mitosis the nuclear lamina is dissociated by well established phosphorylation- dependent mechanisms. A-type lamins are, however, also phosphorylated during interphase. A recent study identified 20 interphase phosphorylation sites on lamin A/C and explored their functions related to lamin dynamics; movements, localization and solubility. Here we discuss these findings in the light of lamin functions in health and disease. PMID:25793944

  5. β-Amyloid induces nuclear protease-mediated lamin fragmentation independent of caspase activation.

    PubMed

    Ramasamy, Vijay Sankar; Islam, Md Imamul; Haque, Md Aminul; Shin, Song Yub; Park, Il-Seon

    2016-06-01

    β-Amyloid (Aβ), a hallmark peptide of Alzheimer's disease, induces both caspase-dependent apoptosis and non-apoptotic cell death. In this study, we examined caspase-independent non-apoptotic cell death preceding caspase activation in Aβ42-treated cells. We first determined the optimal treatment conditions for inducing cell death without caspase activation and selected a double-treatment method involving the incubation of cells with Aβ42 for 4 and 6h (4+6h sample). We observed that levels of lamin A (LA) and lamin B (LB) were reduced in the 4+6h samples. This reduction was decreased by treatment with suc-AAPF-CMK, an inhibitor of nuclear scaffold (NS) protease, but not by treatment with z-VAD-FMK, a pan-caspase inhibitor. In addition, suc-AAPF-CMK decreased the changes in nuclear morphology observed in cells in the 4+6h samples, which were different from nuclear fragmentation observed in STS-treated cells. Furthermore, suc-AAPF-CMK inhibited cell death in the 4+6h samples. LA and LB fragmentation occurred in the isolated nuclei and was also inhibited by suc-AAPF-CMK. Together, these data indicated that the fragmentation of LA and LB in the Aβ42-treated cells was induced by an NS protease, whose identity is not clearly determined yet. A correlation between Aβ42 toxicity and the lamin fragmentation by NS protease suggests that inhibition of the protease could be an effective method for controlling the pathological process of AD. PMID:26876308

  6. Molecular Genetic Analysis of the Nested Drosophila melanogaster Lamin C Gene

    PubMed Central

    Schulze, Sandra R.; Curio-Penny, Beatrice; Li, Yuhong; Imani, Reza A.; Rydberg, Lena; Geyer, Pamela K.; Wallrath, Lori L.

    2005-01-01

    Lamins are intermediate filaments that line the inner surface of the nuclear envelope, providing structural support and making contacts with chromatin. There are two types of lamins, A- and B-types, which differ in structure and expression. Drosophila possesses both lamin types, encoded by the LamC (A-type) and lamin Dm0 (B-type) genes. LamC is nested within an intron of the essential gene ttv. We demonstrate that null mutations in LamC are lethal, and expression of a wild-type LamC transgene rescues lethality of LamC but not ttv mutants. Mutations in the human A-type lamin gene lead to diseases called laminopathies. To determine if Drosophila might serve as a useful model to study lamin biology and disease mechanisms, we generated transgenic flies expressing mutant LamC proteins modeled after human disease-causing lamins. These transgenic animals display a nuclear lamin aggregation phenotype remarkably similar to that observed when human mutant A-type lamins are expressed in mammalian cells. LamC aggregates also cause disorganization of lamin Dm0, indicating interdependence of both lamin types for proper lamina assembly. Taken together, these data provide the first detailed genetic analysis of the LamC gene and support using Drosophila as a model to study the role of lamins in disease. PMID:15965247

  7. In silico synchronization reveals regulators of nuclear ruptures in lamin A/C deficient model cells

    PubMed Central

    Robijns, J.; Molenberghs, F.; Sieprath, T.; Corne, T. D. J.; Verschuuren, M.; De Vos, W. H.

    2016-01-01

    The nuclear lamina is a critical regulator of nuclear structure and function. Nuclei from laminopathy patient cells experience repetitive disruptions of the nuclear envelope, causing transient intermingling of nuclear and cytoplasmic components. The exact causes and consequences of these events are not fully understood, but their stochastic occurrence complicates in-depth analyses. To resolve this, we have established a method that enables quantitative investigation of spontaneous nuclear ruptures, based on co-expression of a firmly bound nuclear reference marker and a fluorescent protein that shuttles between the nucleus and cytoplasm during ruptures. Minimally invasive imaging of both reporters, combined with automated tracking and in silico synchronization of individual rupture events, allowed extracting information on rupture frequency and recovery kinetics. Using this approach, we found that rupture frequency correlates inversely with lamin A/C levels, and can be reduced in genome-edited LMNA knockout cells by blocking actomyosin contractility or inhibiting the acetyl-transferase protein NAT10. Nuclear signal recovery followed a kinetic that is co-determined by the severity of the rupture event, and could be prolonged by knockdown of the ESCRT-III complex component CHMP4B. In conclusion, our approach reveals regulators of nuclear rupture induction and repair, which may have critical roles in disease development. PMID:27461848

  8. In silico synchronization reveals regulators of nuclear ruptures in lamin A/C deficient model cells.

    PubMed

    Robijns, J; Molenberghs, F; Sieprath, T; Corne, T D J; Verschuuren, M; De Vos, W H

    2016-01-01

    The nuclear lamina is a critical regulator of nuclear structure and function. Nuclei from laminopathy patient cells experience repetitive disruptions of the nuclear envelope, causing transient intermingling of nuclear and cytoplasmic components. The exact causes and consequences of these events are not fully understood, but their stochastic occurrence complicates in-depth analyses. To resolve this, we have established a method that enables quantitative investigation of spontaneous nuclear ruptures, based on co-expression of a firmly bound nuclear reference marker and a fluorescent protein that shuttles between the nucleus and cytoplasm during ruptures. Minimally invasive imaging of both reporters, combined with automated tracking and in silico synchronization of individual rupture events, allowed extracting information on rupture frequency and recovery kinetics. Using this approach, we found that rupture frequency correlates inversely with lamin A/C levels, and can be reduced in genome-edited LMNA knockout cells by blocking actomyosin contractility or inhibiting the acetyl-transferase protein NAT10. Nuclear signal recovery followed a kinetic that is co-determined by the severity of the rupture event, and could be prolonged by knockdown of the ESCRT-III complex component CHMP4B. In conclusion, our approach reveals regulators of nuclear rupture induction and repair, which may have critical roles in disease development. PMID:27461848

  9. In silico synchronization reveals regulators of nuclear ruptures in lamin A/C deficient model cells

    NASA Astrophysics Data System (ADS)

    Robijns, J.; Molenberghs, F.; Sieprath, T.; Corne, T. D. J.; Verschuuren, M.; de Vos, W. H.

    2016-07-01

    The nuclear lamina is a critical regulator of nuclear structure and function. Nuclei from laminopathy patient cells experience repetitive disruptions of the nuclear envelope, causing transient intermingling of nuclear and cytoplasmic components. The exact causes and consequences of these events are not fully understood, but their stochastic occurrence complicates in-depth analyses. To resolve this, we have established a method that enables quantitative investigation of spontaneous nuclear ruptures, based on co-expression of a firmly bound nuclear reference marker and a fluorescent protein that shuttles between the nucleus and cytoplasm during ruptures. Minimally invasive imaging of both reporters, combined with automated tracking and in silico synchronization of individual rupture events, allowed extracting information on rupture frequency and recovery kinetics. Using this approach, we found that rupture frequency correlates inversely with lamin A/C levels, and can be reduced in genome-edited LMNA knockout cells by blocking actomyosin contractility or inhibiting the acetyl-transferase protein NAT10. Nuclear signal recovery followed a kinetic that is co-determined by the severity of the rupture event, and could be prolonged by knockdown of the ESCRT-III complex component CHMP4B. In conclusion, our approach reveals regulators of nuclear rupture induction and repair, which may have critical roles in disease development.

  10. Nucleoplasmic localization of prelamin A: implications for prenylation-dependent lamin A assembly into the nuclear lamina.

    PubMed Central

    Lutz, R J; Trujillo, M A; Denham, K S; Wenger, L; Sinensky, M

    1992-01-01

    The synthesis of the nuclear lamina protein lamin A requires the prenylation-dependent processing of its precursor protein, prelamin A. Unlike p21ras, which undergoes similar initial posttranslational modifications, maturation of lamin A results in the proteolytic removal of the prenylated portion of the molecule. We have used an in vitro prenylation system to demonstrate the nature of the prenyl substituent on prelamin A to be a farnesyl group. Further, the in vitro farnesylation of prelamin A requires an intact cysteine-aliphatic-aliphatic-other (CAAX) amino acid sequence motif at its carboxyl terminus. The effect of blocking the prenylation of prelamin A on its localization and assembly into the nuclear lamina was investigated by indirect immunofluorescence. Expression of wild-type prelamin A in lovastatin-treated cells showed that nonprenylated prelamin A accumulated as nucleoplasmic particles. Upon addition of mevalonate to lovastatin-treated cells, the wild-type lamin A was incorporated into the lamina within 3 hr. Expression of a mutant lamin A in which the carboxyl-terminal 21 amino acids were deleted resulted in a lamin molecule that was directly assembled into the lamina. These results indicate that the carboxyl-terminal peptide of prelamin A blocks its proper assembly into the nuclear lamina and that the prenylation-initiated removal of this peptide can occur in the nucleus. Images PMID:1557405

  11. Dysregulated interactions between lamin A and SUN1 induce abnormalities in the nuclear envelope and endoplasmic reticulum in progeric laminopathies.

    PubMed

    Chen, Zi-Jie; Wang, Wan-Ping; Chen, Yu-Ching; Wang, Jing-Ya; Lin, Wen-Hsin; Tai, Lin-Ai; Liou, Gan-Guang; Yang, Chung-Shi; Chi, Ya-Hui

    2014-04-15

    Hutchinson-Gilford progeria syndrome (HGPS) is a human progeroid disease caused by a point mutation on the LMNA gene. We reported previously that the accumulation of the nuclear envelope protein SUN1 contributes to HGPS nuclear aberrancies. However, the mechanism by which interactions between mutant lamin A (also known as progerin or LAΔ50) and SUN1 produce HGPS cellular phenotypes requires further elucidation. Using light and electron microscopy, this study demonstrated that SUN1 contributes to progerin-elicited structural changes in the nuclear envelope and the endoplasmic reticulum (ER) network. We further identified two domains through which full-length lamin A associates with SUN1, and determined that the farnesylated cysteine within the CaaX motif of lamin A has a stronger affinity for SUN1 than does the lamin A region containing amino acids 607 to 656. Farnesylation of progerin enhanced its interaction with SUN1 and reduced SUN1 mobility, thereby promoting the aberrant recruitment of progerin to the ER membrane during postmitotic assembly of the nuclear envelope, resulting in the accumulation of SUN1 over consecutive cellular divisions. These results indicate that the dysregulated interaction of SUN1 and progerin in the ER during nuclear envelope reformation determines the progression of HGPS. PMID:24522183

  12. Polyphyly of nuclear lamin genes indicates an early eukaryotic origin of the metazoan-type intermediate filament proteins

    PubMed Central

    Kollmar, Martin

    2015-01-01

    The nuclear lamina is a protein meshwork associated with the inner side of the nuclear envelope contributing structural, signalling and regulatory functions. Here, I report on the evolution of an important component of the lamina, the lamin intermediate filament proteins, across the eukaryotic tree of life. The lamins show a variety of protein domain and sequence motif architectures beyond the classical α-helical rod, nuclear localisation signal, immunoglobulin domain and CaaX motif organisation, suggesting extension and adaptation of functions in many species. I identified lamin genes not only in metazoa and Amoebozoa as previously described, but also in other opisthokonts including Ichthyosporea and choanoflagellates, in oomycetes, a sub-family of Stramenopiles, and in Rhizaria, implying that they must have been present very early in eukaryotic evolution if not even the last common ancestor of all extant eukaryotes. These data considerably extend the current perception of lamin evolution and have important implications with regard to the evolution of the nuclear envelope. PMID:26024016

  13. Mapping of lamin A- and progerin-interacting genome regions.

    PubMed

    Kubben, Nard; Adriaens, Michiel; Meuleman, Wouter; Voncken, Jan Willem; van Steensel, Bas; Misteli, Tom

    2012-10-01

    Mutations in the A-type lamins A and C, two major components of the nuclear lamina, cause a large group of phenotypically diverse diseases collectively referred to as laminopathies. These conditions often involve defects in chromatin organization. However, it is unclear whether A-type lamins interact with chromatin in vivo and whether aberrant chromatin-lamin interactions contribute to disease. Here, we have used an unbiased approach to comparatively map genome-wide interactions of gene promoters with lamin A and progerin, the mutated lamin A isoform responsible for the premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS) in mouse cardiac myoytes and embryonic fibroblasts. We find that lamin A-associated genes are predominantly transcriptionally silent and that loss of lamin association leads to the relocation of peripherally localized genes, but not necessarily to their activation. We demonstrate that progerin induces global changes in chromatin organization by enhancing interactions with a specific subset of genes in addition to the identified lamin A-associated genes. These observations demonstrate disease-related changes in higher order genome organization in HGPS and provide novel insights into the role of lamin-chromatin interactions in chromatin organization. PMID:22610065

  14. The D4Z4 Macrosatellite Repeat Acts as a CTCF and A-Type Lamins-Dependent Insulator in Facio-Scapulo-Humeral Dystrophy

    PubMed Central

    Boussouar, Amina; Foerster, Andrea M.; Rondier, Delphine; Sacconi, Sabrina; Desnuelle, Claude; Gilson, Eric; Magdinier, Frédérique

    2009-01-01

    Both genetic and epigenetic alterations contribute to Facio-Scapulo-Humeral Dystrophy (FSHD), which is linked to the shortening of the array of D4Z4 repeats at the 4q35 locus. The consequence of this rearrangement remains enigmatic, but deletion of this 3.3-kb macrosatellite element might affect the expression of the FSHD-associated gene(s) through position effect mechanisms. We investigated this hypothesis by creating a large collection of constructs carrying 1 to >11 D4Z4 repeats integrated into the human genome, either at random sites or proximal to a telomere, mimicking thereby the organization of the 4q35 locus. We show that D4Z4 acts as an insulator that interferes with enhancer–promoter communication and protects transgenes from position effect. This last property depends on both CTCF and A-type Lamins. We further demonstrate that both anti-silencing activity of D4Z4 and CTCF binding are lost upon multimerization of the repeat in cells from FSHD patients compared to control myoblasts from healthy individuals, suggesting that FSHD corresponds to a gain-of-function of CTCF at the residual D4Z4 repeats. We propose that contraction of the D4Z4 array contributes to FSHD physio-pathology by acting as a CTCF-dependent insulator in patients. PMID:19247430

  15. Lamins as cancer biomarkers.

    PubMed

    Foster, Clare R; Przyborski, Stefan A; Wilson, Robert G; Hutchison, Christopher J

    2010-02-01

    Lamins are multifunctional proteins that are often aberrantly expressed or localized in tumours. Here, we endeavour to assess their uses as cancer biomarkers: to diagnose tumours, analyse cancer characteristics and predict patient survival. It appears that the nature of lamin function in cancer is very complex. Lamin expression can be variable between and even within cancer subtypes, which limits their uses as diagnostic biomarkers. Expression of A-type lamins is a marker of differentiated tumour cells and has been shown to be a marker of good or poor patient survival depending on tumour subtype. Further research into the functions of lamins in cancer cells and the mechanisms that determine its patterns of expression may provide more potential uses of lamins as cancer biomarkers. PMID:20074078

  16. Lamin B1 Polymorphism Influences Morphology of the Nuclear Envelope, Cell Cycle Progression, and Risk of Neural Tube Defects in Mice

    PubMed Central

    De Castro, Sandra C. P.; Malhas, Ashraf; Leung, Kit-Yi; Gustavsson, Peter; Vaux, David J.; Copp, Andrew J.; Greene, Nicholas D. E.

    2012-01-01

    Neural tube defects (NTDs), including spina bifida and anencephaly, are common birth defects whose complex multigenic causation has hampered efforts to delineate their molecular basis. The effect of putative modifier genes in determining NTD susceptibility may be investigated in mouse models, particularly those that display partial penetrance such as curly tail, a strain in which NTDs result from a hypomorphic allele of the grainyhead-like-3 gene. Through proteomic analysis, we found that the curly tail genetic background harbours a polymorphic variant of lamin B1, lacking one of a series of nine glutamic acid residues. Lamins are intermediate filament proteins of the nuclear lamina with multiple functions that influence nuclear structure, cell cycle properties, and transcriptional regulation. Fluorescence loss in photobleaching showed that the variant lamin B1 exhibited reduced stability in the nuclear lamina. Genetic analysis demonstrated that the variant also affects neural tube closure: the frequency of spina bifida and anencephaly was reduced three-fold when wild-type lamin B1 was bred into the curly tail strain background. Cultured fibroblasts expressing variant lamin B1 show significantly increased nuclear dysmorphology and diminished proliferative capacity, as well as premature senescence, associated with reduced expression of cyclins and Smc2, and increased expression of p16. The cellular basis of spinal NTDs in curly tail embryos involves a proliferation defect localised to the hindgut epithelium, and S-phase progression was diminished in the hindgut of embryos expressing variant lamin B1. These observations indicate a mechanistic link between altered lamin B1 function, exacerbation of the Grhl3-mediated cell proliferation defect, and enhanced susceptibility to NTDs. We conclude that lamin B1 is a modifier gene of major effect for NTDs resulting from loss of Grhl3 function, a role that is likely mediated via the key function of lamin B1 in maintaining

  17. Src1 is a Protein of the Inner Nuclear Membrane Interacting with the Dictyostelium Lamin NE81

    PubMed Central

    Batsios, Petros; Ren, Xiang; Baumann, Otto; Larochelle, Denis A.; Gräf, Ralph

    2016-01-01

    The nuclear envelope (NE) consists of the outer and inner nuclear membrane (INM), whereby the latter is bound to the nuclear lamina. Src1 is a Dictyostelium homologue of the helix-extension-helix family of proteins, which also includes the human lamin-binding protein MAN1. Both endogenous Src1 and GFP-Src1 are localized to the NE during the entire cell cycle. Immuno-electron microscopy and light microscopy after differential detergent treatment indicated that Src1 resides in the INM. FRAP experiments with GFP-Src1 cells suggested that at least a fraction of the protein could be stably engaged in forming the nuclear lamina together with the Dictyostelium lamin NE81. Both a BioID proximity assay and mis-localization of soluble, truncated mRFP-Src1 at cytosolic clusters consisting of an intentionally mis-localized mutant of GFP-NE81 confirmed an interaction of Src1 and NE81. Expression GFP-Src11–646, a fragment C-terminally truncated after the first transmembrane domain, disrupted interaction of nuclear membranes with the nuclear lamina, as cells formed protrusions of the NE that were dependent on cytoskeletal pulling forces. Protrusions were dependent on intact microtubules but not actin filaments. Our results indicate that Src1 is required for integrity of the NE and highlight Dictyostelium as a promising model for the evolution of nuclear architecture. PMID:26999214

  18. Prepatterning of differentiation-driven nuclear lamin A/C-associated chromatin domains by GlcNAcylated histone H2B.

    PubMed

    Rønningen, Torunn; Shah, Akshay; Oldenburg, Anja R; Vekterud, Kristin; Delbarre, Erwan; Moskaug, Jan Øivind; Collas, Philippe

    2015-12-01

    Dynamic interactions of nuclear lamins with chromatin through lamin-associated domains (LADs) contribute to spatial arrangement of the genome. Here, we provide evidence for prepatterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs. We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. Lamin A/C LADs are found both in active and repressive chromatin contexts that can be influenced by cell differentiation status. De novo formation of adipogenic lamin A/C LADs occurs nonrandomly on GADs, which consist of megabase-size intergenic and repressive chromatin domains. Accordingly, whereas predifferentiation lamin A/C LADs are gene-rich, post-differentiation LADs harbor repressive features reminiscent of lamin B1 LADs. Release of lamin A/C from genes directly involved in glycolysis concurs with their transcriptional up-regulation after adipogenic induction, and with downstream elevations in H2BS112GlcNAc levels and O-GlcNAc cycling. Our results unveil an epigenetic prepatterning of adipogenic LADs by GADs, suggesting a coupling of developmentally regulated lamin A/C-genome interactions to a metabolically sensitive chromatin modification. PMID:26359231

  19. Simple Separation of Functionally Distinct Populations of Lamin-Binding Proteins.

    PubMed

    Berk, Jason M; Wilson, Katherine L

    2016-01-01

    The inner membrane of the nuclear envelope (NE) is home to hundreds of integral membrane proteins (NE transmembrane proteins, "NETs") with conserved or tissue-specific roles in genome organization and nuclear function. Nearly all characterized NETs bind A- or B-type lamins directly. However, hundreds of NETs remain uncharacterized, collectively posing an enormous gap that must be bridged to understand nuclear function and genome biology. We provide technically simple protocols for the separation and recovery of functionally distinct populations of NETs and A-type lamins. This protocol was developed for emerin, an inner nuclear membrane protein that binds lamins and barrier-to-autointegration factor (BANF1) as a component of nuclear lamina structure, and has diverse roles in nuclear assembly, signaling, and gene regulation. This protocol separates easily solubilized ("easy") populations of nuclear lamina proteins (emerin, lamin A, BAF) from "sonication-dependent" populations. Depending on cell type, the "easy" and "sonication-dependent" fractions each contain up to about half the available emerin, A-type lamins, and BAF, whereas B-type lamins and histone H3 are predominantly sonication dependent. The two populations of emerin have distinct posttranslational modifications, and only one population associates with BAF. This method may be useful for functional screening or analysis of other lamin-associated proteins, including novel NETs emerging from proteomic studies. PMID:26778555

  20. The major nucleoside triphosphatase in pea (Pisum sativum L.) nuclei and in rat liver nuclei share common epitopes also present in nuclear lamins

    NASA Technical Reports Server (NTRS)

    Tong, C. G.; Dauwalder, M.; Clawson, G. A.; Hatem, C. L.; Roux, S. J.

    1993-01-01

    The major nucleoside triphosphatase (NTPase) activities in mammalian and pea (Pisum sativum L.) nuclei are associated with enzymes that are very similar both biochemically and immunochemically. The major NTPase from rat liver nuclei appears to be a 46-kD enzyme that represents the N-terminal portion of lamins A and C, two lamina proteins that apparently arise from the same gene by alternate splicing. Monoclonal antibody (MAb) G2, raised to human lamin C, both immunoprecipitates the major (47 kD) NTPase in pea nuclei and recognizes it in western blot analyses. A polyclonal antibody preparation raised to the 47-kD pea NTPase (pc480) reacts with the same lamin bands that are recognized by MAb G2 in mammalian nuclei. The pc480 antibodies also bind to the same lamin-like bands in pea nuclear envelope-matrix preparations that are recognized by G2 and three other MAbs known to bind to mammalian lamins. In immunofluorescence assays, pc480 and anti-lamin antibodies stain both cytoplasmic and nuclear antigens in plant cells, with slightly enhanced staining along the periphery of the nuclei. These results indicate that the pea and rat liver NTPases are structurally similar and that, in pea nuclei as in rat liver nuclei, the major NTPase is probably derived from a lamin precursor by proteolysis.

  1. Myopathic Lamin Mutations Cause Reductive Stress and Activate the Nrf2/Keap-1 Pathway

    PubMed Central

    Dialynas, George; Shrestha, Om K.; Ponce, Jessica M.; Zwerger, Monika; Thiemann, Dylan A.; Young, Grant H.; Moore, Steven A.; Yu, Liping; Lammerding, Jan; Wallrath, Lori L.

    2015-01-01

    Mutations in the human LMNA gene cause muscular dystrophy by mechanisms that are incompletely understood. The LMNA gene encodes A-type lamins, intermediate filaments that form a network underlying the inner nuclear membrane, providing structural support for the nucleus and organizing the genome. To better understand the pathogenesis caused by mutant lamins, we performed a structural and functional analysis on LMNA missense mutations identified in muscular dystrophy patients. These mutations perturb the tertiary structure of the conserved A-type lamin Ig-fold domain. To identify the effects of these structural perturbations on lamin function, we modeled these mutations in Drosophila Lamin C and expressed the mutant lamins in muscle. We found that the structural perturbations had minimal dominant effects on nuclear stiffness, suggesting that the muscle pathology was not accompanied by major structural disruption of the peripheral nuclear lamina. However, subtle alterations in the lamina network and subnuclear reorganization of lamins remain possible. Affected muscles had cytoplasmic aggregation of lamins and additional nuclear envelope proteins. Transcription profiling revealed upregulation of many Nrf2 target genes. Nrf2 is normally sequestered in the cytoplasm by Keap-1. Under oxidative stress Nrf2 dissociates from Keap-1, translocates into the nucleus, and activates gene expression. Unexpectedly, biochemical analyses revealed high levels of reducing agents, indicative of reductive stress. The accumulation of cytoplasmic lamin aggregates correlated with elevated levels of the autophagy adaptor p62/SQSTM1, which also binds Keap-1, abrogating Nrf2 cytoplasmic sequestration, allowing Nrf2 nuclear translocation and target gene activation. Elevated p62/SQSTM1 and nuclear enrichment of Nrf2 were identified in muscle biopsies from the corresponding muscular dystrophy patients, validating the disease relevance of our Drosophila model. Thus, novel connections were made

  2. Lamina-associated polypeptide (LAP)2α and nucleoplasmic lamins in adult stem cell regulation and disease.

    PubMed

    Gesson, Kevin; Vidak, Sandra; Foisner, Roland

    2014-05-01

    A-type lamins are components of the lamina network at the nuclear envelope, which mediates nuclear stiffness and anchors chromatin to the nuclear periphery. However, A-type lamins are also found in the nuclear interior. Here we review the roles of the chromatin-associated, nucleoplasmic LEM protein, lamina-associated polypeptide 2α (LAP2α) in the regulation of A-type lamins in the nuclear interior. The lamin A/C-LAP2α complex may be involved in the regulation of the retinoblastoma protein-mediated pathway and other signaling pathways balancing proliferation and differentiation, and in the stabilization of higher-order chromatin organization throughout the nucleus. Loss of LAP2α in mice leads to selective depletion of the nucleoplasmic A-type lamin pool, promotes the proliferative stem cell phenotype of tissue progenitor cells, and delays stem cell differentiation. These findings support the hypothesis that LAP2α and nucleoplasmic lamins are regulators of adult stem cell function and tissue homeostasis. Finally, we discuss potential implications of this concept for defining the molecular disease mechanisms of lamin-linked diseases such as muscular dystrophy and premature aging syndromes. PMID:24374133

  3. Lamin-Binding Proteins in Caenorhabditis elegans.

    PubMed

    Dobrzynska, Agnieszka; Askjaer, Peter; Gruenbaum, Yosef

    2016-01-01

    The nuclear lamina, composed of lamins and numerous lamin-associated proteins, is required for mechanical stability, mechanosensing, chromatin organization, developmental gene regulation, mRNA transcription, DNA replication, nuclear assembly, and nuclear positioning. Mutations in lamins or lamin-binding proteins cause at least 18 distinct human diseases that affect specific tissues such as muscle, adipose, bone, nerve, or skin, and range from muscular dystrophies to lipodystrophy, peripheral neuropathy, or accelerated aging. Caenorhabditis elegans has unique advantages in studying lamin-binding proteins. These advantages include the low complexity of genes encoding lamin and lamin-binding proteins, advanced transgenic techniques, simple application of RNA interference, sophisticated genetic strategies, and a large collection of mutant lines. This chapter provides detailed and comprehensive protocols for the genetic and phenotypic analysis of lamin-binding proteins in C. elegans. PMID:26778571

  4. Incomplete processing of mutant lamin A in Hutchinson-Gilford progeria leads to nuclear abnormalities, which are reversed by farnesyltransferase inhibition.

    PubMed

    Glynn, Michael W; Glover, Thomas W

    2005-10-15

    Hutchinson-Gilford progeria syndrome (HGPS) is typically caused by mutations in codon 608 (G608G) of the LMNA gene, which activates a cryptic splice site resulting in the in-frame loss of 150 nucleotides from the lamin A message. The deleted region includes a protein cleavage site that normally removes 15 amino acids, including a CAAX box farnesylation site, from the lamin A protein. We investigated the processing of the C-terminus of the mutant protein, 'progerin', and found that it does not undergo cleavage and, indeed, remains farnesylated. The retention of the farnesyl group may have numerous consequences, as farnesyl groups increase lipophilicity and are involved in membrane association and in protein interactions, and is likely to be an important factor in the HGPS phenotype. To further investigate this, we studied the effects of farnesylation inhibition on nuclear phenotypes in cells expressing normal and mutant lamin A. Expression of a GFP-progerin fusion protein in normal fibroblasts caused a high incidence of nuclear abnormalities, as was also seen in HGPS fibroblasts, and resulted in abnormal nuclear localization of GFP-progerin in comparison with the localization pattern of GFP-lamin A. Expression of a GFP-lamin A fusion containing a mutation preventing the final cleavage step, causing the protein to remain farnesylated, displayed identical localization patterns and nuclear abnormalities as in HGPS cells and in cells expressing GFP-progerin. Exposure to a farnesyltransferase inhibitor (FTI), PD169541, caused a significant improvement in the nuclear morphology of cells expressing GFP-progerin and in HGPS cells. These results implicate the abnormal farnesylation of progerin in the cellular phenotype in HGPS cells and suggest that FTIs may represent a therapeutic option for patients with HGPS. PMID:16126733

  5. Knock-down of methyl CpG-binding protein 2 (MeCP2) causes alterations in cell proliferation and nuclear lamins expression in mammalian cells

    PubMed Central

    2012-01-01

    Background MeCP2 (CpG-binding protein 2) is a nuclear multifunctional protein involved in several cellular processes, like large-scale chromatin reorganization and architecture, and transcriptional regulation. In recent years, a non-neuronal role for MeCP2 has emerged in cell growth and proliferation. Mutations in the MeCP2 gene have been reported to determine growth disadvantages in cultured lymphocyte cells, and its functional ablation suppresses cell growth in glial cells and proliferation in mesenchymal stem cells and prostate cancer cells. MeCP2 interacts with lamin B receptor (LBR) and with Heterochromatin Protein 1 (HP1) at the nuclear envelope (NE), suggesting that it could be part of complexes involved in attracting heterochromatin at the nuclear periphery and in mediating gene silencing. The nuclear lamins, major components of the lamina, have a role in maintaining NE integrity, in orchestrating mitosis, in DNA replication and transcription, in regulation of mitosis and apoptosis and in providing anchoring sites for chromatin domains. In this work, we inferred that MeCP2 might have a role in nuclear envelope stability, thereby affecting the proliferation pattern of highly proliferating systems. Results By performing knock-down (KD) of MeCP2 in normal murine (NIH-3 T3) and in human prostate transformed cells (PC-3 and LNCaP), we observed a strong proliferation decrease and a defect in the cell cycle progression, with accumulation of cells in S/G2M, without triggering a strong apoptotic and senescent phenotype. In these cells, KD of MeCP2 evidenced a considerable decrease of the levels of lamin A, lamin C, lamin B1 and LBR proteins. Moreover, by confocal analysis we confirmed the reduction of lamin A levels, but we also observed an alteration in the shape of the nuclear lamina and an irregular nuclear rim. Conclusions Our results that indicate reduced levels of NE components, are consistent with a hypothesis that the deficiency of MeCP2 might cause the

  6. The assembly of C. elegans lamins into macroscopic fibers.

    PubMed

    Zingerman-Koladko, Irena; Khayat, Maayan; Harapin, Jan; Shoseyov, Oded; Gruenbaum, Yosef; Salman, Ahmad; Medalia, Ohad; Ben-Harush, Kfir

    2016-10-01

    Intermediate filament (IF) proteins are known mainly by their propensity to form viscoelastic filamentous networks within cells. In addition, IF-proteins are essential parts of various biological materials, such as horn and hagfish slime threads, which exhibit a range of mechanical properties from hard to elastic. These properties and their self-assembly nature made IF-proteins attractive building blocks for biomimetic and biological materials in diverse applications. Here we show that a type V IF-protein, the Caenorhabditis elegans nuclear lamin (Ce-lamin), is a promising building block for protein-based fibers. Electron cryo-tomography of vitrified sections enabled us to depict the higher ordered assembly of the Ce-lamin into macroscopic fibers through the creation of paracrystalline fibers, which are prominent in vitro structures of lamins. The lamin fibers respond to tensile force as other IF-protein-based fibers, i.e., hagfish slime threads, and possess unique mechanical properties that may potentially be used in certain applications. The self-assembly nature of lamin proteins into a filamentous structure, which is further assembled into a complex network, can be easily modulated. This knowledge may lead to a better understanding of the relationship in IF-proteins-based fibers and materials, between their hierarchical structures and their mechanical properties. PMID:27341289

  7. B-type lamins in health and disease☆

    PubMed Central

    Hutchison, C.J.

    2014-01-01

    For over two decades, B-type lamins were thought to have roles in fundamental processes including correct assembly of nuclear envelopes, DNA replication, transcription and cell survival. Recent studies have questioned these roles and have instead emphasised the role of these proteins in tissue building and tissue integrity, particularly in tissues devoid of A-type lamins. Other studies have suggested that the expression of B-type lamins in somatic cells influences the rate of entry into states of cellular senescence. In humans duplication of the LMNB1 gene (encoding lamin B1) causes an adult onset neurodegenerative disorder, termed autosomal dominant leukodystrophy, whilst very recently, LMNB1 has been implicated as a susceptibility gene in neural tube defects. This is consistent with studies in mice that reveal a critical role for B-type lamins in neuronal migration and brain development. In this review, I will consider how different model systems have contributed to our understanding of the functions of B-type lamins and which of those functions are critical for human health and disease. PMID:24380701

  8. SINC, a type III secreted protein of Chlamydia psittaci, targets the inner nuclear membrane of infected cells and uninfected neighbors

    PubMed Central

    Mojica, Sergio A.; Hovis, Kelley M.; Frieman, Matthew B.; Tran, Bao; Hsia, Ru-ching; Ravel, Jacques; Jenkins-Houk, Clifton; Wilson, Katherine L.; Bavoil, Patrik M.

    2015-01-01

    SINC, a new type III secreted protein of the avian and human pathogen Chlamydia psittaci, uniquely targets the nuclear envelope of C. psittaci–infected cells and uninfected neighboring cells. Digitonin-permeabilization studies of SINC-GFP–transfected HeLa cells indicate that SINC targets the inner nuclear membrane. SINC localization at the nuclear envelope was blocked by importazole, confirming SINC import into the nucleus. Candidate partners were identified by proximity to biotin ligase-fused SINC in HEK293 cells and mass spectrometry (BioID). This strategy identified 22 candidates with high confidence, including the nucleoporin ELYS, lamin B1, and four proteins (emerin, MAN1, LAP1, and LBR) of the inner nuclear membrane, suggesting that SINC interacts with host proteins that control nuclear structure, signaling, chromatin organization, and gene silencing. GFP-SINC association with the native LEM-domain protein emerin, a conserved component of nuclear “lamina” structure, or with a complex containing emerin was confirmed by GFP pull down. Our findings identify SINC as a novel bacterial protein that targets the nuclear envelope with the capability of globally altering nuclear envelope functions in the infected host cell and neighboring uninfected cells. These properties may contribute to the aggressive virulence of C. psittaci. PMID:25788290

  9. Specific contribution of lamin A and lamin C in the development of laminopathies

    SciTech Connect

    Sylvius, Nicolas Hathaway, Andrea; Boudreau, Emilie; Gupta, Pallavi; Labib, Sarah; Bolongo, Pierrette M.; Rippstein, Peter; McBride, Heidi; Bilinska, Zofia T.; Tesson, Frederique

    2008-08-01

    Mutations in the lamin A/C gene are involved in multiple human disorders for which the pathophysiological mechanisms are partially understood. Conflicting results prevail regarding the organization of lamin A and C mutants within the nuclear envelope (NE) and on the interactions of each lamin to its counterpart. We over-expressed various lamin A and C mutants both independently and together in COS7 cells. When expressed alone, lamin A with cardiac/muscular disorder mutations forms abnormal aggregates inside the NE and not inside the nucleoplasm. Conversely, the equivalent lamin C organizes as intranucleoplasmic aggregates that never connect to the NE as opposed to wild type lamin C. Interestingly, the lamin C molecules present within these aggregates exhibit an abnormal increased mobility. When co-expressed, the complex formed by lamin A/C aggregates in the NE. Lamin A and C mutants for lipodystrophy behave similarly to the wild type. These findings reveal that lamins A and C may be differentially affected depending on the mutation. This results in multiple possible physiological consequences which likely contribute in the phenotypic variability of laminopathies. The inability of lamin C mutants to join the nuclear rim in the absence of lamin A is a potential pathophysiological mechanism for laminopathies.

  10. Laminated electromagnetic pump stator core

    DOEpatents

    Fanning, A.W.

    1995-08-08

    A stator core for an electromagnetic pump includes a plurality of circumferentially abutting tapered laminations extending radially outwardly from a centerline axis to collectively define a radially inner bore and a radially outer circumference. Each of the laminations includes radially inner and outer edges and has a thickness increasing from the inner edge toward the outer edge to provide a substantially continuous path adjacent the circumference. This pump is used in nuclear fission reactors. 19 figs.

  11. Photoresist laminate

    DOEpatents

    Andrade, A.D.; Galbraith, L.K.

    1979-10-01

    The disclosure relates to a laminated negative dry-film photoresist for the production of thick, as well as thin, patterns with vertical sidewalls. Uniform depthwise exposure in a photoresist layer is effected by the use of an ultraviolet filtering top layer.

  12. The Caenorhabditis elegans SUN protein UNC-84 interacts with lamin to transfer forces from the cytoplasm to the nucleoskeleton during nuclear migration

    PubMed Central

    Bone, Courtney R.; Tapley, Erin C.; Gorjánácz, Mátyás; Starr, Daniel A.

    2014-01-01

    Nuclear migration is a critical component of many cellular and developmental processes. The nuclear envelope forms a barrier between the cytoplasm, where mechanical forces are generated, and the nucleoskeleton. The LINC complex consists of KASH proteins in the outer nuclear membrane and SUN proteins in the inner nuclear membrane that bridge the nuclear envelope. How forces are transferred from the LINC complex to the nucleoskeleton is poorly understood. The Caenorhabditis elegans lamin, LMN-1, is required for nuclear migration and interacts with the nucleoplasmic domain of the SUN protein UNC-84. This interaction is weakened by the unc-84(P91S) missense mutation. These mutant nuclei have an intermediate nuclear migration defect—live imaging of nuclei or LMN-1::GFP shows that many nuclei migrate normally, others initiate migration before subsequently failing, and others fail to begin migration. At least one other component of the nucleoskeleton, the NET5/Samp1/Ima1 homologue SAMP-1, plays a role in nuclear migration. We propose a nut-and-bolt model to explain how forces are dissipated across the nuclear envelope during nuclear migration. In this model, SUN/KASH bridges serve as bolts through the nuclear envelope, and nucleoskeleton components LMN-1 and SAMP-1 act as both nuts and washers on the inside of the nucleus. PMID:25057012

  13. Physiological and Pathological Aging Affects Chromatin Dynamics, Structure and Function at the Nuclear Edge

    PubMed Central

    Robin, Jérôme D.; Magdinier, Frédérique

    2016-01-01

    Lamins are intermediate filaments that form a complex meshwork at the inner nuclear membrane. Mammalian cells express two types of Lamins, Lamins A/C and Lamins B, encoded by three different genes, LMNA, LMNB1, and LMNB2. Mutations in the LMNA gene are associated with a group of phenotypically diverse diseases referred to as laminopathies. Lamins interact with a large number of binding partners including proteins of the nuclear envelope but also chromatin-associated factors. Lamins not only constitute a scaffold for nuclear shape, rigidity and resistance to stress but also contribute to the organization of chromatin and chromosomal domains. We will discuss here the impact of A-type Lamins loss on alterations of chromatin organization and formation of chromatin domains and how disorganization of the lamina contributes to the patho-physiology of premature aging syndromes. PMID:27602048

  14. Physiological and Pathological Aging Affects Chromatin Dynamics, Structure and Function at the Nuclear Edge.

    PubMed

    Robin, Jérôme D; Magdinier, Frédérique

    2016-01-01

    Lamins are intermediate filaments that form a complex meshwork at the inner nuclear membrane. Mammalian cells express two types of Lamins, Lamins A/C and Lamins B, encoded by three different genes, LMNA, LMNB1, and LMNB2. Mutations in the LMNA gene are associated with a group of phenotypically diverse diseases referred to as laminopathies. Lamins interact with a large number of binding partners including proteins of the nuclear envelope but also chromatin-associated factors. Lamins not only constitute a scaffold for nuclear shape, rigidity and resistance to stress but also contribute to the organization of chromatin and chromosomal domains. We will discuss here the impact of A-type Lamins loss on alterations of chromatin organization and formation of chromatin domains and how disorganization of the lamina contributes to the patho-physiology of premature aging syndromes. PMID:27602048

  15. Lamin B1 and lamin B2 are long-lived proteins with distinct functions in retinal development.

    PubMed

    Razafsky, David; Ward, Candace; Potter, Chloe; Zhu, Wanqiu; Xue, Yunlu; Kefalov, Vladimir J; Fong, Loren G; Young, Stephen G; Hodzic, Didier

    2016-06-15

    Lamin B1 and lamin B2 are essential building blocks of the nuclear lamina, a filamentous meshwork lining the nucleoplasmic side of the inner nuclear membrane. Deficiencies in lamin B1 and lamin B2 impair neurodevelopment, but distinct functions for the two proteins in the development and homeostasis of the CNS have been elusive. Here we show that embryonic depletion of lamin B1 in retinal progenitors and postmitotic neurons affects nuclear integrity, leads to the collapse of the laminB2 meshwork, impairs neuronal survival, and markedly reduces the cellularity of adult retinas. In stark contrast, a deficiency of lamin B2 in the embryonic retina has no obvious effect on lamin B1 localization or nuclear integrity in embryonic retinas, suggesting that lamin B1, but not lamin B2, is strictly required for nucleokinesis during embryonic neurogenesis. However, the absence of lamin B2 prevents proper lamination of adult retinal neurons, impairs synaptogenesis, and reduces cone photoreceptor survival. We also show that lamin B1 and lamin B2 are extremely long-lived proteins in rod and cone photoreceptors. OF interest, a complete absence of both proteins during postnatal life has little or no effect on the survival and function of cone photoreceptors. PMID:27075175

  16. Lamin B1 and lamin B2 are long-lived proteins with distinct functions in retinal development

    PubMed Central

    Razafsky, David; Ward, Candace; Potter, Chloe; Zhu, Wanqiu; Xue, Yunlu; Kefalov, Vladimir J.; Fong, Loren G.; Young, Stephen G.; Hodzic, Didier

    2016-01-01

    Lamin B1 and lamin B2 are essential building blocks of the nuclear lamina, a filamentous meshwork lining the nucleoplasmic side of the inner nuclear membrane. Deficiencies in lamin B1 and lamin B2 impair neurodevelopment, but distinct functions for the two proteins in the development and homeostasis of the CNS have been elusive. Here we show that embryonic depletion of lamin B1 in retinal progenitors and postmitotic neurons affects nuclear integrity, leads to the collapse of the laminB2 meshwork, impairs neuronal survival, and markedly reduces the cellularity of adult retinas. In stark contrast, a deficiency of lamin B2 in the embryonic retina has no obvious effect on lamin B1 localization or nuclear integrity in embryonic retinas, suggesting that lamin B1, but not lamin B2, is strictly required for nucleokinesis during embryonic neurogenesis. However, the absence of lamin B2 prevents proper lamination of adult retinal neurons, impairs synaptogenesis, and reduces cone photoreceptor survival. We also show that lamin B1 and lamin B2 are extremely long-lived proteins in rod and cone photoreceptors. OF interest, a complete absence of both proteins during postnatal life has little or no effect on the survival and function of cone photoreceptors. PMID:27075175

  17. Laminate article

    DOEpatents

    Williams, Robert K.; Paranthaman, Mariappan; Chirayil, Thomas G.; Lee, Dominic F.; Goyal, Amit; Feenstra, Roeland

    2002-01-01

    A laminate article comprises a substrate and a biaxially textured (RE.sub.x A.sub.(1-x)).sub.2 O.sub.2-(x/2) buffer layer over the substrate, wherein 0laminate article can include a layer of YBCO over the (RE.sub.x A.sub.(1-x)).sub.2 O.sub.2-(x/2) buffer layer. A layer of CeO.sub.2 between the YBCO layer and the (RE.sub.x A.sub.(1-x)).sub.2 O.sub.2-(x/2) buffer layer can also be include. Further included can be a layer of YSZ between the CeO.sub.2 layer and the (RE.sub.x A.sub.(1-x)).sub.2 O.sub.2-(x/2) buffer layer. The substrate can be a biaxially textured metal, such as nickel. A method of forming the laminate article is also disclosed.

  18. Significance of host cell kinases in herpes simplex virus type 1 egress and lamin-associated protein disassembly from the nuclear lamina

    SciTech Connect

    Leach, Natalie R.; Roller, Richard J.

    2010-10-10

    The nuclear lamina is thought to be a steric barrier to the herpesvirus capsid. Disruption of the lamina accompanied by phosphorylation of lamina proteins is a conserved feature of herpesvirus infection. In HSV-1-infected cells, protein kinase C (PKC) alpha and delta isoforms are recruited to the nuclear membrane and PKC delta has been implicated in phosphorylation of emerin and lamin B. We tested two critical hypotheses about the mechanism and significance of lamina disruption. First, we show that chemical inhibition of all PKC isoforms reduced viral growth five-fold and inhibited capsid egress from the nucleus. However, specific inhibition of either conventional PKCs or PKC delta does not inhibit viral growth. Second, we show hyperphosphorylation of emerin by viral and cellular kinases is required for its disassociation from the lamina. These data support hypothesis that phosphorylation of lamina components mediates lamina disruption during HSV nuclear egress.

  19. Interphase phosphorylation of lamin A.

    PubMed

    Kochin, Vitaly; Shimi, Takeshi; Torvaldson, Elin; Adam, Stephen A; Goldman, Anne; Pack, Chan-Gi; Melo-Cardenas, Johanna; Imanishi, Susumu Y; Goldman, Robert D; Eriksson, John E

    2014-06-15

    Nuclear lamins form the major structural elements that comprise the nuclear lamina. Loss of nuclear structural integrity has been implicated as a key factor in the lamin A/C gene mutations that cause laminopathies, whereas the normal regulation of lamin A assembly and organization in interphase cells is still undefined. We assumed phosphorylation to be a major determinant, identifying 20 prime interphase phosphorylation sites, of which eight were high-turnover sites. We examined the roles of these latter sites by site-directed mutagenesis, followed by detailed microscopic analysis - including fluorescence recovery after photobleaching, fluorescence correlation spectroscopy and nuclear extraction techniques. The results reveal three phosphorylation regions, each with dominant sites, together controlling lamin A structure and dynamics. Interestingly, two of these interphase sites are hyper-phosphorylated in mitotic cells and one of these sites is within the sequence that is missing in progerin of the Hutchinson-Gilford progeria syndrome. We present a model where different phosphorylation combinations yield markedly different effects on the assembly, subunit turnover and the mobility of lamin A between, and within, the lamina, the nucleoplasm and the cytoplasm of interphase cells. PMID:24741066

  20. Mammalian telomeres and their partnership with lamins

    PubMed Central

    Burla, Romina; La Torre, Mattia; Saggio, Isabella

    2016-01-01

    ABSTRACT Chromosome ends are complex structures, which require a panel of factors for their elongation, replication, and protection. We describe here the mechanics of mammalian telomeres, dynamics and maintainance in relation to lamins. Multiple biochemical connections, including association of telomeres to the nuclear envelope and matrix, of telomeric proteins to lamins, and of lamin-associated proteins to chromosome ends, underline the interplay between lamins and telomeres. Paths toward senescence, such as defective telomere replication, altered heterochromatin organization, and impaired DNA repair, are common to lamins' and telomeres' dysfunction. The convergence of phenotypes can be interpreted through a model of dynamic, lamin-controlled functional platforms dedicated to the function of telomeres as fragile sites. The features of telomeropathies and laminopathies, and of animal models underline further overlapping aspects, including the alteration of stem cell compartments. We expect that future studies of basic biology and on aging will benefit from the analysis of this telomere-lamina interplay. PMID:27116558

  1. Lamin B receptor

    PubMed Central

    Olins, Ada L; Rhodes, Gale; Welch, David B Mark; Zwerger, Monika

    2010-01-01

    Lamin B receptor (LBR) is an integral membrane protein of the interphase nuclear envelope (NE). The N-terminal end resides in the nucleoplasm, binding to lamin B and heterochromatin, with the interactions disrupted during mitosis. The C-terminal end resides within the inner nuclear membrane, retreating with the ER away from condensing chromosomes during mitotic NE breakdown. Some of these properties are interpretable in terms of our current structural knowledge of LBR, but many of the structural features remain unknown. LBR apparently has an evolutionary history which brought together at least two ancient conserved structural domains (i.e., Tudor and sterol reductase). This convergence may have occurred with the emergence of the chordates and echinoderms. It is not clear what survival values have maintained LBR structure during evolution. But it seems likely that roles in post-mitotic nuclear reformation, interphase NE growth and compartmentalization of nuclear architecture might have provided some evolutionary advantage to preservation of the LBR gene. PMID:21327105

  2. Lamins as mediators of oxidative stress

    SciTech Connect

    Sieprath, Tom; Darwiche, Rabih; De Vos, Winnok H.

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer The nuclear lamina defines structural and functional properties of the cell nucleus. Black-Right-Pointing-Pointer Lamina dysfunction leads to a broad spectrum of laminopathies. Black-Right-Pointing-Pointer Recent data is reviewed connecting laminopathies to oxidative stress. Black-Right-Pointing-Pointer A framework is proposed to explain interactions between lamins and oxidative stress. -- Abstract: The nuclear lamina defines both structural and functional properties of the eukaryotic cell nucleus. Mutations in the LMNA gene, encoding A-type lamins, lead to a broad spectrum of diseases termed laminopathies. While different hypotheses have been postulated to explain disease development, there is still no unified view on the mechanistic basis of laminopathies. Recent observations indicate that laminopathies are often accompanied by altered levels of reactive oxygen species and a higher susceptibility to oxidative stress at the cellular level. In this review, we highlight the role of reactive oxygen species for cell function and disease development in the context of laminopathies and present a framework of non-exclusive mechanisms to explain the reciprocal interactions between a dysfunctional lamina and altered redox homeostasis.

  3. Hybrid composite laminate structures

    NASA Technical Reports Server (NTRS)

    Chamis, C. C.; Lark, R. F. (Inventor)

    1977-01-01

    An invention which relates to laminate structures and specifically to essentially anisotropic fiber composite laminates is described. Metal foils are selectively disposed within the laminate to produce increased resistance to high velocity impact, fracture, surface erosion, and other stresses within the laminate.

  4. Lamin A, farnesylation and aging.

    PubMed

    Reddy, Sita; Comai, Lucio

    2012-01-01

    Lamin A is a component of the nuclear envelope that is synthesized as a precursor prelamin A molecule and then processed into mature lamin A through sequential steps of posttranslational modifications and proteolytic cleavages. Remarkably, over 400 distinct point mutations have been so far identified throughout the LMNA gene, which result in the development of at least ten distinct human disorders, collectively known as laminopathies, among which is the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS). The majority of HGPS cases are associated with a single point mutation in the LMNA gene that causes the production of a permanently farnesylated mutant lamin A protein termed progerin. The mechanism by which progerin leads to premature aging and the classical HGPS disease phenotype as well as the relationship between this disorder and the onset of analogous symptoms during the lifespan of a normal individual are not well understood. Yet, recent studies have provided critical insights on the cellular processes that are affected by accumulation of progerin and have suggested that cellular alterations in the lamin A processing pathway leading to the accumulation of farnesylated prelamin A intermediates may play a role in the aging process in the general population. In this review we provide a short background on lamin A and its maturation pathway and discuss the current knowledge of how progerin or alterations in the prelamin A processing pathway are thought to influence cell function and contribute to human aging. PMID:21871450

  5. Lamin A, farnesylation and aging

    SciTech Connect

    Reddy, Sita; Comai, Lucio

    2012-01-01

    Lamin A is a component of the nuclear envelope that is synthesized as a precursor prelamin A molecule and then processed into mature lamin A through sequential steps of posttranslational modifications and proteolytic cleavages. Remarkably, over 400 distinct point mutations have been so far identified throughout the LMNA gene, which result in the development of at least ten distinct human disorders, collectively known as laminopathies, among which is the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS). The majority of HGPS cases are associated with a single point mutation in the LMNA gene that causes the production of a permanently farnesylated mutant lamin A protein termed progerin. The mechanism by which progerin leads to premature aging and the classical HGPS disease phenotype as well as the relationship between this disorder and the onset of analogous symptoms during the lifespan of a normal individual are not well understood. Yet, recent studies have provided critical insights on the cellular processes that are affected by accumulation of progerin and have suggested that cellular alterations in the lamin A processing pathway leading to the accumulation of farnesylated prelamin A intermediates may play a role in the aging process in the general population. In this review we provide a short background on lamin A and its maturation pathway and discuss the current knowledge of how progerin or alterations in the prelamin A processing pathway are thought to influence cell function and contribute to human aging.

  6. Sustained accumulation of prelamin A and depletion of lamin A/C both cause oxidative stress and mitochondrial dysfunction but induce different cell fates

    PubMed Central

    Sieprath, Tom; Corne, Tobias DJ; Nooteboom, Marco; Grootaert, Charlotte; Rajkovic, Andreja; Buysschaert, Benjamin; Robijns, Joke; Broers, Jos LV; Ramaekers, Frans CS; Koopman, Werner JH; Willems, Peter HGM; De Vos, Winnok H

    2015-01-01

    The cell nucleus is structurally and functionally organized by lamins, intermediate filament proteins that form the nuclear lamina. Point mutations in genes that encode a specific subset of lamins, the A-type lamins, cause a spectrum of diseases termed laminopathies. Recent evidence points to a role for A-type lamins in intracellular redox homeostasis. To determine whether lamin A/C depletion and prelamin A accumulation differentially induce oxidative stress, we have performed a quantitative microscopy-based analysis of reactive oxygen species (ROS) levels and mitochondrial membrane potential (Δψm) in human fibroblasts subjected to sustained siRNA-mediated knockdown of LMNA and ZMPSTE24, respectively. We measured a highly significant increase in basal ROS levels and an even more prominent rise of induced ROS levels in lamin A/C depleted cells, eventually resulting in Δψm hyperpolarization and apoptosis. Depletion of ZMPSTE24 on the other hand, triggered a senescence pathway that was associated with moderately increased ROS levels and a transient Δψm depolarization. Both knockdowns were accompanied by an upregulation of several ROS detoxifying enzymes. Taken together, our data suggest that both persistent prelamin A accumulation and lamin A/C depletion elevate ROS levels, but to a different extent and with different effects on cell fate. This may contribute to the variety of disease phenotypes witnessed in laminopathies. PMID:25996284

  7. Cooperative Activity of GABP with PU.1 or C/EBPε Regulates Lamin B Receptor Gene Expression, Implicating Their Roles in Granulocyte Nuclear Maturation.

    PubMed

    Malu, Krishnakumar; Garhwal, Rahul; Pelletier, Margery G H; Gotur, Deepali; Halene, Stephanie; Zwerger, Monika; Yang, Zhong-Fa; Rosmarin, Alan G; Gaines, Peter

    2016-08-01

    Nuclear segmentation is a hallmark feature of mammalian neutrophil differentiation, but the mechanisms that control this process are poorly understood. Gene expression in maturing neutrophils requires combinatorial actions of lineage-restricted and more widely expressed transcriptional regulators. Examples include interactions of the widely expressed ETS transcription factor, GA-binding protein (GABP), with the relatively lineage-restricted E-twenty-six (ETS) factor, PU.1, and with CCAAT enhancer binding proteins, C/EBPα and C/EBPε. Whether such cooperative interactions between these transcription factors also regulate the expression of genes encoding proteins that control nuclear segmentation is unclear. We investigated the roles of ETS and C/EBP family transcription factors in regulating the gene encoding the lamin B receptor (LBR), an inner nuclear membrane protein whose expression is required for neutrophil nuclear segmentation. Although C/EBPε was previously shown to bind the Lbr promoter, surprisingly, we found that neutrophils derived from Cebpe null mice exhibited normal Lbr gene and protein expression. Instead, GABP provided transcriptional activation through the Lbr promoter in the absence of C/EBPε, and activities supported by GABP were greatly enhanced by either C/EBPε or PU.1. Both GABP and PU.1 bound Ets sites in the Lbr promoter in vitro, and in vivo within both early myeloid progenitors and differentiating neutrophils. These findings demonstrate that GABP, PU.1, and C/EBPε cooperate to control transcription of the gene encoding LBR, a nuclear envelope protein that is required for the characteristic lobulated morphology of mature neutrophils. PMID:27342846

  8. The tail domain of lamin B1 is more strongly modulated by divalent cations than lamin A

    PubMed Central

    Ganesh, Sairaam; Qin, Zhao; Spagnol, Stephen T; Biegler, Matthew T; Coffey, Kelli A; Kalinowski, Agnieszka; Buehler, Markus J; Dahl, Kris Noel

    2015-01-01

    The nucleoskeleton contains mainly nuclear intermediate filaments made of lamin proteins. Lamins provide nuclear structure and also play a role in various nuclear processes including signal transduction, transcription regulation and chromatin organization. The disparate functions of lamins may be related to the intrinsic disorder of the tail domains, which allows for altered and promiscuous binding. Here, we show modulation of lamin tail domain structures in the presence of divalent cations. We utilize changes in fluorescence of tryptophan residues within the Ig-fold flanked by disordered regions to experimentally measure protein thermodynamics. Using spectroscopy experiments and molecular dynamics simulations, we show that the tail domain of lamin B1 shows enhanced association with both Ca2+ and Mg2+ compared to the tail domain of lamin A. Binding curves show a similar KD between protein and ion (250–300 μM) for both proteins with both ions. However, we observe a maximum binding of ions to lamin B1 tail domain which is 2–3 times greater than that for lamin A tail domain by both experiment and simulation. Using simulations, we show that divalent ion association alters the Ig-fold by pinning flanking regions. With cells in culture, we observe altered lamin B1 organization in the presence of excess Mg2+ more so than for lamin A. We suggest that the differential sensitivity to divalent cations contributes to the vastly different functionalities and binding of the 2 proteins. PMID:25807068

  9. Interaction between the inner nuclear membrane lamin B receptor and the heterochromatic methyl binding protein, MeCP2

    SciTech Connect

    Guarda, Alessia; Bolognese, Fabrizio; Bonapace, Ian Marc; Badaracco, Gianfranco

    2009-07-01

    The nuclear membrane has an important role for the dynamic regulation of the genome, besides the well-established cytoskeletal function. The nuclear lamina is emerging as an important player in the organization of the position and functional state of interphase chromosomes. Epigenetic modifications such as DNA methylation and histone modifications are required for genome reprogramming during development, tissue-specific gene expression and global gene silencing. The Methyl-CpG binding protein MeCP2 binds methyl-CpG dinucleotides in the mammalian genome and functions as a transcriptional repressor in vivo by interacting with Sin3A, thereby recruiting histone deacetylases (HDAC). MeCP2 also mediates the formation of higher-order chromatin structures contributing to determine the architectural organization of the nucleus. In this paper, we show that MeCP2 interacts in vitro and in vivo with the inner nuclear membrane protein LBR and that the unstructured aminoacidic sequence linking the MBD and TRD domains of MeCP2 is responsible for this association. The formation of an LBR-MeCP2 protein complex might help providing a molecular explanation to the distribution of part of the heterochromatin at the nuclear periphery linked to inner membrane.

  10. Systematic identification of pathological lamin A interactors

    PubMed Central

    Dittmer, Travis A.; Sahni, Nidhi; Kubben, Nard; Hill, David E.; Vidal, Marc; Burgess, Rebecca C.; Roukos, Vassilis; Misteli, Tom

    2014-01-01

    Laminopathies are a collection of phenotypically diverse diseases that include muscular dystrophies, cardiomyopathies, lipodystrophies, and premature aging syndromes. Laminopathies are caused by >300 distinct mutations in the LMNA gene, which encodes the nuclear intermediate filament proteins lamin A and C, two major architectural elements of the mammalian cell nucleus. The genotype–phenotype relationship and the basis for the pronounced tissue specificity of laminopathies are poorly understood. Here we seek to identify on a global scale lamin A–binding partners whose interaction is affected by disease-relevant LMNA mutations. In a screen of a human genome–wide ORFeome library, we identified and validated 337 lamin A–binding proteins. Testing them against 89 known lamin A disease mutations identified 50 disease-associated interactors. Association of progerin, the lamin A isoform responsible for the premature aging disorder Hutchinson–Gilford progeria syndrome, with its partners was largely mediated by farnesylation. Mapping of the interaction sites on lamin A identified the immunoglobulin G (IgG)–like domain as an interaction hotspot and demonstrated that lamin A variants, which destabilize the Ig-like domain, affect protein–protein interactions more globally than mutations of surface residues. Analysis of a set of LMNA mutations in a single residue, which result in three phenotypically distinct diseases, identified disease-specific interactors. The results represent a systematic map of disease-relevant lamin A interactors and suggest loss of tissue-specific lamin A interactions as a mechanism for the tissue-specific appearance of laminopathic phenotypes. PMID:24623722

  11. Systematic identification of pathological lamin A interactors.

    PubMed

    Dittmer, Travis A; Sahni, Nidhi; Kubben, Nard; Hill, David E; Vidal, Marc; Burgess, Rebecca C; Roukos, Vassilis; Misteli, Tom

    2014-05-01

    Laminopathies are a collection of phenotypically diverse diseases that include muscular dystrophies, cardiomyopathies, lipodystrophies, and premature aging syndromes. Laminopathies are caused by >300 distinct mutations in the LMNA gene, which encodes the nuclear intermediate filament proteins lamin A and C, two major architectural elements of the mammalian cell nucleus. The genotype-phenotype relationship and the basis for the pronounced tissue specificity of laminopathies are poorly understood. Here we seek to identify on a global scale lamin A-binding partners whose interaction is affected by disease-relevant LMNA mutations. In a screen of a human genome-wide ORFeome library, we identified and validated 337 lamin A-binding proteins. Testing them against 89 known lamin A disease mutations identified 50 disease-associated interactors. Association of progerin, the lamin A isoform responsible for the premature aging disorder Hutchinson-Gilford progeria syndrome, with its partners was largely mediated by farnesylation. Mapping of the interaction sites on lamin A identified the immunoglobulin G (IgG)-like domain as an interaction hotspot and demonstrated that lamin A variants, which destabilize the Ig-like domain, affect protein-protein interactions more globally than mutations of surface residues. Analysis of a set of LMNA mutations in a single residue, which result in three phenotypically distinct diseases, identified disease-specific interactors. The results represent a systematic map of disease-relevant lamin A interactors and suggest loss of tissue-specific lamin A interactions as a mechanism for the tissue-specific appearance of laminopathic phenotypes. PMID:24623722

  12. Identification of differential protein interactors of lamin A and progerin.

    PubMed

    Kubben, Nard; Voncken, Jan Willem; Demmers, Jeroen; Calis, Chantal; van Almen, Geert; Pinto, Yigal; Misteli, Tom

    2010-01-01

    The nuclear lamina is an interconnected meshwork of intermediate filament proteins underlying the nuclear envelope. The lamina is an important regulator of nuclear structural integrity as well as nuclear processes, including transcription, DNA replication and chromatin remodeling. The major components of the lamina are A- and B-type lamins. Mutations in lamins impair lamina functions and cause a set of highly tissue-specific diseases collectively referred to as laminopathies. The phenotypic diversity amongst laminopathies is hypothesized to be caused by mutations affecting specific protein interactions, possibly in a tissue-specific manner. Current technologies to identify interaction partners of lamin A and its mutants are hampered by the insoluble nature of lamina components. To overcome the limitations of current technologies, we developed and applied a novel, unbiased approach to identify lamin A-interacting proteins. This approach involves expression of the high-affinity OneSTrEP-tag, precipitation of lamin-protein complexes after reversible protein cross-linking and subsequent protein identification by mass spectrometry. We used this approach to identify in mouse embryonic fibroblasts and cardiac myocyte NklTAg cell lines proteins that interact with lamin A and its mutant isoform progerin, which causes the premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS). We identified a total of 313 lamina-interacting proteins, including several novel lamin A interactors, and we characterize a set of 35 proteins which preferentially interact with lamin A or progerin. PMID:21327095

  13. Lamin A is not synthesized as a larger precursor polypeptide.

    PubMed

    Lebel, S; Raymond, Y

    1987-12-16

    Isolation of rat liver nuclei in the presence of N-ethylmaleimide (NEM) led to the recovery in the final nuclear matrix of a higher molecular weight form of lamin A. The 2 kDa larger form was identified as lamin A by isoelectric point determination, recognition by an anti-lamin A and C monoclonal antibody and peptide mapping using V8 protease and N-chlorosuccinimide. The 2 kDa extension was tentatively localized to the carboxy-terminus of lamin A. Pulse-chase labeling and immunoprecipitation studies using baby hamster kidney cells showed that lysis of the cells in the presence of NEM allowed the recovery of a stable higher molecular weight form of lamin A. We conclude from these results that NEM prevented the degradation of the native form of lamin A previously thought to represent a higher molecular weight transient precursor form. PMID:3426582

  14. Honeycomb-laminate composite structure

    NASA Technical Reports Server (NTRS)

    Gilwee, W. J., Jr.; Parker, J. A. (Inventor)

    1977-01-01

    A honeycomb-laminate composite structure was comprised of: (1) a cellular core of a polyquinoxaline foam in a honeycomb structure, and (2) a layer of a noncombustible fibrous material impregnated with a polyimide resin laminated on the cellular core. A process for producing the honeycomb-laminate composite structure and articles containing the honeycomb-laminate composite structure is described.

  15. The telomeric protein AKTIP interacts with A- and B-type lamins and is involved in regulation of cellular senescence

    PubMed Central

    Burla, Romina; Carcuro, Mariateresa; Torre, Mattia La; Fratini, Federica; Crescenzi, Marco; D'Apice, Maria Rosaria; Spitalieri, Paola; Raffa, Grazia Daniela; Astrologo, Letizia; Lattanzi, Giovanna; Cundari, Enrico; Raimondo, Domenico; Biroccio, Annamaria; Gatti, Maurizio

    2016-01-01

    AKTIP is a shelterin-interacting protein required for replication of telomeric DNA. Here, we show that AKTIP biochemically interacts with A- and B-type lamins and affects lamin A, but not lamin C or B, expression. In interphase cells, AKTIP localizes at the nuclear rim and in discrete regions of the nucleoplasm just like lamins. Double immunostaining revealed that AKTIP partially co-localizes with lamin B1 and lamin A/C in interphase cells, and that proper AKTIP localization requires functional lamin A. In mitotic cells, AKTIP is enriched at the spindle poles and at the midbody of late telophase cells similar to lamin B1. AKTIP-depleted cells show senescence-associated markers and recapitulate several aspects of the progeroid phenotype. Collectively, our results indicate that AKTIP is a new player in lamin-related processes, including those that govern nuclear architecture, telomere homeostasis and cellular senescence. PMID:27512140

  16. The telomeric protein AKTIP interacts with A- and B-type lamins and is involved in regulation of cellular senescence.

    PubMed

    Burla, Romina; Carcuro, Mariateresa; Torre, Mattia La; Fratini, Federica; Crescenzi, Marco; D'Apice, Maria Rosaria; Spitalieri, Paola; Raffa, Grazia Daniela; Astrologo, Letizia; Lattanzi, Giovanna; Cundari, Enrico; Raimondo, Domenico; Biroccio, Annamaria; Gatti, Maurizio; Saggio, Isabella

    2016-08-01

    AKTIP is a shelterin-interacting protein required for replication of telomeric DNA. Here, we show that AKTIP biochemically interacts with A- and B-type lamins and affects lamin A, but not lamin C or B, expression. In interphase cells, AKTIP localizes at the nuclear rim and in discrete regions of the nucleoplasm just like lamins. Double immunostaining revealed that AKTIP partially co-localizes with lamin B1 and lamin A/C in interphase cells, and that proper AKTIP localization requires functional lamin A. In mitotic cells, AKTIP is enriched at the spindle poles and at the midbody of late telophase cells similar to lamin B1. AKTIP-depleted cells show senescence-associated markers and recapitulate several aspects of the progeroid phenotype. Collectively, our results indicate that AKTIP is a new player in lamin-related processes, including those that govern nuclear architecture, telomere homeostasis and cellular senescence. PMID:27512140

  17. ERK1/2 MAP kinases promote cell cycle entry by rapid, kinase-independent disruption of retinoblastoma-lamin A complexes.

    PubMed

    Rodríguez, Javier; Calvo, Fernando; González, José M; Casar, Berta; Andrés, Vicente; Crespo, Piero

    2010-11-29

    As orchestrators of essential cellular processes like proliferation, ERK1/2 mitogen-activated protein kinase signals impact on cell cycle regulation. A-type lamins are major constituents of the nuclear matrix that also control the cell cycle machinery by largely unknown mechanisms. In this paper, we disclose a functional liaison between ERK1/2 and lamin A whereby cell cycle progression is regulated. We demonstrate that lamin A serves as a mutually exclusive dock for ERK1/2 and the retinoblastoma (Rb) protein. Our results reveal that, immediately after their postactivation entrance in the nucleus, ERK1/2 dislodge Rb from its interaction with lamin A, thereby facilitating its rapid phosphorylation and consequently promoting E2F activation and cell cycle entry. Interestingly, these effects are independent of ERK1/2 kinase activity. We also show that cellular transformation and tumor cell proliferation are dependent on the balance between lamin A and nuclear ERK1/2 levels, which determines Rb accessibility for phosphorylation/inactivation. PMID:21115804

  18. Differentiation of C2C12 myoblasts expressing lamin A mutated at a site responsible for Emery-Dreifuss muscular dystrophy is improved by inhibition of the MEK-ERK pathway and stimulation of the PI3-kinase pathway

    SciTech Connect

    Favreau, Catherine; Delbarre, Erwan; Courvalin, Jean-Claude; Buendia, Brigitte

    2008-04-01

    Mutation R453W in A-type lamins, that are major nuclear envelope proteins, generates Emery-Dreifuss muscular dystrophy. We previously showed that mouse myoblasts expressing R453W-lamin A incompletely exit the cell cycle and differentiate into myocytes with a low level of multinucleation. Here we attempted to improve differentiation by treating these cells with a mixture of PD98059, an extracellular-regulated kinase (ERK) kinase (also known as mitogen-activated kinase, MEK) inhibitor, and insulin-like growth factor-II, an activator of phosphoinositide 3-kinase. We show that mouse myoblasts expressing R453W-lamin A were sensitive to the drug treatment as shown by (i) an increase in multinucleation, (ii) downregulation of proliferation markers (cyclin D1, hyperphosphorylated Rb), (iii) upregulation of myogenin, and (iv) sustained activation of p21 and cyclin D3. However, nuclear matrix anchorage of p21 and cyclin D3 in a complex with hypophosphorylated Rb that is critical to trigger cell cycle arrest and myogenin induction was deficient and incompletely restored by drug treatment. As the turn-over of R453W-lamin A at the nuclear envelope was greatly enhanced, we propose that R453W-lamin A impairs the capacity of the nuclear lamina to serve as scaffold for substrates of the MEK-ERK pathway and for MyoD-induced proteins that play a role in the differentiation process.

  19. Tying up loose ends: telomeres, genomic instability and lamins.

    PubMed

    Gonzalo, Susana; Eissenberg, Joel C

    2016-04-01

    On casual inspection, the eukaryotic nucleus is a deceptively simple organelle. Far from being a bag of chromatin, the nucleus is, in some ways, a structural and functional extension of the chromosomes it contains. Recently, interest has intensified in how chromosome compartmentalization and dynamics affect nuclear function. Different studies uncovered functional interactions between chromosomes and the filamentous nuclear meshwork comprised of lamin proteins. Here, we summarize recent research suggesting that telomeres, the capping structures that protect chromosome ends, are stabilized by lamin-binding and that alterations in nuclear lamins lead to defects in telomere compartmentalization, homeostasis and function. Telomere dysfunction contributes to the genomic instability that characterizes aging-related diseases, and might be an important factor in the pathophysiology of lamin-related diseases. PMID:27010504

  20. Suppression of proliferative defects associated with processing-defective lamin A mutants by hTERT or inactivation of p53.

    PubMed

    Kudlow, Brian A; Stanfel, Monique N; Burtner, Christopher R; Johnston, Elijah D; Kennedy, Brian K

    2008-12-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare, debilitating disease with early mortality and rapid onset of aging-associated pathologies. It is linked to mutations in LMNA, which encodes A-type nuclear lamins. The most frequent HGPS-associated LMNA mutation results in a protein, termed progerin, with an internal 50 amino acid deletion and, unlike normal A-type lamins, stable farnesylation. The cellular consequences of progerin expression underlying the HGPS phenotype remain poorly understood. Here, we stably expressed lamin A mutants, including progerin, in otherwise identical primary human fibroblasts to compare the effects of different mutants on nuclear morphology and cell proliferation. We find that expression of progerin leads to inhibition of proliferation in a high percentage of cells and slightly premature senescence in the population. Expression of a stably farnesylated mutant of lamin A phenocopied the immediate proliferative defects but did not result in premature senescence. Either p53 inhibition or, more surprisingly, expression of the catalytic subunit of telomerase (hTERT) suppressed the early proliferative defects associated with progerin expression. These findings lead us to propose that progerin may interfere with telomere structure or metabolism in a manner suppressible by increased telomerase levels and possibly link mechanisms leading to progeroid phenotypes to those of cell immortalization. PMID:18843043

  1. Laminate armor and related methods

    SciTech Connect

    Chu, Henry S; Lillo, Thomas M; Zagula, Thomas M

    2013-02-26

    Laminate armor and methods of manufacturing laminate armor. Specifically, laminate armor plates comprising a commercially pure titanium layer and a titanium alloy layer bonded to the commercially pure titanium outer layer are disclosed, wherein an average thickness of the titanium alloy inner layer is about four times an average thickness of the commercially pure titanium outer layer. In use, the titanium alloy layer is positioned facing an area to be protected. Additionally, roll-bonding methods for manufacturing laminate armor plates are disclosed.

  2. Laminated BEAM loops

    NASA Astrophysics Data System (ADS)

    Danisch, Lee A.

    1996-10-01

    BEAM sensors include treated loops of optical fiber that modulate optical throughput with great sensitivity and linearity, in response to curvature of the loop out of its plane. This paper describes BEAM sensors that have two loops treated in opposed fashion, hermetically sealed in flexible laminations. The sensors include an integrated optoelectronics package that extracts curvature information from the treated portion of the loops while rejecting common mode errors. The laminated structure is used to sense various parameters including displacement, force, pressure, flow, and acceleration.

  3. Conserved lamin A protein expression in differentiated cells in the earthworm Eudrilus eugeniae.

    PubMed

    Kalidas, Ramamoorthy M; Raja, Subramanian Elaiya; Mydeen, Sheik Abdul Kader Nagoor Meeran; Samuel, Selvan Christyraj Johnson Retnaraj; Durairaj, Selvan Christyraj Jackson; Nino, Gopi D; Palanichelvam, Karuppaiah; Vaithi, Arumugaswami; Sudhakar, Sivasubramaniam

    2015-09-01

    Lamin A is an intermediate filament protein found in most of the differentiated vertebrate cells but absent in stem cells. It shapes the skeletal frame structure beneath the inner nuclear membrane of the cell nucleus. As there are few studies of the expression of lamin A in invertebrates, in the present work, we have analyzed the sequence, immunochemical conservation and expression pattern of lamin A protein in the earthworm Eudrilus eugeniae, a model organism for tissue regeneration. The expression of lamin A has been confirmed in E. eugeniae by immunoblot. Its localization in the nuclear membrane has been observed by immunohistochemistry using two different rabbit anti-sera raised against human lamin A peptides, which are located at the C-terminus of the lamin A protein. These two antibodies detected 70 kDa lamin A protein in mice and a single 65 kDa protein in the earthworm. The Oct-4 positive undifferentiated blastemal tissues of regenerating earthworm do not express lamin A, while the Oct-4 negative differentiated cells express lamin A. This pattern was also confirmed in the earthworm prostate gland. The present study is the first evidence for the immunochemical identification of lamin A and Oct-4 in the earthworm. Along with the partial sequence obtained from the earthworm genome, the present results suggest that lamin A protein and its expression pattern is conserved from the earthworm to humans. PMID:25858151

  4. Lamins regulate cell trafficking and lineage maturation of adult human hematopoietic cells

    PubMed Central

    Shin, Jae-Won; Spinler, Kyle R.; Swift, Joe; Chasis, Joel A.; Mohandas, Narla; Discher, Dennis E.

    2013-01-01

    Hematopoietic stem and progenitor cells, as well as nucleated erythroblasts and megakaryocytes, reside preferentially in adult marrow microenvironments whereas other blood cells readily cross the endothelial barrier into the circulation. Because the nucleus is the largest organelle in blood cells, we hypothesized that (i) cell sorting across microporous barriers is regulated by nuclear deformability as controlled by lamin-A and -B, and (ii) lamin levels directly modulate hematopoietic programs. Mass spectrometry-calibrated intracellular flow cytometry indeed reveals a lamin expression map that partitions human blood lineages between marrow and circulating compartments (P = 0.00006). B-type lamins are highly variable and predominate only in CD34+ cells, but migration through micropores and nuclear flexibility in micropipette aspiration both appear limited by lamin-A:B stoichiometry across hematopoietic lineages. Differentiation is also modulated by overexpression or knockdown of lamins as well as retinoic acid addition, which regulates lamin-A transcription. In particular, erythroid differentiation is promoted by high lamin-A and low lamin-B1 expression whereas megakaryocytes of high ploidy are inhibited by lamin suppression. Lamins thus contribute to both trafficking and differentiation. PMID:24191023

  5. Laminated rare earth structure and method of making

    DOEpatents

    Senor, David J [West Richland, WA; Johnson, Roger N [Richland, WA; Reid, Bruce D [Pasco, WA; Larson, Sandra [Richland, WA

    2002-07-30

    A laminated structure having two or more layers, wherein at least one layer is a metal substrate and at least one other layer is a coating comprising at least one rare earth element. For structures having more than two layers, the coating and metal substrate layers alternate. In one embodiment of the invention, the structure is a two-layer laminate having a rare earth coating electrospark deposited onto a metal substrate. In another embodiment of the invention, the structure is a three-layer laminate having the rare earth coating electrospark deposited onto a first metal substrate and the coating subsequently abonded to a second metal substrate. The bonding of the coating to the second metal substrate may be accomplished by hot pressing, hot rolling, high deformation rate processing, or combinations thereof. The laminated structure may be used in nuclear components where reactivity control or neutron absorption is desired and in non-nuclear applications such as magnetic and superconducting films.

  6. Aberrant localization of lamin B receptor (LBR) in cellular senescence in human cells.

    PubMed

    Arai, Rumi; En, Atsuki; Ukekawa, Ryo; Miki, Kensuke; Fujii, Michihiko; Ayusawa, Dai

    2016-05-13

    5-Bromodeoxyuridine (BrdU), a thymidine analogue, induces cellular senescence in mammalian cells. BrdU induces cellular senescence probably through the regulation of chromatin because BrdU destabilizes or disrupts nucleosome positioning and decondenses heterochromatin. Since heterochromatin is tethered to the nuclear periphery through the interaction with the nuclear envelope proteins, we examined the localization of the several nuclear envelope proteins such as lamins, lamin-interacting proteins, nuclear pore complex proteins, and nuclear transport proteins in senescent cells. We have shown here that lamin B receptor (LBR) showed a change in localization in both BrdU-induced and replicative senescent cells. PMID:27059139

  7. Coupled actin-lamin biopolymer networks and protecting DNA

    NASA Astrophysics Data System (ADS)

    Zhang, Tao; Rocklin, D. Zeb; Mao, Xiaoming; Schwarz, J. M.

    The mechanical properties of cells are largely determined by networks of semiflexible biopolymers forming the cytoskeleton. Similarly, the mechanical properties of cell nuclei are also largely determined by networks of semiflexible biopolymers forming the nuclear cytoskeleton. In particular, a network of filamentous lamin sits just inside the inner nuclear membrane to presumably protect the heart of the cell nucleus--the DNA. It has been demonstrated over the past decade that the actin cytoskeletal biopolymer network and the lamin biopolymer network are coupled via a sequence of proteins bridging the outer and inner nuclear membranes, known as the LINC complex. We, therefore, probe the consequences of such a coupling in a model biopolymer network system via numerical simulations to understand the resulting deformations in the lamin network in response to perturbations in the actin cytoskeletal network. We find, for example, that the force transmission across the coupled system can depend sensitively on the concentration of LINC complexes. Such study could have implications for mechanical mechanisms of the regulation of transcription since DNA couples to lamin via lamin-binding domains so that deformations in the lamin network may result in deformations in the DNA.

  8. A peculiar lamin in a peculiar mammal: Expression of lamin LIII in platypus (Ornithorhynchus anatinus).

    PubMed

    Peter, Annette; Khandekar, Shaunak; Deakin, Janine E; Stick, Reimer

    2015-11-01

    Platypus (Ornithorhynchus anatinus) holds a unique phylogenetic position at the base of the mammalian lineage due to an amalgamation of mammalian and sauropsid-like features. Here we describe the set of four lamin genes for platypus. Lamins are major components of the nuclear lamina, which constitutes a main component of the nucleoskeleton and is involved in a wide range of nuclear functions. Vertebrate evolution was accompanied by an increase in the number of lamin genes from a single gene in their closest relatives, the tunicates and cephalochordates, to four genes in the vertebrate lineage. Of the four genes the LIII gene is characterized by the presence of two alternatively spliced CaaX-encoding exons. In amphibians and fish LIII is the major lamin protein in oocytes and early embryos. The LIII gene is conserved throughout the vertebrate lineage, with the notable exception of marsupials and placental mammals, which have lost the LIII gene. Here we show that platypus has retained an LIII gene, albeit with a significantly altered structure and with a radically different expression pattern. The platypus LIII gene contains only a single CaaX-encoding exon and the head domain together with coil 1a and part of coil1b of the platypus LIII protein is replaced by a novel short non-helical N-terminus. It is expressed exclusively in the testis. These features resemble those of male germ cell-specific lamins in placental mammals, in particular those of lamin C2. Our data suggest (i) that the specific functions of LIII, which it fulfills in all other vertebrates, is no longer required in mammals and (ii) once it had been freed from these functions has undergone structural alterations and has adopted a new functionality in monotremes. PMID:26213206

  9. Lamin A/C, laminopathies and premature ageing.

    PubMed

    Liu, Baohua; Zhou, Zhongjun

    2008-06-01

    Lamin A/C belongs to type V intermediate filaments and constitutes the nuclear lamina and nuclear matrix, where a variety of nuclear activities occur. Lamin A/C protein is firstly synthesized as a precursor and is further proteolytically processed by the zinc metallo-proteinase Ste24 (Zmpste24). Lamin A/C mutations cause a series of human diseases, collectively called laminopathies, the most severe of which is Hutchinson Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD) which arises due to an unsuccessful maturation of prelamin A. Although the exact underlying molecular mechanisms are still poorly understood, genomic instability, defective nuclear mechanics and mechanotransduction, have been hypothesized to be responsible for laminopathy-based premature ageing. Removal of unprocessed prelamin A (progerin) or rescue of defective DNA repair could be potential therapeutic strategies for the treatment of HGPS in future. PMID:18366013

  10. cDNA cloning of the developmentally regulated lamin LIII of Xenopus laevis.

    PubMed Central

    Stick, R

    1988-01-01

    Lamins are nucleoskeletal proteins which form intermediate type filaments in close association with the inner nuclear envelope membrane. Based on molecular and biochemical properties the lamins were grouped as type-A and type-B lamins, respectively. I have cloned the cDNA encoding lamin LIII of Xenopus which is the lamin protein present in oocyte nuclei and in cleavage nuclei. The data presented here indicate that a pool of maternal lamin LIII RNA is synthesized very early in oogenesis and that it continues to be present until gastrulation when the vast majority of the LIII RNA is degraded. Despite the similarities shared by all lamin proteins, the lamin LIII sequence neither possesses the features diagnostic for either type-A or type-B lamins nor does it show greater sequence similarity to one of the lamin types than to the other and thus it may represent a third type of lamin protein which may reflect its special function in oogenesis and early development. Images PMID:3181134

  11. 78 FR 19007 - Certain Products Having Laminated Packaging, Laminated Packaging, and Components Thereof...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-28

    ... COMMISSION Certain Products Having Laminated Packaging, Laminated Packaging, and Components Thereof.... 1337, on behalf of Lamina Packaging Innovations LLC of Longview, Texas. An amended complaint was filed... importation of certain products having laminated packaging, laminated packaging, and components thereof...

  12. 78 FR 13083 - Products Having Laminated Packaging, Laminated Packaging, and Components Thereof; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-26

    ... COMMISSION Products Having Laminated Packaging, Laminated Packaging, and Components Thereof; Notice of... Commission has received a complaint entitled Products Having Laminated ] Packaging, Laminated Packaging, and... filed on behalf of Lamina Packaging Innovations LLC on February 20, 2013. The complaint...

  13. Investigation of the entry characteristics of dust samplers of a type used in the British nuclear industry

    NASA Astrophysics Data System (ADS)

    Mark, D.; Vincent, J. H.; Stevens, D. C.; Marshall, M.

    Experiments have been carried out in a large wind tunnel to investigate the entry characteristics of dust samplers—both static and personal—of the type used to monitor 'total' airborne radioactive paniculate in the British nuclear industry. These samplers were exposed to test dusts of closely-graded fused alumina under experimental conditions relevant to the environmental conditions found in nuclear industry workplaces. For the static samplers (60-mm open face filter holders), performance was determined by reference to a 10-mm isokinetic probe. The resultant aspiration efficiency ( A) was found to be close to unity for the range of environmental conditions found in the nuclear industry workplace and for particles with aerodynamic diameter up to about 30 μm. Also it is unaffected by mounting the sampler itself on the large bluff body of the sampling pump. The performances of the personal samplers (of the 25-mm filter holder type) were assessed in terms of the ratio ( R) between the mass of dust entering each personal sampler when worn on the body of a mannequin and that entering the mouth of the mannequin under simulated breathing. The results show that, for nuclear industry workplace conditions, the personal samplers reflect satisfactorily the health-related 'total' dust exposure of the wearer.

  14. Thermally stable laminating resins

    NASA Technical Reports Server (NTRS)

    Jones, R. J.; Vaughan, R. W.; Burns, E. A.

    1972-01-01

    Improved thermally stable laminating resins were developed based on the addition-type pyrolytic polymerization. Detailed monomer and polymer synthesis and characterization studies identified formulations which facilitate press molding processing and autoclave fabrication of glass and graphite fiber reinforced composites. A specific resin formulation, termed P10P was utilized to prepare a Courtaulds HMS reinforced simulated airfoil demonstration part by an autoclave molding process.

  15. Laminated piezoelectric transformer

    NASA Technical Reports Server (NTRS)

    Vazquez Carazo, Alfredo (Inventor)

    2006-01-01

    A laminated piezoelectric transformer is provided using the longitudinal vibration modes for step-up voltage conversion applications. The input portions are polarized to deform in a longitudinal plane and are bonded to an output portion. The deformation of the input portions is mechanically coupled to the output portion, which deforms in the same longitudinal direction relative to the input portion. The output portion is polarized in the thickness direction relative its electrodes, and piezoelectrically generates a stepped-up output voltage.

  16. BioID Identification of Lamin-Associated Proteins.

    PubMed

    Mehus, Aaron A; Anderson, Ruthellen H; Roux, Kyle J

    2016-01-01

    A- and B-type lamins support the nuclear envelope, contribute to heterochromatin organization, and regulate a myriad of nuclear processes. The mechanisms by which lamins function in different cell types and the mechanisms by which lamin mutations cause over a dozen human diseases (laminopathies) remain unclear. The identification of proteins associated with lamins is likely to provide fundamental insight into these mechanisms. BioID (proximity-dependent biotin identification) is a unique and powerful method for identifying protein-protein and proximity-based interactions in living cells. BioID utilizes a mutant biotin ligase from bacteria that is fused to a protein of interest (bait). When expressed in living cells and stimulated with excess biotin, this BioID-fusion protein promiscuously biotinylates directly interacting and vicinal endogenous proteins. Following biotin-affinity capture, the biotinylated proteins can be identified using mass spectrometry. BioID thus enables screening for physiologically relevant protein associations that occur over time in living cells. BioID is applicable to insoluble proteins such as lamins that are often refractory to study by other methods and can identify weak and/or transient interactions. We discuss the use of BioID to elucidate novel lamin-interacting proteins and its applications in a broad range of biological systems, and provide detailed protocols to guide new applications. PMID:26778550

  17. Crystal structures of the coil 2B fragment and the globular tail domain of human lamin B1

    SciTech Connect

    Ruan, Jianbin; Xu, Chao; Bian, Chuanbing; Lam, Robert; Wang, Jia-Pey; Kania, Joanna; Min, Jinrong; Zang, Jianye

    2012-07-18

    We present here the crystal structures of human lamin B1 globular tail domain and coiled 2B domain, which adopt similar folds to Ig-like domain and coiled-coil domain of lamin A, respectively. Despite the overall similarity, we found an extra intermolecular disulfide bond in the lamin B1 coil 2B domain, which does not exist in lamin A/C. In addition, the structural analysis indicates that interactions at the lamin B1 homodimer interface are quite different from those of lamin A/C. Thus our research not only reveals the diversely formed homodimers among lamin family members, but also sheds light on understanding the important roles of lamin B1 in forming the nuclear lamina matrix.

  18. Symmetric Composite Laminate Stress Analysis

    NASA Technical Reports Server (NTRS)

    Wang, T.; Smolinski, K. F.; Gellin, S.

    1985-01-01

    It is demonstrated that COSMIC/NASTRAN may be used to analyze plate and shell structures made of symmetric composite laminates. Although general composite laminates cannot be analyzed using NASTRAN, the theoretical development presented herein indicates that the integrated constitutive laws of a symmetric composite laminate resemble those of a homogeneous anisotropic plate, which can be analyzed using NASTRAN. A detailed analysis procedure is presented, as well as an illustrative example.

  19. Solar cell module lamination process

    DOEpatents

    Carey, Paul G.; Thompson, Jesse B.; Aceves, Randy C.

    2002-01-01

    A solar cell module lamination process using fluoropolymers to provide protection from adverse environmental conditions and thus enable more extended use of solar cells, particularly in space applications. A laminate of fluoropolymer material provides a hermetically sealed solar cell module structure that is flexible and very durable. The laminate is virtually chemically inert, highly transmissive in the visible spectrum, dimensionally stable at temperatures up to about 200.degree. C. highly abrasion resistant, and exhibits very little ultra-violet degradation.

  20. Structural protein 4.1R is integrally involved in nuclear envelope protein localization, centrosome–nucleus association and transcriptional signaling

    PubMed Central

    Meyer, Adam J.; Almendrala, Donna K.; Go, Minjoung M.; Krauss, Sharon Wald

    2011-01-01

    The multifunctional structural protein 4.1R is required for assembly and maintenance of functional nuclei but its nuclear roles are unidentified. 4.1R localizes within nuclei, at the nuclear envelope, and in cytoplasm. Here we show that 4.1R, the nuclear envelope protein emerin and the intermediate filament protein lamin A/C co-immunoprecipitate, and that 4.1R-specific depletion in human cells by RNA interference produces nuclear dysmorphology and selective mislocalization of proteins from several nuclear subcompartments. Such 4.1R-deficiency causes emerin to partially redistribute into the cytoplasm, whereas lamin A/C is disorganized at nuclear rims and displaced from nucleoplasmic foci. The nuclear envelope protein MAN1, nuclear pore proteins Tpr and Nup62, and nucleoplasmic proteins NuMA and LAP2α also have aberrant distributions, but lamin B and LAP2β have normal localizations. 4.1R-deficient mouse embryonic fibroblasts show a similar phenotype. We determined the functional effects of 4.1R-deficiency that reflect disruption of the association of 4.1R with emerin and A-type lamin: increased nucleus–centrosome distances, increased β-catenin signaling, and relocalization of β-catenin from the plasma membrane to the nucleus. Furthermore, emerin- and lamin-A/C-null cells have decreased nuclear 4.1R. Our data provide evidence that 4.1R has important functional interactions with emerin and A-type lamin that impact upon nuclear architecture, centrosome–nuclear envelope association and the regulation of β-catenin transcriptional co-activator activity that is dependent on β-catenin nuclear export. PMID:21486941

  1. Lamin A/C Is a Risk Biomarker in Colorectal Cancer

    PubMed Central

    Willis, Naomi D.; Cox, Thomas R.; Rahman-Casañs, Syed F.; Smits, Kim; Przyborski, Stefan A.; van den Brandt, Piet; van Engeland, Manon; Weijenberg, Matty; Wilson, Robert G.; de Bruïne, Adriaan; Hutchison, Christopher J.

    2008-01-01

    Background A-type lamins are type V intermediate filament proteins encoded by the gene LMNA. Mutations in LMNA give rise to diverse degenerative diseases related to premature ageing. A-type lamins also influence the activity of the Retinoblastoma protein (pRb) and oncogenes such a β-catenin. Consequently, it has been speculated that expression of A-type lamins may also influence tumour progression. Methodology/Principal Findings An archive of colorectal cancer (CRC) and normal colon tissue was screened for expression of A-type lamins. We used the Cox proportional hazard ratio (HR) method to investigate patient survival. Using CRC cell lines we investigated the effects of lamin A expression on other genes by RT-PCR; on cell growth by FACS analysis; and on invasiveness by cell migration assays and siRNA knockdown of targeted genes. We found that lamin A is expressed in colonic stem cells and that patients with A-type lamin-expressing tumours have significantly worse prognosis than patients with A-type lamin negative tumours (HR = 1.85, p = 0.005). To understand this finding, we established a model system based upon expression of GFP-lamin A in CRC cells. We found that expression of GFP-lamin A in these cells did not affect cell proliferation but did promote greatly increased cell motility and invasiveness. The reason for this increased invasiveness was that expression of lamin A promoted up-regulation of the actin bundling protein T-plastin, leading to down regulation of the cell adhesion molecule E-cadherin. Conclusions Expression of A-type lamins increases the risk of death from CRC because its presence gives rise to increased invasiveness and potentially a more stem cell-like phenotype. This report directly links A-type lamin expression to tumour progression and raises the profile of LMNA from one implicated in multiple but rare genetic conditions to a gene involved in one of the commonest diseases in the Western World. PMID:18714339

  2. The LMNA mutation p.Arg321Ter associated with dilated cardiomyopathy leads to reduced expression and a skewed ratio of lamin A and lamin C proteins

    SciTech Connect

    Al-Saaidi, Rasha; Rasmussen, Torsten B.; Palmfeldt, Johan; Nissen, Peter H.; Beqqali, Abdelaziz; Hansen, Jakob; Pinto, Yigal M.; Boesen, Thomas; Mogensen, Jens; Bross, Peter

    2013-11-15

    Dilated cardiomyopathy (DCM) is a disease of the heart muscle characterized by cardiac chamber enlargement and reduced systolic function of the left ventricle. Mutations in the LMNA gene represent the most frequent known genetic cause of DCM associated with disease of the conduction systems. The LMNA gene generates two major transcripts encoding the nuclear lamina major components lamin A and lamin C by alternative splicing. Both haploinsuffiency and dominant negative effects have been proposed as disease mechanism for premature termination codon (PTC) mutations in LMNA. These mechanisms however are still not clearly established. In this study, we used a representative LMNA nonsense mutation, p.Arg321Ter, to shed light on the molecular disease mechanisms. Cultured fibroblasts from three DCM patients carrying this mutation were analyzed. Quantitative reverse transcriptase PCR and sequencing of these PCR products indicated that transcripts from the mutant allele were degraded by the nonsense-mediated mRNA decay (NMD) mechanism. The fact that no truncated mutant protein was detectable in western blot (WB) analysis strengthens the notion that the mutant transcript is efficiently degraded. Furthermore, WB analysis showed that the expression of lamin C protein was reduced by the expected approximately 50%. Clearly decreased lamin A and lamin C levels were also observed by immunofluorescence microscopy analysis. However, results from both WB and nano-liquid chromatography/mass spectrometry demonstrated that the levels of lamin A protein were more reduced suggesting an effect on expression of lamin A from the wild type allele. PCR analysis of the ratio of lamin A to lamin C transcripts showed unchanged relative amounts of lamin A transcript suggesting that the effect on the wild type allele was operative at the protein level. Immunofluorescence microscopy analysis showed no abnormal nuclear morphology of patient fibroblast cells. Based on these data, we propose that

  3. Beach lamination: Nature and origin

    USGS Publications Warehouse

    Clifton, H.E.

    1969-01-01

    A distinctive two-fold sedimentation unit characterizes lamination in the upper swash zone of beaches. Within the unit a fine and/or a heavy mineral rich layer at the base grades upward into a coarser and/or a heavy mineral poor layer at the top. This distinctive type of lamination results from grain segregation within bed flow during wave backwash. ?? 1969.

  4. Holographic nondestructive testing of laminates

    NASA Technical Reports Server (NTRS)

    Stuckenberg, F. H.

    1973-01-01

    Very small differences in laminate thickness result in interference fringes in holograph image. These indicate presence of unbonded area. Theoretical knowledge of membrane deflection may be used in conjunction with reduced number of pretest experiments to determine number of optical fringes that should appear for given laminate.

  5. Self-Healing Laminate System

    NASA Technical Reports Server (NTRS)

    Beiermann, Brett A. (Inventor); Keller, Michael W. (Inventor); White, Scott R. (Inventor); Sottos, Nancy R. (Inventor)

    2016-01-01

    A laminate material may include a first flexible layer, and a self-healing composite layer in contact with the first flexible layer. The composite layer includes an elastomer matrix, a plurality of first capsules including a polymerizer, and a corresponding activator for the polymerizer. The laminate material may self-heal when subjected to a puncture or a tear.

  6. Cloning and Characterization of Sf9 Cell Lamin and the Lamin Conformational Changes during Autographa californica multiple nucleopolyhedrovirus Infection.

    PubMed

    Wei, Wenqiang; Wang, Hongju; Li, Xiaoya; Fang, Na; Yang, Shili; Liu, Hongyan; Kang, Xiaonan; Sun, Xiulian; Ji, Shaoping

    2016-01-01

    At present, the details of lamina alterations after baculovirus infection remain elusive. In this study, a lamin gene in the Sf9 cell line of Spodoptera frugiperda was cloned. The open reading frame (orf) of the Sf9 lamin was 1860 bp and encoded a protein with a molecular weight of 70 kDa. A transfection assay with a red fluorescence protein (rfp)-lamin fusion protein indicated that Sf9 lamin was localized in the nuclear rim. Transmission electron microscopy observations indicated that Autographa californica multiple nucleopolyhedrovirus (AcMNPV) nucleocapsids may pass through the nuclear envelope. Immunofluorescence assay indicated that the lamina showed a ruffled staining pattern with the formation of invaginations in the Sf9 cells infected with AcMNPV, while it was evenly distributed at the nuclear periphery of mock-infected cells. Western blotting results indicated that the total amount of lamin in the baculovirus-infected Sf9 cells was significantly decreased compared with the mock-infected cells. These results imply that AcMNPV infection induces structural and biochemical rearrangements of lamina of Sf9 cells. PMID:27164127

  7. Cloning and Characterization of Sf9 Cell Lamin and the Lamin Conformational Changes during Autographa californica multiple nucleopolyhedrovirus Infection

    PubMed Central

    Wei, Wenqiang; Wang, Hongju; Li, Xiaoya; Fang, Na; Yang, Shili; Liu, Hongyan; Kang, Xiaonan; Sun, Xiulian; Ji, Shaoping

    2016-01-01

    At present, the details of lamina alterations after baculovirus infection remain elusive. In this study, a lamin gene in the Sf9 cell line of Spodoptera frugiperda was cloned. The open reading frame (orf) of the Sf9 lamin was 1860 bp and encoded a protein with a molecular weight of 70 kDa. A transfection assay with a red fluorescence protein (rfp)-lamin fusion protein indicated that Sf9 lamin was localized in the nuclear rim. Transmission electron microscopy observations indicated that Autographa californica multiple nucleopolyhedrovirus (AcMNPV) nucleocapsids may pass through the nuclear envelope. Immunofluorescence assay indicated that the lamina showed a ruffled staining pattern with the formation of invaginations in the Sf9 cells infected with AcMNPV, while it was evenly distributed at the nuclear periphery of mock-infected cells. Western blotting results indicated that the total amount of lamin in the baculovirus-infected Sf9 cells was significantly decreased compared with the mock-infected cells. These results imply that AcMNPV infection induces structural and biochemical rearrangements of lamina of Sf9 cells. PMID:27164127

  8. Proteins that associate with lamins: Many faces, many functions

    SciTech Connect

    Schirmer, Eric C. . E-mail: e.schirmer@ed.ac.uk; Foisner, Roland . E-mail: roland.foisner@meduniwien.ac.at

    2007-06-10

    Lamin-associated polypeptides (LAPs) comprise inner nuclear membrane proteins tightly associated with the peripheral lamin scaffold as well as proteins forming stable complexes with lamins in the nucleoplasm. The involvement of LAPs in a wide range of human diseases may be linked to an equally bewildering range of their functions, including sterol reduction, histone modification, transcriptional repression, and Smad- and {beta}-catenin signaling. Many LAPs are likely to be at the center of large multi-protein complexes, components of which may dictate their functions, and a few LAPs have defined enzymatic activities. Here we discuss the definition of LAPs, review their many binding partners, elaborate their functions in nuclear architecture, chromatin organization, gene expression and signaling, and describe what is currently known about their links to human disease.

  9. Purification of Lamins and Soluble Fragments of NETs.

    PubMed

    Makarov, Alexandr A; Rizzotto, Andrea; Meinke, Peter; Schirmer, Eric C

    2016-01-01

    Lamins and associated nuclear envelope transmembrane proteins (NETs) present unique problems for biochemical studies. Lamins form insoluble intermediate filament networks, associate with chromatin, and are also connected via specific NETs to the cytoskeleton, thus further complicating their isolation and purification from mammalian cells. Adding to this complexity, NETs at the inner nuclear membrane function in three distinct environments: (a) their nucleoplasmic domain(s) can bind lamins, chromatin, and transcriptional regulators; (b) they possess one or more integral transmembrane domains; and (c) their lumenal domain(s) function in the unique reducing environment of the nuclear envelope/ER lumen. This chapter describes strategic considerations and protocols to facilitate biochemical studies of lamins and NET proteins in vitro. Studying these proteins in vitro typically involves first expressing specific polypeptide fragments in bacteria and optimizing conditions to purify each fragment. We describe parameters for choosing specific fragments and designing purification strategies and provide detailed purification protocols. Biochemical studies can provide fundamental knowledge including binding strengths and the molecular consequences of disease-causing mutations that will be essential to understand nuclear envelope-genome interactions and nuclear envelope linked disease mechanisms. PMID:26778554

  10. Amphibian oocyte nuclei expressing lamin A with the progeria mutation E145K exhibit an increased elastic modulus.

    PubMed

    Kaufmann, Anna; Heinemann, Fabian; Radmacher, Manfred; Stick, Reimer

    2011-01-01

    Mutations in the human lamin A gene (LMNA) cause a wide range of diseases (laminopathies). Among these is the Hutchinson-Gilford progeria syndrome (HGPS), a rare premature aging disease. Most HGPS patients carry a silent point mutation, which activates a cryptic splice site resulting in the expression of a permanently isoprenylated and truncated lamin AΔ50/progerin. Another type of mutant lamin A namely, E145K-lamin A, also causes HGPS. E145K-lamin A induces profound changes in the nuclear architecture of patient cells as well as after expression in cultured cells. The E145K mutation is located in the α-helical central domain of lamin A, which is involved in lamin filament assembly. In vitro analyses of purified E145K-lamin A have revealed severe assembly defects into higher order lamin structures, which indicates an abnormal lateral association of protofilaments. To analyze how the altered assembly observed in vitro might influence the mechanics of a nuclear lamina formed by E145K-lamin A, mutant and wild type lamin A were ectopically expressed in amphibian oocytes. Both types form a lamina consisting of multi-layered sheets of filaments at the inner side of the nuclear envelope. The mechanical properties of isolated nuclei were measured by atomic force microscopy (AFM). From the resulting force curves, the stiffness of the lamina was estimated. The thickness of the resulting lamin A layer was then measured by TEM. The two parameters allowed us to estimate the elastic modulus (Young's modulus) of the lamina. Lamin A sheets made from E145K filaments have a higher Young's modulus compared to wild type filaments, i.e. the E145K-lamin A sheets are more rigid than wild type laminae of comparable thickness. PMID:21941106

  11. Significance of 1B and 2B domains in modulating elastic properties of lamin A.

    PubMed

    Bera, Manindra; Ainavarapu, Sri Rama Koti; Sengupta, Kaushik

    2016-01-01

    Nuclear lamins are type V intermediate filament proteins which form an elastic meshwork underlying the inner nuclear membrane. Lamins directly contribute to maintain the nuclear shape and elasticity. More than 400 mutations have been reported in lamin A that are involved in diseases known as laminopathies. These mutations are scattered mainly in the lamin rod domain along with some in its C-terminal domain. The contribution of the rod domain towards the elasticity of lamin A molecule was hitherto unknown. Here, we have elucidated the significance of the 1B and 2B domains of the rod in modulating the elastic behavior of lamin A by single-molecule force spectroscopy. In addition, we have also studied the network forming capacity of these domains and their corresponding viscoelastic behavior. We have shown that the 1B domain has the ability to form a lamin-like network and resists larger deformation. However at the single-molecular level, both the domains have comparable mechanical properties. The self-assembly of the 1B domain contributes to the elasticity of the lamin A network. PMID:27301336

  12. Significance of 1B and 2B domains in modulating elastic properties of lamin A

    PubMed Central

    Bera, Manindra; Ainavarapu, Sri Rama Koti; Sengupta, Kaushik

    2016-01-01

    Nuclear lamins are type V intermediate filament proteins which form an elastic meshwork underlying the inner nuclear membrane. Lamins directly contribute to maintain the nuclear shape and elasticity. More than 400 mutations have been reported in lamin A that are involved in diseases known as laminopathies. These mutations are scattered mainly in the lamin rod domain along with some in its C-terminal domain. The contribution of the rod domain towards the elasticity of lamin A molecule was hitherto unknown. Here, we have elucidated the significance of the 1B and 2B domains of the rod in modulating the elastic behavior of lamin A by single-molecule force spectroscopy. In addition, we have also studied the network forming capacity of these domains and their corresponding viscoelastic behavior. We have shown that the 1B domain has the ability to form a lamin-like network and resists larger deformation. However at the single-molecular level, both the domains have comparable mechanical properties. The self-assembly of the 1B domain contributes to the elasticity of the lamin A network. PMID:27301336

  13. Vacuum lamination of photovoltaic modules

    NASA Technical Reports Server (NTRS)

    Burger, D. R.

    1982-01-01

    Vacuum lamination of terrestrial photovoltaic modules is a new high volume process requiring new equipment and newly develop materials. Equipment development, materials research, and some research in related fields and testing methods are discussed.

  14. Internal Stresses in Laminated Construction

    NASA Technical Reports Server (NTRS)

    Heim, A L; Knauss, A C; Seutter, Louis

    1923-01-01

    This report reviews the procedure employed in an investigation of the sources and influence of internal stresses in laminated construction, and discusses the influence of shrinkage and swelling stresses caused by atmospheric conditions upon the tensile strength across grain in laminated construction with special reference to airplane propellers. The investigation covered three sources of internal stress, namely, the combination of plain-sawed and quarter-sawed material in the same construction, the gluing together of laminations of different moisture contents, and the gluing together of laminations of different densities. Glued specimens and free specimens, made up under various manufacturing conditions, were subjected to various climatic changes inducing internal stresses and then were tested.

  15. Laminated electromagnetic pump stator core

    DOEpatents

    Fanning, Alan W.

    1995-01-01

    A stator core for an electromagnetic pump includes a plurality of circumferentially abutting tapered laminations extending radially outwardly from a centerline axis to collectively define a radially inner bore and a radially outer circumference. Each of the laminations includes radially inner and outer edges and has a thickness increasing from the inner edge toward the outer edge to provide a substantially continuous path adjacent the circumference.

  16. Conserved cysteine residues in the mammalian lamin A tail are essential for cellular responses to ROS generation.

    PubMed

    Pekovic, Vanja; Gibbs-Seymour, Ian; Markiewicz, Ewa; Alzoghaibi, Fahad; Benham, Adam M; Edwards, Robert; Wenhert, Manfred; von Zglinicki, Thomas; Hutchison, Christopher J

    2011-12-01

    Pre-lamin A and progerin have been implicated in normal aging, and the pathogenesis of age-related degenerative diseases is termed 'laminopathies'. Here, we show that mature lamin A has an essential role in cellular fitness and that oxidative damage to lamin A is involved in cellular senescence. Primary human dermal fibroblasts (HDFs) aged replicatively or by pro-oxidants acquire a range of dysmorphic nuclear shapes. We observed that conserved cysteine residues in the lamin A tail domain become hyperoxidized in senescent fibroblasts, which inhibits the formation of lamin A inter- and intramolecular disulfide bonds. Both in the absence of lamin A and in the presence of a lamin A cysteine-to-alanine mutant, which eliminates these cysteine residues (522, 588, and 591), mild oxidative stress induced nuclear disorganization and led to premature senescence as a result of decreased tolerance to ROS stimulators. Human dermal fibroblasts lacking lamin A or expressing the lamin A cysteine-to-alanine mutant displayed a gene expression profile of ROS-responsive genes characteristic of chronic ROS stimulation. Our findings suggest that the conserved C-terminal cysteine residues are essential for lamin A function and that loss or oxidative damage to these cysteine residues promotes cellular senescence. PMID:21951640

  17. Nucleoplasmic Lamin A/C and Polycomb group of proteins: An evolutionarily conserved interplay

    PubMed Central

    Marullo, F.; Cesarini, E.; Antonelli, L.; Gregoretti, F.; Oliva, G.; Lanzuolo, C.

    2016-01-01

    ABSTRACT Nuclear lamins are the main components of the nuclear lamina at the nuclear periphery, providing mechanical support to the nucleus. However, recent findings suggest that lamins also reside in the nuclear interior, as a distinct and dynamic pool with critical roles in transcriptional regulation. In our work we found a functional and evolutionary conserved crosstalk between Lamin A/C and the Polycomb group (PcG) of proteins, this being required for the maintenance of the PcG repressive functions. Indeed, Lamin A/C knock-down causes PcG foci dispersion and defects in PcG-mediated higher order structures, thereby leading to impaired PcG mediated transcriptional repression. By using ad-hoc algorithms for image analysis and PLA approaches we hereby show that PcG proteins are preferentially located in the nuclear interior where they interact with nucleoplasmic Lamin A/C. Taken together, our findings suggest that nuclear components, such as Lamin A/C, functionally interact with epigenetic factors to ensure the correct transcriptional program maintenance. PMID:26930442

  18. Nucleoplasmic Lamin A/C and Polycomb group of proteins: An evolutionarily conserved interplay.

    PubMed

    Marullo, F; Cesarini, E; Antonelli, L; Gregoretti, F; Oliva, G; Lanzuolo, C

    2016-04-25

    Nuclear lamins are the main components of the nuclear lamina at the nuclear periphery, providing mechanical support to the nucleus. However, recent findings suggest that lamins also reside in the nuclear interior, as a distinct and dynamic pool with critical roles in transcriptional regulation. In our work we found a functional and evolutionary conserved crosstalk between Lamin A/C and the Polycomb group (PcG) of proteins, this being required for the maintenance of the PcG repressive functions. Indeed, Lamin A/C knock-down causes PcG foci dispersion and defects in PcG-mediated higher order structures, thereby leading to impaired PcG mediated transcriptional repression. By using ad-hoc algorithms for image analysis and PLA approaches we hereby show that PcG proteins are preferentially located in the nuclear interior where they interact with nucleoplasmic Lamin A/C. Taken together, our findings suggest that nuclear components, such as Lamin A/C, functionally interact with epigenetic factors to ensure the correct transcriptional program maintenance. PMID:26930442

  19. Identification of lamin B-regulated chromatin regions based on chromatin landscapes.

    PubMed

    Zheng, Xiaobin; Kim, Youngjo; Zheng, Yixian

    2015-07-15

    Lamins, the major structural components of the nuclear lamina (NL) found beneath the nuclear envelope, are known to interact with most of the nuclear peripheral chromatin in metazoan cells. Although NL-chromatin associations correlate with a repressive chromatin state, the role of lamins in tethering chromatin to NL and how such tether influences gene expression have remained challenging to decipher. Studies suggest that NL proteins regulate chromatin in a context-dependent manner. Therefore understanding the context of chromatin states based on genomic features, including chromatin-NL interactions, is important to the study of lamins and other NL proteins. By modeling genome organization based on combinatorial patterns of chromatin association with lamin B1, core histone modification, and core and linker histone occupancy, we report six distinct large chromatin landscapes, referred to as histone lamin landscapes (HiLands)-red (R), -orange (O), -yellow (Y), -green (G), -blue (B), and -purple (P), in mouse embryonic stem cells (mESCs). This HiLands model demarcates the previously mapped lamin-associated chromatin domains (LADs) into two HiLands, HiLands-B and HiLands-P, which are similar to facultative and constitutive heterochromatins, respectively. Deletion of B-type lamins in mESCs caused a reduced interaction between regions of HiLands-B and NL as measured by emerin-chromatin interaction. Our findings reveal the importance of analyzing specific chromatin types when studying the function of NL proteins in chromatin tether and regulation. PMID:25995381

  20. Identification of lamin B–regulated chromatin regions based on chromatin landscapes

    PubMed Central

    Zheng, Xiaobin; Kim, Youngjo; Zheng, Yixian

    2015-01-01

    Lamins, the major structural components of the nuclear lamina (NL) found beneath the nuclear envelope, are known to interact with most of the nuclear peripheral chromatin in metazoan cells. Although NL–chromatin associations correlate with a repressive chromatin state, the role of lamins in tethering chromatin to NL and how such tether influences gene expression have remained challenging to decipher. Studies suggest that NL proteins regulate chromatin in a context-dependent manner. Therefore understanding the context of chromatin states based on genomic features, including chromatin–NL interactions, is important to the study of lamins and other NL proteins. By modeling genome organization based on combinatorial patterns of chromatin association with lamin B1, core histone modification, and core and linker histone occupancy, we report six distinct large chromatin landscapes, referred to as histone lamin landscapes (HiLands)-red (R), -orange (O), -yellow (Y), -green (G), -blue (B), and -purple (P), in mouse embryonic stem cells (mESCs). This HiLands model demarcates the previously mapped lamin-associated chromatin domains (LADs) into two HiLands, HiLands-B and HiLands-P, which are similar to facultative and constitutive heterochromatins, respectively. Deletion of B-type lamins in mESCs caused a reduced interaction between regions of HiLands-B and NL as measured by emerin–chromatin interaction. Our findings reveal the importance of analyzing specific chromatin types when studying the function of NL proteins in chromatin tether and regulation. PMID:25995381

  1. Thermoelastic analysis of laminated plates. I - Symmetric specially orthotropic laminates

    SciTech Connect

    Wu, C.H.; Tauchert, T.R.

    1980-04-01

    Thermally induced deformations and stress resultants in symmetric laminated plates are analyzed. The method of M. Levy is used to study the transverse bending of a specially orthotropic laminate having two simply supported edges and subject to a temperature distribution that does not vary in a direction parallel to the simple supports. A solution is also obtained for the problem of in-plane stretching of the plate middle surface caused by a general three-dimensional temperature field. As an illustrative example, the thermoelastic response of a unidirectionally fiber-reinforced plate to a temperature variation that is linear in the thickness direction is computed.

  2. Impedances of Laminated Vacuum Chambers

    SciTech Connect

    Burov, A.; Lebedev, V.; /Fermilab

    2011-06-22

    First publications on impedance of laminated vacuum chambers are related to early 70s: those are of S. C. Snowdon [1] and of A. G. Ruggiero [2]; fifteen years later, a revision paper of R. Gluckstern appeared [3]. All the publications were presented as Fermilab preprints, and there is no surprise in that: the Fermilab Booster has its laminated magnets open to the beam. Being in a reasonable mutual agreement, these publications were all devoted to the longitudinal impedance of round vacuum chambers. The transverse impedance and the flat geometry case were addressed in more recent paper of K. Y. Ng [4]. The latest calculations of A. Macridin et al. [5] revealed some disagreement with Ref. [4]; this fact stimulated us to get our own results on that matter. Longitudinal and transverse impendances are derived for round and flat laminated vacuum chambers. Results of this paper agree with Ref. [5].

  3. Basic mechanics of laminated composite plates

    NASA Technical Reports Server (NTRS)

    Nettles, Alan T.

    1994-01-01

    The mechanics of laminated composite materials is presented in a clear manner with only essential derivations included. The constitutive equations in all of their forms are developed and then summarized in a separate section. The effects of hygrothermal effects are included. The prediction of the engineering constants for a laminate are derived. Strength of laminated composites is not covered.

  4. Evidence for modification of lamin B by a product of mevalonic acid

    SciTech Connect

    Wolda, S.L.; Glomset, J.A.

    1988-05-05

    Previous work from this laboratory has shown that a derivative of mevalonic acid is post-translationally incorporated into a number of specific proteins in Swiss 3T3 cells. Neither the nature of the modification nor the identities of the modified proteins have been determined to date. Here the authors describe results concerning modified proteins of approximately 67 kDa from HeLa cells and Chinese hamster ovary cells. They show that these proteins are specific to the nucleus and remain associated with a Triton/salt-insoluble nuclear fraction. Furthermore, immunological studies demonstrate that one of the modified proteins comigrates on two-dimensional gels with lamin B, a structural protein associated with the nuclear envelope. Using antibodies directed against lamin B in an immunoprecipitation experiment, they further show that this mevalonic acid-modified protein specifically coprecipitates with lamin B. These results support the hypothesis that lamin B is modified by a derivative of mevalonic acid.

  5. Defective lamin A-Rb signaling in Hutchinson-Gilford Progeria Syndrome and reversal by farnesyltransferase inhibition.

    PubMed

    Marji, Jackleen; O'Donoghue, Seán I; McClintock, Dayle; Satagopam, Venkata P; Schneider, Reinhard; Ratner, Desiree; Worman, Howard J; Gordon, Leslie B; Djabali, Karima

    2010-01-01

    Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare premature aging disorder caused by a de novo heterozygous point mutation G608G (GGC>GGT) within exon 11 of LMNA gene encoding A-type nuclear lamins. This mutation elicits an internal deletion of 50 amino acids in the carboxyl-terminus of prelamin A. The truncated protein, progerin, retains a farnesylated cysteine at its carboxyl terminus, a modification involved in HGPS pathogenesis. Inhibition of protein farnesylation has been shown to improve abnormal nuclear morphology and phenotype in cellular and animal models of HGPS. We analyzed global gene expression changes in fibroblasts from human subjects with HGPS and found that a lamin A-Rb signaling network is a major defective regulatory axis. Treatment of fibroblasts with a protein farnesyltransferase inhibitor reversed the gene expression defects. Our study identifies Rb as a key factor in HGPS pathogenesis and suggests that its modulation could ameliorate premature aging and possibly complications of physiological aging. PMID:20559568

  6. Multilayer printed wiring board lamination

    SciTech Connect

    Lula, J.W.

    1980-06-01

    The relationship of delamination resistance of multilayer PWBs made from GF material to manufacturing process variables was investigated. A unique quantitative test method developed during this project shows that delamination resistance is highly sensitive to material conditioning, to innerlayer surface treatment, and to post-lamination storage conditions, but is relatively insensitive to cure cycle variations.

  7. Beyond lamins: other structural components of the nucleoskeleton

    PubMed Central

    Zhong, Zhixia; Wilson, Katherine L.; Dahl, Kris Noel

    2010-01-01

    The nucleus is bordered by a double bilayer nuclear envelope, communicates with the cytoplasm via embedded nuclear pore complexes, and is structurally supported by an underlying nucleoskeleton. The nucleoskeleton includes nuclear intermediate filaments formed by lamin proteins, which provide major structural and mechanical support to the nucleus. However other structural proteins also contribute to the function of nucleoskeleton and help connect it to the cytoskeleton. This chapter reviews nucleoskeletal components beyond lamins, and summarizes specific methods and strategies useful for analyzing nuclear structural proteins including actin, spectrin, titin, LINC complex proteins and nuclear spindle matrix proteins. These components can localize to highly specific functional subdomains at the nuclear envelope or nuclear interior, and can interact either stably or dynamically with a variety of partners. These components confer upon the nucleoskeleton a functional diversity and mechanical resilience that appears to rival the cytoskeleton. To facilitate the exploration of this understudied area of biology, we summarize methods useful for localizing, solubilizing and immunoprecipitating nuclear structural proteins, and a state-of-the-art method to measure a newly-recognized mechanical property of nucleus. PMID:20816232

  8. Beyond lamins other structural components of the nucleoskeleton.

    PubMed

    Zhong, Zhixia; Wilson, Katherine L; Dahl, Kris Noel

    2010-01-01

    The nucleus is bordered by a double bilayer nuclear envelope, communicates with the cytoplasm via embedded nuclear pore complexes, and is structurally supported by an underlying nucleoskeleton. The nucleoskeleton includes nuclear intermediate filaments formed by lamin proteins, which provide major structural and mechanical support to the nucleus. However, other structural proteins also contribute to the function of the nucleoskeleton and help connect it to the cytoskeleton. This chapter reviews nucleoskeletal components beyond lamins and summarizes specific methods and strategies useful for analyzing nuclear structural proteins including actin, spectrin, titin, linker of nucleoskeleton and cytoskeleton (LINC) complex proteins, and nuclear spindle matrix proteins. These components can localize to highly specific functional subdomains at the nuclear envelope or nuclear interior and can interact either stably or dynamically with a variety of partners. These components confer upon the nucleoskeleton a functional diversity and mechanical resilience that appears to rival the cytoskeleton. To facilitate the exploration of this understudied area of biology, we summarize methods useful for localizing, solubilizing, and immunoprecipitating nuclear structural proteins, and a state-of-the-art method to measure a newly-recognized mechanical property of nucleus. PMID:20816232

  9. Steady state response of unsymmetrically laminated plates

    SciTech Connect

    Hosokawa, Kenji; Kawashima, Katsuya; Sakata, Toshiyuki

    1995-11-01

    A numerical approach for analyzing the forced vibration problem of a symmetrically laminated FRP (fiber reinforced plastic) composite plate was proposed by the authors. In the present paper, this approach is modified for application to an unsymmetrically laminated FRP composite plate. Numerical calculations are carried out for the clamped antisymmetrically laminated rectangular and elliptical plates which are a kind of unsymmetrically laminated plate. Then,, the effects of the lamina material and the fiber orientation angle on the steady state response are discussed. Furthermore, it is investigated that what structural damping factor is most influenced on the steady state response of an antisymmetrically laminated plate.

  10. Vacuum multilayer lamination of printed wiring boards

    NASA Astrophysics Data System (ADS)

    Wilkus, J. W.

    1992-11-01

    This experiment investigates vacuum multilayer lamination of rigid/flex, epoxy glass, polyimide glass, and polyimide quartz printed wiring boards. The effectiveness of the vacuum in removing entrapped air during the lamination cycle is demonstrated. The results of the experiment have also shown that vacuum lamination of epoxy glass multilayers improves the delamination resistance. Thus, epoxy glass multilayers that have been vacuum laminated will be able to withstand soldering temperatures longer without delaminating. Also, the experiment shows that vacuum multilayer lamination does not significantly change thickness, layer-to-layer registration, glass transition temperature, dielectric spacing between conductors, electrical resistance following thermal shock test, and other critical printed wiring board properties.

  11. Microstress prediction in composite laminate

    NASA Astrophysics Data System (ADS)

    Hutapea, Parsaoran

    2000-10-01

    The objective of this research is to develop a macroscopic theory, which can provide the connection between macromechanics and micromechanics in characterizing the micro-stress of composite laminates near edges and holes. The micropolar theory, a class of higher-order elasticity theory, of composite laminate mechanics is implemented in a well-known Pipes-Pagano free edge boundary problem. The micropolar homogenization method to determine the micropolar anisotropic effective elastic moduli is presented. A displacement-based finite element method based on micropolar theory in anisotropic solids is developed in analyzing composite laminates. The effects of fiber volume fraction and cell size on the normal stress along the artificial interface of the composite laminate are also investigated. The stress response based on micropolar theory is compared with those deduced from the micromechanics and classical elasticity theory. Special attention of the investigation focuses on the stress fields near the free edge where the high macrostress gradient occurs. The normal stresses along the artificial interface and especially, the microstress along the fiber/matrix interface on the critical cell near the free edge where the high macrostress gradient detected are the focus of this investigation. These microstresses are expected to dominate the failure initiation process in composite laminate. The implementation of micropolar analysis on the prediction of microstress of the critical cell near the free edge is found to be in very good agreement with "exact" microstress solutions. It is demonstrated that the micropolar theory is able to capture the microstress correctly from the homogenized solutions.

  12. Chromatin binding and polymerization of the endogenous Xenopus egg lamins: the opposing effects of glycogen and ATP.

    PubMed

    Lourim, D; Krohne, G

    1998-12-18

    We have previously identified and quantitated three B-type lamin isoforms present in the nuclei of mature Xenopus laevis oocytes, and in cell-free egg extracts. As Xenopus egg extracts are frequently used to analyze nuclear envelope assembly and lamina functions, we felt it was imperative that the polymerization and chromatin-binding properties of the endogenous B-type egg lamins be investigated. While we have demonstrated that soluble B-type lamins bind to chromatin, we have also observed that the polymerization of egg lamins does not require membranes or chromatin. Lamin assembly is enhanced by the addition of glycogen/glucose, or by the depletion of ATP from the extract. Moreover, the polymerization of egg cytosol lamins and their binding to demembranated sperm or chromatin assembled from naked lambda-DNA is inhibited by an ATP regeneration system. These ATP-dependent inhibitory activities can be overcome by the coaddition of glycogen to egg cytosol. We have observed that glycogen does not alter ATP levels during cytosol incubation, but rather, as glycogen-enhanced lamin polymerization is inhibited by okadaic acid, we conclude that glycogen activates protein phosphatases. Because protein phosphatase 1 (PP1) is the only phosphatase known to be specifically regulated by glycogen our data indicate that PP1 is involved in lamin polymerization. Our results show that ATP and glycogen effect lamin polymerization and chromatin binding by separate and opposing mechanisms. PMID:9819358

  13. Lamin in inflammation and aging.

    PubMed

    Tran, Joseph R; Chen, Haiyang; Zheng, Xiaobin; Zheng, Yixian

    2016-06-01

    Aging is characterized by a progressive loss of tissue function and an increased susceptibility to injury and disease. Many age-associated pathologies manifest an inflammatory component, and this has led to the speculation that aging is at least in part caused by some form of inflammation. However, whether or not inflammation is truly a cause of aging, or is a consequence of the aging process is unknown. Recent work using Drosophila has uncovered a mechanism where the progressive loss of lamin-B in the fat body upon aging triggers systemic inflammation. This inflammatory response perturbs the local immune response of the neighboring gut tissue and leads to hyperplasia. Here, we will discuss the literature connecting lamins to aging and inflammation. PMID:27023494

  14. Postbuckling of laminated anisotropic panels

    NASA Technical Reports Server (NTRS)

    Jeffrey, Glenda L.

    1987-01-01

    A two-part study of the buckling and postbuckling of laminated anisotropic plates with bending-extensional coupling is presented. The first part involves the development and application of a modified Rayleigh-Ritz analysis technique. Modifications made to the classical technique can be grouped into three areas. First, known symmetries of anisotropic panels are exploited in the selection of approximation functions. Second, a reduced basis technique based on these same symmetries is applied in the linear range. Finally, geometric boundary conditions are enforced via an exterior penalty function approach, rather than relying on choice of approximation functions to satisfy these boundary conditions. Numerical results are presented for both the linear and nonlinear range, with additional studies made to determine the effect of variation in penalty parameter and number of basis vectors. In the second part, six panels possessing anisotropy and bending-extensional coupling are tested. Detailed comparisons are made between experiment and finite element results in order to gain insight into the postbuckling and failure characteristics of such panels. The panels are constructed using two different lamination sequences, and panels with three different aspect ratios were constructed for each lamination sequence.

  15. Lamin B1 protein is required for dendrite development in primary mouse cortical neurons

    PubMed Central

    Giacomini, Caterina; Mahajani, Sameehan; Ruffilli, Roberta; Marotta, Roberto; Gasparini, Laura

    2016-01-01

    Lamin B1, a key component of the nuclear lamina, plays an important role in brain development and function. A duplication of the human lamin B1 (LMNB1) gene has been linked to adult-onset autosomal dominant leukodystrophy, and mouse and human loss-of-function mutations in lamin B1 are susceptibility factors for neural tube defects. In the mouse, experimental ablation of endogenous lamin B1 (Lmnb1) severely impairs embryonic corticogenesis. Here we report that in primary mouse cortical neurons, LMNB1 overexpression reduces axonal outgrowth, whereas deficiency of endogenous Lmnb1 results in aberrant dendritic development. In the absence of Lmnb1, both the length and complexity of dendrites are reduced, and their growth is unresponsive to KCl stimulation. This defective dendritic outgrowth stems from impaired ERK signaling. In Lmnb1-null neurons, ERK is correctly phosphorylated, but phospho-ERK fails to translocate to the nucleus, possibly due to delocalization of nuclear pore complexes (NPCs) at the nuclear envelope. Taken together, these data highlight a previously unrecognized role of lamin B1 in dendrite development of mouse cortical neurons through regulation of nuclear shuttling of specific signaling molecules and NPC distribution. PMID:26510501

  16. Laminate delamination due to thermal gradients

    SciTech Connect

    Hutchinson, J.W.; Lu, T.J.

    1995-10-01

    Flaw-induced delamination of orthotropic laminates subject to through-thickness temperature gradients is analyzed. A crack-like flaw impedes heat flow through the laminate, producing thermal stresses and crack tip stress intensities. The focus is on delamination cracks which propagate under steady-state conditions. The steady-state analysis becomes accurate for a crack whose length is about one laminate thickness. Moreover, the analysis provides realistic fail-safe criteria for excluding delamination.

  17. Geometrically nonlinear analysis of laminated elastic structures

    NASA Technical Reports Server (NTRS)

    Reddy, J. N.

    1984-01-01

    Laminated composite plates and shells that can be used to model automobile bodies, aircraft wings and fuselages, and pressure vessels among many other were analyzed. The finite element method, a numerical technique for engineering analysis of structures, is used to model the geometry and approximate the solution. Various alternative formulations for analyzing laminated plates and shells are developed and their finite element models are tested for accuracy and economy in computation. These include the shear deformation laminate theory and degenerated 3-D elasticity theory for laminates.

  18. Symmetries in laminated composite plates

    NASA Technical Reports Server (NTRS)

    Noor, A. K.

    1976-01-01

    The different types of symmetry exhibited by laminated anisotropic fibrous composite plates are identified and contrasted with the symmetries of isotropic and homogeneous orthotropic plates. The effects of variations in the fiber orientation and the stacking sequence of the layers on the symmetries exhibited by composite plates are discussed. Both the linear and geometrically nonlinear responses of the plates are considered. A simple procedure is presented for exploiting the symmetries in the finite element analysis. Examples are given of square, skew and polygonal plates where use of symmetry concepts can significantly reduce the scope and cost of analysis.

  19. Impact damage in composite laminates

    NASA Technical Reports Server (NTRS)

    Grady, Joseph E.

    1988-01-01

    Damage tolerance requirements have become an important consideration in the design and fabrication of composite structural components for modern aircraft. The ability of a component to contain a flaw of a given size without serious loss of its structural integrity is of prime concern. Composite laminates are particularly susceptible to damage caused by transverse impact loading. The ongoing program described is aimed at developing experimental and analytical methods that can be used to assess damage tolerance capabilities in composite structures subjected to impulsive loading. Some significant results of this work and the methodology used to obtain them are outlined.

  20. Hypertonic-induced lamin A/C synthesis and distribution to nucleoplasmic speckles is mediated by TonEBP/NFAT5 transcriptional activator

    SciTech Connect

    Favale, Nicolas O.; Sterin Speziale, Norma B.; Fernandez Tome, Maria C.

    2007-12-21

    Lamin A/C is the most studied nucleoskeletal constituent. Lamin A/C expression indicates cell differentiation and is also a structural component of nuclear speckles, which are involved in gene expression regulation. Hypertonicity has been reported to induce renal epithelial cell differentiation and expression of TonEBP (NFAT5), a transcriptional activator of hypertonicity-induced gene transcription. In this paper, we investigate the effect of hypertonicity on lamin A/C expression in MDCK cells and the involvement of TonEBP. Hypertonicity increased lamin A/C expression and its distribution to nucleoplasm with speckled pattern. Microscopy showed codistribution of TonEBP and lamin A/C in nucleoplasmic speckles, and immunoprecipitation demonstrated their interaction. TonEBP silencing caused lamin A/C redistribution from nucleoplasmic speckles to the nuclear rim, followed by lamin decrease, thus showing that hypertonicity induces lamin A/C speckles through a TonEBP-dependent mechanism. We suggest that lamin A/C speckles could serve TonEBP as scaffold thus favoring its role in hypertonicity.

  1. Silicone modified resins for graphite fiber laminates

    NASA Technical Reports Server (NTRS)

    Frost, L. W.; Bower, G. M.

    1980-01-01

    Six silicone modified resins were selected for evaluation in unidirectional filament wound graphite laminates. Neat samples of these resins had 1,000 C char residues of 6-63%. The highest flexural values measured for the laminates were a strength of 1,220 MPa and a modulus of 105 GPa. The highest interlaminar shear strength was 72 MPa.

  2. Lamin-like analogues in plants: the characterization of NMCP1 in Allium cepa.

    PubMed

    Ciska, Malgorzata; Masuda, Kiyoshi; Moreno Díaz de la Espina, Susana

    2013-04-01

    The nucleoskeleton of plants contains a peripheral lamina (also called plamina) and, even though lamins are absent in plants, their roles are still fulfilled in plant nuclei. One of the most intriguing topics in plant biology concerns the identity of lamin protein analogues in plants. Good candidates to play lamin functions in plants are the members of the NMCP (nuclear matrix constituent protein) family, which exhibit the typical tripartite structure of lamins. This paper describes a bioinformatics analysis and classification of the NMCP family based on phylogenetic relationships, sequence similarity and the distribution of conserved regions in 76 homologues. In addition, NMCP1 in the monocot Allium cepa characterized by its sequence and structure, biochemical properties, and subnuclear distribution and alterations in its expression throughout the root were identified. The results demonstrate that these proteins exhibit many similarities to lamins (structural organization, conserved regions, subnuclear distribution, and solubility) and that they may fulfil the functions of lamins in plants. These findings significantly advance understanding of the structural proteins of the plant lamina and nucleoskeleton and provide a basis for further investigation of the protein networks forming these structures. PMID:23378381

  3. Regulation of homologous recombinational repair by lamin B1 in radiation-induced DNA damage.

    PubMed

    Liu, Ning-Ang; Sun, Jiying; Kono, Kazuteru; Horikoshi, Yasunori; Ikura, Tsuyoshi; Tong, Xing; Haraguchi, Tokuko; Tashiro, Satoshi

    2015-06-01

    DNA double-strand breaks (DSBs) are the major lethal lesion induced by ionizing radiation (IR). RAD51-dependent homologous recombination (HR) is one of the most important pathways in DSB repair and genome integrity maintenance. However, the mechanism of HR regulation by RAD51 remains unclear. To understand the mechanism of RAD51-dependent HR, we searched for interacting partners of RAD51 by a proteomics analysis and identified lamin B1 in human cells. Lamins are nuclear lamina proteins that play important roles in the structural organization of the nucleus and the regulation of chromosome functions. Immunoblotting analyses revealed that siRNA-mediated lamin B1 depletion repressed the DNA damage-dependent increase of RAD51 after IR. The repression was abolished by the proteasome inhibitor MG132, suggesting that lamin B1 stabilizes RAD51 by preventing proteasome-mediated degradation in cells with IR-induced DNA damage. We also showed that lamin B1 depletion repressed RAD51 focus formation and decreased the survival rates after IR. On the basis of these results, we propose that lamin B1 promotes DSB repair and cell survival by maintaining the RAD51 protein levels for HR upon DSB induction after IR. PMID:25733566

  4. Calcium Causes a Conformational Change in Lamin A Tail Domain that Promotes Farnesyl-Mediated Membrane Association

    PubMed Central

    Kalinowski, Agnieszka; Qin, Zhao; Coffey, Kelli; Kodali, Ravi; Buehler, Markus J.; Lösche, Mathias; Dahl, Kris Noel

    2013-01-01

    Lamin proteins contribute to nuclear structure and function, primarily at the inner nuclear membrane. The posttranslational processing pathway of lamin A includes farnesylation of the C-terminus, likely to increase membrane association, and subsequent proteolytic cleavage of the C-terminus. Hutchinson Gilford progeria syndrome is a premature aging disorder wherein a mutant version of lamin A, Δ50 lamin A, retains its farnesylation. We report here that membrane association of farnesylated Δ50 lamin A tail domains requires calcium. Experimental evidence and molecular dynamics simulations collectively suggest that the farnesyl group is sequestered within a hydrophobic region in the tail domain in the absence of calcium. Calcium binds to the tail domain with an affinity KD ≈ 250 μM where it alters the structure of the Ig-fold and increases the solvent accessibility of the C-terminus. In 2 mM CaCl2, the affinity of the farnesylated protein to a synthetic membrane is KD ≈ 2 μM, as measured with surface plasmon resonance, but showed a combination of aggregation and binding. Membrane binding in the absence of calcium could not be detected. We suggest that a conformational change induced in Δ50 lamin A with divalent cations plays a regulatory role in the posttranslational processing of lamin A, which may be important in disease pathogenesis. PMID:23708364

  5. Universality of the frequency spectrum of laminates

    NASA Astrophysics Data System (ADS)

    Shmuel, Gal; Band, Ram

    2016-07-01

    We show that the frequency spectrum of two-component elastic laminates admits a universal structure, independent of the geometry of the periodic-cell and the specific physical properties. The compactness of the structure enables us to rigorously derive the maximal width, the expected width, and the density of the band-gaps - ranges of frequencies at which waves cannot propagate. In particular, we find that the density of these band-gaps is a universal property of classes of laminates. Rules for tailoring laminates according to desired spectrum properties thereby follow. We show that the frequency spectrum of various finitely deformed laminates are also endowed with the same compact structure. Finally, we explain how our results generalize for laminates with an arbitrary number of components, based on the form of their dispersion relation.

  6. Wettability of graphene-laminated micropillar structures

    NASA Astrophysics Data System (ADS)

    Bong, Jihye; Seo, Keumyoung; Park, Ji-Hoon; Ahn, Joung Real; Ju, Sanghyun

    2014-12-01

    The wetting control of graphene is of great interest for electronic, mechanical, architectural, and bionic applications. In this study, the wettability of graphene-laminated micropillar structures was manipulated by changing the height of graphene-laminated structures and employing the trichlorosilane (HDF-S)-based self-assembly monolayer. Graphene-laminated micropillar structures with HDF-S exhibited higher hydrophobicity (contact angle of 129.5°) than pristine graphene thin film (78.8°), pristine graphene-laminated micropillar structures (97.5°), and HDF-S self-assembled graphene thin film (98.5°). Wetting states of the graphene-laminated micropillar structure with HDF-S was also examined by using a urea solution, which flowed across the surface without leaving any residues.

  7. Wettability of graphene-laminated micropillar structures

    SciTech Connect

    Bong, Jihye; Seo, Keumyoung; Ju, Sanghyun E-mail: shju@kgu.ac.kr; Park, Ji-Hoon; Ahn, Joung Real E-mail: shju@kgu.ac.kr

    2014-12-21

    The wetting control of graphene is of great interest for electronic, mechanical, architectural, and bionic applications. In this study, the wettability of graphene-laminated micropillar structures was manipulated by changing the height of graphene-laminated structures and employing the trichlorosilane (HDF-S)-based self-assembly monolayer. Graphene-laminated micropillar structures with HDF-S exhibited higher hydrophobicity (contact angle of 129.5°) than pristine graphene thin film (78.8°), pristine graphene-laminated micropillar structures (97.5°), and HDF-S self-assembled graphene thin film (98.5°). Wetting states of the graphene-laminated micropillar structure with HDF-S was also examined by using a urea solution, which flowed across the surface without leaving any residues.

  8. Stationary turbine component with laminated skin

    DOEpatents

    James, Allister W.

    2012-08-14

    A stationary turbine engine component, such as a turbine vane, includes a internal spar and an external skin. The internal spar is made of a plurality of spar laminates, and the external skin is made of a plurality of skin laminates. The plurality of skin laminates interlockingly engage the plurality of spar laminates such that the external skin is located and held in place. This arrangement allows alternative high temperature materials to be used on turbine engine components in areas where their properties are needed without having to make the entire component out of such material. Thus, the manufacturing difficulties associated with making an entire component of such a material and the attendant high costs are avoided. The skin laminates can be made of advanced generation single crystal superalloys, intermetallics and refractory alloys.

  9. Isoprenylation is required for the processing of the lamin A precursor

    SciTech Connect

    Beck, L.A.; Hosick, T.J.; Sinensky, M. )

    1990-05-01

    The nuclear lamina proteins, prelamin A, lamin B, and a 70-kD lamina-associated protein, are posttranslationally modified by a metabolite derived from mevalonate. This modification can be inhibited by treatment with (3-R,S)-3-fluoromevalonate, demonstrating that it is isoprenoid in nature. We have examined the association between isoprenoid metabolism and processing of the lamin A precursor in human and hamster cells. Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase by mevinolin (lovastatin) specifically depletes endogenous isoprenoid pools and inhibits the conversion of prelamin A to lamin A. Prelamin A processing is also blocked by mevalonate starvation of Mev-1, a CHO cell line auxotrophic for mevalonate. Moreover, inhibition of prelamin A processing by mevinolin treatment is rapidly reversed by the addition of exogenous mevalonate. Processing of prelamin A is, therefore, dependent on isoprenoid metabolism. Analysis of the conversion of prelamin A to lamin A by two independent methods, immunoprecipitation and two-dimensional nonequilibrium pH gel electrophoresis, demonstrates that a precursor-product relationship exists between prelamin A and lamin A. Analysis of R,S-(5-3H(N))mevalonate-labeled cells shows that the rate of turnover of the isoprenoid group from prelamin A is comparable to the rate of conversion of prelamin A to lamin A. These results suggest that during the proteolytic maturation of prelamin A, the isoprenylated moiety is lost. A significant difference between prelamin A processing, and that of p21ras and the B-type lamins that undergo isoprenylation-dependent proteolytic maturation, is that the mature form of lamin A is no longer isoprenylated.

  10. Mutant lamin A links prophase to a p53 independent senescence program

    PubMed Central

    Moiseeva, Olga; Lessard, Frédéric; Acevedo-Aquino, Mariana; Vernier, Mathieu; Tsantrizos, Youla S; Ferbeyre, Gerardo

    2015-01-01

    Expression of oncogenes or short telomeres can trigger an anticancer response known as cellular senescence activating the p53 and RB tumor suppressor pathways. This mechanism is switched off in most tumor cells by mutations in p53 and RB signaling pathways. Surprisingly, p53 disabled tumor cells could be forced into senescence by expression of a mutant allele of the nuclear envelope protein lamin A. The pro-senescence lamin A mutant contains a deletion in the sequence required for processing by the protease ZMPSTE24 leading to accumulation of farnesylated lamin A in the nuclear envelope. In addition, the serine at position 22, a target for CDK1-dependent phosphorylation, was mutated to alanine, preventing CDK1-catalyzed nuclear envelope disassembly. The accumulation of this mutant lamin A compromised prophase to prometaphase transition leading to invaginations of the nuclear lamina, nuclear fragmentation and impaired chromosome condensation. Cells exited this impaired mitosis without cytokinesis and re-replicated their DNA ultimately arresting in interphase as polyploid cells with features of cellular senescence including increased expression of inflammatory gene products and a significant reduction of tumorigenicity in vivo. PMID:26029982

  11. Lamin A/C and emerin regulate MKL1-SRF activity by modulating actin dynamics.

    PubMed

    Ho, Chin Yee; Jaalouk, Diana E; Vartiainen, Maria K; Lammerding, Jan

    2013-05-23

    Laminopathies, caused by mutations in the LMNA gene encoding the nuclear envelope proteins lamins A and C, represent a diverse group of diseases that include Emery-Dreifuss muscular dystrophy (EDMD), dilated cardiomyopathy (DCM), limb-girdle muscular dystrophy, and Hutchison-Gilford progeria syndrome. Most LMNA mutations affect skeletal and cardiac muscle by mechanisms that remain incompletely understood. Loss of structural function and altered interaction of mutant lamins with (tissue-specific) transcription factors have been proposed to explain the tissue-specific phenotypes. Here we report in mice that lamin-A/C-deficient (Lmna(-/-)) and Lmna(N195K/N195K) mutant cells have impaired nuclear translocation and downstream signalling of the mechanosensitive transcription factor megakaryoblastic leukaemia 1 (MKL1), a myocardin family member that is pivotal in cardiac development and function. Altered nucleo-cytoplasmic shuttling of MKL1 was caused by altered actin dynamics in Lmna(-/-) and Lmna(N195K/N195K) mutant cells. Ectopic expression of the nuclear envelope protein emerin, which is mislocalized in Lmna mutant cells and also linked to EDMD and DCM, restored MKL1 nuclear translocation and rescued actin dynamics in mutant cells. These findings present a novel mechanism that could provide insight into the disease aetiology for the cardiac phenotype in many laminopathies, whereby lamin A/C and emerin regulate gene expression through modulation of nuclear and cytoskeletal actin polymerization. PMID:23644458

  12. Lamin A/C and emerin regulate MKL1/SRF activity by modulating actin dynamics

    PubMed Central

    Ho, Chin Yee; Jaalouk, Diana E.; Vartiainen, Maria K.; Lammerding, Jan

    2013-01-01

    Laminopathies, caused by mutations in the LMNA gene encoding the nuclear envelope proteins lamins A and C, represent a diverse group of diseases that include Emery-Dreifuss Muscular Dystrophy (EDMD), dilated cardiomyopathy (DCM), limb-girdle muscular dystrophy, and Hutchison-Gilford progeria syndrome (HGPS).1 The majority of LMNA mutations affect skeletal and cardiac muscle by mechanisms that remain incompletely understood. Loss of structural function and disturbed interaction of mutant lamins with (tissue-specific) transcription factors have been proposed to explain the tissue-specific phenotypes.1 We report here that lamin A/C-deficient (Lmna−/−) and Lmna N195K mutant cells have impaired nuclear translocation and downstream signaling of the mechanosensitive transcription factor megakaryoblastic leukaemia 1 (MKL1), a myocardin family member that is pivotal in cardiac development and function.2 Disturbed nucleo-cytoplasmic shuttling of MKL1 was caused by altered actin dynamics in Lmna−/− and N195K mutant cells. Ectopic expression of the nuclear envelope protein emerin, which is mislocalized in Lmna mutant cells and also linked to EDMD and DCM, restored MKL1 nuclear translocation and rescued actin dynamics in mutant cells. These findings present a novel mechanism that could provide insight into the disease etiology for the cardiac phenotype in many laminopathies, whereby lamins A/C and emerin regulate gene expression through modulation of nuclear and cytoskeletal actin polymerization. PMID:23644458

  13. Structure-function relationship of biological gels revealed by multiple-particle tracking and differential interference contrast microscopy: The case of human lamin networks

    NASA Astrophysics Data System (ADS)

    Panorchan, Porntula; Wirtz, Denis; Tseng, Yiider

    2004-10-01

    Lamin B1 filaments organize into a thin dense meshwork underlying the nucleoplasmic side of the nuclear envelope. Recent experiments in vivo suggest that lamin B1 plays a key structural role in the nuclear envelope, but the intrinsic mechanical properties of lamin B1 networks remain unknown. To assess the potential mechanical contribution of lamin B1 in maintaining the integrity and providing structural support to the nucleus, we measured the micromechanical properties and examined the ultrastructural distribution of lamin B1 networks in vitro using particle tracking methods and differential interference contrast (DIC) microscopy. We exploit various surface chemistries of the probe microspheres (carboxylated, polyethylene glycol-coated, and amine-modified) to differentiate lamin-rich from lamin-poor regions and to rigorously extract local viscoelastic moduli from the mean-squared displacements of noninteracting particles. Our results show that human lamin B1 can, even in the absence of auxiliary proteins, form stiff and yet extremely porous networks that are well suited to provide structural strength to the nuclear lamina. Combining DIC microscopy and particle tracking allows us to relate directly the local organization of a material to its local mechanical properties, a general methodology that can be extended to living cells.

  14. Critical current of laminated and non-laminated BSCCO superconducting composite tape under bending strain

    NASA Astrophysics Data System (ADS)

    Matsubayashi, H.; Mukai, Y.; Arai, T.; Shin, J. K.; Ochiai, S.; Okuda, H.; Osamura, K.; Otto, A.; Malozemoff, A.

    2009-10-01

    It has been reported that, when the (Bi,Pb) 2Sr 2Ca 2Cu 3O x (hereafter noted as BSCCO)/Ag/Ag-alloy tape is laminated with stainless steel, the tensile strain tolerance of critical current is much improved. In this study, using the non-laminated and laminated BSCCO composite tapes fabricated at American Superconductor Corporation, the influences of lamination on the critical current and its distribution under bending strain were studied. The analysis of the measured variation of average critical current with bending strain based on the damage evolution model revealed that the laminated stainless steel acts to suppress the fracture of the BSCCO filaments. The experimentally observed high critical current retention of the laminated tape up to high bending strain was accounted for by the suppression of fracture of BSCCO filaments stated above and enhancement of the compressive residual strain in the filaments. The distributions of local critical current in non-laminated and laminated composite tape were described well by the three-parameter Weibull distribution function within the bending strain lower than 1.1%. The coefficient of variation of distribution of critical current of the laminated tape was similar to that of the non-laminated one under the same strain distribution in the core.

  15. Lamin A/C sustains PcG protein architecture, maintaining transcriptional repression at target genes

    PubMed Central

    Cesarini, Elisa; Mozzetta, Chiara; Marullo, Fabrizia; Gregoretti, Francesco; Gargiulo, Annagiusi; Columbaro, Marta; Cortesi, Alice; Antonelli, Laura; Di Pelino, Simona; Squarzoni, Stefano; Palacios, Daniela; Zippo, Alessio; Bodega, Beatrice; Oliva, Gennaro

    2015-01-01

    Beyond its role in providing structure to the nuclear envelope, lamin A/C is involved in transcriptional regulation. However, its cross talk with epigenetic factors—and how this cross talk influences physiological processes—is still unexplored. Key epigenetic regulators of development and differentiation are the Polycomb group (PcG) of proteins, organized in the nucleus as microscopically visible foci. Here, we show that lamin A/C is evolutionarily required for correct PcG protein nuclear compartmentalization. Confocal microscopy supported by new algorithms for image analysis reveals that lamin A/C knock-down leads to PcG protein foci disassembly and PcG protein dispersion. This causes detachment from chromatin and defects in PcG protein–mediated higher-order structures, thereby leading to impaired PcG protein repressive functions. Using myogenic differentiation as a model, we found that reduced levels of lamin A/C at the onset of differentiation led to an anticipation of the myogenic program because of an alteration of PcG protein–mediated transcriptional repression. Collectively, our results indicate that lamin A/C can modulate transcription through the regulation of PcG protein epigenetic factors. PMID:26553927

  16. Direct Composite Laminate Veneers: Three Case Reports

    PubMed Central

    Korkut, Bora; Yanıkoğlu, Funda; Günday, Mahir

    2013-01-01

    Re-establishing a patient’s lost dental esthetic appearance is one of the most important topics for contemporary dentistry. New treatment materials and methods have been coming on the scene, day by day, in order to achieve such an aim. Most dentists prefer more conservative and aesthetic approaches, such as direct and indirect laminate veneer restorations, instead of full-ceramic crowns for anteriors where aesthetics is really important. Laminate veneers are restorations which are envisioned to correct existing abnormalities, esthetic deficiencies and discolo-rations. Laminate veneer restorations may be processed in two different ways: direct or indirect. Direct laminate veneers have no need to be prepared in the laboratory and are based on the principle of application of a composite material directly to the prepared tooth surface in the dental clinic. Indirect laminate veneers may be produced from composite materials or ceramics, which are cemented to the tooth with an adhesive resin. In this case report, direct composite laminate veneer technique used for three patients with esthetic problems related to fractures, discolorations and an old prolapsed restoration, is described and six-month follow-ups are discussed. As a conclusion, direct laminate veneer restorations may be a treatment option for patients with the esthetic problems of anterior teeth in cases similar to those reported here. PMID:23875090

  17. Indentation law for composite laminates

    NASA Technical Reports Server (NTRS)

    Yang, S. H.

    1981-01-01

    Static indentation tests are described for glass/epoxy and graphite/epoxy composite laminates with steel balls as the indentor. Beam specimens clamped at various spans were used for the tests. Loading, unloading, and reloading data were obtained and fitted into power laws. Results show that: (1) contact behavior is not appreciably affected by the span; (2) loading and reloading curves seem to follow the 1.5 power law; and (3) unloading curves are described quite well by a 2.5 power law. In addition, values were determined for the critical indentation, alpha sub cr which can be used to predict permanent indentations in unloading. Since alpha sub cr only depends on composite material properties, only the loading and an unloading curve are needed to establish the complete loading-unloading-reloading behavior.

  18. Damage of hybrid composite laminates

    NASA Astrophysics Data System (ADS)

    Haery, Haleh A.; Kim, Ho Sung

    2013-08-01

    Hybrid laminates consisting of woven glass fabric/epoxy composite plies and woven carbon fabric/epoxy composite plies are studied for fatigue damage and residual strength. A theoretical framework based on the systems approach is proposed as a guide to deal with the complexity involving uncertainties and a large number of variables in the hybrid composite system. A relative damage sensitivity factor expression was developed for quantitative comparisons between non-hybrid and hybrid composites. Hypotheses derived from the theoretical framework were tested and verified. The first hypothesis was that the difference between two different sets of properties produces shear stress in interface between carbon fibre reinforced plastics (CRP) and glass fibre reinforced plastics (GRP), and eventually become a source for CRP/GRP interfacial delamination or longitudinal cracking. The second hypothesis was that inter-fibre bundle delamination occurs more severely to CRP sub-system than GRP sub-system.

  19. Flat laminated microbial mat communities

    NASA Astrophysics Data System (ADS)

    Franks, Jonathan; Stolz, John F.

    2009-10-01

    Flat laminated microbial mats are complex microbial ecosystems that inhabit a wide range of environments (e.g., caves, iron springs, thermal springs and pools, salt marshes, hypersaline ponds and lagoons, methane and petroleum seeps, sea mounts, deep sea vents, arctic dry valleys). Their community structure is defined by physical (e.g., light quantity and quality, temperature, density and pressure) and chemical (e.g., oxygen, oxidation/reduction potential, salinity, pH, available electron acceptors and donors, chemical species) parameters as well as species interactions. The main primary producers may be photoautotrophs (e.g., cyanobacteria, purple phototrophs, green phototrophs) or chemolithoautophs (e.g., colorless sulfur oxidizing bacteria). Anaerobic phototrophy may predominate in organic rich environments that support high rates of respiration. These communities are dynamic systems exhibiting both spatial and temporal heterogeneity. They are characterized by steep gradients with microenvironments on the submillimeter scale. Diel oscillations in the physical-chemical profile (e.g., oxygen, hydrogen sulfide, pH) and species distribution are typical for phototroph-dominated communities. Flat laminated microbial mats are often sites of robust biogeochemical cycling. In addition to well-established modes of metabolism for phototrophy (oxygenic and non-oxygenic), respiration (both aerobic and anaerobic), and fermentation, novel energetic pathways have been discovered (e.g., nitrate reduction couple to the oxidation of ammonia, sulfur, or arsenite). The application of culture-independent techniques (e.g., 16S rRNA clonal libraries, metagenomics), continue to expand our understanding of species composition and metabolic functions of these complex ecosystems.

  20. Severe laminitis in multiple zoo species.

    PubMed

    Wiedner, Ellen; Holland, Jeff; Trupkiewicz, John; Uzal, Francisco

    2014-01-01

    A 10-year record review from a zoological institution in the western USA identified four cases of severe laminitis resulting in rotation and protrusion of the third phalanx through the sole. Laminitis is reported in a Masai giraffe (Giraffa camelopardalis tippelskirchi), a Sichuan takin (Budorcas taxicolor tibetana), a greater Malayan chevrotain (Tragulus napu) and a giant eland (Taurotragus derbianus). This is the first report of severe laminitis with pedal bone rotation and protrusion in multiple species of non-domestic hoofstock, and the first report of this disease in three of these species (takin, chevrotain, and giant eland). PMID:24730432

  1. Probabilistic methods for the calculation of laminate properties

    SciTech Connect

    Mcmanus, H.L. )

    1993-06-01

    A method for calculating the properties of advanced composite laminates, including their variations due to known variations in the properties of the individual plies and the laminate geometry, is presented. The method is useful for understanding scatter in the measured properties of composite laminates. This scatter is particularly important in the design of ultra-low coefficient of thermal expansion (CTE) laminates. Such laminates are designed with a theoretically zero CTE, but in practice have a distribution of nonzero CTEs. Information useful for designing ultra-low expansion laminates is discussed. A practical limit on how close to zero the CTE of a laminate can be assumed to be is found. 10 refs.

  2. Behaviour of Mechanically Laminated CLT Members

    NASA Astrophysics Data System (ADS)

    Kuklík, P.; Velebil, L.

    2015-11-01

    Cross laminated timber (CLT) is one of the structural building systems based on the lamination of multiple layers, where each layer is oriented perpendicularly to each other. Recent requirements are placed to develop an alternative process based on the mechanical lamination of the layers, which is of particular interest to our research group at the University Centre for Energy Efficient Buildings. The goal is to develop and verify the behaviour of mechanically laminated CLT wall panels exposed to shear stresses in the plane. The shear resistance of mechanically jointed CLT is ensured by connecting the layers by screws. The paper deals with the experimental analysis focused on the determination of the torsional stiffness and the slip modulus of crossing areas for different numbers of orthogonally connected layers. The results of the experiments were compared with the current analytical model.

  3. Method for fabricating laminated uranium composites

    DOEpatents

    Chapman, L.R.

    1983-08-03

    The present invention is directed to a process for fabricating laminated composites of uranium or uranium alloys and at least one other metal or alloy. The laminated composites are fabricated by forming a casting of the molten uranium with the other metal or alloy which is selectively positioned in the casting and then hot-rolling the casting into a laminated plate in or around which the casting components are metallurgically bonded to one another to form the composite. The process of the present invention provides strong metallurgical bonds between the laminate components primarily since the bond disrupting surface oxides on the uranium or uranium alloy float to the surface of the casting to effectively remove the oxides from the bonding surfaces of the components.

  4. Free edge effects in laminated composites

    NASA Technical Reports Server (NTRS)

    Herakovich, C. T.

    1989-01-01

    The fundamental mechanics of free-edge effects in laminated fiber-reinforced composites is examined, reviewing the results of recent experimental and analytical investigations. The derivation of the governing equations for the basic problem is outlined, including the equilibrium and mismatch conditions and the elasticity formulation, and experimental data on axial displacement and shear strain in angle-ply laminates are summarized. Numerical predictions of free-edge deformation and interlaminar and through-thickness stress distributions are presented for cross-ply, angle-ply, and quasi-isotropic laminates, and the mechanisms of edge damage and failure in angle-ply laminates are briefly characterized. Extensive diagrams, drawings, graphs, and photographs are provided.

  5. TRF2 and lamin A/C interact to facilitate the functional organization of chromosome ends

    PubMed Central

    Wood, Ashley M.; Danielsen, Jannie M. Rendtlew; Lucas, Catherine A.; Rice, Ellen L.; Scalzo, David; Shimi, Takeshi; Goldman, Robert D.; Smith, Erica D.; Le Beau, Michelle M.; Kosak, Steven T.

    2014-01-01

    Telomeres protect the ends of linear genomes, and the gradual loss of telomeres is associated with cellular ageing. Telomere protection involves the insertion of the 3′ overhang facilitated by telomere repeat-binding factor 2 (TRF2) into telomeric DNA, forming t-loops. We present evidence suggesting that t-loops can also form at interstitial telomeric sequences in a TRF2-dependent manner, forming an interstitial t-loop (ITL). We demonstrate that TRF2 association with interstitial telomeric sequences is stabilized by co-localization with A-type lamins (lamin A/C). We also find that lamin A/C interacts with TRF2 and that reduction in levels of lamin A/C or mutations in LMNA that cause an autosomal dominant premature ageing disorder—Hutchinson Gilford Progeria Syndrome (HGPS)—lead to reduced ITL formation and telomere loss. We propose that cellular and organismal ageing are intertwined through the effects of the interaction between TRF2 and lamin A/C on chromosome structure. PMID:25399868

  6. Development of a laminate fatigue analysis

    NASA Technical Reports Server (NTRS)

    Roderick, G. L.; Obrien, T. K.; Whitcomb, J. D.

    1980-01-01

    A fatigue analysis technique developed to predict damage growth in notched laminates is described. Features of the analysis include: criteria to relate matrix failure to cyclic stresses in and between plies; correlation of delamination growth with strain-release rate; and in-plane shear modulus change is related to cyclic shear stresses. A simplified finite element model is used to determine stresses in laminates that contain matrix damage. Failure criteria are integrated with the finite element model to form the fatigue analysis.

  7. An essential GT motif in the lamin A promoter mediates activation by CREB-binding protein

    SciTech Connect

    Janaki Ramaiah, M.; Parnaik, Veena K. . E-mail: veenap@ccmb.res.in

    2006-09-29

    Lamin A is an important component of nuclear architecture in mammalian cells. Mutations in the human lamin A gene lead to highly degenerative disorders that affect specific tissues. In studies directed towards understanding the mode of regulation of the lamin A promoter, we have identified an essential GT motif at -55 position by reporter gene assays and mutational analysis. Binding of this sequence to Sp transcription factors has been observed in electrophoretic mobility shift assays and by chromatin immunoprecipitation studies. Further functional analysis by co-expression of recombinant proteins and ChIP assays has shown an important regulatory role for CREB-binding protein in promoter activation, which is mediated by the GT motif.

  8. Mutation Glu82Lys in lamin A/C gene is associated with cardiomyopathy and conduction defect

    SciTech Connect

    Wang Hu; Wang Jizheng; Zheng Weiyue; Wang Xiaojian; Wang Shuxia; Song Lei; Zou Yubao; Yao Yan; Hui Rutai . E-mail: huirutai@sglab.org

    2006-05-26

    Dilated cardiomyopathy is a form of heart muscle disease characterized by impaired systolic function and ventricular dilation. The mutations in lamin A/C gene have been linked to dilated cardiomyopathy. We screened genetic mutations in a large Chinese family of 50 members including members with dilated cardiomyopathy and found a Glu82Lys substitution mutation in the rod domain of the lamin A/C protein in eight family members, three of them have been diagnosed as dilated cardiomyopathy, one presented with heart dilation. The pathogenic mechanism of lamin A/C gene defect is poorly understood. Glu82Lys mutated lamin A/C and wild type protein was transfected into HEK293 cells. The mutated protein was not properly localized at the inner nuclear membrane and the emerin protein, which interacts with lamin A/C, was also aberrantly distributed. The nuclear membrane structure was disrupted and heterochromatin was aggregated aberrantly in the nucleus of the HEK293 cells stably transfected with mutated lamin A/C gene as determined by transmission electron microscopy.

  9. Lamin A Is an Endogenous SIRT6 Activator and Promotes SIRT6-Mediated DNA Repair.

    PubMed

    Ghosh, Shrestha; Liu, Baohua; Wang, Yi; Hao, Quan; Zhou, Zhongjun

    2015-11-17

    The nuclear lamins are essential for various molecular events in the nucleus, such as chromatin organization, DNA replication, and provision of mechanical support. A specific point mutation in the LMNA gene creates a truncated prelamin A termed progerin, causing Hutchinson-Gilford progeria syndrome (HGPS). SIRT6 deficiency leads to defective genomic maintenance and accelerated aging similar to HGPS, suggesting a potential link between lamin A and SIRT6. Here, we report that lamin A is an endogenous activator of SIRT6 and facilitates chromatin localization of SIRT6 upon DNA damage. Lamin A promotes SIRT6-dependent DNA-PKcs (DNA-PK catalytic subunit) recruitment to chromatin, CtIP deacetylation, and PARP1 mono-ADP ribosylation in response to DNA damage. The presence of progerin jeopardizes SIRT6 activation and compromises SIRT6-mediated molecular events in response to DNA damage. These data reveal a critical role for lamin A in regulating SIRT6 activities, suggesting that defects in SIRT6 functions contribute to impaired DNA repair and accelerated aging in HGPS. PMID:26549451

  10. Eliminating the synthesis of mature lamin A reduces disease phenotypes in mice carrying a Hutchinson-Gilford progeria syndrome allele.

    PubMed

    Yang, Shao H; Qiao, Xin; Farber, Emily; Chang, Sandy Y; Fong, Loren G; Young, Stephen G

    2008-03-14

    Hutchinson-Gilford progeria syndrome is caused by the synthesis of a mutant form of prelamin A, which is generally called progerin. Progerin is targeted to the nuclear rim, where it interferes with the integrity of the nuclear lamina, causes misshapen cell nuclei, and leads to multiple aging-like disease phenotypes. We created a gene-targeted allele yielding exclusively progerin (Lmna HG) and found that heterozygous mice (Lmna HG/+) exhibit many phenotypes of progeria. In this study, we tested the hypothesis that the phenotypes elicited by the Lmna HG allele might be modulated by compositional changes in the nuclear lamina. To explore this hypothesis, we bred mice harboring one Lmna HG allele and one Lmna LCO allele (a mutant allele that produces lamin C but no lamin A). We then compared the phenotypes of Lmna HG/LCO mice (which produce progerin and lamin C) with littermate Lmna HG/+ mice (which produce lamin A, lamin C, and progerin). Lmna HG/LCO mice exhibited improved HG/LCO fibroblasts had fewer misshapen nuclei than Lmna HG/+ fibroblasts (p < 0.0001). A likely explanation for these differences was uncovered; the amount of progerin in Lmna HG/LCO fibroblasts and tissues was lower than in Lmna HG/+ fibroblasts and tissues. These studies suggest that compositional changes in the nuclear lamina can influence both the steady-state levels of progerin and the severity of progeria-like disease phenotypes. PMID:18178963

  11. Decreased Bone Formation and Osteopenia in Lamin A/C-Deficient Mice

    PubMed Central

    Vidal, Christopher; McCorquodale, Thomas; Herrmann, Markus; Fatkin, Diane; Duque, Gustavo

    2011-01-01

    Age-related bone loss is associated with changes in bone cellularity with characteristically low levels of osteoblastogenesis. The mechanisms that explain these changes remain unclear. Although recent in vitro evidence has suggested a new role for proteins of the nuclear envelope in osteoblastogenesis, the role of these proteins in bone cells differentiation and bone metabolism in vivo remains unknown. In this study, we used the lamin A/C null (Lmna−/−) mice to identify the role of lamin A/C in bone turnover and bone structure in vivo. At three weeks of age, histological and micro computed tomography measurements of femurs in Lmna−/− mice revealed a significant decrease in bone mass and microarchitecture in Lmna−/− mice as compared with their wild type littermates. Furthermore, quantification of cell numbers after normalization with bone surface revealed a significant reduction in osteoblast and osteocyte numbers in Lmna−/− mice compared with their WT littermates. In addition, Lmna−/− mice have significantly lower osteoclast number, which show aberrant changes in their shape and size. Finally, mechanistic analysis demonstrated that absence of lamin A/C is associated with increase expression of MAN-1 a protein of the nuclear envelope closely regulated by lamin A/C, which also colocalizes with Runx2 thus affecting its capacity as osteogenic transcription factor. In summary, these data clearly indicate that the presence of lamin A/C is necessary for normal bone turnover in vivo and that absence of lamin A/C induces low bone turnover osteopenia resembling the cellular changes of age-related bone loss. PMID:21547077

  12. Mechanical Behavior of Fabric-Film Laminates

    NASA Technical Reports Server (NTRS)

    Said, Magdi S.

    1999-01-01

    Inflatable structures are gaining wide support in planetary scientific missions as well as commercial applications. For such applications a new class of materials made of laminating thin homogenous films to lightweight fabrics are being considered us structura1 gas envelops. The emerging composite materials are a result of recent advances in the manufacturing cf 1ightweight, high strength fibers, fabrics and scrims. The lamination of these load-carrying members with the proper gas barrier film results in wide range of materials suitable for various loading and environmental conditions. Polyester - based woven fabrics laminated to thin homogeneus film of polyester (Maylar) is an example of this class. This fabric/ film laminate is being considered for the development a material suitable for building large gas envelopes for use in the NASA Ultra Long Duration Balloon Program (ULDB). Compared to commercial homogeneus films, the material provides relatively high strength to weight ratio as well as better resistance to crack and tear propagation. The purpose of this papers is to introduce the mechanical behavior of this class of multi-layers composite and to highlight some of the concerns observed during the characterization of these laminate composites.

  13. Lamination residual stresses in fiber composites

    NASA Technical Reports Server (NTRS)

    Daniel, I. M.; Liber, T.

    1975-01-01

    An experimental investigation was conducted to determine the magnitude of lamination residual stresses in angle-ply composites and to evaluate their effects on composite structural integrity. The materials investigated were boron/epoxy, boron/polyimide, graphite/low modulus epoxy, graphite/high modulus epoxy, graphite/polyimide and s-glass/epoxy. These materials were fully characterized. Static properties of laminates were also determined. Experimental techniques using embedded strain gages were developed and used to measure residual strains during curing. The extent of relaxation of lamination residual stresses was investigated. It was concluded that the degree of such relaxation is low. The behavior of angle-ply laminates subjected to thermal cycling, tensile load cycling, and combined thermal cycling with tensile load was investigated. In most cases these cycling programs did not have any measurable influence on residual strength and stiffness of the laminates. In the tensile load cycling tests, the graphite/polyimide shows the highest endurance with 10 million cycle runouts at loads up to 90 percent of the static strength.

  14. Evaluation of Behaviours of Laminated Glass

    NASA Astrophysics Data System (ADS)

    Sable, L.; Japins, G.; Kalnins, K.

    2015-11-01

    Visual appearance of building facades and other load bearing structures, which now are part of modern architecture, is the reason why it is important to investigate in more detail the reliability of laminated glass for civil structures. Laminated glass in particular has become one of the trendy materials, for example Apple© stores have both load carrying capacity and transparent appearance. Glass has high mechanical strength and relatively medium density, however, the risk of sudden brittle failure like concrete or other ceramics determine relatively high conservatism in design practice of glass structures. This should be changed as consumer requirements evolve calling for a safe and reliable design methodology and corresponding building standards. A design methodology for glass and glass laminates should be urgently developed and included as a chapter in Eurocode. This paper presents initial experimental investigation of behaviour of simple glass sheets and laminated glass samples in 4-point bending test. The aim of the current research is to investigate laminated glass characteristic values and to verify the obtained experimental results with finite element method for glass and EVA material in line with future European Structural Design of Glass Components code.

  15. Development of tough, moisture resistant laminating resins

    NASA Technical Reports Server (NTRS)

    Brand, R. A.; Harrison, E. S.

    1982-01-01

    Tough, moisture resistant laminating resins for employment with graphite fibers were developed. The new laminating resins exhibited cost, handleability and processing characteristics equivalent to 394K (250 F) curing epoxies. The laminating resins were based on bisphenol A dicyanate and monofunctional cyanates with hydrophobic substituents. These resins sorb only small quantities of moisture at equilibrium (0.5% or less) with minimal glass transition temperature depression and represent an improvement over epoxies which sorb around 2% moisture at equilibrium. Toughening was accomplished by the precipitation of small diameter particles of butadiene nitrile rubber throughout the resin matrix. The rubber domains act as microcrack termini and energy dissipation sites, allowing increased stress accommodation prior to catastrophic failure. A unique blend of amine terminated butadiene nitrile elastomer (MW 2,000) and a high nitrile content butadiene nitrile rubber yielded the desired resin morphology.

  16. Structural reliability analysis of laminated CMC components

    NASA Technical Reports Server (NTRS)

    Duffy, Stephen F.; Palko, Joseph L.; Gyekenyesi, John P.

    1991-01-01

    For laminated ceramic matrix composite (CMC) materials to realize their full potential in aerospace applications, design methods and protocols are a necessity. The time independent failure response of these materials is focussed on and a reliability analysis is presented associated with the initiation of matrix cracking. A public domain computer algorithm is highlighted that was coupled with the laminate analysis of a finite element code and which serves as a design aid to analyze structural components made from laminated CMC materials. Issues relevant to the effect of the size of the component are discussed, and a parameter estimation procedure is presented. The estimation procedure allows three parameters to be calculated from a failure population that has an underlying Weibull distribution.

  17. Plated lamination structures for integrated magnetic devices

    DOEpatents

    Webb, Bucknell C.

    2014-06-17

    Semiconductor integrated magnetic devices such as inductors, transformers, etc., having laminated magnetic-insulator stack structures are provided, wherein the laminated magnetic-insulator stack structures are formed using electroplating techniques. For example, an integrated laminated magnetic device includes a multilayer stack structure having alternating magnetic and insulating layers formed on a substrate, wherein each magnetic layer in the multilayer stack structure is separated from another magnetic layer in the multilayer stack structure by an insulating layer, and a local shorting structure to electrically connect each magnetic layer in the multilayer stack structure to an underlying magnetic layer in the multilayer stack structure to facilitate electroplating of the magnetic layers using an underlying conductive layer (magnetic or seed layer) in the stack as an electrical cathode/anode for each electroplated magnetic layer in the stack structure.

  18. Preliminary evaluation of hybrid titanium composite laminates

    NASA Technical Reports Server (NTRS)

    Miller, J. L.; Progar, D. J.; Johnson, W. S.; St.clair, T. L.

    1994-01-01

    In this study, the mechanical response of hybrid titanium composite laminates (HTCL) was evaluated at room and elevated temperatures. Also, the use of an elastic-plastic laminate analysis program for predicting the tensile response from constituent properties was verified. The improvement in mechanical properties achieved by the laminates was assessed by comparing the results of static strength and constant amplitude fatigue tests to those for monolithic titanium sheet. Two HTCL were fabricated with different fiber volume fractions, resin layer thicknesses, and resins. One panel was thicker and was more poorly bonded in comparison to other. Consequently, the former had a lower tensile strength, while fewer cracks grew in this panel and at a slower rate. Both panels showed an improvement in fatigue life of almost two orders of magnitude. The model predictions were also in good agreement with the experimental results for both HTCL panels.

  19. Silicone modified resins for graphite fiber laminates

    NASA Technical Reports Server (NTRS)

    Frost, L. W.; Bower, G. M.

    1979-01-01

    The development of silicon modified resins for graphite fiber laminates which will prevent the dispersal of graphite fibers when the composites are burned is discussed. Eighty-five silicone modified resins were synthesized and evaluated including unsaturated polyesters, thermosetting methacrylates, epoxies, polyimides, and phenolics. Neat resins were judged in terms of Si content, homogeneity, hardness, Char formation, and thermal stability. Char formation was estimated by thermogravimetry to 1,000 C in air and in N2. Thermal stability was evaluated by isothermal weight loss measurements for 200 hrs in air at three temperatures. Four silicone modified epoxies were selected for evaluation in unidirectional filament wound graphite laminates. Neat samples of these resins had 1,000 C char residues of 25 to 50%. The highest flexural values measured for the laminates were a strength of 140 kpsi and a modulus of 10 Mpsi. The highest interlaminar shear strength was 5.3 kpsi.

  20. Stochastic damage evolution in textile laminates

    NASA Technical Reports Server (NTRS)

    Dzenis, Yuris A.; Bogdanovich, Alexander E.; Pastore, Christopher M.

    1993-01-01

    A probabilistic model utilizing random material characteristics to predict damage evolution in textile laminates is presented. Model is based on a division of each ply into two sublaminas consisting of cells. The probability of cell failure is calculated using stochastic function theory and maximal strain failure criterion. Three modes of failure, i.e. fiber breakage, matrix failure in transverse direction, as well as matrix or interface shear cracking, are taken into account. Computed failure probabilities are utilized in reducing cell stiffness based on the mesovolume concept. A numerical algorithm is developed predicting the damage evolution and deformation history of textile laminates. Effect of scatter of fiber orientation on cell properties is discussed. Weave influence on damage accumulation is illustrated with the help of an example of a Kevlar/epoxy laminate.

  1. Nonlinear effects on composite laminate thermal expansion

    NASA Technical Reports Server (NTRS)

    Hashin, Z.; Rosen, B. W.; Pipes, R. B.

    1979-01-01

    Analyses of Graphite/Polyimide laminates shown that the thermomechanical strains cannot be separated into mechanical strain and free thermal expansion strain. Elastic properties and thermal expansion coefficients of unidirectional Graphite/Polyimide specimens were measured as a function of temperature to provide inputs for the analysis. The + or - 45 degrees symmetric Graphite/Polyimide laminates were tested to obtain free thermal expansion coefficients and thermal expansion coefficients under various uniaxial loads. The experimental results demonstrated the effects predicted by the analysis, namely dependence of thermal expansion coefficients on load, and anisotropy of thermal expansion under load. The significance of time dependence on thermal expansion was demonstrated by comparison of measured laminate free expansion coefficients with and without 15 day delay at intermediate temperature.

  2. On thermal edge effects in composite laminates

    NASA Technical Reports Server (NTRS)

    Herakovich, C. T.

    1976-01-01

    Results are presented for a finite-element investigation of the combined influence of edge effects due to mechanical and thermal mismatch in composite laminates with free edges. Laminates of unidirectional boron/epoxy symmetrically bonded to sheets of aluminum and titanium were studied. It is shown that interlaminar thermal stresses may be more significant than the interlaminar stresses due to loading only. In addition, the stresses due to thermal mismatch may be of the same sign as those due to Poisson's mismatch or they may be of opposite sign depending upon material properties, stacking sequence, and direction of loading. The paper concludes with a brief discussion of thermal stresses in all-composite laminates.

  3. Damage initiation and propagation in metal laminates

    SciTech Connect

    Riddle, R.A.; Lesuer, D.R.; Syn, C.K.

    1996-07-26

    The metal laminates proposed here for aircraft structures are Al alloy interlayers between Al alloy based metal matrix composite (MMC) plates reinforced with Si carbide particles. Properties to be tailored for jet engine fan containment and wing and auxiliary support structures include the important property fracture toughness. A method was developed for simulating and predicting crack initiation/growth using finite element analysis and fracture mechanics. An important key in predicting the failure is the tie- break slideline with prescribed (chosen based on J Integral calculations) effective plastic strain to failure in elements along the slideline. More development of the method is needed, particularly in its correlation with experimental data from various fracture toughness and strength tests of metal laminates. Results show that delamination at the interface of the ductile interlayer and MMC material can add significantly to the energy required to propagate a crack through a metal laminate. 11 figs, 7 refs.

  4. Elastic constants of layers in isotropic laminates.

    PubMed

    Heyliger, Paul R; Ledbetter, Hassel; Kim, Sudook; Reimanis, Ivar

    2003-11-01

    The individual laminae elastic constants in multilayer laminates composed of dissimilar isotropic layers were determined using ultrasonic-resonance spectroscopy and the linear theory of elasticity. Ultrasonic resonance allows one to measure the free-vibration response spectrum of a traction-free solid under periodic vibration. These frequencies depend on pointwise density, laminate dimensions, layer thickness, and layer elastic constants. Given a material with known mass but unknown constitution, this method allows one to extract the elastic constants and density of the constituent layers. This is accomplished by measuring the frequencies and then minimizing the differences between these and those calculated using the theory of elasticity for layered media to select the constants that best replicate the frequency-response spectrum. This approach is applied to a three-layer, unsymmetric laminate of WpCu, and very good agreement is found with the elastic constants of the two constituent materials. PMID:14649998

  5. Adhesives for laminating polyimide insulated flat conductor cable

    NASA Technical Reports Server (NTRS)

    Montermoso, J. C.; Saxton, T. R.; Taylor, R. L.

    1967-01-01

    Polymer adhesive laminates polyimide-film flat conductor cable. It is obtained by reacting an appropriate diamine with a dianhydride. The adhesive has also been used in the lamination of copper to copper for the preparation of multilayer circuit boards.

  6. Linker of nucleoskeleton and cytoskeleton (LINC) complex-mediated actin-dependent nuclear positioning orients centrosomes in migrating myoblasts

    PubMed Central

    Chang, Wakam; Antoku, Susumu; Östlund, Cecilia; Worman, Howard J; Gundersen, Gregg G

    2015-01-01

    Myoblast migration is essential for muscle development and repair; however, the factors that contribute to the polarity of migrating myoblasts are relatively unknown. We find that randomly migrating C2C12 myoblasts orient their centrosomes in the direction of migration. Using wounded monolayers, we further show that centrosome orientation is stimulated by the serum factor lysophosphatidic acid (LPA) and involves the rearward movement of the nucleus while the centrosome is maintained at the cell centroid. The rate of nuclear movement correlated with that of actin retrograde flow and both cytochalasin D and blebbistatin prevented nuclear movement and centrosome orientation. Actin-dependent rearward nuclear movement in fibroblasts is mediated by assembly of nuclear membrane nesprin-2G and SUN2 LINC complexes into transmembrane actin-associated nuclear (TAN) lines anchored by A-type lamins and emerin. In C2C12 myoblasts, depletion of nesprin-2G, SUN2 or lamin A/C prevented nuclear movement and endogenous nesprin-2G and a chimeric GFP-mini-nesprin-2G formed TAN lines during nuclear movement. Depleting nesprin-2G strongly interfered with directed cell migration and reduced the efficiency of myoblast fusion into multinucleated myotubes. Our results show that nuclear movement contributes to centrosome orientation and polarity for efficient migration and fusion of myoblasts. Given that mutations in the genes encoding A-type lamins, nesprin-2 and SUN2 cause Emery-Dreifuss muscular dystrophy and related myopathies, our results have implications for understanding the mechanism of disease pathogenesis. PMID:25587885

  7. Fracture behavior of laminated discontinuously reinforced aluminum material

    SciTech Connect

    Osman, T.M. |; Lewandowski, J.J.; Lesuer, D.R.; Syn, C.K.; Hunt, W.H. Jr

    1994-05-01

    Laminated metallic composites are being developed for applications which require high specific stiffness and fracture resistance. Recent work with laminated discontinuously reinforced aluminum (DRA) materials has demonstrated the potential for marked improvements in stable crack growth resistance via extrinsic toughening. The purpose of this work is to compare the fracture mechanisms and fracture resistance of laminated DRA materials to unlaminated DRA materials. In particular, the production of extensive stable crack growth and the associated improvement in damage tolerance in DRA laminates is documented.

  8. Reliability analysis of continuous fiber composite laminates

    NASA Technical Reports Server (NTRS)

    Thomas, David J.; Wetherhold, Robert C.

    1991-01-01

    This paper describes two methods, the maximum distortion energy (MDE) and the principle of independent action (PIA), developed for the analysis of the reliability of a single continuous composite lamina. It is shown that, for the typical laminated plate structure, the individual lamina reliabilities can be combined in order to produce the upper and the lower bounds of reliability for the laminate, similar in nature to the bounds on properties produced from variational elastic methods. These limits were derived for both the interactive and the model failure considerations. Analytical expressions were also derived for the sensitivity of the reliability limits with respect to changes in the Weibull parameters and in loading conditions.

  9. Composite laminate free edge reinforcement concepts

    NASA Technical Reports Server (NTRS)

    Howard, W. E.; Gossard, T., Jr.; Jones, R. M.

    1985-01-01

    The presence of a free edge in a laminated composite structure can result in delamination of the composite under certain loading conditions. Linear finite element analysis predicts large or even singular interlaminar stresses near the free edge. Edge reinforcements which will reduce these interlaminar stresses, prevent or delay the onset of delaminations, and thereby increase the strength and life of the structure were studied. Finite element models are used to analyze reinforced laminates which were subsequently fabricated and loaded to failure in order to verify the analysis results.

  10. Ultrasonic transducer with laminated coupling wedge

    DOEpatents

    Karplus, Henry H. B.

    1976-08-03

    An ultrasonic transducer capable of use in a high-temperature environment incorporates a laminated metal coupling wedge including a reflecting edge shaped as a double sloping roof and a transducer crystal backed by a laminated metal sound absorber disposed so as to direct sound waves through the coupling wedge and into a work piece, reflections from the interface between the coupling wedge and the work piece passing to the reflecting edge. Preferably the angle of inclination of the two halves of the reflecting edge are different.

  11. Phosphorylation statuses at different residues of lamin B2, B1, and A/C dynamically and independently change throughout the cell cycle

    SciTech Connect

    Kuga, Takahisa; Nozaki, Naohito; Matsushita, Kazuyuki; Nomura, Fumio; Tomonaga, Takeshi

    2010-08-15

    Lamins, major components of the nuclear lamina, undergo phosphorylation at multiple residues during cell cycle progression, but their detailed phosphorylation kinetics remain largely undetermined. Here, we examined changes in the phosphorylation of major phosphorylation residues (Thr14, Ser17, Ser385, Ser387, and Ser401) of lamin B2 and the homologous residues of lamin B1, A/C during the cell cycle using novel antibodies to the site-specific phosphorylation. The phosphorylation levels of these residues independently changed during the cell cycle. Thr14 and Ser17 were phosphorylated during G{sub 2}/M phase to anaphase/telophase. Ser385 was persistently phosphorylated during mitosis to G{sub 1} phase, whereas Ser387 was phosphorylated discontinuously in prophase and G{sub 1} phase. Ser401 phosphorylation was enhanced in the G{sub 1}/S boundary. Immunoprecipitation using the phospho-antibodies suggested that metaphase-phosphorylation at Thr14, Ser17, and Ser385 of lamins occurred simultaneously, whereas G{sub 1}-phase phosphorylation at Ser385 and Ser387 occurred in distinct pools or with different timings. Additionally, we showed that lamin B2 phosphorylated at Ser17, but not Ser385, Ser387 and Ser401, was exclusively non-ionic detergent soluble, depolymerized forms in growing cells, implicating specific involvement of Ser17 phosphorylation in lamin depolymerization and nuclear envelope breakdown. These results suggest that the phosphorylations at different residues of lamins might play specific roles throughout the cell cycle.

  12. Energy Saving Glass Lamination via Selective Radio Frequency Heating

    SciTech Connect

    Allan, Shawn M; Baranova, Inessa; Poley, Joseph; Reis, Henrique

    2012-02-27

    This project focused on advancing radio-frequency (RF) lamination technology closer to commercial implementation, in order to reduce the energy intensity of glass lamination by up to 90%. Lamination comprises a wide range of products including autoglass, architectural safety and innovative design glass, transparent armor (e.g. bullet proof glass), smart glass, mirrors, and encapsulation of photovoltaics. Lamination is also the fastest growing segment of glass manufacturing, with photovoltaics, architectural needs, and an anticipated transition to laminated side windows in vehicles. The state-of-the-art for glass lamination is to use autoclaves, which apply heat and uniform gas pressure to bond the laminates over the course of 1 to 18 hours. Laminates consist of layers of glass or other materials bonded with vinyl or urethane interlayers. In autoclaving, significant heat energy is lost heating the chamber, pressurized air, glass racks, and the glass. In RF lamination, the heat is generated directly in the vinyl interlayer, causing it to heat and melt quickly, in just 1 to 10 minutes, without significantly heating the glass or the equipment. The main purpose of this project was to provide evidence that low energy, rapid RF lamination quality met the same standards as conventionally autoclaved windows. The development of concepts for laminating curved glass with RF lamination was a major goal. Other primary goals included developing a stronger understanding of the lamination product markets described above, and to refine the potential benefits of commercial implementation. The scope of the project was to complete implementation concept studies in preparation for continuation into advanced development, pilot studies, and commercial implementation. The project consisted of 6 main tasks. The first dealt with lamination with poly-vinyl butyral (PVB) interlayers, which prior work had shown difficulties in achieving good quality laminates, working with Pilkington North

  13. Energy Saving Glass Lamination via Selective Radio Frequency Heating

    SciTech Connect

    Allan, Shawn M.

    2012-02-27

    This project focused on advancing radio-frequency (RF) lamination technology closer to commercial implementation, in order to reduce the energy intensity of glass lamination by up to 90%. Lamination comprises a wide range of products including autoglass, architectural safety and innovative design glass, transparent armor (e.g. bullet proof glass), smart glass, mirrors, and encapsulation of photovoltaics. Lamination is also the fastest growing segment of glass manufacturing, with photovoltaics, architectural needs, and an anticipated transition to laminated side windows in vehicles. The state-of-the-art for glass lamination is to use autoclaves, which apply heat and uniform gas pressure to bond the laminates over the course of 1 to 18 hours. Laminates consist of layers of glass or other materials bonded with vinyl or urethane interlayers. In autoclaving, significant heat energy is lost heating the chamber, pressurized air, glass racks, and the glass. In RF lamination, the heat is generated directly in the vinyl interlayer, causing it to heat and melt quickly, in just 1 to 10 minutes, without significantly heating the glass or the equipment. The main purpose of this project was to provide evidence that low energy, rapid RF lamination quality met the same standards as conventionally autoclaved windows. The development of concepts for laminating curved glass with RF lamination was a major goal. Other primary goals included developing a stronger understanding of the lamination product markets described above, and to refine the potential benefits of commercial implementation. The scope of the project was to complete implementation concept studies in preparation for continuation into advanced development, pilot studies, and commercial implementation. The project consisted of 6 main tasks. The first dealt with lamination with poly-vinyl butyral (PVB) interlayers, which prior work had shown difficulties in achieving good quality laminates, working with Pilkington North

  14. Regulation of prelamin A but not lamin C by miR-9, a brain-specific microRNA.

    PubMed

    Jung, Hea-Jin; Coffinier, Catherine; Choe, Youngshik; Beigneux, Anne P; Davies, Brandon S J; Yang, Shao H; Barnes, Richard H; Hong, Janet; Sun, Tao; Pleasure, Samuel J; Young, Stephen G; Fong, Loren G

    2012-02-14

    Lamins A and C, alternatively spliced products of the LMNA gene, are key components of the nuclear lamina. The two isoforms are found in similar amounts in most tissues, but we observed an unexpected pattern of expression in the brain. Western blot and immunohistochemistry studies showed that lamin C is abundant in the mouse brain, whereas lamin A and its precursor prelamin A are restricted to endothelial cells and meningeal cells and are absent in neurons and glia. Prelamin A transcript levels were low in the brain, but this finding could not be explained by alternative splicing. In lamin A-only knockin mice, where alternative splicing is absent and all the output of the gene is channeled into prelamin A transcripts, large amounts of lamin A were found in peripheral tissues, but there was very little lamin A in the brain. Also, in knockin mice expressing exclusively progerin (a toxic form of prelamin A found in Hutchinson-Gilford progeria syndrome), the levels of progerin in the brain were extremely low. Further studies showed that prelamin A expression, but not lamin C expression, is down-regulated by a brain-specific microRNA, miR-9. Expression of miR-9 in cultured cells reduced lamin A expression, and this effect was abolished when the miR-9-binding site in the prelamin A 3' UTR was mutated. The down-regulation of prelamin A expression in the brain could explain why mouse models of Hutchinson-Gilford progeria syndrome are free of central nervous system pathology. PMID:22308344

  15. Multi-layer laminate structure and manufacturing method

    DOEpatents

    Keenihan, James R.; Cleereman, Robert J.; Eurich, Gerald; Graham, Andrew T.; Langmaid, Joe A.

    2012-04-24

    The present invention is premised upon a multi-layer laminate structure and method of manufacture, more particularly to a method of constructing the multi-layer laminate structure utilizing a laminate frame and at least one energy activated flowable polymer.

  16. Multi-layer laminate structure and manufacturing method

    SciTech Connect

    Keenihan, James R.; Cleereman, Robert J.; Eurich, Gerald; Graham, Andrew T.; Langmaid, Joe A.

    2013-01-29

    The present invention is premised upon a multi-layer laminate structure and method of manufacture, more particularly to a method of constructing the multi-layer laminate structure utilizing a laminate frame and at least one energy activated flowable polymer.

  17. Methods to Monitor DNA Repair Defects and Genomic Instability in the Context of a Disrupted Nuclear Lamina.

    PubMed

    Gonzalo, Susana; Kreienkamp, Ray

    2016-01-01

    The organization of the genome within the nuclear space is viewed as an additional level of regulation of genome function, as well as a means to ensure genome integrity. Structural proteins associated with the nuclear envelope, in particular lamins (A- and B-type) and lamin-associated proteins, play an important role in genome organization. Interestingly, there is a whole body of evidence that links disruptions of the nuclear lamina with DNA repair defects and genomic instability. Here, we describe a few standard techniques that have been successfully utilized to identify mechanisms behind DNA repair defects and genomic instability in cells with an altered nuclear lamina. In particular, we describe protocols to monitor changes in the expression of DNA repair factors (Western blot) and their recruitment to sites of DNA damage (immunofluorescence); kinetics of DNA double-strand break repair after ionizing radiation (neutral comet assays); frequency of chromosomal aberrations (FISH, fluorescence in situ hybridization); and alterations in telomere homeostasis (Quantitative-FISH). These techniques have allowed us to shed some light onto molecular mechanisms by which alterations in A-type lamins induce genomic instability, which could contribute to the pathophysiology of aging and aging-related diseases. PMID:27147057

  18. Reliability analysis of continuous fiber composite laminates

    NASA Technical Reports Server (NTRS)

    Thomas, David J.; Wetherhold, Robert C.

    1990-01-01

    A composite lamina may be viewed as a homogeneous solid whose directional strengths are random variables. Calculation of the lamina reliability under a multi-axial stress state can be approached by either assuming that the strengths act separately (modal or independent action), or that they interact through a quadratic interaction criterion. The independent action reliability may be calculated in closed form, while interactive criteria require simulations; there is currently insufficient data to make a final determination of preference between them. Using independent action for illustration purposes, the lamina reliability may be plotted in either stress space or in a non-dimensional representation. For the typical laminated plate structure, the individual lamina reliabilities may be combined in order to produce formal upper and lower bounds of reliability for the laminate, similar in nature to the bounds on properties produced from variational elastic methods. These bounds are illustrated for a (0/plus or minus 15)sub s Graphite/Epoxy (GR/EP) laminate. And addition, simple physically plausible phenomenological rules are proposed for redistribution of load after a lamina has failed. These rules are illustrated by application to (0/plus or minus 15)sub s and (90/plus or minus 45/0)sub s GR/EP laminates and results are compared with respect to the proposed bounds.

  19. Doped LZO buffer layers for laminated conductors

    DOEpatents

    Paranthaman, Mariappan Parans [Knoxville, TN; Schoop, Urs [Westborough, MA; Goyal, Amit [Knoxville, TN; Thieme, Cornelis Leo Hans [Westborough, MA; Verebelyi, Darren T [Oxford, MA; Rupich, Martin W [Framingham, MA

    2010-03-23

    A laminated conductor includes a metallic substrate having a surface, a biaxially textured buffer layer supported by the surface of the substrate, the biaxially textured buffer layer comprising LZO and a dopant for mitigating metal diffusion through the LZO, and a biaxially textured conductor layer supported by the biaxially textured buffer layer.

  20. Laminated insulators having heat dissipation means

    DOEpatents

    Niemann, R.C.; Mataya, K.F.; Gonczy, J.D.

    1980-04-24

    A laminated body is provided with heat dissipation capabilities. The insulator body is formed by dielectric layers interleaved with heat conductive layers, and bonded by an adhesive to form a composite structure. The heat conductive layers include provision for connection to an external thermal circuit.

  1. Down-regulation of the Lamin A/C in neuroblastoma triggers the expansion of tumor initiating cells.

    PubMed

    Nardella, Marta; Guglielmi, Loredana; Musa, Carla; Iannetti, Ilaria; Maresca, Giovanna; Amendola, Donatella; Porru, Manuela; Carico, Elisabetta; Sessa, Giuseppe; Camerlingo, Rosalba; Dominici, Carlo; Megiorni, Francesca; Milan, Marika; Bearzi, Claudia; Rizzi, Roberto; Pirozzi, Giuseppe; Leonetti, Carlo; Bucci, Barbara; Mercanti, Delio; Felsani, Armando; D'Agnano, Igea

    2015-10-20

    Tumor-initiating cells constitute a population within a tumor mass that shares properties with normal stem cells and is considered responsible for therapy failure in many cancers. We have previously demonstrated that knockdown of the nuclear envelope component Lamin A/C in human neuroblastoma cells inhibits retinoic acid-mediated differentiation and results in a more aggressive phenotype. In addition, Lamin A/C is often lost in advanced tumors and changes in the nuclear envelope composition occur during tumor progression. Based on our previous data and considering that Lamin A/C is expressed in differentiated tissues, we hypothesize that the lack of Lamin A/C could predispose cells toward a stem-like phenotype, thus influencing the development of tumor-initiating cells in neuroblastoma. This paper demonstrates that knockdown of Lamin A/C triggers the development of a tumor-initiating cell population with self-renewing features in human neuroblastoma cells. We also demonstrates that the development of TICs is due to an increased expression of MYCN gene and that in neuroblastoma exists an inverse relationship between LMNA and MYCN expression. PMID:26439802

  2. Down-regulation of the Lamin A/C in neuroblastoma triggers the expansion of tumor initiating cells

    PubMed Central

    Nardella, Marta; Guglielmi, Loredana; Musa, Carla; Iannetti, Ilaria; Maresca, Giovanna; Amendola, Donatella; Porru, Manuela; Carico, Elisabetta; Sessa, Giuseppe; Camerlingo, Rosalba; Dominici, Carlo; Megiorni, Francesca; Milan, Marika; Bearzi, Claudia; Rizzi, Roberto; Pirozzi, Giuseppe; Leonetti, Carlo; Bucci, Barbara; Mercanti, Delio; Felsani, Armando; D'Agnano, Igea

    2015-01-01

    Tumor-initiating cells constitute a population within a tumor mass that shares properties with normal stem cells and is considered responsible for therapy failure in many cancers. We have previously demonstrated that knockdown of the nuclear envelope component Lamin A/C in human neuroblastoma cells inhibits retinoic acid-mediated differentiation and results in a more aggressive phenotype. In addition, Lamin A/C is often lost in advanced tumors and changes in the nuclear envelope composition occur during tumor progression. Based on our previous data and considering that Lamin A/C is expressed in differentiated tissues, we hypothesize that the lack of Lamin A/C could predispose cells toward a stem-like phenotype, thus influencing the development of tumor-initiating cells in neuroblastoma. This paper demonstrates that knockdown of Lamin A/C triggers the development of a tumor-initiating cell population with self-renewing features in human neuroblastoma cells. We also demonstrates that the development of TICs is due to an increased expression of MYCN gene and that in neuroblastoma exists an inverse relationship between LMNA and MYCN expression. PMID:26439802

  3. Compression failure of angle-ply laminates

    NASA Technical Reports Server (NTRS)

    Peel, Larry D.; Hyer, Michael W.; Shuart, Mark J.

    1991-01-01

    The present work deals with modes and mechanisms of failure in compression of angle-ply laminates. Experimental results were obtained from 42 angle-ply IM7/8551-7a specimens with a lay-up of ((plus or minus theta)/(plus or minus theta)) sub 6s where theta, the off-axis angle, ranged from 0 degrees to 90 degrees. The results showed four failure modes, these modes being a function of off-axis angle. Failure modes include fiber compression, inplane transverse tension, inplane shear, and inplane transverse compression. Excessive interlaminar shear strain was also considered as an important mode of failure. At low off-axis angles, experimentally observed values were considerably lower than published strengths. It was determined that laminate imperfections in the form of layer waviness could be a major factor in reducing compression strength. Previously developed linear buckling and geometrically nonlinear theories were used, with modifications and enhancements, to examine the influence of layer waviness on compression response. The wavy layer is described by a wave amplitude and a wave length. Linear elastic stress-strain response is assumed. The geometrically nonlinear theory, in conjunction with the maximum stress failure criterion, was used to predict compression failure and failure modes for the angle-ply laminates. A range of wave length and amplitudes were used. It was found that for 0 less than or equal to theta less than or equal to 15 degrees failure was most likely due to fiber compression. For 15 degrees less than theta less than or equal to 35 degrees, failure was most likely due to inplane transverse tension. For 35 degrees less than theta less than or equal to 70 degrees, failure was most likely due to inplane shear. For theta less than 70 degrees, failure was most likely due to inplane transverse compression. The fiber compression and transverse tension failure modes depended more heavily on wave length than on wave amplitude. Thus using a single

  4. Determining Shear Stress Distribution in a Laminate

    NASA Technical Reports Server (NTRS)

    Bednarcyk, Brett A.; Aboudi, Jacob; Yarrington, Phillip W.

    2010-01-01

    A "simplified shear solution" method approximates the through-thickness shear stress distribution within a composite laminate based on an extension of laminated beam theory. The method does not consider the solution of a particular boundary value problem; rather, it requires only knowledge of the global shear loading, geometry, and material properties of the laminate or panel. It is thus analogous to lamination theory in that ply-level stresses can be efficiently determined from global load resultants at a given location in a structure and used to evaluate the margin of safety on a ply-by-ply basis. The simplified shear solution stress distribution is zero at free surfaces, continuous at ply boundaries, and integrates to the applied shear load. The method has been incorporated within the HyperSizer commercial structural sizing software to improve its predictive capability for designing composite structures. The HyperSizer structural sizing software is used extensively by NASA to design composite structures. In the case of through-thickness shear loading on panels, HyperSizer previously included a basic, industry-standard, method for approximating the resulting shear stress distribution in sandwich panels. However, no such method was employed for solid laminate panels. The purpose of the innovation is to provide an approximation of the through-thickness shear stresses in a solid laminate given the through-thickness shear loads (Qx and Qy) on the panel. The method was needed for implementation within the HyperSizer structural sizing software so that the approximated ply-level shear stresses could be utilized in a failure theory to assess the adequacy of a panel design. The simplified shear solution method was developed based on extending and generalizing bi-material beam theory to plate-like structures. It is assumed that the through-thickness shear stresses arise due to local bending of the laminate induced by the through-thickness shear load, and by imposing

  5. Fatigue damage development of various CFRP-laminates

    NASA Technical Reports Server (NTRS)

    Schulte, K.; Baron, CH.

    1988-01-01

    The chronic strength and fatigue behavior of a woven carbon-fiber reinforced laminate in a balanced eight-shaft satin weave style was compared to nonwoven laminates with an equivalent cross-ply layup. Half the fibers were arranged in the direction of the load and the other half perpendicular to it. Two types of nonwoven laminates consisting of continuous fibers and aligned discontinuous fibers, both produced from carbon fiber prepregs, were studied. The cross-ply laminate with continuous fiber showed the best characteristics with regard to both static strength and fatigue. The similarities and differences in damage mechanisms in the laminates are described.

  6. Nonlinear laminate analysis for metal matrix fiber composites

    NASA Technical Reports Server (NTRS)

    Chamis, C. C.; Sinclair, J. H.

    1981-01-01

    A nonlinear laminate analysis is described for predicting the mechanical behavior (stress-strain relationships) of angle-ply laminates in which the matrix is strained nonlinearly by both the residual stress and the mechanical load and in which additional nonlinearities are induced due to progressive fiber fractures and ply relative rotations. The nonlinear laminate analysis is based on linear composite mechanics and a piece-wise linear laminate analysis to handle the nonlinear responses. Results obtained by using this nonlinear analysis on boron-fiber/aluminum-matrix angle-ply laminates agree well with experimental data. The results shown illustrate the in situ ply stress-strain behavior and synergistic strength enhancement.

  7. Nonlinear laminate analysis for metal matrix fiber composites

    NASA Technical Reports Server (NTRS)

    Chamis, C. C.; Sinclair, J. H.

    1981-01-01

    A nonlinear laminate analysis is described for predicting the mechanical behavior (stress-strain relationships) of angleplied laminates in which the matrix is strained nonlinearly by both the residual stress and the mechanical load and in which additional nonlinearities are induced due to progressive fiber fractures and ply relative rotations. The nonlinear laminate analysis (NLA) is based on linear composite mechanics and a piece wise linear laminate analysis to handle the nonlinear responses. Results obtained by using this nonlinear analysis on boron fiber/aluminum matrix angleplied laminates agree well with experimental data. The results shown illustrate the in situ ply stress-strain behavior and synergistic strength enhancement.

  8. Progressive delamination in polymer matrix composite laminates: A new approach

    NASA Technical Reports Server (NTRS)

    Chamis, C. C.; Murthy, P. L. N.; Minnetyan, L.

    1992-01-01

    A new approach independent of stress intensity factors and fracture toughness parameters has been developed and is described for the computational simulation of progressive delamination in polymer matrix composite laminates. The damage stages are quantified based on physics via composite mechanics while the degradation of the laminate behavior is quantified via the finite element method. The approach accounts for all types of composite behavior, laminate configuration, load conditions, and delamination processes starting from damage initiation, to unstable propagation, and to laminate fracture. Results of laminate fracture in composite beams, panels, plates, and shells are presented to demonstrate the effectiveness and versatility of this new approach.

  9. Edge effects in angle-ply composite laminates

    NASA Technical Reports Server (NTRS)

    Hsu, P. W.; Herakovich, C. T.

    1977-01-01

    This paper presents the results of a zeroth-order solution for edge effects in angle-ply composite laminates obtained using perturbation techniques and a limiting free body approach. The general solution for edge effects in laminates of arbitrary angle ply is applied to the special case of a (+ or - 45)s graphite/epoxy laminate. Interlaminar stress distributions are obtained as a function of the laminate thickness-to-width ratio and compared to finite difference results. The solution predicts stable, continuous stress distributions, determines finite maximum tensile interlaminar normal stress and provides mathematical evidence for singular interlaminar shear stresses in (+ or - 45) graphite/epoxy laminates.

  10. Study on mechanical properties of laminated rubber bearing with small shape factor

    SciTech Connect

    Mazda, T.; Ootori, Y.; Yabana, S.; Hirata, K.; Ishida, K.

    1995-12-01

    Laminated rubber bearings with a small shape factor are regarded as one of the most promising isolation devices to reduce the vertical seismic load of a nuclear power plant. In this study, three types of natural rubber bearings with different aspect ratios (diameter/total thickness of rubber) and one high-damping rubber bearing are tested under varied loading conditions. Basic characteristics and ultimate characteristics of the bearings are made clear, and applicability of estimation formula and analysis method are verified.

  11. Novel Remanufacturing Process of Recycled Polytetrafluoroethylene(PTFE)/GF Laminate

    NASA Astrophysics Data System (ADS)

    Xi, Z.; Ghita, O. R.; Johnston, P.; Evans, K. E.

    2011-01-01

    Currently, the PTFE/GF laminate and PTFE PCB manufacturers are under considerable pressure to address the recycling issues due to Waste Electrical and Electronic Equipment (WEEE) Directive, shortage of landfill capacity and cost of disposal. This study is proposing a novel manufacture method for reuse of the mechanical ground PTFE/Glass fibre (GF) laminate and production of the first reconstitute PTFE/GF laminate. The reconstitute PTFE/GF laminate proposed here consists of a layer of recycled sub-sheet, additional layers of PTFE and PTFE coated glass cloth, also covered by copper foils. The reconstitute PTFE/GF laminate showed good dielectric properties. Therefore, there is potential to use the mechanical ground PTFE/GF laminate powder to produce reconstitute PTFE/GF laminate, for use in high frequencies PCB applications.

  12. Ultrasonic monitoring of asymmetric carbon fibre reinforced aluminum laminates

    NASA Astrophysics Data System (ADS)

    Zhao, Junqing; Yang, Fan; Wang, Rongguo

    2013-08-01

    Asymmetric carbon fibre reinforced aluminum alloy laminates was manufactured for the purpose with repeat tensile test, which will be applied in composite pressure vessel. Ultrasonic C scan and A scan approach are used to evaluate the damage of the asymmetric CFRP-Al (carbon fibre reinforced aluminum alloy) laminates. Nondestructive detection is carried out for the CFRP-Al laminates before and after tensile test. Comparison results and pulse echo analysis show that when subjected to repeat tensile test with 70% elastic limit strain load of the CFRP laminates, the interface debonding between CFRP and Al will not occur but the delamination within CFRP laminates becomes the main damage of the asymmetric CFRP-Al laminates. This investigation indicated that combined ultrasonic C scan and A scan is available for damage evaluation of fibre metal laminates.

  13. Tensile stress-strain behavior of boron/aluminum laminates

    NASA Technical Reports Server (NTRS)

    Sova, J. A.; Poe, C. C., Jr.

    1978-01-01

    The tensile stress-strain behavior of five types of boron/aluminum laminates was investigated. Longitudinal and transverse stress-strain curves were obtained for monotonic loading to failure and for three cycles of loading to successively higher load levels. The laminate strengths predicted by assuming that the zero deg plies failed first correlated well with the experimental results. The stress-strain curves for all the boron/aluminum laminates were nonlinear except at very small strains. Within the small linear regions, elastic constants calculated from laminate theory corresponded to those obtained experimentally to within 10 to 20 percent. A limited amount of cyclic loading did not affect the ultimate strength and strain for the boron/aluminum laminates. The laminates, however, exhibited a permanent strain on unloading. The Ramberg-Osgood equation was fitted to the stress-strain curves to obtain average curves for the various laminates.

  14. Autophagy mediates degradation of nuclear lamina

    PubMed Central

    Dou, Zhixun; Xu, Caiyue; Donahue, Greg; Shimi, Takeshi; Pan, Ji-An; Zhu, Jiajun; Ivanov, Andrejs; Capell, Brian C.; Drake, Adam M.; Shah, Parisha P.; Catanzaro, Joseph M.; Ricketts, M. Daniel; Lamark, Trond; Adam, Stephen A.; Marmorstein, Ronen; Zong, Wei-Xing; Johansen, Terje; Goldman, Robert D.; Adams, Peter D.; Berger, Shelley L.

    2015-01-01

    Macroautophagy (hereafter referred to as autophagy) is a catabolic membrane trafficking process that degrades a variety of cellular constituents, and is associated with human diseases1–3. While extensive studies have focused on autophagic turnover of cytoplasmic materials, little is known regarding the role of autophagy in degrading nuclear components. Here we report that the autophagy machinery mediates degradation of nuclear lamina components in mammals. The autophagy protein LC3/Atg8, which is involved in autophagy membrane trafficking and substrate delivery4–6, is present in the nucleus and directly interacts with the nuclear lamina protein Lamin B1, and binds to lamin-associated domains (LADs) on chromatin. This LC3-Lamin B1 interaction does not downregulate Lamin B1 during starvation, but mediates its degradation upon oncogenic insults, such as by activated Ras. Lamin B1 degradation is achieved by nucleus-to-cytoplasm transport that delivers Lamin B1 to the lysosome. Inhibiting autophagy or the LC3-Lamin B1 interaction prevents activated Ras-induced Lamin B1 loss and attenuates oncogene-induced senescence in primary human cells. Our study suggests this new function of autophagy as a guarding mechanism protecting cells from tumorigenesis. PMID:26524528

  15. Micromechanical Modeling of Impact Damage Mechanisms in Unidirectional Composite Laminates

    NASA Astrophysics Data System (ADS)

    Meng, Qinghua; Wang, Zhenqing

    2016-05-01

    Composite laminates are susceptible to the transverse impact loads resulting in significant damage such as matrix cracking, fiber breakage and delamination. In this paper, a micromechanical model is developed to predict the impact damage of composite laminates based on microstructure and various failure models of laminates. The fiber and matrix are represented by the isotropic and elastic-plastic solid, and their impact failure behaviors are modeled based on shear damage model. The delaminaton failure is modeling by the interface element controlled by cohesive damage model. Impact damage mechanisms of laminate are analyzed by using the micromechanical model proposed. In addition, the effects of impact energy and laminated type on impact damage behavior of laminates are investigated. Due to the damage of the surrounding matrix near the impact point caused by the fiber deformation, the surface damage area of laminate is larger than the area of ​​impact projectile. The shape of the damage area is roughly rectangle or elliptical with the major axis extending parallel to the fiber direction in the surface layer of laminate. The alternating laminated type with two fiber directions is more propitious to improve the impact resistance of laminates.

  16. Fatigue Damage Mechanisms in Advanced Hybrid Titanium Composite Laminates

    NASA Technical Reports Server (NTRS)

    Johnson, W. Steven; Rhymer, Donald W.; St.Clair, Terry L. (Technical Monitor)

    2000-01-01

    Hybrid Titanium Composite Laminates (HTCL) are a type of hybrid composite laminate with promise for high-speed aerospace applications, specifically designed for improved damage tolerance and strength at high-temperature (350 F, 177 C). However, in previous testing, HTCL demonstrated a propensity to excessive delamination at the titanium/PMC interface following titanium cracking. An advanced HTCL has been constructed with an emphasis on strengthening this interface, combining a PETI-5/IM7 PMC with Ti-15-3 foils prepared with an alkaline-perborate surface treatment. This paper discusses how the fatigue capabilities of the "advanced" HTCL compare to the first generation HTCL which was not modified for interface optimization, in both tension-tension (R = 0.1) and tension-compression (R=-0.2). The advanced HTCL under did not demonstrate a significant improvement in fatigue life, in either tension-tension or tension-compression loading. However, the advanced HTCL proved much more damage tolerant. The R = 0.1 tests revealed the advanced HTCL to increase the fatigue life following initial titanium ply damage up to 10X that of the initial HTCL at certain stress levels. The damage progression following the initial ply damage demonstrated the effect of the strengthened PMC/titanium interface. Acetate film replication of the advanced HTCL edges showed a propensity for some fibers in the adjacent PMC layers to fail at the point of titanium crack formation, suppressing delamination at the Ti/PMC interface. The inspection of failure surfaces validated these findings, revealing PMC fibers bonded to the majority of the titanium surfaces. Tension compression fatigue (R = -0.2) demonstrated the same trends in cycles between initial damage and failure, damage progression, and failure surfaces. Moreover, in possessing a higher resistance to delamination, the advanced HTCL did not exhibit buckling following initial titanium ply cracking under compression unlike the initial HTCL.

  17. Transverse shear stiffness of laminated anisotropic shells

    NASA Technical Reports Server (NTRS)

    Cohen, G. A.

    1978-01-01

    Equations are derived for the transverse shear stiffness of laminated anisotropic shells. Without making assumptions for thickness distribution for either transverse shear stresses or strains, constitutive equations for the transverse shear deformation theory of anisotropic heterogeneous shells are found. The equations are based on Taylor series expansions about a generic point for stress resultants and couples, identically satisfying plate equilibrium equations. These equations are used to find statically correct expressions for in-surface stresses, transverse shear stresses, and the area density of transverse shear strain energy, in terms of transverse shear stress resultants and redundants. The application of Castigliano's theorem of least work minimizes shear strain energy with respect to the redundants. Examples are presented for several laminated walls. Good agreement is found between the results and those of exact three-dimensional elasticity solutions for the cylindrical bending of a plate.

  18. Indirect laminate veneer: a conservative novel approach.

    PubMed

    Prajapati, Paranjay; Sethuraman, Rajesh; Naveen, Y G; Patel, Jayanti R

    2013-01-01

    Various treatment options and materials are available for restoration of an endodontically treated tooth. Laminate veneer is conservative treatment usually employed for aesthetic correction or improvement. The indirect composite is available in a wide range of shades and specific characterisation is easily performed chair side in the operatory area, which makes it a quick procedure and time saving for both the patient and the dentist. The physical properties and optical properties are good enough to use it as indirect restorative material, so in this particular case it was the material of choice for fabrication of laminate veneer on anterior tooth. In this case, the endodontically treated tooth with a fractured incisal edge was restored with indirect composite material. PMID:23975914

  19. Investigating Delamination Migration in Composite Tape Laminates

    NASA Technical Reports Server (NTRS)

    Ratcliffe, James G.; DeCarvalho, Nelson V.

    2014-01-01

    A modification to a recently developed test specimen designed to investigate migration of a delamination between neighboring ply interfaces in tape laminates is presented. The specimen is a cross-ply laminated beam consisting of 40 plies with a polytetrafluoroethylene insert spanning part way along its length. The insert is located between a lower 0-degree ply (specimen length direction) and a stack of four 90-degree plies (specimen width direction). The modification involved a stacking sequence that promotes stable delamination growth prior to migration, and included a relocation of the insert from the specimen midplane to the interface between plies 14 and 15. Specimens were clamped at both ends onto a rigid baseplate and loaded on their upper surface via a piano hinge assembly, resulting in a predominantly flexural loading condition. Tests were conducted with the load-application point positioned at various locations along a specimen's span. This position affected the sequence of damage events during a test.

  20. Thermal stresses in thick laminated composite shells

    NASA Technical Reports Server (NTRS)

    Yuan, F. G.

    1993-01-01

    The paper provides an analytical formulation to investigate the thermomechanical behavior of thick composite shells subjected to a temperature distribution which varies arbitrarily in the radial direction. For illustrative purposes, shells under uniform temperature change are presented. It is found that thermal twist would occur even for symmetric laminated shells. Under uniform temperature rise, results for off-axis graphite/epoxy shells show that extensional-shear coupling can cause tensile radial stress throughout the shell and tensile hoop stress in the inner region. Laminated graphite/epoxy shells can exhibit negative effective thermal expansion coefficients in the longitudinal and transverse directions. Finally, the stacking sequence has a strong influence on the thermal stress distributions.

  1. Laminated grid and web magnetic cores

    DOEpatents

    Sefko, John; Pavlik, Norman M.

    1984-01-01

    A laminated magnetic core characterized by an electromagnetic core having core legs which comprise elongated apertures and edge notches disposed transversely to the longitudinal axis of the legs, such as high reluctance cores with linear magnetization characteristics for high voltage shunt reactors. In one embodiment the apertures include compact bodies of microlaminations for more flexibility and control in adjusting permeability and/or core reluctance.

  2. Process Yields Strong, Void-Free Laminates

    NASA Technical Reports Server (NTRS)

    Bryant, L. E.; Covington, E. W., III; Dale, W. J.; Hall, E. T., Jr; Justice, J. E.; Taylor, E. C.; Wilson, M. L.

    1983-01-01

    Need for lightweight materials as structural components for future space transportation systems stimulated development of systematic method for manufacturing a polyimide/graphite composite. Laminates manufactured by process are void-free, exhibit excellent thermo-oxidative stability up to 315 degrees C (600 degrees F) and are 40 percent lighter than aluminum. Process is precise, repeatable, and ideally suited for researchers and small-lot producers of composite materials.

  3. Triangular Element For Analyzing Elasticity Of Laminates

    NASA Technical Reports Server (NTRS)

    Martin, C. Wayne; Lung, S. F.; Gupta, K. K.

    1991-01-01

    Flat triangular element developed for use in finite-element analyses of stress and strain in laminated plates made of such materials as plywood or advanced fiber/epoxy composite materials. Has multiple layers, each of which can have different isotropic or orthotropic elastic properties. Many such elements used in finite-element mesh to calculate stiffness of plate. Formulation of element straight-forward, and calculation of its stiffness matrix simple and fast.

  4. Nondimensional impact models for composite laminates

    NASA Technical Reports Server (NTRS)

    Sankar, B. V.; Nguyen, P. T.; Ku, C.

    1990-01-01

    The equations governing the problem of low-velocity impact of a simply supported rectangular laminated plate are nondimensionalized such that the problem is defined in terms of five dimensionless parameters. A parametric study using the Graeco-Latin Factorial Plan is performed. Semi-empirical formulas for maximum impact force, impact duration, and maximum back surface strains are obtained. It is found that some of the simple impact models provide the bounds for the case of impact on a finite extent plate.

  5. Characteristics of laminates with delamination control strips

    NASA Technical Reports Server (NTRS)

    Sun, C. T.; Goering, J. C.; Alper, J. M.; Gause, L. W.

    1992-01-01

    Tough resin is needed to resist delamination crack propagation. However, modulus often has to be compromised because it is difficult to retain both high modulus and toughness in a matrix material. A potential solution is to use a hybrid system in which tough resin strips are included within a conventional matrix composite. By adjusting the spacing of the tough resin strips, maximum delamination size can be controlled. Experimental results for impact damage and subsequent damage propagation in laminates containing tough resin strips are reported. Plain adhesive strips and fiber-reinforced tough resin composite strips were used in constructing the hybrid laminates. Test results indicated that size of delamination inflicted by impact was confined between the tough resin strips. As a result, significantly increased residual compressive strength was obtained. Impacted laminates containing tough resin strips were also fatigue tested. It was found that these strips reduced the growth of the impact damage area relative to the growth seen in coupons with no tough resin strips. Damage growth from an open hole under tension fatigue was evaluated using both tough resin strips and glass fiber reinforced tough resin strips. Unreinforced tough resin strips retarded delamination growth from the open hole, but did not stop matrix cracks growing in the fiber direction. Fiber reinforced tough resin strips did not contain axial delamination growth from the open hole. However, they did act as crack arresters, stopping the through-the-thickness tension crack originating from the hole.

  6. Modeling Composite Laminate Crushing for Crash Analysis

    NASA Technical Reports Server (NTRS)

    Fleming, David C.; Jones, Lisa (Technical Monitor)

    2002-01-01

    Crash modeling of composite structures remains limited in application and has not been effectively demonstrated as a predictive tool. While the global response of composite structures may be well modeled, when composite structures act as energy-absorbing members through direct laminate crushing the modeling accuracy is greatly reduced. The most efficient composite energy absorbing structures, in terms of energy absorbed per unit mass, are those that absorb energy through a complex progressive crushing response in which fiber and matrix fractures on a small scale dominate the behavior. Such failure modes simultaneously include delamination of plies, failure of the matrix to produce fiber bundles, and subsequent failure of fiber bundles either in bending or in shear. In addition, the response may include the significant action of friction, both internally (between delaminated plies or fiber bundles) or externally (between the laminate and the crushing surface). A figure shows the crushing damage observed in a fiberglass composite tube specimen, illustrating the complexity of the response. To achieve a finite element model of such complex behavior is an extremely challenging problem. A practical crushing model based on detailed modeling of the physical mechanisms of crushing behavior is not expected in the foreseeable future. The present research describes attempts to model composite crushing behavior using a novel hybrid modeling procedure. Experimental testing is done is support of the modeling efforts, and a test specimen is developed to provide data for validating laminate crushing models.

  7. Hygrothermal stability of laminated CFRP composite mirrors

    NASA Astrophysics Data System (ADS)

    Pryor, Mark K.

    2000-07-01

    This paper is intended to address accuracy issues associated with hygrothermal stability of ultra-lightweight composite mirror structures. Hygrothermal stability of a mirror is ultimately defined as its optical performance when subjected to temperature or moisture variations. Stability is dictated by a combination of material behavior and geometric configuration. Ideally, an isotropic material could be used that is lightweight, has high stiffness, and has no response to temperature or moisture variances. This type of material would therefore be independent of geometry. Quasi-isotropic laminated CFRP composite materials offer most of these characteristics, but are transversely isotropic with near zero hygrothermal response in the plane of the laminate and a relatively high response through the thickness. Typically, mirrors made from laminated material consist of a thin curved shell supported by an array of ribs. Interference problems arise at the rib/shell interface resulting in a `print-through' effect by the ribs. Also, adhesive used to bond the ribs to the shell pull the shell causing additional `print-through'. Additional sources of instabilities result from material variances, processing, and assembly. These multiple sources of instabilities superimpose onto each other resulting in the structures overall hygrothermal stability.

  8. Superconductivity in Ca-doped graphene laminates

    NASA Astrophysics Data System (ADS)

    Chapman, J.; Su, Y.; Howard, C. A.; Kundys, D.; Grigorenko, A. N.; Guinea, F.; Geim, A. K.; Grigorieva, I. V.; Nair, R. R.

    2016-03-01

    Despite graphene’s long list of exceptional electronic properties and many theoretical predictions regarding the possibility of superconductivity in graphene, its direct and unambiguous experimental observation has not been achieved. We searched for superconductivity in weakly interacting, metal decorated graphene crystals assembled into so-called graphene laminates, consisting of well separated and electronically decoupled graphene crystallites. We report robust superconductivity in all Ca-doped graphene laminates. They become superconducting at temperatures (Tc) between ≈4 and ≈6 K, with Tc’s strongly dependent on the confinement of the Ca layer and the induced charge carrier concentration in graphene. We find that Ca is the only dopant that induces superconductivity in graphene laminates above 1.8 K among several dopants used in our experiments, such as potassium, caesium and lithium. By revealing the tunability of the superconducting response through doping and confinement of the metal layer, our work shows that achieving superconductivity in free-standing, metal decorated monolayer graphene is conditional on an optimum confinement of the metal layer and sufficient doping, thereby bringing its experimental realization within grasp.

  9. Distributed dynamic load on composite laminates

    NASA Astrophysics Data System (ADS)

    Langella, A.; Lopresto, V.; Caprino, G.

    2016-05-01

    An experimental activity conducted in order to assess the impact behavior at room and low temperature of carbon fibre in vinylester resin laminates used in the shipbuilding industry, was reported. The conditions which reproduce the impact of a hull at low temperature with a solid body suspended in the water was reproduced. A test equipment was designed and realized to reproduce the real material behaviour in water to obtain a load distribution on the entire surface of the specimen. The results were obtained impacting the laminates placed between the cilyndrical steel impactor and a bag containing water. A falling weight machine, equipped with an instrumented steel impactor and a thermal chamber, was adopted for the experimental tests. The impact behaviour in hostile environments was compared to the behaviour at room temperature and the data obtained under distributed load conditions were compared with the results from concentrated loads: a completely different behaviour was observed between the two different loading conditions in terms of load-displacement curve. The effect of the impact on the laminates has been related with the delaminations, evaluated by ultrasonic scanning, and the indentation.

  10. Characteristics of laminates with delamination control strips

    SciTech Connect

    Sun, C.T.; Goering, J.C.; Alper, J.M.; Gause, L.W.

    1992-09-01

    Tough resin is needed to resist delamination crack propagation. However, modulus often has to be compromised because it is difficult to retain both high modulus and toughness in a matrix material. A potential solution is to use a hybrid system in which tough resin strips are included within a conventional matrix composite. By adjusting the spacing of the tough resin strips, maximum delamination size can be controlled. Experimental results for impact damage and subsequent damage propagation in laminates containing tough resin strips are reported. Plain adhesive strips and fiber-reinforced tough resin composite strips were used in constructing the hybrid laminates. Test results indicated that size of delamination inflicted by impact was confined between the tough resin strips. As a result, significantly increased residual compressive strength was obtained. Impacted laminates containing tough resin strips were also fatigue tested. It was found that these strips reduced the growth of the impact damage area relative to the growth seen in coupons with no tough resin strips. Damage growth from an open hole under tension fatigue was evaluated using both tough resin strips and glass fiber reinforced tough resin strips. Unreinforced tough resin strips retarded delamination growth from the open hole, but did not stop matrix cracks growing in the fiber direction. Fiber reinforced tough resin strips did not contain axial delamination growth from the open hole. However, they did act as crack arresters, stopping the through-the-thickness tension crack originating from the hole.

  11. Superconductivity in Ca-doped graphene laminates.

    PubMed

    Chapman, J; Su, Y; Howard, C A; Kundys, D; Grigorenko, A N; Guinea, F; Geim, A K; Grigorieva, I V; Nair, R R

    2016-01-01

    Despite graphene's long list of exceptional electronic properties and many theoretical predictions regarding the possibility of superconductivity in graphene, its direct and unambiguous experimental observation has not been achieved. We searched for superconductivity in weakly interacting, metal decorated graphene crystals assembled into so-called graphene laminates, consisting of well separated and electronically decoupled graphene crystallites. We report robust superconductivity in all Ca-doped graphene laminates. They become superconducting at temperatures (Tc) between ≈4 and ≈6 K, with Tc's strongly dependent on the confinement of the Ca layer and the induced charge carrier concentration in graphene. We find that Ca is the only dopant that induces superconductivity in graphene laminates above 1.8 K among several dopants used in our experiments, such as potassium, caesium and lithium. By revealing the tunability of the superconducting response through doping and confinement of the metal layer, our work shows that achieving superconductivity in free-standing, metal decorated monolayer graphene is conditional on an optimum confinement of the metal layer and sufficient doping, thereby bringing its experimental realization within grasp. PMID:26979564

  12. Superconductivity in Ca-doped graphene laminates

    PubMed Central

    Chapman, J.; Su, Y.; Howard, C. A.; Kundys, D.; Grigorenko, A. N.; Guinea, F.; Geim, A. K.; Grigorieva, I. V.; Nair, R. R.

    2016-01-01

    Despite graphene’s long list of exceptional electronic properties and many theoretical predictions regarding the possibility of superconductivity in graphene, its direct and unambiguous experimental observation has not been achieved. We searched for superconductivity in weakly interacting, metal decorated graphene crystals assembled into so-called graphene laminates, consisting of well separated and electronically decoupled graphene crystallites. We report robust superconductivity in all Ca-doped graphene laminates. They become superconducting at temperatures (Tc) between ≈4 and ≈6 K, with Tc’s strongly dependent on the confinement of the Ca layer and the induced charge carrier concentration in graphene. We find that Ca is the only dopant that induces superconductivity in graphene laminates above 1.8 K among several dopants used in our experiments, such as potassium, caesium and lithium. By revealing the tunability of the superconducting response through doping and confinement of the metal layer, our work shows that achieving superconductivity in free-standing, metal decorated monolayer graphene is conditional on an optimum confinement of the metal layer and sufficient doping, thereby bringing its experimental realization within grasp. PMID:26979564

  13. Laminate articles on biaxially textured metal substrates

    DOEpatents

    Beach, David B.; Morrell, Jonathan S.; Paranthaman, Mariappan; Chirayil, Thomas; Specht, Eliot D.; Goyal, Amit

    2003-12-16

    A laminate article comprises a substrate and a biaxially textured (RE.sup.1.sub.x RE.sup.2.sub.(1-x)).sub.2 O.sub.3 buffer layer over the substrate, wherein 0laminate article can include a layer of YBCO over the (RE.sup.1.sub.x RE.sup.2.sub.(1-x)).sub.2 O.sub.3 buffer layer. A layer of CeO.sub.2 between the YBCO layer and the (RE.sup.1.sub.x RE.sup.2.sub.(1-x)).sub.2 O.sub.3 buffer can also be include. Further included can be a layer of YSZ between the CeO.sub.2 layer and the (R.sup.1.sub.x RE.sup.2.sub.(1-x)).sub.2 O.sub.3 buffer layer. The substrate can be a biaxially textured metal, such as nickel. A method of forming the laminate article is also disclosed.

  14. Downregulation of lamin A by tumor suppressor AIMP3/p18 leads to a progeroid phenotype in mice.

    PubMed

    Oh, Young Sun; Kim, Dae Gyu; Kim, Gyuyoup; Choi, Eung-Chil; Kennedy, Brian K; Suh, Yousin; Park, Bum Joon; Kim, Sunghoon

    2010-10-01

    Although AIMP3/p18 is normally associated with the macromolecular tRNA synthetase complex, recent reports have revealed a new role of AIMP3 in tumor suppression. In this study, we generated a transgenic mouse that overexpresses AIMP3 and characterized the associated phenotype in vivo and in vitro. Surprisingly, the AIMP3 transgenic mouse exhibited a progeroid phenotype, and the cells that overexpressed AIMP3 showed accelerated senescence and defects in nuclear morphology. We found that overexpression of AIMP3 resulted in proteasome-dependent degradation of mature lamin A, but not of lamin C, prelamin A, or progerin. The resulting imbalance in the protein levels of lamin A isoforms, namely altered stoichiometry of prelamin A and progerin to lamin A, appeared to be responsible for a phenotype that resembled progeria. An increase in the level of endogenous AIMP3 has been observed in aged human tissues and cells. The findings in this report suggest that AIMP3 is a specific regulator of mature lamin A and imply that enhanced expression of AIMP3 might be a factor driving cellular and/or organismal aging. PMID:20726853

  15. Homogenized Creep Behavior of CFRP Laminates at High Temperature

    NASA Astrophysics Data System (ADS)

    Fukuta, Y.; Matsuda, T.; Kawai, M.

    In this study, creep behavior of a CFRP laminate subjected to a constant stress is analyzed based on the time-dependent homogenization theory developed by the present authors. The laminate is a unidirectional carbon fiber/epoxy laminate T800H/#3631 manufactured by Toray Industries, Inc. Two kinds of creep analyses are performed. First, 45° off-axis creep deformation of the laminate at high temperature (100°C) is analyzed with three kinds of creep stress levels, respectively. It is shown that the present theory accurately predicts macroscopic creep behavior of the unidirectional CFRP laminate observed in experiments. Then, high temperature creep deformations at a constant creep stress are simulated with seven kinds of off-axis angles, i.e., θ = 0°, 10°, 30°, 45°, 60°, 75°, 90°. It is shown that the laminate has marked in-plane anisotropy with respect to the creep behavior.

  16. Processing and mechanical characterization of alumina laminates

    NASA Astrophysics Data System (ADS)

    Montgomery, John K.

    2002-08-01

    Single-phase ceramics that combine property gradients or steps in monolithic bodies are sought as alternatives to ceramic composites made of dissimilar materials. This work describes novel processing methods to produce stepped-density (or laminated) alumina single-phase bodies that maintain their mechanical integrity. One arrangement consists of a stiff, dense bulk material with a thin, flaw tolerant, porous exterior layer. Another configuration consists of a lightweight, low-density bulk material with a thin, hard, wear resistant exterior layer. Alumina laminates with strong interfaces have been successfully produced in this work using two different direct-casting processes. Gelcasting is a useful near-net shape processing technique that has been combined with several techniques, such as reaction bonding of aluminum oxide and the use of starch as a fugative filler, to successfully produced stepped-density alumina laminates. The other direct casting process that has been developed in this work is thermoreversible gelcasting (TRG). This is a reversible gelation process that has been used to produce near-net shape dense ceramic bodies. Also, individual layers can be stacked together and heated to produce laminates. Bilayer laminate samples were produced with varied thickness of porous and dense layers. It was shown that due to the difference in modulus and hardness, transverse cracking is found upon Hertzian contact when the dense layer is on the exterior. In the opposite arrangement, compacted damage zones formed in the porous material and no damage occurred in the underlying dense layer. Flaw tolerant behavior of the porous exterior/dense underlayer was examined by measuring biaxial strength as a function of Vickers indentation load. It was found that the thinnest layer of porous material results in the greatest flaw tolerance. Also, higher strength was exhibited at large indentation loads when compared to dense monoliths. The calculated stresses on the surfaces

  17. Novel origin of lamin-derived cytoplasmic intermediate filaments in tardigrades

    PubMed Central

    Hering, Lars; Bouameur, Jamal-Eddine; Reichelt, Julian; Magin, Thomas M; Mayer, Georg

    2016-01-01

    Intermediate filament (IF) proteins, including nuclear lamins and cytoplasmic IF proteins, are essential cytoskeletal components of bilaterian cells. Despite their important role in protecting tissues against mechanical force, no cytoplasmic IF proteins have been convincingly identified in arthropods. Here we show that the ancestral cytoplasmic IF protein gene was lost in the entire panarthropod (onychophoran + tardigrade + arthropod) rather than arthropod lineage and that nuclear, lamin-derived proteins instead acquired new cytoplasmic roles at least three times independently in collembolans, copepods, and tardigrades. Transcriptomic and genomic data revealed three IF protein genes in the tardigrade Hypsibius dujardini, one of which (cytotardin) occurs exclusively in the cytoplasm of epidermal and foregut epithelia, where it forms belt-like filaments around each epithelial cell. These results suggest that a lamin derivative has been co-opted to enhance tissue stability in tardigrades, a function otherwise served by cytoplasmic IF proteins in all other bilaterians. DOI: http://dx.doi.org/10.7554/eLife.11117.001 PMID:26840051

  18. In Situ Detection of Interactions Between Nuclear Envelope Proteins and Partners.

    PubMed

    Barateau, Alice; Buendia, Brigitte

    2016-01-01

    Proximity ligation assay (PLA) appears as a quick and easy technique to visualize within fixed cells the occurrence and in situ distribution of protein complexes. PLA has been validated to detect protein-protein interactions within the nuclear compartment. Here, we describe a protocol which allows the detection of interactions between A-type nuclear lamins and either LEM-domain proteins (such as emerin, integrated within the inner nuclear membrane, and LAP2α which accumulates within the nucleoplasm) or gene regulatory factors (e.g., the transcription factor SREBP1). The distinct amounts and patterns of PLA signals obtained for various complexes highlight the pertinence of using PLA to reveal in situ where and to which extent nuclear envelope proteins bind specific partners. PMID:27147040

  19. A unified theory for laminated plates

    NASA Astrophysics Data System (ADS)

    Guiamatsia Tafeuvoukeng, Irene

    A literature survey on plate and beam theories show how the advent of the finite element method and the variational method circa 1940 have been a great stimulant for the research in this field. The initial thin plate formulation has been incrementally expanded to treat the isotropic thick plate, the anisotropic single layer, and then laminated plates. It appears however that current formulations still fall into one of two categories: (1) The formulation is tailored for a specific laminate and/or loading case; (2) or the formulation is too complicated to be of practical relevance. In this work a new unifying approach to laminated plate formulation is presented. All laminated plates, including sandwich panels, subjected to any surface load and with any boundary conditions are treated within a single model. In addition, the fundamental behavior of the plate as a two-dimensional structural element is explained. The novel idea is the introduction of fundamental state solutions, which are analytical far field stress and strain solutions of the laminated plate subjected to a set of hierarchical primary loads, the fundamental loads. These loads are carefully selected to form a basis of the load space, and corresponding solutions are superposed to obtain extremely accurate predictions of the three dimensional solution. six,y,z =aklx,y sikl z where i = 1,..., 6; 1=1,...,l max is a substate of the kth fundamental state k=1,2,3,... Typically, a fundamental state solution is expressed as a through-thickness function (z), while the amplitudes of each fundamental load are found from two dimensional finite element solution as a function of in-plane coordinates (x,y). Three major contributions are produced in this work: (1) A complete calibration of the plate as a two-dimensional structure is performed with pure bending and constant shear fundamental states. (2) There are four independent ways to apply a constant shear resultant on a plate, as opposed to one for a beam. This makes

  20. Energy Saving Glass Lamination via Selective Radio-Frequency Heating

    SciTech Connect

    Shulman, Holly S.; Allan, Shawn M.

    2009-11-11

    This Inventions and Innovations program supported the technical and commercial research and development needed to elevate Ceralink's energy saving process for flat glass lamination from bench scale to a self-supporting technology with significant potential for growth. Radio-frequency heating was any un-explored option for laminating glass prior to this program. With significant commercial success through time and energy savings in the wood, paper, and plastics industries, RF heating was found to have significant promise for the energy intensive glass lamination industry. A major technical goal of the program was to demonstrate RF lamination across a wide range of laminate sizes and materials. This was successfully accomplished, dispelling many skeptics' concerns about the abilities of the technology. Ceralink laminated panels up to 2 ft x 3 ft, with four sets processed simultaneously, in a 3 minute cycle. All major categories of interlayer materials were found to work with RF lamination. In addition to laminating glass, other materials including photovoltaic silicon solar cells, light emitting diodes, metallized glass, plastics (acrylic and polycarbonate), and ceramics (alumina) were found compatible with the RF process. This opens up a wide range of commercial opportunities beyond the initially targeted automotive industry. The dramatic energy savings reported for RF lamination at the bench scale were found to be maintained through the scale up of the process. Even at 2 ft x 3 ft panel sizes, energy savings are estimated to be at least 90% compared to autoclaving or vacuum lamination. With targeted promotion through conference presentations, press releases and internet presence, RF lamination has gained significant attention, drawing large audiences at American Ceramic Society meetings. The commercialization success of the project includes the establishment of a revenue-generating business model for providing process development and demonstrations for potential RF

  1. Fracture behavior of thick, laminated graphite/epoxy composites

    NASA Technical Reports Server (NTRS)

    Harris, C. E.; Morris, D. H.

    1984-01-01

    The effect of laminate thickness on the fracture behavior of laminated graphite epoxy (T300/5208) composites was studied. The predominantly experimental research program included the study of the 0/+ or - 45/90 sub ns and 0/90 sub ns laminates with thickness of 8, 32, 64, 96 and 120 plies and the 0/+ or - 45 sub ns laminate with thickness of 6, 30, 60, 90 and 120 plies. The research concentrated on the measurement of fracture toughness utilizing the center-cracked tension, compact tension and three point bend specimen configurations. The development of subcritical damage at the crack tip was studied nondestructively using enhanced X-ray radiography and destructively using the laminate deply technique. The test results showed fracture toughness to be a function of laminate thickness. The fracture toughness of the 0 + or - 45/90 sub ns and 0/90 sub ns laminates decreased with increasing thickness and asymptotically approached lower bound values of 30 ksi square root of in. (1043 MPa square root of mm and 25 ksi square root of in (869 MPa square root of mm respectively. In contrast to the other two laminates, the fracture toughness of the 0/+ or - 45 sub ns laminate increased sharply with increasing thickness but reached an upper plateau value of 40 ksi square root of in (1390 MPa square root of mm) at 30 plies. Fracture toughness was independent of crack size for both thin and thick laminates for all three laminate types except for the 0/90 sub 2s laminate which spilt extensively. The center cracked tension, three point bend and compact tension specimens gave comparable results.

  2. Tension fatigue analysis and life prediction for composite laminates

    NASA Technical Reports Server (NTRS)

    O'Brien, T. K.; Rigamonti, M.; Zanotti, C.

    1989-01-01

    A methodology is presented for the tension fatigue analysis and life prediction of composite laminates subjected to tension fatigue loading. The methodology incorporates both the generic fracture mechanics characterization of delamination and the assessment of the infuence of damage on laminate fatigue life. Tension fatigue tests were conducted on quasi-isotropic and orthotropic glass epoxy, graphite epoxy, and glass/graphite epoxy hybrid laminates, demonstrating good agreement between measured and predicted lives.

  3. Technical specifications for the successful fabrication of laminated seismic isolation bearings

    SciTech Connect

    Kulak, R.F.

    1992-05-01

    High damping laminated elastomeric bearings are becoming one of the preferred devices for isolating large buildings and structures. IN the United States, the current reference design for the Advanced Liquid Metal Reactor uses laminated bearings for seismic isolation. These bearing are constructed from alternating layers of rubber and steel plates. They are typically designed for shear strains between 50 to 100 percent and expected to sustain two to three times these levels for beyond design basis loading considerations. The technical specifications used to procure these bearings are an important factor in assuring that the bearings that are installed under nuclear structures meet the performance requirements of the design. The key aspects of the current version of the Technical Specifications are discussed in this paper.

  4. Technical specifications for the successful fabrication of laminated seismic isolation bearings

    SciTech Connect

    Kulak, R.F.

    1992-01-01

    High damping laminated elastomeric bearings are becoming one of the preferred devices for isolating large buildings and structures. IN the United States, the current reference design for the Advanced Liquid Metal Reactor uses laminated bearings for seismic isolation. These bearing are constructed from alternating layers of rubber and steel plates. They are typically designed for shear strains between 50 to 100 percent and expected to sustain two to three times these levels for beyond design basis loading considerations. The technical specifications used to procure these bearings are an important factor in assuring that the bearings that are installed under nuclear structures meet the performance requirements of the design. The key aspects of the current version of the Technical Specifications are discussed in this paper.

  5. Impact damage resistance of thin stitched carbon/epoxy laminates

    NASA Astrophysics Data System (ADS)

    Francesconi, L.; Aymerich, F.

    2015-07-01

    The study examines the influence of through-thickness stitching on the damage response of thin cross-ply carbon/epoxy laminates subjected to low-velocity impacts. Instrumented impact tests were carried out on unstitched and polyethylene stitched laminates and the resulting damage was assessed in detail by X-radiography analyses. The results of the observations carried out during the experimental analyses are illustrated and discussed to identify the mechanical role played by through-thickness reinforcement and to highlight the influence of the laminate layup on the impact resistance of stitched laminates.

  6. Cured shape prediction of the bistable hybrid composite laminate

    NASA Astrophysics Data System (ADS)

    Dai, Fu-hong; Zhang, Bo-ming; Du, Shan-yi

    2009-07-01

    A bistable unsymmetric hybrid composite laminate with quite high stiffness and large shape change is presented. Rayleigh-Ritz method is used to predict the cured shape and the predited results agree well with the experimentals. The critical loads switching between different shapes are tested. It shows that the critical load for hybrid composite laminates increases greatly (up to 10 times) compared with the pure fiber reinforced polymer matrix composite laminates. The influence of different geometric and material properites on the bistable shape is discussed. It reveals that the present hybrid bistable laminate is more designable and miscellaneous.

  7. Sound transmission into a laminated composite cylindrical shell

    NASA Technical Reports Server (NTRS)

    Koval, L. R.

    1980-01-01

    In the context of the transmission of airborne noise into an aircraft fuselage, a mathematical model is presented for the transmission of an oblique plane sound wave into a laminated composite circular cylindrical shell. Numerical results are obtained for geometry typical of a narrow-bodied jet transport. Results indicate that from the viewpoint of noise attenuation on laminated composite shell does not appear to offer any significant advantage over an aluminum shell. However, the transmission loss of a laminated composite shell is sensitive to the orientation of the fibers and this suggests the possibility of using a laminated composite shell to tailor the noise attenuation characteristics to meet a specific need.

  8. Residual stress and crack propagation in laminated composites

    SciTech Connect

    Yttergren, R.M.F.; Zeng, K.; Rowcliffe, D.J.

    1994-12-31

    Residual stress distributions in several laminated ceramic composites were measured by an indentation technique. The material included alumina-zirconia laminated composites, containing strong interfaces, and alumina-porcelain laminated composites with both weak and strong interfaces. The residual stress in these material originates from the mismatch of the thermal properties, differences in elastic properties, and different shrinkage of the laminates during sintering. An experimental technique is presented which gives a direct view of the residual stress state in the materials. Values of residual tensile stress are presented as a function of position relative to the interface in each material.

  9. The Displacement Perspective During Ultimate Failure of Composite Laminates

    NASA Astrophysics Data System (ADS)

    Pal, P.; Bhar, A.

    2013-04-01

    This paper deals with the studies on the state of displacement of symmetric and anti-symmetric angle-ply and cross-ply laminated composite plates during its ultimate failure, subjected to transverse static load. First-order shear deformation theory (FSDT) is employed in conjunction with the finite element approach using eight-noded quadratic isoparametric element. The free vibration analyses of isotropic and laminated composite plates are carried out to ensure the overall validity of the present finite element formulation. The mid surface of the laminate is considered as the reference plane. The principal material directions in different laminae are oriented to produce a laminated structural element capable of resisting loads in several directions. The stiffness of a composite laminate is obtained from the properties of the constituent laminae. The affected stiffness of the failed lamina is discarded completely after the failure of weakest ply. The rigidity matrix of the laminate with remaining laminae is re-established. The re-evaluation process continues until the laminate fails completely. To investigate the displacement behaviour of laminates during the ultimate failure, parametric studies are carried out for different cases by varying the stacking sequences, fiber orientations, layer thicknesses, aspect ratios and the number of layers in the laminate. The comparison of results in terms of non-dimensional natural frequencies and ply-by-ply failure analyses obtained from the present investigation are made with those available in the reported literature.

  10. Extrinsic fracture mechanisms in two laminated metal composites

    SciTech Connect

    Lesuer, D.; Syn, C.; Riddle, R.; Sherby, O.

    1994-11-29

    The crack growth behavior and fracture toughness of two laminated metal composites (6090/SiC/25p laminated with 5182 and ultrahigh-carbon steel laminated with brass) have been studied in both ``crack arrester`` and ``crack divider`` orientations. The mechanisms of crack growth were analyzed and extrinsic toughening mechanisms were found to contribute significantly to the toughness. The influence of laminate architecture (layer thickness and component volume function), component material properties and residual stress on these mechanisms and the resulting crack growth resistance are discussed.

  11. The innate immunity adaptor SARM translocates to the nucleus to stabilize lamins and prevent DNA fragmentation in response to pro-apoptotic signaling.

    PubMed

    Sethman, Chad R; Hawiger, Jacek

    2013-01-01

    Sterile alpha and armadillo-motif containing protein (SARM), a highly conserved and structurally unique member of the MyD88 family of Toll-like receptor adaptors, plays an important role in innate immunity signaling and apoptosis. Its exact mechanism of intracellular action remains unclear. Apoptosis is an ancient and ubiquitous process of programmed cell death that results in disruption of the nuclear lamina and, ultimately, dismantling of the nucleus. In addition to supporting the nuclear membrane, lamins serve important roles in chromatin organization, epigenetic regulation, transcription, nuclear transport, and mitosis. Mutations and other damage that destabilize nuclear lamins (laminopathies) underlie a number of intractable human diseases. Here, we report that SARM translocates to the nucleus of human embryonic kidney cells by using its amino-terminal Armadillo repeat region. Within the nucleus, SARM forms a previously unreported lattice akin to the nuclear lamina scaffold. Moreover, we show that SARM protects lamins from apoptotic degradation and reduces internucleosomal DNA fragmentation in response to signaling induced by the proinflammatory cytokine Tumor Necrosis Factor alpha. These findings indicate an important link between the innate immunity adaptor SARM and stabilization of nuclear lamins during inflammation-driven apoptosis in human cells. PMID:23923041

  12. 78 FR 48903 - Certain Products Having Laminated Packaging, Laminated Packaging, and Components Thereof...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-12

    ... infringement of certain claims of nine patents. 78 FR 19,007. The subject products are certain laminated... industry requirement.'' 78 FR 19,008. The ALJ conducted a hearing on the domestic-industry issue on May 16... the complainant did not satisfy the economic prong of the domestic industry requirement. On...

  13. Micromechanics of composite laminate compression failures

    NASA Technical Reports Server (NTRS)

    Guynn, E. Gail; Bradley, Walter L.

    1988-01-01

    The purpose of this annual progress report is to summarize the work effort and results accomplished from July 1987 through July 1988 on NASA Research Grant NAG1-659 entitled Micromechanics of Composite Laminate Compressive Failure. The report contains: (1) the objective of the proposed research, (2) the summary of accomplishments, (3) a more extensive review of compression literature, (4) the planned material (and corresponding properties) received to date, (5) the results for three possible specimen geometries, experimental procedures planned, and current status of the experiments, and (6) the work planned for the next contract year.

  14. Strength of composite laminates under biaxial loads

    NASA Astrophysics Data System (ADS)

    Hinton, M. J.; Soden, P. D.; Kaddour, A. S.

    1996-05-01

    Five well known failure criteria and one simple progressive model have been used in conjunction with laminate theory, which allows for nonlinear lamina shear behaviour, to predict the initial and final failure strengths of filament wound composite tubes. The predictions have been compared with experimental leakage and fracture stresses for ±75°, ±55° and ±45° filament wound GRP tubes subjected to a wide range of biaxial stress systems including biaxial compression. In some cases the fracture strengths were a factor of 10 higher than the initial failure predictions. The simple progressive failure theory predictions gave the best agreement with the experimental results.

  15. Laminated anisotropic reinforced plastic plates and shells

    NASA Technical Reports Server (NTRS)

    Korolev, V. I.

    1981-01-01

    Basic technical theories and engineering calculation equations for anisotropic plates and shells made of rigid reinforced plastics, mainly laminated fiberglass, are presented and discussed. Solutions are given for many problems of design of structural plates and shells, including curved sections and tanks, as well as two chapters on selection of the optimum materials, are given. Accounting for interlayer shearing and transverse separation, which are new engineering properties, are discussed. Application of the results obtained to thin three ply plates and shells wth a light elastic filler is presented and discussed.

  16. Fabrication of Multi-Ply Birefringent Fibrous Composite Laminates

    NASA Technical Reports Server (NTRS)

    Daniel, I.; Niiro, T.

    1984-01-01

    Fabrication method produces unidirectional, multi-ply, transparent birefringent fibrous composite laminates for use in macromechanical stress analysis conducted by means of anisotropic photoelasticity. New laminates glass-fiber-reinforced plastics for which matrix and fibers have same index of refraction. Method utilized in structural applications of composites.

  17. Buckling of angle-ply laminated circular cylindrical shells

    NASA Technical Reports Server (NTRS)

    Hirano, Y.

    1979-01-01

    This note presents closed-form solutions for axisymmetrical and axially unsymmetrical buckling of angle-ply laminated circular cylindrical shells under axial compression. The axisymmetrical and axially unsymmetrical buckling stress are found to be different from each other, and the best lamination angles which give the highest buckling stress are obtained.

  18. Self-heating forecasting for thick laminate specimens in fatigue

    NASA Astrophysics Data System (ADS)

    Lahuerta, F.; Westphal, T.; Nijssen, R. P. L.

    2014-12-01

    Thick laminate sections can be found from the tip to the root in most common wind turbine blade designs. Obtaining accurate and reliable design data for thick laminates is subject of investigations, which include experiments on thick laminate coupons. Due to the poor thermal conductivity properties of composites and the material self-heating that occurs during the fatigue loading, high temperature gradients may appear through the laminate thickness. In the case of thick laminates in high load regimes, the core temperature might influence the mechanical properties, leading to premature failures. In the present work a method to forecast the self-heating of thick laminates in fatigue loading is presented. The mechanical loading is related with the laminate self-heating, via the cyclic strain energy and the energy loss ratio. Based on this internal volumetric heat load a thermal model is built and solved to obtain the temperature distribution in the transient state. Based on experimental measurements of the energy loss factor for 10mm thick coupons, the method is described and the resulting predictions are compared with experimental surface temperature measurements on 10 and 30mm UD thick laminate specimens.

  19. Hole-thru-laminate mounting supports for photovoltaic modules

    SciTech Connect

    Wexler, Jason; Botkin, Jonathan; Culligan, Matthew; Detrick, Adam

    2015-02-17

    A mounting support for a photovoltaic module is described. The mounting support includes a pedestal having a surface adaptable to receive a flat side of a photovoltaic module laminate. A hole is disposed in the pedestal, the hole adaptable to receive a bolt or a pin used to couple the pedestal to the flat side of the photovoltaic module laminate.

  20. Stress concentration factors around a circular hole in laminated composites

    NASA Technical Reports Server (NTRS)

    Ueng, C. E. S.

    1976-01-01

    Stress concentration factors around a circular hole in a composite laminate are determined. The specific case investigated is a four layer (-45/45/45/-45 degs) graphite epoxy laminate. The factors are determined experimentally by means of electrical resistance strain gages, and analytically by using a hybrid finite element analysis.

  1. A MEMS lamination technology based on sequential multilayer electrodeposition

    SciTech Connect

    Kim, M; Kim, J; Herrault, F; Schafer, R; Allen, MG

    2013-08-06

    A MEMS lamination technology based on sequential multilayer electrodeposition is presented. The process comprises three main steps: (1) automated sequential electrodeposition of permalloy (Ni80Fe20) structural and copper sacrificial layers to form multilayer structures of significant total thickness; (2) fabrication of polymeric anchor structures through the thickness of the multilayer structures and (3) selective removal of copper. The resulting structure is a set of air-insulated permalloy laminations, the separation of which is sustained by insulating polymeric anchor structures. Individual laminations have precisely controllable thicknesses ranging from 500 nm to 5 mu m, and each lamination layer is electrically isolated from adjacent layers by narrow air gaps of similar scale. In addition to air, interlamination insulators based on polymers are investigated. Interlamination air gaps with very high aspect ratio (>1:100) can be filled with polyvinylalcohol and polydimethylsiloxane. The laminated structures are characterized using scanning electron microscopy and atomic force microscopy to directly examine properties such as the roughness and the thickness uniformity of the layers. In addition, the quality of the electrical insulation between the laminations is evaluated by quantifying the eddy current within the sample as a function of frequency. Fabricated laminations are comprised of uniform, smooth (surface roughness < 100 nm) layers with effective electrical insulation for all layer thicknesses and insulator approaches studied. Such highly laminated structures have potential uses ranging from energy conversion to applications where composite materials with highly anisotropic mechanical or thermal properties are required.

  2. A Laminated Track for the Inductrack System: Theory and Experiment

    SciTech Connect

    Post, R F; Hoburg, J F

    2004-01-12

    A laminated structure, composed of stacks of thin conducting sheets, has several advantages over a litz-wire ladder as the ''track'' wherein levitating currents are induced by a permanent magnet array on a moving vehicle. Modeling and experimental results for the laminated track are described and evaluated in this paper.

  3. Better Thermal Insulation in Solar-Array Laminators

    NASA Technical Reports Server (NTRS)

    Burger, D. R.; Knox, J. F.

    1984-01-01

    Glass marbles improve temperature control. Modified vacuum laminator for photovoltaic solar arrays includes thermal insulation made of conventional glass marbles. Marbles serve as insulation for temperature control of lamination process at cure temperatures as high as 350 degrees F. Used to replace original insulation made of asbestos cement.

  4. Lamin B Receptor Recognizes Specific Modifications of Histone H4 in Heterochromatin Formation*

    PubMed Central

    Hirano, Yasuhiro; Hizume, Kohji; Kimura, Hiroshi; Takeyasu, Kunio; Haraguchi, Tokuko; Hiraoka, Yasushi

    2012-01-01

    Inner nuclear membrane proteins provide a structural framework for chromatin, modulating transcription beneath the nuclear envelope. Lamin B receptor (LBR) is a classical inner nuclear membrane protein that associates with heterochromatin, and its mutations are known to cause Pelger-Huët anomaly in humans. However, the mechanisms by which LBR organizes heterochromatin remain to be elucidated. Here, we show that LBR represses transcription by binding to chromatin regions that are marked by specific histone modifications. The tudor domain (residues 1–62) of LBR primarily recognizes histone H4 lysine 20 dimethylation and is essential for chromatin compaction, whereas the whole nucleoplasmic region (residues 1–211) is required for transcriptional repression. We propose a model in which the nucleoplasmic domain of LBR tethers epigenetically marked chromatin to the nuclear envelope and transcriptional repressors are loaded onto the chromatin through their interaction with LBR. PMID:23100253

  5. The strength of laminated composite materials under repeated impact loading

    NASA Technical Reports Server (NTRS)

    Rotem, Assa

    1988-01-01

    When low velocity and energy impact is exerted on a laminated composite material, in a perpendicular direction to the plane of the laminate, invisible damage may develop. It is shown analytically and experimentally that the invisible damage occurs during the first stage of contact between the impactor and the laminate and is a result of the contact stresses. However, the residual flexural strength changes only slightly, because it depends mainly on the outer layers, and these remain undamaged. Repeated impact intensifies the damage inside the laminate and causes larger bending under equivalent impact load. Finally, when the damage is most severe, even though it is still invisible, the laminate fails because of bending on the tension side. If the repeated impact is halted before final fracture occurs the residual strength and modulus would decrease by a certain amount.

  6. Deposition of laminated shale: A field and experimental study

    NASA Astrophysics Data System (ADS)

    Carey, Daniel L.; Roy, David C.

    1985-03-01

    Intermittently laminated shale of the Jemtland Formation in Maine is characterized by thin lenticular silt segregations interlaced with argillaceous and organic material (including graptolites). This shale is thinly interbedded with nonlaminated shale, siltstone, and thicker turbidite graywacke beds. Experiments suggest that the intermittently laminated shale was deposited by silt/clay-laden currents and may have been part of an upward turbidite progression from parallel-laminated silt (>60% silt), through intermittently laminated mud (40 to 60% silt), to nonlaminated mud (20 to 40% silt). Intermittently laminated mud may be produced from silt/clay flows that are: decelerating at a constant silt content, losing silt at constant velocity; or both decelerating and losing silt.

  7. Matrix cracking in laminated composites under monotonic and cyclic loadings

    NASA Technical Reports Server (NTRS)

    Allen, David H.; Lee, Jong-Won

    1991-01-01

    An analytical model based on the internal state variable (ISV) concept and the strain energy method is proposed for characterizing the monotonic and cyclic response of laminated composites containing matrix cracks. A modified constitution is formulated for angle-ply laminates under general in-plane mechanical loading and constant temperature change. A monotonic matrix cracking criterion is developed for predicting the crack density in cross-ply laminates as a function of the applied laminate axial stress. An initial formulation for a cyclic matrix cracking criterion for cross-ply laminates is also discussed. For the monotonic loading case, a number of experimental data and well-known models are compared with the present study for validating the practical applicability of the ISV approach.

  8. Near-threshold fatigue crack growth in aluminum composite laminates

    SciTech Connect

    Hoffman, P.B.; Gibeling, J.C.

    1995-03-15

    One promising method for improving the mechanical properties of particulate MMCs is to laminate the brittle composite with a more ductile component. A system currently being developed at Lawrence Livermore National Laboratory (LLNL) is a multilayer laminate consisting of alternating layers of AA6090/SiC/25p and more ductile AA5182. In order to further examine the effects of lamination on fatigue crack propagation mechanics and mechanisms, the fatigue crack growth behavior of the aluminum composite laminate developed at LLNL was examined. The laminate and the AA6090/SiC/25p component were studied in the T6 heat treatment condition for subsequent comparison. Fatigue crack surfaces were examined using scanning electron microscopy for further insight into crack growth mechanisms.

  9. Vibration suppression of composite laminated plate with nonlinear energy sink

    NASA Astrophysics Data System (ADS)

    Zhang, Ye-Wei; Zhang, Hao; Hou, Shuai; Xu, Ke-Fan; Chen, Li-Qun

    2016-06-01

    The composite laminated plate is widely used in supersonic aircraft. So, there are many researches about the vibration suppression of composite laminated plate. In this paper, nonlinear energy sink (NES) as an effective method to suppress vibration is studied. The coupled partial differential governing equations of the composite laminated plate with the nonlinear energy sink (NES) are established by using the Hamilton principle. The fourth-order Galerkin discrete method is used to truncate the partial differential equations, which are solved by numerical integration method. Meanwhile study about the precise effectiveness of the nonlinear energy sink (NES) by discussing the different installation location of the nonlinear energy sink (NES) at the same speed. The results indicate that the nonlinear energy sink (NES) can significantly suppress the severe vibration of the composite laminated plate with speed wind loadings in to protect the composite laminated plate from excessive vibration.

  10. Free Vibration of Uncertain Unsymmetrically Laminated Beams

    NASA Technical Reports Server (NTRS)

    Kapania, Rakesh K.; Goyal, Vijay K.

    2001-01-01

    Monte Carlo Simulation and Stochastic FEA are used to predict randomness in the free vibration response of thin unsymmetrically laminated beams. For the present study, it is assumed that randomness in the response is only caused by uncertainties in the ply orientations. The ply orientations may become random or uncertain during the manufacturing process. A new 16-dof beam element, based on the first-order shear deformation beam theory, is used to study the stochastic nature of the natural frequencies. Using variational principles, the element stiffness matrix and mass matrix are obtained through analytical integration. Using a random sequence a large data set is generated, containing possible random ply-orientations. This data is assumed to be symmetric. The stochastic-based finite element model for free vibrations predicts the relation between the randomness in fundamental natural frequencies and the randomness in ply-orientation. The sensitivity derivatives are calculated numerically through an exact formulation. The squared fundamental natural frequencies are expressed in terms of deterministic and probabilistic quantities, allowing to determine how sensitive they are to variations in ply angles. The predicted mean-valued fundamental natural frequency squared and the variance of the present model are in good agreement with Monte Carlo Simulation. Results, also, show that variations between plus or minus 5 degrees in ply-angles can affect free vibration response of unsymmetrically and symmetrically laminated beams.

  11. Hygrothermally stable laminated composites with optimal coupling

    NASA Astrophysics Data System (ADS)

    Haynes, Robert Andrew

    This work begins by establishing the necessary and sufficient conditions for hygrothermal stability of composite laminates. An investigation is performed into the range of coupling achievable from within all hygrothermally stable families. The minimum number of plies required to create an asymmetric hygrothermally stable stacking sequence is found to be five. Next, a rigorous and general approach for determining designs corresponding to optimal levels of coupling is established through the use of a constrained optimization procedure. Couplings investigated include extension-twist, bend-twist, extension-bend, shear-twist, and anticlastic. For extension-twist and bend-twist coupling, specimens from five- through ten-ply laminates are manufactured and tested to demonstrate hygrothermal stability and achievable levels of coupling. Nonlinear models and finite element analysis are developed, and predictions are verified through comparison with test results. Sensitivity analyses are performed to demonstrate the robustness of the hygrothermal stability and couplings to deviations in ply angle, typical of manufacturing tolerances. Comparisons are made with current state-of-the-art suboptimal layups, and significant increases in coupling over previously known levels are demonstrated.

  12. Laminated ceramic components for microfluidic applications

    NASA Astrophysics Data System (ADS)

    Matson, Dean W.; Martin, Peter M.; Bennett, Wendy D.; Stewart, Donald C.; Bonham, Charles C.

    1999-08-01

    Applications for micro fluidic components continue to expand as the benefits resulting from the small volumes and light weight of such devices are recognized. Such benefits are particularly attractive for man-portable and automotive devices where reduction of weight is critical. As applications expand, so too does the need for the development of methods for producing micro fluidic components from unconventional materials (i.e., materials other than silicon). At the Pacific Northwest National Laboratory, we are currently developing processes for producing laminated multilevel ceramic components containing microchannel features that will find applications in micro fluidic chemical processing and energy management systems. Thin layers of green ceramic tape are patterned with micro fluidic flow features using one of a number of cutting processes. The patterned layers are then stacked and laminated with other layers of green tape, ceramic plate, or other materials using a series of processing steps. The resulting monolithic, leak-tight micro fluidic ceramic components are capable of tolerating high temperature or chemically corrosive environments. Fabrication issues associated with the use of the green ceramic tape for this type of application will be discussed, and examples of test components produced using these processes will be presented.

  13. Development of a heterogeneous laminating resin system

    NASA Technical Reports Server (NTRS)

    Biermann, T. F.; Hopper, L. C.

    1985-01-01

    The factors which effect the impact resistance of laminating resin systems and yet retain equivalent performance with the conventional 450 K curing epoxy matrix systems in other areas were studied. Formulation work was conducted on two systems, an all-epoxy and an epoxy/bismaleimide, to gain fundamental information on the effect formulation changes have upon neat resin and composite properties. The all-epoxy work involved formulations with various amounts and combinations of eight different epoxy resins, four different hardeners, fifteen different toughening agents, a filler, and a catalyst. The epoxy/bismaleimide effort improved formulations with various amounts and combinations of nine different resins, four different hardeners, eight different toughening agents, four different catalysts, and a filler. When a formulation appeared to offer the proper combination of properties required for a laminating resin Celion 3K-70P fabric was prepregged. Initial screening tests on composites primarily involved Gardner type impact and measurement of short beam shear strengths under dry and hot/wet conditions.

  14. Magnetic sheet steel lamination detection, phase 1

    NASA Astrophysics Data System (ADS)

    Carignan, F. J.; Syniuta, W. D.

    1980-08-01

    Research to assess the feasibility of a nondestructive magnetic inspection technique for detecting defective sheet steel is reported. A major problem in the deep drawing and stamping industry is the failure of sheet steel due to laminations which occur when the steel is formed into various shapes or processed further. A continuous nondestructive testing method was developed based upon differences in magnetic properties of acceptable steel and defective steel. The technique assumes an increase in the magnetic hardness of the defect compared to the base material. Experimental results obtained with the artificial flaw demonstrate that it is possible to sense magnetic differences in sheet steel if the differences are large enough. However, as the differences in magnetic hardness diminish, or where thin surface defects or internal laminations occur, detection becomes increasingly difficult. Moreoever, it has not been established that all sheet steel defects are magnetically harder than unflawed material. It was concluded that the technique, which can detect only some flaws and is incapable of detecting many important defects, would be only marginally useful.

  15. Geometrically nonlinear behavior of piezoelectric laminated plates

    NASA Astrophysics Data System (ADS)

    Rabinovitch, Oded

    2005-08-01

    The geometrically nonlinear behavior of piezo-laminated plates actuated with isotropic or anisotropic piezoelectric layers is analytically investigated. The analytical model is derived using the variational principle of virtual work along with the lamination and plate theories, the von Karman large displacement and moderate rotation kinematic relations, and the anisotropic piezoelectric constitutive laws. A solution strategy that combines the approach of the method of lines, the advantages of the finite element concept, and the variational formulation is developed. This approach yields a set of nonlinear ordinary differential equations with nonlinear boundary conditions, which are solved using the multiple-shooting method. Convergence and verification of the model are examined through comparison with linear and nonlinear results of other approximation methods. The nonlinear response of two active plate structures is investigated numerically. The first plate is actuated in bending using monolithic piezoceramic layers and the second one is actuated in twist using macro-fiber composites. The results quantitatively reveal the complicated in-plane stress state associated with the piezoelectric actuation and the geometrically nonlinear coupling of the in-plane and out-of-plane responses of the plate. The influence of the nonlinear effects ranges from significant stiffening in certain combinations of electrical loads and boundary conditions to amplifications of the induced deflections in others. The paper closes with a summary and conclusions.

  16. Bending analysis of laminated composite box beams

    SciTech Connect

    Tripathy, A.K.; Patel, H.J.; Pang, S.S. . Dept. of Mechanical Engineering)

    1994-01-01

    Box beams are widely used in weight reduction structures such as aircraft wings. The use of composite box beams further reduces the weight factor for such structures with the same deflection and stress as that of isotropic box beams. The difference in the behavior of composite box beam with different fiber orientation, number of plies, and number of stringers also provides a wide range of designing parameters to achieve the required performance for a given problem. A bending analysis has been carried out for the study of deflections and stresses for box beams of different material (isotropic and laminated composites), size, and number of stringers subjected to different kinds of loading conditions. A finite element model has been developed based on the strain energy principle, and the results are compared with an available commercial code COSMOS/M.'' Experiments using aluminum and scotchply composite laminates were conducted to verify the results. An optimal design for size and number of stiffeners for a given loading condition has been achieved. Investigations have also been carried out to find the effect of transverse shear on the span-wise normal stress.

  17. Nuclear envelope: positioning nuclei and organizing synapses

    PubMed Central

    Razafsky, David; Hodzic, Didier

    2015-01-01

    The nuclear envelope plays an essential role in nuclear positioning within cells and tissues. This review highlights advances in understanding the mechanisms of nuclear positioning during skeletal muscle and central nervous system development. New findings, particularly about Atype lamins and Nesprin1, may link nuclear envelope integrity to synaptic integrity. Thus synaptic defects, rather than nuclear mispositioning, may underlie human pathologies associated with mutations of nuclear envelope proteins. PMID:26079712

  18. Buckling analysis of laminated thin shells in a hot environment

    NASA Technical Reports Server (NTRS)

    Gotsis, Pascal K.; Guptil, James D.

    1993-01-01

    Results are presented of parametric studies to assess the effects of various parameters on the buckling behavior of angle-ply, laminated thin shells in a hot environment. These results were obtained by using a three-dimensional finite element analysis. An angle-ply, laminated thin shell with fiber orientation of (theta/-theta)(sub 2) was subjected to compressive mechanical loads. The laminated thin shell had a cylindrical geometry. The laminate contained T300 graphite fibers embedded in an intermediate-modulus, high-strength (IMHS) matrix. The fiber volume fraction was 55 percent and the moisture content was 2 percent. The residual stresses induced into the laminate structure during the curing were taken into account. Parametric studies were performed to examine the effect on the critical buckling load of the following parameters: cylinder length and thickness, internal hydrostatic pressure, different ply thicknesses, different temperature profiles through the thickness of the structure, and different lay up configurations and fiber volume fractions. In conjunction with these parameters the ply orientation was varied from 0 deg to 90 deg. Seven ply angles were examined: 0 deg, 15 deg, 30 deg, 45 deg, 60 deg, 75 deg, and 90 deg. The results show that the ply angle theta and the laminate thickness had significant effects on the critical buckling load. The fiber volume fraction, the fiber orientations, and the internal hydrostatic pressure had important effects on the critical buckling load. The cylinder length had a moderate influence on the buckling load. The thin shell with (theta/-theta)(sub 2) or (theta/-theta)(sub s) angle-ply laminate had better buckling-load performance than the thin shell with (theta)(sub 4) angle-ply laminate. The temperature profiles through the laminate thickness and various laminates with the different ply thicknesses has insignificant effects on the buckling behavior of the thin shells.

  19. Laminated wave turbulence: Generic algorithms iii

    NASA Astrophysics Data System (ADS)

    Kartashova, Elena; Kartashov, Alexey

    2007-07-01

    Model of laminated wave turbulence allows to study statistical and discrete layers of turbulence in the frame of the same model. Statistical layer is described by Zakharov-Kolmogorov energy spectra in the case of irrational enough dispersion function. Discrete layer is covered by some system(s) of Diophantine equations while their form is determined by wave dispersion function. This presents a very special computational challenge to solve Diophantine equations in many variables, usually 6 to 8, in high degrees, say 16, in integers of order 1016 and more. Generic algorithms for solving this problem in the case of irrational dispersion function have been presented in our previous papers (corresponds to many types of water waves). In this paper, we present a new algorithm for the case of rational dispersion functions (atmospheric planetary waves, drift waves, etc.)

  20. Eddy current losses in ferromagnetic laminations

    SciTech Connect

    Serpico, C.; Visone, C.; Mayergoyz, I. D.; Basso, V.; Miano, G.

    2000-05-01

    It is demonstrated through the comparison of analytical, numerical, and experimental results that the existence of excess eddy current losses can be explained by the peculiar nature of the nonlinear diffusion of electromagnetic fields in magnetically nonlinear laminations. The essence of this peculiar nature is that nonlinear diffusion occurs as inward progress of almost rectangular profiles of magnetic flux density of variable height. Approximating actual profiles of magnetic flux density by rectangular ones, the problem of nonlinear diffusion can be treated analytically by using a simple model. The accuracy and the limit of applicability of the rectangular profile model are discussed by comparing its predictions with finite elements numerical solutions of nonlinear diffusion equation as well as with experimental results. (c) 2000 American Institute of Physics.

  1. Reliability analysis of ceramic matrix composite laminates

    NASA Technical Reports Server (NTRS)

    Thomas, David J.; Wetherhold, Robert C.

    1991-01-01

    At a macroscopic level, a composite lamina may be considered as a homogeneous orthotropic solid whose directional strengths are random variables. Incorporation of these random variable strengths into failure models, either interactive or non-interactive, allows for the evaluation of the lamina reliability under a given stress state. Using a non-interactive criterion for demonstration purposes, laminate reliabilities are calculated assuming previously established load sharing rules for the redistribution of load as the failure of laminae occur. The matrix cracking predicted by ACK theory is modeled to allow a loss of stiffness in the fiber direction. The subsequent failure in the fiber direction is controlled by a modified bundle theory. Results using this modified bundle model are compared with previous models which did not permit separate consideration of matrix cracking, as well as to results obtained from experimental data.

  2. Compression failure of angle-ply laminates

    NASA Technical Reports Server (NTRS)

    Peel, L. D.; Hyer, M. W.; Shuart, M. J.

    1992-01-01

    Test results from the compression loading of (+ or - Theta/ - or + Theta)(sub 6s) angle-ply IM7-8551-7a specimens, 0 less than or = Theta less than or = 90 degs, are presented. The observed failure strengths and modes are discussed, and typical stress-strain relations shown. Using classical lamination theory and the maximum stress criterion, an attempt is made to predict failure stress as a function of Theta. This attempt results in poor correlation with test results and thus a more advanced model is used. The model, which is based on a geometrically nonlinear theory, and which was taken from previous work, includes the influence of observed layer waviness. The waviness is described by the wave length and the wave amplitude. The theory is briefly described and results from the theory are correlated with test results. It is shown that by using levels of waviness observed in the specimens, the correlation between predictions and observations is good.

  3. Impact resistance of composite laminated sandwich plates

    NASA Astrophysics Data System (ADS)

    Kim, Chun-Gon; Jun, Eui-Jin

    1992-01-01

    Investigated are the effects of face layup sequence and core density of a sandwich plate on the impact delamination area of the laminated facesheet. The sandwich plate is made of graphite/epoxy faces and Nomex honeycomb core. The size and shape of delamination due to impact at each interply location have been measured by the room temperature deply technique. The shape of the interply delamination under impact is, in general, found to be two-lobed. The shape exhibits very peculiar regularity under various experimental conditions. The quantitative measurement of delamination size has shown that the face layup with small relative orientation between adjacent plies and high density core are desirable in sandwich plates to reduce the impact delamination.

  4. Development of a Heterogeneous Laminating Resin

    NASA Technical Reports Server (NTRS)

    Gosnell, R.

    1984-01-01

    The feasibility of toughening the common types of matrix resins such as Narmco 5208 by utilizing a heterogeneous additive was examined. Some basic concepts and principles in the toughening of matrix resins for advanced composites were studied. The following conclusions were advanced: (1) the use of damage volume as a guide for measurement of impact resistance appears to be a valid determination; (2) short beam shear is a good test to determine the effect of toughening agents on mechanical properties; (3) rubber toughening results in improved laminate impact strength, but with substantial loss in high temperature dry and wet strength; (4) in the all-epoxy systems, the polycarbonate toughening agent seemed to be the most effective, although hot-wet strength is sacrificed; ABS was not as effective; and (5) in general, the toughened all-epoxy systems showed better damage tolerance, but less hot-wet strength; toughened bismaleimides had better hot-wet strength.

  5. Permeability After Impact Testing of Composite Laminates

    NASA Technical Reports Server (NTRS)

    Nettles, Alan T.

    2003-01-01

    Since composite laminates are beginning to be identified for use in reusable launch vehicle propulsion systems, an understanding of their permeance is needed. A foreign object impact event can cause a localized area of permeability (leakage) in a polymer matrix composite and it is the aim of this study to assess a method of quantifying permeability-after-impact results. A simple test apparatus is presented and variables that could affect the measured values of permeability-after-impact were assessed. Once it was determined that valid numbers were being measured, a fiber/resin system was impacted at various impact levels and the resulting permeability measured, first with a leak check solution (qualitative) then using the new apparatus (quantitative). The results showed that as the impact level increased, so did the measured leakage. As the pressure to the specimen was increased, the leak rate was seen to increase in a non-linear fashion for almost all of the specimens tested.

  6. Permeability After Impact Testing of Composite Laminates

    NASA Technical Reports Server (NTRS)

    Nettles, A.T.; Munafo, Paul (Technical Monitor)

    2002-01-01

    Since composite laminates are beginning to be identified for use in reusable launch vehicle propulsion systems, an understanding of their permeance is needed. A foreign object impact event can cause a localized area of permeability (leakage) in a polymer matrix composite and it is the aim of this study to assess a method of quantifying permeability-after-impact results. A simple test apparatus is presented and variables that could affect the measured values of permeability-after-impact were assessed. Once it was determined that valid numbers were being measured, a fiber/resin system was impacted at various impact levels and the resulting permeability measured, first with a leak check solution (qualitative) then using the new apparatus (quantitative). The results showed that as the impact level increased, so did the measured leakage. As the pressure to the specimen was increased, the leak rate was seen to increase in a non-linear fashion for almost all of the specimens tested.

  7. Analysis of "Kiss" Bonds Between Composite Laminates

    NASA Astrophysics Data System (ADS)

    Poveromo, Scott L.; Earthman, James C.

    2014-06-01

    One of the leading challenges to designing lightweight, cost-effective bonded structures is to detect low shear strength "kiss" bonds where no other defects such as voids and cracks exist. To develop a nondestructive testing method that is sensitive to kiss bonds, standards need to be fabricated with known strength values. In the current work, we attempt to create kiss bonds in between carbon fiber composite laminates that have been bonded with epoxy film adhesive and epoxy paste adhesive. Based on ultrasonic testing, when creating true kiss bonds using film adhesives, a complete disbond could not be avoided because of thermally induced stresses during the high-temperature cure. However, further work demonstrated that kiss bonds can be formed using room-temperature curable epoxy paste adhesives by creating an amine blush on the epoxy surface or applying a release agent on the bonding surfaces.

  8. Micromechanics of composite laminate compression failure

    NASA Technical Reports Server (NTRS)

    Guynn, E. Gail; Bradley, Walter L.

    1986-01-01

    The Dugdale analysis for metals loaded in tension was adapted to model the failure of notched composite laminates loaded in compression. Compression testing details, MTS alignment verification, and equipment needs were resolved. Thus far, only 2 ductile material systems, HST7 and F155, were selected for study. A Wild M8 Zoom Stereomicroscope and necessary attachments for video taping and 35 mm pictures were purchased. Currently, this compression test system is fully operational. A specimen is loaded in compression, and load vs shear-crippling zone size is monitored and recorded. Data from initial compression tests indicate that the Dugdale model does not accurately predict the load vs damage zone size relationship of notched composite specimens loaded in compression.

  9. Nuclear reactor safety device

    DOEpatents

    Hutter, E.

    1983-08-15

    A safety device is described for use in a nuclear reactor for axially repositioning a control rod with respect to the reactor core in the event of a thermal excursion. It comprises a laminated strip helically configured to form a tube, said tube being in operative relation to said control rod. The laminated strip is formed of at least two materials having different thermal coefficients of expansion, and is helically configured such that the material forming the outer lamina of the tube has a greater thermal coefficient of expansion than the material forming the inner lamina of said tube. In the event of a thermal excursion the laminated strip will tend to curl inwardly so that said tube will increase in length, whereby as said tube increases in length it exerts a force on said control rod to axially reposition said control rod with respect to said core.

  10. Nuclear reactor safety device

    DOEpatents

    Hutter, Ernest

    1986-01-01

    A safety device is disclosed for use in a nuclear reactor for axially repositioning a control rod with respect to the reactor core in the event of an upward thermal excursion. Such safety device comprises a laminated helical ribbon configured as a tube-like helical coil having contiguous helical turns with slidably abutting edges. The helical coil is disclosed as a portion of a drive member connected axially to the control rod. The laminated ribbon is formed of outer and inner laminae. The material of the outer lamina has a greater thermal coefficient of expansion than the material of the inner lamina. In the event of an upward thermal excursion, the laminated helical coil curls inwardly to a smaller diameter. Such inward curling causes the total length of the helical coil to increase by a substantial increment, so that the control rod is axially repositioned by a corresponding amount to reduce the power output of the reactor.

  11. Body fat distribution in women with familial partial lipodystrophy caused by mutation in the lamin A/C gene

    PubMed Central

    Monteiro, Luciana Z.; Foss-Freitas, Maria C.; Júnior Montenegro, Renan M.; Foss, Milton C.

    2012-01-01

    Familial partial lipodystrophy (FPLD), Dunnigan variety, is an autosomal dominant disorder caused due to missense mutations in the lamin A/C (LMNA) gene encoding nuclear lamina proteins. Patients with FPLD are predisposed to metabolic complications of insulin resistance such as diabetes. We sought to evaluate and compare body fat distribution with dual-emission X-ray absorptiometry in women with and without FPLD and identify densitometric, clinical and metabolic features. PMID:22276265

  12. Analysis of a hybrid, unidirectional buffer strip laminate

    NASA Technical Reports Server (NTRS)

    Dharani, L. R.; Goree, J. G.

    1983-01-01

    A method of analysis capable of predicting accurately the fracture behavior of a unidirectional composite laminate containing symmetrically placed buffer strips is presented. As an example, for a damaged graphite/epoxy laminate, the results demonstrate the manner in which to select the most efficient combination of buffer strip properties necessary to inhibit crack growth. Ultimate failure of the laminate after crack arrest can occur under increasing load either by continued crack extension through the buffer strips or the crack can jump the buffer strips. For some typical hybrid materials it is found that a buffer strip spacing-to-width ratio of about four to one is the most efficient.

  13. Multi-Layer Laminated Thin Films for Inflatable Structures

    NASA Technical Reports Server (NTRS)

    Yavrouian, Andre; Plett, Gary; Mannella, Jerami

    2005-01-01

    Special-purpose balloons and other inflatable structures would be constructed as flexible laminates of multiple thin polymeric films interspersed with layers of adhesive, according to a proposal. In the original intended application, the laminate would serve as the envelope of the Titan Aerobot a proposed robotic airship for exploring Titan (one of the moons of Saturn). Potential terrestrial applications for such flexible laminates could include blimps and sails. In the original application, the multi-layered laminate would contain six layers of 0.14-mil (0.0036-mm)-thick Mylar (or equivalent) polyethylene terephthalate film with a layer of adhesive between each layer of Mylar . The overall thickness and areal density of this laminate would be nearly the same as those of 1-mil (0.0254-mm)-thick monolayer polyethylene terephthalate sheet. However, the laminate would offer several advantages over the monolayer sheet, especially with respect to interrelated considerations of flexing properties, formation of pinholes, and difficulty or ease of handling, as discussed next. Most of the damage during flexing of the laminate would be localized in the outermost layers, where the radii of bending in a given bend would be the largest and, hence, the bending stress would be the greatest. The adverse effects of formation of pinholes would be nearly completely mitigated in the laminate because a pinhole in a given layer would not propagate to adjacent layers. Hence, the laminate would tend to remain effective as a barrier to retain gas. Similar arguments can be made regarding cracks: While a crack could form as a result of stress or a defect in the film material, a crack would not propagate into adjacent layers, and the adjacent layer(s) would even arrest propagation of the crack. In the case of the monolayer sheet, surface damage (scratches, dents, permanent folds, pinholes, and the like) caused by handling would constitute or give rise to defects that could propagate through

  14. Accurate stress resultants equations for laminated composite deep thick shells

    SciTech Connect

    Qatu, M.S.

    1995-11-01

    This paper derives accurate equations for the normal and shear force as well as bending and twisting moment resultants for laminated composite deep, thick shells. The stress resultant equations for laminated composite thick shells are shown to be different from those of plates. This is due to the fact the stresses over the thickness of the shell have to be integrated on a trapezoidal-like shell element to obtain the stress resultants. Numerical results are obtained and showed that accurate stress resultants are needed for laminated composite deep thick shells, especially if the curvature is not spherical.

  15. Vibration analysis of rotating thin laminated composite shell of revolution

    SciTech Connect

    Suzuki, K.; Shikanai, G.; Takayama, K.

    1995-11-01

    An exact solution procedure is presented for solving free vibrations of a rotating thin laminated composite shell of revolution having meridionally constant curvature. Based on the classical lamination theory, equations of motion and boundary conditions are obtained from the stationally conditions of the Lagrangian. The equations of motion are solved exactly by using a power series expansion for symmetrically laminated, cross-ply shells. Frequencies and mode shapes of the shells having both ends clamped and both ends freely supported are presented showing their variations with rotating angular velocity, number of laminae and other parameters.

  16. Axisymmetric vibrations of laminated composite conical shells with varying thickness

    SciTech Connect

    Shikanai, G.; Suzuki, K.; Kojima, M.

    1995-11-01

    An exact solution procedure is presented for solving axisymmetric free vibrations of laminated composite conical shells with varying thickness. Based on the classical lamination theory neglecting shear deformation and rotary inertia, equations of motion and boundary conditions are obtained from the stationary conditions of the Lagrangian. The equations of motion are solved exactly by using a power series expansion for symmetrically laminated, cross-ply conical shells. Numerical studies are made for conical shells having both ends clamped to show the effects of the number of laminae, stacking sequences and other parameters upon the frequencies.

  17. An approximate solution for interlaminar stresses in composite laminates

    NASA Technical Reports Server (NTRS)

    Rose, Cheryl A.; Herakovich, Carl T.

    1993-01-01

    An efficient approximate solution for interlaminar stresses in finite width, symmetric and unsymmetric laminated composites subjected to axial and/or bending loads is presented. The solution is based upon statically admissible stress fields which take into consideration local property mismatch effects and global equilibrium requirements. Unknown constants in the assumed stress states are determined through minimization of the laminate complementary energy. Typical results are presented for through-thickness and interlaminar stress distributions for angle-ply and cross-ply laminates subjected to axial loading. It is shown that the present formulation represents an improved, efficient approximate solution for interlaminar stresses.

  18. Analysis of a hybrid-undirectional buffer strip laminate

    NASA Technical Reports Server (NTRS)

    Dharani, L. R.; Goree, J. G.

    1983-01-01

    A method of analysis capable of predicting accurately the fracture behavior of a unidirectional composite laminate containing symmetrically placed buffer strips is presented. As an example, for a damaged graphite/epoxy laminate, the results demonstrate the manner in which to select the most efficient combination of buffer strip properties necessary to inhibit crack growth. Ultimate failure of the laminate after the arrest can occur under increasing load either by continued crack extension through the buffer strips or the crack can jump the buffer strips. For some typical hybrid materials it is found that a buffer strip spacing to width ratio of about four to one is the most efficient.

  19. Interlaminar stresses in composite laminates: A perturbation analysis

    NASA Technical Reports Server (NTRS)

    Hsu, P. W.; Herakovich, C. T.

    1976-01-01

    A general method of solution for an elastic balanced symmetric composite laminate subject to a uniaxial extension was developed based upon a perturbation analysis of a limiting free body containing an interfacial plane. The solution satisfies more physical requirements and boundary conditions than previous investigations, and predicts smooth continuous interlaminar stresses with no instabilities. It determines the finite maximum intensity for the interlaminar normal stress in all laminates, provides mathematical evidences for the singular stresses in angle-ply laminates, suggests the need for the experimental determination of an important problem parameter, and introduces a viable means for solving related problems of practical interest.

  20. Improved PMR Polyimides For Heat-Stable Laminates

    NASA Technical Reports Server (NTRS)

    Vannucci, R. D.; Malarik, D. C.; Papadapoulos, D. S.; Waters, John F.

    1994-01-01

    Second-generation PMR-type polyimides (PMR-II polyimides) of enhanced thermo-oxidative stability prepared by substitution of para-aminostyrene (PAS) end caps for nadic-ester (NE) end caps used in prior PMR-II polyimides. Laminates unidirectionally reinforced with graphite fibers and made with PAS-capped resins exhibited thermo-oxidative stabilities significantly greater than those of similar laminates made with NE-capped PMR-II resins. One new laminate exhibited high retention of weight and strength after 1,000 h of exposure to air at 371 degrees C.

  1. Wave propagation in graphite/epoxy laminates due to impact

    NASA Technical Reports Server (NTRS)

    Tan, T. M.; Sun, C. T.

    1982-01-01

    The low velocity impact response of graphite-epoxy laminates is investigated theoretically and experimentally. A nine-node isoparametric finite element in conjunction with an empirical contact law was used for the theoretical investigation. Flat laminates subjected to pendulum impact were used for the experimental investigation. Theoretical results are in good agreement with strain gage experimental data. The collective results of the investigation indicate that the theoretical procedure describes the impact response of the laminate up to about 150 in/sec. impact velocity.

  2. Notched strength of composite laminates: Predictions and experiments - A review

    NASA Technical Reports Server (NTRS)

    Awerbuch, J.; Madhukar, M. S.

    1985-01-01

    A self-contained review of several semiempirical fracture models for predicting notched strength of composite laminates is presented, based on notched strength data on 70 different laminate configurations of graphite/epoxy, boron/aluminum, and graphite/polyimide. Emphasis is placed on experimental results concerning such failure factors as delamination, splitting, and size of damage zone. Moreover, the fracture model parameters are correlated with the notch sensitivity of composite laminates, and the applicability of the correlations in describing the material notch sensitivity is evaluated. The predictions provided by the different models were found to be identical for all practical purposes.

  3. Laminated metals composites fracture and ballistic impact behavior

    SciTech Connect

    Lesuer, D.R.; Syn, C.K.; Sherby, O.D.; Wadsworth, J.

    1998-01-20

    Recent advances in the fracture and ballistic impact response of laminated metal composites (LMCs) are reviewed. The laminate structure can provide significant improvements to these properties relative to the component materials. Typical fracture and ballistic impact properties in LMCs are illustrated for systems containing Al alloys and Al matrix composites. The unique mechanisms operating in a layered structure that contribute to fracture or ballistic impact resistance are discussed. The influence of laminate architecture, component material properties and interface strength on mechanisms and properties are briefly reviewed for these Al-based LMCs.

  4. Prediction of microcracking in composite laminates under thermomechanical loading

    SciTech Connect

    Maddocks, J.R.; Mcmanus, H.L.

    1995-01-01

    Composite laminates used in space structures are exposed to both thermal and mechanical loads. Cracks in the matrix form, changing the laminate thermoelastic properties. An analytical methodology is developed to predict microcrack density in a general laminate exposed to an arbitrary thermomechanical load history. The analysis uses a shear lag stress solution in conjunction with an energy-based cracking criterion. Experimental investigation was used to verify the analysis. Correlation between analysis and experiment is generally excellent. The analysis does not capture machining-induced cracking, or observed delayed crack initiation in a few ply groups, but these errors do not prevent the model from being a useful preliminary design tool.

  5. Modelling of thick composites using a layerwise laminate theory

    NASA Technical Reports Server (NTRS)

    Robbins, D. H., Jr.; Reddy, J. N.

    1993-01-01

    The layerwise laminate theory of Reddy (1987) is used to develop a layerwise, two-dimensional, displacement-based, finite element model of laminated composite plates that assumes a piecewise continuous distribution of the tranverse strains through the laminate thickness. The resulting layerwise finite element model is capable of computing interlaminar stresses and other localized effects with the same level of accuracy as a conventional 3D finite element model. Although the total number of degrees of freedom are comparable in both models, the layerwise model maintains a 2D-type data structure that provides several advantages over a conventional 3D finite element model, e.g. simplified input data, ease of mesh alteration, and faster element stiffness matrix formulation. Two sample problems are provided to illustrate the accuracy of the present model in computing interlaminar stresses for laminates in bending and extension.

  6. Analysis of a unidirectional, symmetric buffer strip laminate with damage

    NASA Technical Reports Server (NTRS)

    Dharani, L. R.; Goree, J. G.

    1984-01-01

    A method for predicting the fracture behavior of hybrid buffer strip laminates is presented in which the classical shear-lag model is used to represent the shear stress distribution between adjacent fibers. The method is demonstrated by applying it to a notched graphite/epoxy laminate, and the results show clearly the manner in which the most efficient combination of buffer strip properties can be selected in order to arrest the crack. The ultimate failure stress of the laminate is plotted vs the buffer strip width. It is shown that in the case of graphite-epoxy and S-glass epoxy laminates, the optimum buffer strip spacing to width ratio should be about four to one.

  7. Structural and Dielectric Properties of Subnanometric Laminates of Binary Oxides.

    PubMed

    Kahouli, Abdelkader; Lebedev, Oleg; Ben Elbahri, Marwa; Mercey, Bernard; Prellier, Wilfrid; Riedel, Stefan; Czernohorsky, Malte; Lallemand, Florent; Bunel, Catherine; Lüders, Ulrike

    2015-11-25

    Capacitors with a dielectric material consisting of amorphous laminates of Al2O3 and TiO2 with subnanometer individual layer thicknesses can show strongly enhanced capacitance densities compared to the bulk or laminates with nanometer layer thickness. In this study, the structural and dielectric properties of such subnanometer laminates grown on silicon by state-of-the-art atomic layer deposition are investigated with varying electrode materials. The laminates show a dielectric constant reaching 95 combined with a dielectric loss (tan δ) of about 0.2. The differences of the observed dielectric properties in capacitors with varying electrodes indicate that chemical effects at the interface with the TiN electrode play a major role, while the influence of the local roughness of the individual layers is rather limited. PMID:26523935

  8. Calculation of the room-temperature shapes of unsymmetric laminates

    NASA Technical Reports Server (NTRS)

    Hyer, M. W.

    1981-01-01

    A theory explaining the characteristics of the cured shapes of unsymmetric laminates is presented. The theory is based on an extension of classical lamination theory which accounts for geometric nonlinearities. A Rayleigh-Ritz approach to minimizing the total potential energy is used to obtain quantitative information regarding the room temperature shapes of square T300/5208 (0(2)/90(2))T and (0(4)/90(4))T graphite-epoxy laminates. It is shown that, depending on the thickness of the laminate and the length of the side the square, the saddle shape configuration is actually unstable. For values of length and thickness that render the saddle shape unstable, it is shown that two stable cylindrical shapes exist. The predictions of the theory are compared with existing experimental data.

  9. 11. Detail of laminated arch beams, radiators, pews and portion ...

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

    11. Detail of laminated arch beams, radiators, pews and portion of the office to the left of the sanctuary, facing north - Mountain Home Air Force Base, Base Chapel, 350 Willow Street, Cantonment Area, Mountain Home, Elmore County, ID

  10. Characterization of delamination onset and growth in a composite laminate

    NASA Technical Reports Server (NTRS)

    Obrien, T. K.

    1981-01-01

    The onset and growth of delaminations in unnotched (+ or - 30/+ or - 30/90/90 bar) sub S graphite epoxy laminates is described quantitatively. These laminates, designed to delaminate at the edges under tensile loads, were tested and analyzed. Delamination growth and stiffness loss were monitored nondestructively. Laminate stiffness decreased linearly with delamination size. The strain energy release rate, G, associated with delamination growth, was calculated from two analyses. A critical G for delamination onset was determined, and then was used to predict the onset of delaminations in (+45 sub n/-45 sub n/o sub n/90 sub n) sub s (n=1,2,3) laminates. A delamination resistance curve (R curve) was developed to characterize the observed stable delamination growth under quasi static loading. A power law correlation between G and delamination growth rates in fatigue was established.

  11. Nonlinear analysis of laminated fibrous composites. Ph.D. Thesis

    NASA Technical Reports Server (NTRS)

    Renieri, G. D.; Herakovich, C. T.

    1976-01-01

    A computerized analysis of the nonlinear behavior of fibrous composite laminates including axial loading, thermal loading, temperature dependent properties, and edge effects is presented. Ramberg-Osgood approximations are used to represent lamina stress-strain behavior and percent retention curves are employed to model the variation of properties with temperature. Balanced, symmetric laminates comprised of either boron/epoxy, graphite/epoxy, or borsic-aluminum are analyzed using a quasi-three-dimensional finite element analysis. Results are presented for the interlaminar stress distributions in cross-ply, angle-ply, and more complex laminates. Nonlinear stress-strain curves for a variety of composite laminates in tension and compression are obtained and compared to other existing theories and experimental results.

  12. Solar-Cell Encapsulation by One-Step Lamination

    NASA Technical Reports Server (NTRS)

    Sarbolouki, M. N.

    1983-01-01

    Simple method of potting solar cells reduces encapsulating to one-step lamination process. Simplified process saves time and expense. Potting material is added to two inside faces of solar-cell assembly before they are sandwiched and cured.

  13. Progressive Failure Analysis Methodology for Laminated Composite Structures

    NASA Technical Reports Server (NTRS)

    Sleight, David W.

    1999-01-01

    A progressive failure analysis method has been developed for predicting the failure of laminated composite structures under geometrically nonlinear deformations. The progressive failure analysis uses C(exp 1) shell elements based on classical lamination theory to calculate the in-plane stresses. Several failure criteria, including the maximum strain criterion, Hashin's criterion, and Christensen's criterion, are used to predict the failure mechanisms and several options are available to degrade the material properties after failures. The progressive failure analysis method is implemented in the COMET finite element analysis code and can predict the damage and response of laminated composite structures from initial loading to final failure. The different failure criteria and material degradation methods are compared and assessed by performing analyses of several laminated composite structures. Results from the progressive failure method indicate good correlation with the existing test data except in structural applications where interlaminar stresses are important which may cause failure mechanisms such as debonding or delaminations.

  14. Laminated metamaterial flat lens at millimeter-wave frequencies.

    PubMed

    Kitayama, Daisuke; Yaita, Makoto; Song, Ho-Jin

    2015-09-01

    A flat and thin shape is obviously advantageous not only in terms of reducing the volume of a device, but also in handling and using it. Particularly, laminating or stacking flat devices is an intuitive and straightforward way of tailoring performance and functions. Here, we experimentally demonstrated a laminated flat lens for millimeter-wave frequencies that is based on split-ring resonators (SRRs) composed of multiple layers with different and/or identical index profiles and that exhibits characteristics that are linear combinations of those of the individual lenses. Since the characteristics of the lenses of each layer are preserved regardless of the neighbouring layers, the desired functionalities can be easily implemented simply by laminating elementary lenses designed already. When we laminated two lenses designed for bending or focusing incoming waves at 120 GHz, we clearly observed that the outgoing waves collimated and bended as desired. PMID:26368436

  15. Optimal Synthesis of Hot Composite Laminates with Interphase Layers

    NASA Technical Reports Server (NTRS)

    Rabzak, Christopher; Saravanos, Dimitris A.; Chamis, Christos C.

    1993-01-01

    A method for the optimal grading of a single interphase layer in metal matrix composite laminates for the minimization of residual stresses is described. The capability to simultaneously tailor some fabrication parameters is also incorporated. Applications for unidirectional, cross-ply and quasi-isotropic Graphite/Copper laminates are investigated to assess the potential of interphase layer in reducing matrix residual stresses in various laminate configurations. Simultaneous optimization of interphase and fabrication characteristics appears to be more effective in decreasing residual stresses. The results also indicate that the interphase layer is more effective in lowering residual stresses in unidirectional composites and selectively within individual plies of a laminate. Embedded interphase layers in all the plies did not produce a significant global reduction in residual stresses.

  16. 10. Detail view of pendant lamps, laminated arch beams and ...

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

    10. Detail view of pendant lamps, laminated arch beams and ceiling structure, facing north - Mountain Home Air Force Base, Base Chapel, 350 Willow Street, Cantonment Area, Mountain Home, Elmore County, ID

  17. Fatigue of notched fiber composite laminates. Part 1: Analytical model

    NASA Technical Reports Server (NTRS)

    Mclaughlin, P. V., Jr.; Kulkarni, S. V.; Huang, S. N.; Rosen, B. W.

    1975-01-01

    A description is given of a semi-empirical, deterministic analysis for prediction and correlation of fatigue crack growth, residual strength, and fatigue lifetime for fiber composite laminates containing notches (holes). The failure model used for the analysis is based upon composite heterogeneous behavior and experimentally observed failure modes under both static and fatigue loading. The analysis is consistent with the wearout philosophy. Axial cracking and transverse cracking failure modes are treated together in the analysis. Cracking off-axis is handled by making a modification to the axial cracking analysis. The analysis predicts notched laminate failure from unidirectional material fatique properties using constant strain laminate analysis techniques. For multidirectional laminates, it is necessary to know lamina fatique behavior under axial normal stress, transverse normal stress and axial shear stress. Examples of the analysis method are given.

  18. Fracture analysis of local delaminations in laminated composites

    NASA Technical Reports Server (NTRS)

    Sriram, P.; Armanios, Erian A.

    1988-01-01

    A shear deformation model was developed to analyze local delaminations growing from transverse cracks in 90 degree plies located around the mid plane of symmetric laminates. The predictions of the model agree reasonably with experimental data from T300/934 graphite epoxy laminates. The predicted behavior is such that, in combination with an edge delamination model, the critical loads can be predicted accurately in the range of n from .5 to 8.

  19. Laminated microchannel devices, mixing units and method of making same

    DOEpatents

    Bennett, Wendy D [Kennewick, WA; Hammerstrom, Donald J [West Richland, WA; Martin, Peter M [Kennewick, WA; Matson, Dean W [Kennewick, WA

    2002-10-17

    A laminated microchannel device is described in which there is a unit operation process layer that has longitudinal channel. The longitudinal channel is cut completely through the layer in which the unit process operation resides. Both the device structure and method of making the device provide significant advantages in terms of simplicity and efficiency. A static mixing unit that can be incorporated in the laminated microchannel device is also described.

  20. Support Assembly for Composite Laminate Materials During Roll Press Processing

    NASA Technical Reports Server (NTRS)

    Catella, Luke A.

    2011-01-01

    A composite laminate material is supported during the roll press processing thereof by an assembly having: first and second perforated films disposed adjacent to first and second opposing surfaces of a mixture of uncured resin and fibers defining the composite laminate material, a gas permeable encasement surrounding the mixture and the first and second films, a gas impervious envelope sealed about the gas permeable encasement, and first and second rigid plates clamped about the gas impervious envelope.

  1. Review on antibacterial biocomposites of structural laminated veneer lumber

    PubMed Central

    Chen, Zi-xiang; Lei, Qiong; He, Rui-lin; Zhang, Zhong-feng; Chowdhury, Ahmed Jalal Khan

    2015-01-01

    In this review, the characteristics and applications of structural laminated veneer lumber made from planted forest wood is introduced, and its preparation is explained, including various tree species and slab qualities, treatments for multiple effects and reinforced composites. The relevant factors in the bonding technology and pressing processes as well as the mechanical properties, research direction and application prospects of structural laminated veneer lumber made from planted forest wood are discussed. PMID:26858559

  2. Damage Tolerance of Composite Laminates from an Empirical Perspective

    NASA Technical Reports Server (NTRS)

    Nettles, Alan T.

    2009-01-01

    Damage tolerance consists of analysis and experimentation working together. Impact damage is usually of most concern for laminated composites. Once impacted, the residual compression strength is usually of most interest. Other properties may be of more interest than compression (application dependent). A damage tolerance program is application specific (not everyone is building aircraft). The "Building Block Approach" is suggested for damage tolerance. Advantage can be taken of the excellent fatigue resistance of damaged laminates to save time and costs.

  3. Determination of the technical constants of laminates in oblique directions

    NASA Technical Reports Server (NTRS)

    Vidouse, F.

    1979-01-01

    An off-axis tensile test theory based on Hooke's Law is applied to glass fiber reinforced laminates. A corrective parameter dependent on the characteristics of the strain gauge used is introduced by testing machines set up for isotropic materials. Theoretical results for a variety of strain gauges are compared with those obtained by a finite element method and with experimental results obtained on laminates reinforced with glass.

  4. Mutational and Haplotype Analyses of Families with Familial Partial Lipodystrophy (Dunnigan Variety) Reveal Recurrent Missense Mutations in the Globular C-Terminal Domain of Lamin A/C

    PubMed Central

    Speckman, Rebecca A.; Garg, Abhimanyu; Du, Fenghe; Bennett, Lynda; Veile, Rose; Arioglu, Elif; Taylor, Simeon I.; Lovett, Michael; Bowcock, Anne M.

    2000-01-01

    Familial partial lipodystrophy (FPLD), Dunnigan variety, is an autosomal dominant disorder characterized by marked loss of subcutaneous adipose tissue from the extremities and trunk but by excess fat deposition in the head and neck. The disease is frequently associated with profound insulin resistance, dyslipidemia, and diabetes. We have localized a gene for FPLD to chromosome 1q21-q23, and it has recently been proposed that nuclear lamin A/C is altered in FPLD, on the basis of a novel missense mutation (R482Q) in five Canadian probands. This gene had previously been shown to be altered in autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD-AD) and in dilated cardiomyopathy and conduction-system disease. We examined 15 families with FPLD for mutations in lamin A/C. Five families harbored the R482Q alteration that segregated with the disease phenotype. Seven families harbored an R482W alteration, and one family harbored a G465D alteration. All these mutations lie within exon 8 of the lamin A/C gene—an exon that has also been shown to harbor different missense mutations that are responsible for EDMD-AD. Mutations could not be detected in lamin A/C in one FPLD family in which there was linkage to chromosome 1q21-q23. One family with atypical FPLD harbored an R582H alteration in exon 11 of lamin A. This exon does not comprise part of the lamin C coding region. All mutations in FPLD affect the globular C-terminal domain of the lamin A/C protein. In contrast, mutations responsible for dilated cardiomyopathy and conduction-system disease are observed in the rod domain of the protein. The FPLD mutations R482Q and R482W occurred on different haplotypes, indicating that they are likely to have arisen more than once. PMID:10739751

  5. Transparent, resilient human amniotic membrane laminates for corneal transplantation.

    PubMed

    Hariya, Takehiro; Tanaka, Yuji; Yokokura, Shunji; Nakazawa, Toru

    2016-09-01

    This study evaluated a new technique to toughen and optically clarify human amniotic membrane (AM) tissue, which is naturally thin and clouded, and determined the suitability of the altered tissue for corneal transplantation. The technique created a tissue laminate by repeatedly depositing wet layers of AM and dehydrating them, followed by chemical cross-linking to tighten integration at the layer interfaces and within the layers, thereby improving the physical properties of the laminates by increasing light transmittance and mechanical strength. Interestingly, this improvement only occurred in laminates with at least 4 layers. Cross-linking also improved the resistance of the laminates to collagenase degradation, such as occurs in corneal melting. This study also confirmed that the AM tissue was biocompatible by inserting AM monolayers into the corneal stroma of rabbits, and by performing lamellar keratoplasty in rabbits with cross-linked AM laminates. The laminates were sufficiently thick and resilient to need only one set of sutures, whereas in previously described multi-layer AM transplantation technique, each layer required separate sutures. The current findings are a promising advance in the engineering of novel biomaterials and the alteration of existing tissues for medical use. PMID:27267629

  6. The effect of lamination angle on polymer retention

    SciTech Connect

    Gao, H.W.

    1992-09-01

    Polymer retention may be affected by the reservoir geological structure due to lamination of the mineral surfaces. These laminae are very prevalent in Class I reservoirs. To account for the effect of lamination angle on polymer retention, several corefloods with three fired, rectangular, Berea sandstone cores were conducted. The three cores were cut at three different angles, 0, 30, and 90 degrees, with respect to the direction of laminations. A multiple slug retention method was used to determine the retention of a biopolymer in each core. Tracer tests were conducted before and after the biopolymer flow to determine how the retained biopolymer affected the fluid advance. A computed tomography (CT) scanning method was used to monitor the advance of the tracer. All corefloods and tracer tests were conducted at low flow rates similar to that in reservoirs. Coreflood tests revealed that polymer retention, which was mainly caused by mechanical entrapment, was higher in cores that had laminations parallel to the direction of flow than in cores that had crossbed laminae. In cores that had crossbed laminae, polymer retention increased with an increase in the lamination angle. Retained polymer is harmful to the stability of fluid front in cores that have laminations parallel to the direction of flow, but is helpful in cores that have crossbed laminae.

  7. Tracer Lamination in the Stratosphere: A Global Climatology

    NASA Technical Reports Server (NTRS)

    Appenzeller, Christof; Holton, James R.

    1997-01-01

    Vertical soundings of stratospheric ozone often exhibit laminated tracer structures characterized by strong vertical tracer gradients. The change in time of these gradients is used to define a tracer lamination rate. It is shown that this quantity can be calculated by the cross product of the horizontal temperature and horizontal tracer gradients. A climatology based on UARS satellite-borne ozone data and on ozone-like pseudotracer data is presented. Three stratospheric regions with high lamination rates were found: the part of the stratospheric overworld which is influenced by the polar vortex, the part of the lowermost stratosphere which is influenced by the tropopause and a third region in the subtropical lower stratosphere mainly characterized with strong vertical shear. High lamination rates in the stratospheric overworld were absent during summer, whereas in the lowermost stratosphere high lamination rates were found year-round. This is consistent with the occurrence and seasonal variation of the horizontal tracer gradient and vertical shear necessary for tilting the tracer surfaces. During winter, high lamination rates associated with the stratospheric polar vortex are present down to approximately 100 hPa. Several features of the derived climatology are roughly consistent with earlier balloon-borne studies. The patterns in the southern and northern hemisphere are comparable, but details differ as anticipated from a less disturbed and more symmetric southern polar vortex.

  8. Properties of wheat gluten/poly(lactic acid) laminates.

    PubMed

    Cho, Sung-Woo; Gällstedt, Mikael; Hedenqvist, Mikael S

    2010-06-23

    Laminates of compression-molded glycerol-plasticized wheat gluten (WG) films surrounded and supported by poly(lactic acid) (PLA) films have been produced and characterized. The objective was to obtain a fully renewable high gas barrier film with sufficient mechanical integrity to function in, for example, extrusion-coating paper/board applications. It was shown that the lamination made it possible to make films with a broad range of glycerol contents (0-30 wt %) with greater strength than single unsupported WG films. The low plasticizer contents yielded laminates with very good oxygen barrier properties. In addition, whereas the unsupported WG films had an immeasurably high water vapor transmission rate (WVTR), the laminate showed values that were finite and surprisingly, in several cases, also lower than that of PLA. Besides being a mechanical support (as evidenced by bending and tensile data) and a shield between the WG and surrounding moisture, the PLA layer also prevented the loss of the glycerol plasticizer from the WG layer. This was observed after the laminate had been aged on an "absorbing" blotting paper for up to 17 weeks. The interlayer adhesion (peel strength) decreased with decreasing glycerol content and increasing WG film molding temperature (130 degrees C instead of 110 degrees C). The latter effect was probably due to a higher protein aggregation, as revealed by infrared spectroscopy. The lamination temperature (110-140 degrees C) did not, however, have a major effect on the final peel strength. PMID:20504031

  9. Bending Boundary Layers in Laminated-Composite Circular Cylindrical Shells

    NASA Technical Reports Server (NTRS)

    Nemeth, Michael P.; Smeltzer, Stanley S., III

    2000-01-01

    An analytical, parametric study of the attenuation of bending boundary layers or edge effects in balanced and unbalanced, symmetrically and unsymmetrically laminated thin cylindrical shells is presented for nine contemporary material systems. The analysis is based on the linear Sanders-Koiter shell equations and specializations to the Love-Kirchhoff shell equations and Donnell's equations are included. Two nondimensional parameters are identified that characterize and quantify the effects of laminate orthotropy and laminate anisotropy on the bending boundary-layer decay length in a very general and encompassing manner. A substantial number of structural design technology results are presented for a wide range of laminated-composite cylinders. For all the laminate constructions considered, the results show that the differences between results that were obtained with the Sanders-Koiter shell equations, the Love-Kirchhoff shell equations, and Donnell's equations are negligible. The results also show that the effect of anisotropy in the form of coupling between pure bending and twisting has a negligible effect on the size of the bending boundary-layer decay length of the balanced, symmetrically laminated cylinders considered. Moreover, the results show that coupling between the various types of shell anisotropies has a negligible effect on the calculation of the bending boundary-layer decay length in most cases. The results also show that in some cases neglecting the shell anisotropy results in underestimating the bending boundary-layer decay length and in other cases it results in an overestimation.

  10. Response of automated tow placed laminates to stress concentrations

    NASA Technical Reports Server (NTRS)

    Cairns, Douglas S.; Ilcewicz, Larry B.; Walker, Tom

    1993-01-01

    In this study, the response of laminates with stress concentrations is explored. Automated Tow Placed (ATP, also known as Fiber Placement) laminates are compared to conventional tape layup manufacturing. Previous tensile fracture tests on fiber placed laminates show an improvement in tensile fracture of large notches over 20 percent compared to tape layup laminates. A hierarchial modeling scheme is presented. In this scheme, a global model is developed for laminates with notches. A local model is developed to study the influence of inhomogeneities at the notch tip, which are a consequence of the fiber placement manufacturing technique. In addition, a stacked membrane model was developed to study delaminations and splitting on a ply-by-ply basis. The results indicate that some benefit with respect to tensile fracture (up to 11 percent) can be gained from inhomogeneity alone, but that the most improvement may be obtained with splitting and delaminations which are more severe in the case of fiber placement compared to tape layup. Improvements up to 36 percent were found from the model for fiber placed laminates with damage at the notch tip compared to conventional tape layup.

  11. Higher order finite element analysis of thick composite laminates

    NASA Technical Reports Server (NTRS)

    Goering, J.; Kim, H. J.

    1992-01-01

    A higher order, sub-parametric, laminated, 3D solid finite element was used for the analysis of very thick laminated composite plates. The geometry of this element is defined by four nodes in the X-Y plane which define a prism of material through the thickness of the laminate. There are twenty-four degrees of freedom at each node; translations at the upper and lower surfaces of the laminate in each of the three coordinate directions, and the derivatives of these translations with respect to each coordinate. This choice of degrees of freedom leads to displacement and strain compatibility at the corners. Stacking sequence effects are accounted for by explicitly integrating the strain energy density through the thickness of the element. The laminated solid element was combined with a gap-contact element to analyze thick laminated composite lugs loaded through flexible pins. The resulting model accounts for pin bending effects that produce non-uniform bearing stresses through the thickness of the lug. A thick composite lug experimental test program was performed, and provided data that was used to validate the analytical model. Two lug geometries and three stacking sequences were tested.

  12. Three dimensional inelastic finite element analysis of laminated composites

    NASA Technical Reports Server (NTRS)

    Griffin, O. H., Jr.; Kamat, M. P.

    1980-01-01

    Formulations of the inelastic response of laminated composites to thermal and mechanical loading are used as the basis for development of the computer NALCOM (Nonlinear Analysis of Laminated Composites) computer program which uses a fully three dimensional isoparametric finite element with 24 nodes and 72 degrees of freedom. An incremental solution is performed with nonlinearities introduced as pseudoloads computed for initial strains. Equilibrium iteration may be performed at every step. Elastic and elastic-plastic response of boron/epoxy and graphite/epoxy graphite/epoxy and problems of curing 0/90 sub s Gr/Ep laminates with and without circular holes are analyzed. Mechanical loading of + or - 45sub s Gr/Ep laminates is modeled and symmetry conditions which exist in angle-ply laminates are discussed. Results are compared to experiments and other analytical models when possible. All models are seen to agree reasonably well with experimetnal results for off-axis tensile coupons. The laminate analyses show the three dimensional effects which are present near holes and free corners.

  13. β-catenin is essential for lamination but not neurogenesis in mouse retinal development

    PubMed Central

    Fu, Xueyao; Sun, Hongxia; Klein, William H.; Mu, Xiuqian

    2007-01-01

    During vertebrate retinal development, the seven retinal cell types differentiate sequentially from a single population of retinal progenitor cells (RPCs) and organize themselves into a distinct laminar structure. The purpose of this study was to determine whether β-catenin, which functions both as a nuclear effector for the canonical Wnt signaling pathway and as a regulator of cell adhesion, is required for retinal neurogenesis or lamination. We used the Cre-loxP system to either eliminate β-catenin or to express a constitutively active form during retinal neurogenesis. Eliminating β-catenin did not affect cell differentiation, but did result in the loss of the radial arrangement of RPCs and caused abnormal migration of differentiated neurons. As a result, the laminar structure was massively disrupted in β-catenin-null retinas, although all retinal cell types still formed. In contrast to other neural tissues, eliminating β-catenin did not significantly reduce the proliferation rate of RPCs; likewise, activating β-catenin ectopically in RPCs did not result in overproliferation, but loss of neural retinal identity. These results indicate that β-catenin is essential during retinal neurogenesis as a regulator of cell adhesion but not as a nuclear effector of the canonical Wnt signaling pathway. The results further imply that retinal lamination and retinal cell differentiation are genetically separable processes. PMID:16959241

  14. Scintigraphic evaluation of digital circulation during the developmental and acute phases of equine laminitis

    SciTech Connect

    Trout, D.R.

    1987-01-01

    Using nuclear isotopic imaging, digital circulation was sequentially evaluated at 24-hour intervals in 11 control horses and in 9 horses affected with acute laminitis, created by administration of a high-starch ration. Following intra-arterial injection of /sup 99m/Tc macroaggregated albumin into the brachiocephalic trunk, a gamma camera and dedicated nuclear medicine computer were used to acquire static images of the right front foot. Dynamic vascular-phase and static interstitial-phase images were also obtained after jugular vein injection of /sup 99m/Tc diethylenetriamine pentaacetic acid. These procedures were performed on standing horses, using either minimal or no tranquilization. The images were quantitatively analyzed for parameters indicative of circulation to the foot as a whole and to specific regions of interest within the foot. There was no evidence of reduced total blood flow to the lamellae during either the developmental or acute phases of laminitis. Although total flow tended to increase throughout the peripheral/external regions of the foot, statistically significant elevations were consistently present only within the lamellae. Changes indicative of decreased total blood flow were noted in the central/internal regions of the foot. These alterations usually occurred coincident with or after the onset of clinical lameness.

  15. Damage growth in composite laminates with interleaves

    NASA Technical Reports Server (NTRS)

    Goree, James G.

    1987-01-01

    The influence of placing interleaves between fiber reinforced plies in multilayered composite laminates is investigated. The geometry of the composite is idealized as two dimensional, isotropic, linearly elastic media made of a damaged layer bonded between two half planes and separated by thin interleaves of low extensional and shear moduli. The damage in the layer is taken in the form of a symmetric crack perpendicular to the interface and may extend up to the interface. The case of an H-shaped crack in the form of a broken layer with delamination along the interface is also analyzed. The interleaves are modeled as distributed shear and tension springs. Fourier integral transform techniques are used to develop solutions in terms of singular integral equations. An asymptotic analysis of the integral equations based on Muskhelishvili's techniques reveals logarithmically singular axial stresses in the half plane at the crack tips for the broken layer. For the H shaped crack, similar singularities are found to exist in the axial stresses at the interface crack tips in the layer and the half plane. The solution of the equations is found numerically for the stresses and displacements by using the Hadamard's concept of direct differentiation of Cauchy integrals as well as Gaussian integration techniques.

  16. Progressive Fracture of Laminated Composite Stiffened Plate

    NASA Technical Reports Server (NTRS)

    Gotsis, Pascalis K.; Chamis, Christos C.; David, Kostantinos; Abdi, Frank

    2007-01-01

    Laminated fiber-reinforced composite stiffened plate with [0/90/plus or minus 45]s plies made of S-Glass/epoxy are evaluated via computational simulation to study damage and fracture progression. The loads are pressure and temperature which varies from 21 to 65.5 C (case I) and from 143.3 to 21 C (case II). An integrated computer code is used for the simulation of the damage progression. Results show that damage initiation begins at low load level, with matrix cracking at the 0 deg. (bottom and top) plies, fiber fracture at the bottom (0 deg.) ply and interply delamination at the top (0 deg. ) ply. Increasing the applied pressure, the damage growth is expended resulting in fracture through the thickness of the structure. At this stage, 90 percent of the plies damage at applied pressure 15.306 MPa for the case I and 15.036 MPa for the case II. After this stage the cracks propagate rapidly and the structure collapses.

  17. Benefits of oxygen incorporation in atomic laminates

    NASA Astrophysics Data System (ADS)

    Dahlqvist, Martin

    2016-04-01

    Atomic laminates such as MAX phases benefit from the addition of oxygen in many ways, from the formation of a protective oxide surface layer with self-healing capabilities when cracks form to the tuning of anisotropic conductivity. In this paper oxygen incorporation and vacancy formation in M 2AlC (M  =  Ti, V, Cr) MAX phases have been studied using first-principles calculations where the focus is on phase stability and electronic structure for different oxygen and/or vacancy configurations. Oxygen prefers different lattice sites depending on M-element and this can be correlated to the number of available non-bonding M d-electrons. In Ti2AlC, oxygen substitutes carbon while in Cr2AlC it is located interstitially within the Al-layer. I predict that oxygen incorporation in Ti2AlC stabilizes the material, which explains the experimentally observed 12.5 at% oxygen (x  =  0.5) in Ti2Al(C1‑x O x ). In addition, it is also possible to use oxygen to stabilize the hypothetical Zr2AlC and Hf2AlC. Hence, oxygen incorporation may be beneficial in many ways. Not only can it make a material more stable, but it also can act as a reservoir for internal self-healing with shorter diffusion paths.

  18. Energy-efficient steels for motor laminations

    NASA Astrophysics Data System (ADS)

    Werner, F. E.; Jaffee, R. I.

    1992-03-01

    Motors use over 60% of all electricity generated, and their losses exceed 200 × 109 kW.hr/year. A significant part of this loss results from eddy currents and hysteretic processes in the motor laminations. These so- called core losses cost motor users about 3 × 109/year. The metallurgy and economics of using various steels are considered, with emphasis on 5- to 125- hp polyphase induction motors. A lower core loss steel, even though it is more expensive, is economically justified most of the time when the operating costs of motors are considered. Impurities must be minimized, and steels can now be made with the principal impurities being less than 30 ppm. Further reduction of core losses depends on using the best steel processing equipment available, production of a consistently low carbon content so that decarburizing during the final anneal can be eliminated, developing a better understanding of the relation between material properties and performance in motors, and an increased willingness by the motor users to pay more for better motors that are cheaper to own in the long run.

  19. Interface fracture and composite deformation of model laminates

    NASA Astrophysics Data System (ADS)

    Fox, Matthew R.

    Model laminates were studied to improve the understanding of composite mechanical behavior. NiAl/Mo and NiAl/Cr model laminates, with a series of interfaces, were bonded at 1100°C. Reaction layers were present in all laminates, varying in thickness with bonding conditions. Interface fracture strengths and resistances were determined under primarily mode II loading conditions using a novel technique, the asymmetrically-loaded shear (ALS) test, in which one layer of the laminate was loaded in compression, producing a stable interface crack. The NiAl/Mo interface was also fractured in four-point bending. A small amount of plasticity was found to play a role in crack initiation. During steady-state mode II interface fracture of NiAl/Mo model laminates, large-scale slip was observed near the crack tip in the NiAl adjacent to the interface. After testing, the local slope and curvature of the interface were characterized at intervals along the interface and at slip locations to qualitatively describe local stresses present at and just ahead of the crack tip. The greatest percentage of slip occurred where closing forces on the crack tip were below the maximum value and were decreasing with crack growth. A mechanism for crack propagation is presented describing the role of large-scale slip in crack propagation. The mechanical response of structural laminates in 3-D stress states, as would be present in a polycrystalline aggregate composed of lamellar grains, are lacking. In order to understand the response of laminates composed of hard and soft phases, Pb/Zn laminates were prepared and tested in compression with varying lamellar orientation relative to the loading axis. A model describing the mechanical response in a general state assuming elastic-perfectly plastic isotropic layers was developed. For the 90° laminate, a different approach was applied, using the friction hill concepts used in forging analyses. With increasing ratios of cross-sectional radius to layer

  20. Testing and simulation of composite laminates under impact loading

    NASA Astrophysics Data System (ADS)

    Dang, Xinglai

    Owing to their high stiffness-to-weight and high strength-to-weight ratios, fiber-reinforced polymer-matrix composite laminates are excellent materials for high-performance structures. However, their properties in the thickness direction are very poor as they are weakly bonded by polymeric matrices through laminate interfaces. Accordingly, when a composite laminate is subjected to impact loading, high interlaminar stresses along with the low interlaminar strengths could easily result in interlaminar damage such as delamination. This thesis investigated the response of composite laminates under low-velocity impact and presented numerical techniques for impact simulation. To begin with, instrumented drop-weight impacts ranging from subperforation to perforation levels were introduced to composite laminates having various dimensions and thicknesses. Damaged composite laminates were then subjected to compression-after-impact tests for evaluations of residual properties. Experimental results revealed that perforation was an important damage milestone since impact parameters such as peak force, contact duration, maximum deflection and energy absorption, and residual properties such as compressive stiffness, strength and energy absorption all reached critical levels as perforation took place. It was also found that thickness played a more important role than in-plane dimensions in perforation process. In order to understand more about the relationship between laminate thickness and perforation resistance and to present an economical method to improve perforation resistance, thick laminated composite plates and their assembled counterparts were investigated and compared. An energy profile correlating the impact energy and absorbed energy at all energy levels for each type of composite plates investigated was established and found to be able to address the relationship between energy and damage. Experimental results concluded that increasing thickness was more efficient

  1. Tape cast bioactive metal-ceramic laminates for structural application

    NASA Astrophysics Data System (ADS)

    Clupper, Daniel Christopher

    Bioglass 45S5, is a silica based glass which is able to rapidly form strong bonds with bone and soft tissue in vivo. It is used clinically to replace damaged ear ossicles and in dental surgery to help maintain the structural integrity of the jaw bone. The goal of the research was to demonstrate that Bioglass can be toughened by lamination with metallic layers while maintaining bioactivity. Improvement of the mechanical properties of Bioglass 45SS would allow for additional clinical applications, such as fracture fixation plates, or vertebral spacers. Bioglass 45S5 was tape cast and laminated with clinically relevant metals (316L, stainless steel and titanium) as well as copper in an effort to demonstrate that the effective toughness, or area under the load-deflection diagram can be increased significantly through ductile layer lamination. The average strength of monolithic tape cast sintered Bioglass was as high as 150 MPa and the toughness measured approximately 1.0 MPa m1/2. Copper-Bioglass laminates clearly demonstrated the toughening effect of metal layers on tape cast sintered Bioglass 45S5. Steel-Bioglass laminates, although less tough than the copper-Bioglass laminates, showed higher strengths. In vitro bioactivity tests of both titanium and steel Bioglass laminates showed the formation of mature and thick hydroxyapatite layers after 24 hours in Tris buffer solution. Under the standard test conditions, the bioactivity of monolithic tape cast sintered Bioglass increased with increasing sintering temperature. For samples sintered at 1000°C, thick crystalline layers of hydroxyapatite formed within 24 hours in Tris buffer solution. The bioactivity of these samples approached that of amorphous bulk Bioglass. Samples processed at 800°C were able to form thick crystalline hydroxyapatite layer after 24 hours when the test solution volume was increased by eight times.

  2. Crush testing, characterizing, and modeling the crashworthiness of composite laminates

    NASA Astrophysics Data System (ADS)

    Garner, David Michael, Jr.

    Research in the field of crashworthiness of composite materials is presented. A new crush test method was produced to characterize the crush behavior of composite laminates. In addition, a model of the crush behavior and a method for rank ordering the energy absorption capability of various laminates were developed. The new crush test method was used for evaluating the crush behavior of flat carbon/epoxy composite specimens at quasi-static and dynamic rates. The University of Utah crush test fixture was designed to support the flat specimen against catastrophic buckling. A gap, where the specimen is unsupported, allowed unhindered crushing of the specimen. In addition, the specimen's failure modes could be clearly observed during crush testing. Extensive crush testing was conducted wherein the crush force and displacement data were collected to calculate the energy absorption, and high speed video was captured during dynamic testing. Crush tests were also performed over a range of fixture gap heights. The basic failure modes were buckling, crack growth, and fracture. Gap height variations resulted in poorly, properly, and overly constrained specimens. In addition, guidelines for designing a composite laminate for crashworthiness were developed. Modeling of the crush behavior consisted of the delamination and fracture of a single ply or group of like plies during crushing. Delamination crack extension was modeled using the mode I energy release rate, G lc, where an elastica approach was used to obtain the strain energy. Variations in Glc were briefly explored with double cantilever beam tests wherein crack extension occurred along a multidirectional ply interface. The model correctly predicted the failure modes for most of the test cases, and offered insight into how the input parameters affect the model. The ranking method related coefficients of the laminate and sublaminate stiffness matrices, the ply locations within the laminate, and the laminate thickness. The

  3. Caspase-3 is required in the apoptotic disintegration of the nuclear matrix

    SciTech Connect

    Kivinen, Katri; Kallajoki, Markku; Taimen, Pekka . E-mail: pekka.taimen@utu.fi

    2005-11-15

    Apoptotic breakdown of cellular structures is largely mediated by caspases. One target of degradation is a proteinaceous framework of the nucleus termed the nuclear matrix. We compared the apoptotic changes of the nuclear matrix in staurosporine-treated caspase-3-deficient MCF-7 cells transfected with intact CASP-3 gene (MCF-7c3) or an empty vector (MCF-7v) as a control. Nuclear Mitotic Apparatus protein (NuMA), lamin A/C and lamin B were used as markers for internal nuclear matrix and peripheral nuclear lamina, respectively. In both cell lines, staurosporine induced rapid cytoplasmic shrinkage and partial chromatin condensation. MCF-7c3 cells formed apoptotic bodies, whereas MCF-7v cells did not. NuMA and lamins were actively cleaved in MCF-7c3 cells following caspase-3 activation, but only minimal or no cleavage was detected in MCF-7v cells. Interestingly, lamin B but not lamin A/C was relocated into cytoplasmic granules in apoptotic MCF-7v cells. Pancaspase inhibitor, z-VAD-fmk, prevented the apoptotic changes, while caspase-3 inhibitor, z-DEVD-fmk, induced lamin B granules in both cell lines. These results show that caspase-3 is involved in the cleavage of NuMA and lamins either directly or by activating other proteases. This may be essential for disintegration of the nuclear structure during apoptosis.

  4. Fracture behavior of unidirectional boron/aluminum composite laminates

    NASA Technical Reports Server (NTRS)

    Goree, J. G.; Jones, W. F.

    1983-01-01

    An experiment was conducted to verify the results of mathematical models which predict the stresses and displacements of fibers and the amount of damage growth in a center-notched lamina as a function of the applied remote stress and the matrix and fiber material properties. A brittle lacquer coating was used to detect the yielding in the matrix while X-ray techniques were used to determine the number of broken fibers in the laminate. The notched strengths and the amounts of damage found in the specimens agree well with those predicted by the mathematical model. It is shown that the amount of damage and the crack opening displacement does not depend strongly on the number of plies in the laminate for a given notch width. By heat-treating certain laminates to increase the yield stress of the alumina matrix, the effect of different matrix properties on the fracture behavior was investigated. The stronger matrix is shown to weaken the notched laminate by decreasing the amount of matrix damage, thereby making the laminate more notch sensitive.

  5. Tunable characteristics of bending resonance frequency in magnetoelectric laminated composites

    NASA Astrophysics Data System (ADS)

    Chen, Lei; Li, Ping; Wen, Yu-Mei; Zhu, Yong

    2013-07-01

    As the magnetoelectric (ME) effect in piezoelectric/magnetostrictive laminated composites is mediated by mechanical deformation, the ME effect is significantly enhanced in the vicinity of resonance frequency. The bending resonance frequency (fr) of bilayered Terfenol-D/PZT (MP) laminated composites is studied, and our analysis predicts that (i) the bending resonance frequency of an MP laminated composite can be tuned by an applied dc magnetic bias (Hdc) due to the ΔE effect; (ii) the bending resonance frequency of the MP laminated composite can be controlled by incorporating FeCuNbSiB layers with different thicknesses. The experimental results show that with Hdc increasing from 0 Oe (1 Oe=79.5775 A/m) to 700 Oe, the bending resonance frequency can be shifted in a range of 32.68 kHz <= fr <= 33.96 kHz. In addition, with the thickness of the FeCuNbSiB layer increasing from 0 μm to 90 μm, the bending resonance frequency of the MP laminated composite gradually increases from 33.66 kHz to 39.18 kHz. This study offers a method of adjusting the strength of dc magnetic bias or the thicknesses of the FeCuNbSiB layer to tune the bending resonance frequency for ME composite, which plays a guiding role in the ME composite design for real applications.

  6. Bending Boundary Layers in Laminated-Composite Circular Cylindrical Shells

    NASA Technical Reports Server (NTRS)

    Nemeth, Michael P.; Smeltzer, Stanley S., III

    2000-01-01

    A study of the attenuation of bending boundary layers in balanced and unbalanced, symmetrically and unsymmetrically laminated cylindrical shells is presented for nine contemporary material systems. The analysis is based on the linear Sanders-Koiter shell equations and specializations to the Love-Kirchhoff shell equations and Donnell's equations are included. Two nondimensional parameters are identified that characterize the effects of laminate orthotropy and anisotropy on the bending boundary-layer decay length in a very general manner. A substantial number of structural design technology results are presented for a wide range of laminated-composite cylinders. For all laminates considered, the results show that the differences between results obtained with the Sanders-Koiter shell equations, the Love-Kirchhoff shell equations, and Donnell's equations are negligible. The results also show that the effect of anisotropy in the form of coupling between pure bending and twisting has a negligible effect on the size of the bending boundary-layer decay length of the balanced, symmetrically laminated cylinders considered. Moreover, the results show that coupling between the various types of shell anisotropies has a negligible effect on the calculation of the bending boundary-layer decay length in most cases. The results also show that, in some cases, neglecting the shell anisotropy results in underestimating the bending boundary-layer decay length and, in other cases, results in an overestimation.

  7. Dynamic Stability of Uncertain Laminated Beams Under Subtangential Loads

    NASA Technical Reports Server (NTRS)

    Goyal, Vijay K.; Kapania, Rakesh K.; Adelman, Howard (Technical Monitor); Horta, Lucas (Technical Monitor)

    2002-01-01

    Because of the inherent complexity of fiber-reinforced laminated composites, it can be challenging to manufacture composite structures according to their exact design specifications, resulting in unwanted material and geometric uncertainties. In this research, we focus on the deterministic and probabilistic stability analysis of laminated structures subject to subtangential loading, a combination of conservative and nonconservative tangential loads, using the dynamic criterion. Thus a shear-deformable laminated beam element, including warping effects, is derived to study the deterministic and probabilistic response of laminated beams. This twenty-one degrees of freedom element can be used for solving both static and dynamic problems. In the first-order shear deformable model used here we have employed a more accurate method to obtain the transverse shear correction factor. The dynamic version of the principle of virtual work for laminated composites is expressed in its nondimensional form and the element tangent stiffness and mass matrices are obtained using analytical integration The stability is studied by giving the structure a small disturbance about an equilibrium configuration, and observing if the resulting response remains small. In order to study the dynamic behavior by including uncertainties into the problem, three models were developed: Exact Monte Carlo Simulation, Sensitivity Based Monte Carlo Simulation, and Probabilistic FEA. These methods were integrated into the developed finite element analysis. Also, perturbation and sensitivity analysis have been used to study nonconservative problems, as well as to study the stability analysis, using the dynamic criterion.

  8. Increasing ferromagnetic resonance frequency using lamination and shape

    NASA Astrophysics Data System (ADS)

    El-Ghazaly, A.; White, R. M.; Wang, S. X.

    2015-05-01

    The magnetic permeability frequency spectrum is one of the most critical properties for the operation of high frequency magnetic devices in the gigahertz regime. Permeability is fairly constant up to the ferromagnetic resonance (FMR) frequency, at which point the relative permeability drops to unity. Extending FMR to higher frequencies is thus imperative for developing GHz-range magnetic devices. The simulation and experimental investigations presented in this paper demonstrate how stacking layers to form a laminated film increases the FMR frequency by allowing flux closure between layers along the induced easy-axis direction. This flux closure reduces the demagnetization factor along the easy-axis direction by two orders of magnitude. This effect, however, is only observable in patterned films where the shape anisotropy is enough to result in variation of the FMR frequency. Experiments using patterned magnetic cores were performed to illustrate this effect. Through detailed investigation of the permeability spectra of both single layer and laminated CoTaZr magnetic films patterned into 500 μm × L films (where L ranged from 200 μm to 1000 μm), the FMR frequency was extracted and proven to increase as a result of lamination. The degree to which the frequency is boosted by lamination increases exponentially as the length of the film is decreased. Through a combination of lamination and shape demagnetization, the effective anisotropy, which directly relates to FMR frequency, was shown to increase by about 100%.

  9. In vitro evidence for a bacterial pathogenesis of equine laminitis.

    PubMed

    Mungall, B A; Kyaw-Tanner, M; Pollitt, C C

    2001-04-01

    Utilizing an in vitro laminitis explant model, we have investigated how bacterial broth cultures and purified bacterial proteases activate matrix metalloproteinases (MMPs) and alter structural integrity of cultured equine lamellar hoof explants. Four Gram-positive Streptococcus spp. and three Gram-negative bacteria all induced a dose-dependent activation of MMP-2 and MMP-9 and caused lamellar explants to separate. MMP activation was deemed to have occurred if a specific MMP inhibitor, batimastat, blocked MMP activity and prevented lamellar separation. Thermolysin and streptococcal pyrogenic exotoxin B (SpeB) both separated explants dose-dependently but only thermolysin was inhibitable by batimastat or induced MMP activation equivalent to that seen with bacterial broths. Additionally, thermolysin and broth MMP activation appeared to be cell dependent as MMP activation did not occur in isolation. These results suggest the rapid increase in streptococcal species in the caecum and colon observed in parallel with carbohydrate induced equine laminitis may directly cause laminitis via production of exotoxin(s) capable of activating resident MMPs within the lamellar structure. Once activated, these MMPs can degrade key components of the basement membrane (BM) hemidesmosome complex, ultimately separating the BM from the epidermal basal cells resulting in the characteristic laminitis histopathology of hoof lamellae. While many different causative agents have been evaluated in the past, the results of this study provide a unifying aetiological mechanism for the development of carbohydrate induced equine laminitis. PMID:11240100

  10. Tension fatigue analysis and life prediction for composite laminates

    NASA Technical Reports Server (NTRS)

    Obrien, T. K.; Rigamonti, M.; Zanotti, C.

    1988-01-01

    A tension fatigue life prediction methodology for composite laminates is presented. Tension fatigue tests were conducted on quasi-isotropic and orthotropic glass epoxy, graphite epoxy, and glass/graphite epoxy hybrid laminates. Edge delamination onset data were used to generate plots of strain energy release rate as a function of cycles to delamination onset. These plots were then used along with strain energy release rate analyses of delaminations initiating at matrix cracks to predict local delamination onset. Stiffness loss was measured experimentally to account for the accumulation of matrix cracks and for delamination growth. Fatigue failure was predicted by comparing the increase in global strain resulting from stiffness loss to the decrease in laminate failure strain resulting from delaminations forming at matrix cracks through the laminate thickness. Good agreement between measured and predicted lives indicated that the through-thickness damage accumulation model can accurately describe fatigue failure for laminates where the delamination onset behavior in fatigue is well characterized, and stiffness loss can be monitored in real time to account for damage growth.

  11. The Cardiomyopathy Lamin A/C D192G Mutation Disrupts Whole-Cell Biomechanics in Cardiomyocytes as Measured by Atomic Force Microscopy Loading-Unloading Curve Analysis

    PubMed Central

    Lanzicher, Thomas; Martinelli, Valentina; Puzzi, Luca; Del Favero, Giorgia; Codan, Barbara; Long, Carlin S.; Mestroni, Luisa; Taylor, Matthew R. G.; Sbaizero, Orfeo

    2015-01-01

    Atomic force microscopy (AFM) cell loading/unloading curves were used to provide comprehensive insights into biomechanical behavior of cardiomyocytes carrying the lamin A/C (LMNA) D192G mutation known to cause defective nuclear wall, myopathy and severe cardiomyopathy. Our results suggested that the LMNA D192G mutation increased maximum nuclear deformation load, nuclear stiffness and fragility as compared to controls. Furthermore, there seems to be a connection between this lamin nuclear mutation and cell adhesion behavior since LMNA D192G cardiomyocytes displayed loss of AFM probe-to-cell membrane adhesion. We believe that this loss of adhesion involves the cytoskeletal architecture since our microscopic analyses highlighted that mutant LMNA may also lead to a morphological alteration in the cytoskeleton. Furthermore, chemical disruption of the actin cytoskeleton by cytochalasin D in control cardiomyocytes mirrored the alterations in the mechanical properties seen in mutant cells, suggesting a defect in the connection between the nucleoskeleton, cytoskeleton and cell adhesion molecules in cells expressing the mutant protein. These data add to our understanding of potential mechanisms responsible for this fatal cardiomyopathy, and show that the biomechanical effects of mutant lamin extend beyond nuclear mechanics to include interference of whole-cell biomechanical properties. PMID:26323789

  12. Nuclear Physics in a biological context

    NASA Astrophysics Data System (ADS)

    Discher, Dennis

    2012-02-01

    A solid tissue can be soft like fat or brain, stiff like striated muscle and heart, or rigid like bone -- and of course every cell has a nucleus that contributes in some way small or large to tissue mechanics. Indeed, nuclei generally exhibit rheology and plasticity that reflects both the chromatin and the nuclear envelope proteins called lamins, all of which change in differentiation. Profiling of tissue nuclei shows that the nuclear intermediate filament protein Lamin-A/C varies over 30-fold between adult tissues and scales strongly with micro-elasticity of tissue, while other nuclear envelope components such as Lamin-B exhibit small variations. Lamin-A/C has been implicated in aging syndromes that affect muscle and fat but not brain, and we find nuclei in brain-derived cells are indeed dominated by Lamin-B and are much softer than nuclei derived from muscle cells with predominantly Lamin-A/C. In vitro, matrix elasticity can affect expression of nuclear envelope components in adult stem cells, and major changes in Lamin-A/C are indeed shown to direct lineage with lower levels favoring soft tissue and higher levels promoting rigid tissue lineage. Further molecular studies provide evidence that the nucleus transduces physical stress. References: (1) J.D. Pajerowski, K.N. Dahl, F.L. Zhong, P.J. Sammak, and D.E. Discher. Physical plasticity of the nucleus in stem cell differentiation. PNAS 104: 15619-15624 (2007). (2) A. Buxboim, I. Ivanova, and D.E. Discher. Matrix Elasticity, Cytoskeletal Forces, and Physics of the Nucleus: how deeply do cells `feel' outside and in? Journal of Cell Science 123: 297-308 (2010).

  13. Mechanisms of compressive failure in woven composites and stitched laminates

    NASA Technical Reports Server (NTRS)

    Cox, B. N.; Dadkhah, M. S.; Inman, R. V.; Morris, W. L.; Schroeder, S.

    1992-01-01

    Stitched laminates and angle interlock woven composites have been studied in uniaxial, in-plane, monotonic compression. Failure mechanisms have been found to depend strongly on both the reinforcement architecture and the degree of constraint imposed by the loading grips. Stitched laminates show higher compressive strength, but are brittle, possessing no load bearing capacity beyond the strain for peak load. Post-mortem inspection shows a localized shear band of buckled and broken fibers, which is evidently the product of an unstably propagating kink band. Similar shear bands are found in the woven composites if the constraint of lateral displacements is weak; but, under strong constraint, damage is not localized but distributed throughout the gauge section. While the woven composites tested are weaker than the stitched laminates, they continue to bear significant loads to compressive strains of approx. 15 percent, even when most damage is confined to a shear band.

  14. Low-temperature mechanical properties of glass/epoxy laminates

    SciTech Connect

    Reed, R. P.; Madhukar, M.; Thaicharoenporn, B.; Martovetsky, N. N.

    2014-01-27

    Selected mechanical properties of glass/epoxy laminate candidates for use in the electrical turn and ground insulation of the ITER Central solenoid (CS) modules were measured. Short-beam shear and flexural tests have been conducted on various E-glass cloth weaves/epoxy laminates at 295 and 77 K. Types of glass weave include 1581, 7500, 7781, and 38050, which represent both satin and plain weaves. The epoxy, planned for use for vacuum-pressure impregnation of the CS module, consists of an anhydride-cured bisphenol F resin system. Inter-laminar shear strength, flexural elastic modulus, and flexural strength have been measured. The data indicate that these properties are dependent on the volume percent of glass. Short-beam shear strength was measured as a function of the span-to-thickness ratio for all laminates at 77 K. Comprehensive fractography was conducted to obtain the failure mode of each short-beam shear test sample.

  15. Low-temperature mechanical properties of glass/epoxy laminates

    NASA Astrophysics Data System (ADS)

    Reed, R. P.; Madhukar, M.; Thaicharoenporn, B.; Martovetsky, N. N.

    2014-01-01

    Selected mechanical properties of glass/epoxy laminate candidates for use in the electrical turn and ground insulation of the ITER Central solenoid (CS) modules were measured. Short-beam shear and flexural tests have been conducted on various E-glass cloth weaves/epoxy laminates at 295 and 77 K. Types of glass weave include 1581, 7500, 7781, and 38050, which represent both satin and plain weaves. The epoxy, planned for use for vacuum-pressure impregnation of the CS module, consists of an anhydride-cured bisphenol F resin system. Inter-laminar shear strength, flexural elastic modulus, and flexural strength have been measured. The data indicate that these properties are dependent on the volume percent of glass. Short-beam shear strength was measured as a function of the span-to-thickness ratio for all laminates at 77 K. Comprehensive fractography was conducted to obtain the failure mode of each short-beam shear test sample.

  16. Design of composite laminates for optimum frequency response

    NASA Astrophysics Data System (ADS)

    Kayikci, Rengin; Sonmez, Fazil O.

    2012-04-01

    In this study, natural frequency response of symmetrically laminated composite plates was optimized. An analytical model accounting for bending-twisting effects was used to determine the laminate natural frequency. Two different problems, fundamental frequency maximization and frequency separation maximization, were considered. Fiber orientation angles were chosen as design variables. Because of the existence of numerous local optimums, a global search algorithm, a variant of simulated annealing, was utilized to find the optimal designs. Results were obtained for different plate aspect ratios. Effects of the number of design variables and the range of values they may take on the optimal frequency were investigated. Problems in which fiber angles showed uncertainty were considered. Optimal frequency response of laminates subjected to static loads was also investigated.

  17. Evaluation of laminated composite structures using ultrasonic attenuation measurement

    NASA Astrophysics Data System (ADS)

    Shen, Peitao; Houghton, J. R.

    The existence of delamination and porosity in laminated composite structures will degrade the strength of the structures. The detection of delamination can be easily obtained using ultrasonic C-scan or A-scan methods. But, the detection of porosity in laminated structures has been a difficult task for years, especially in production condition. This paper will analytically evaluate the current techniques used in industry, and develop accurate attenuation measurement methods for the evaluation of porosity. The test samples, which are used in the laminated structures of the German airbus by Textron Aerostructures, Inc, will be tested using ultrasonic C-scan and grid-based A-scan methods. The digitized waveforms are stored and analyzed using different attenuation measurement algorithms. The volume of porosity is calculated using digital imaging analysis. Finally, the correlation between ultrasonic attenuation and the volume fraction of porosity are calculated and analyzed.

  18. Snap-Through of Unsymmetric Laminates Using Piezocomposite Actuators

    NASA Technical Reports Server (NTRS)

    Schultz, Marc R.; Hyer, Michael W.; Williams, R. Brett; Wilkie, W. Keats; Inman, Daniel J.

    2006-01-01

    The paper discusses the concept of using a piezoceramic actuator bonded to one side of a two-layer unsymmetric cross-ply [0/90]T laminate to provide the moments necessary to snap the laminate from one stable equilibrium shape to another. This concept could be applied to the morphing of structures. A model of this concept, which is based on the Rayleigh-Ritz technique and the use of energy and variational methods, is developed. The experimental phase of the study is discussed, including the measurement of the voltage level needed to snap the laminate. The voltage measurements and shapes are compared with predictions of the models and the agreement between measurements and the predictions are reasonable, both qualitatively and quantitatively. Suggestions for future activities are presented.

  19. Laminate composites with enhanced pyroelectric effects for energy harvesting

    NASA Astrophysics Data System (ADS)

    Chang, H. H. S.; Huang, Z.

    2010-06-01

    A pyroelectric coefficient enhanced 2-2 connectivity laminate composites' energy harvesting credentials have been assessed. The use of the electrothermal coupling factor for laminate composites (kLam2) for such an assessment has been appraised while the experimental samples are evaluated to show a significant improvement in their performance via pyroelectric coefficient enhancement, demonstrative of their great potential in energy harvesting applications. A lead zirconate titanate and stainless steel laminate composite with an 88% pyroelectric coefficient enhancement is shown to increase its maximum power density, efficiency, and electrothermal coupling factor by 254%, while other material pairings have also been evaluated to exhibit great promise in this application owing to a large pyroelectric coefficient enhancement accompanied by a reduction in total thermal mass.

  20. Damage prediction in cross-plied curved composite laminates

    NASA Technical Reports Server (NTRS)

    Martin, Roderick H.; Jackson, Wade C.

    1991-01-01

    Analytical and experimental work is detailed which is required to predict delamination onset and growth in a curved cross plied composite laminate subjected to static and fatigue loads. The composite used was AS4/3501/6, graphite/epoxy. Analytically, a closed form stress analysis and 2-D and 3-D finite element analyses were conducted to determine the stress distribution in an undamaged curved laminate. The finite element analysis was also used to determine values of strain energy release rate at a delamination emanating from a matrix crack in a 90 deg ply. Experimentally, transverse tensile strength and fatigue life were determined from flat 90 deg coupons. The interlaminar tensile strength and fatigue life were determined from double cantilevered beam specimens. Cross plied curved laminates were tested statically and in fatigue to give a comparison to the analytical predictions. A comparison of the fracture mechanics life prediction technique and the strength based prediction technique is given.

  1. Finite element analysis of laminated composite paraboloid of revolution shells

    NASA Astrophysics Data System (ADS)

    Dey, A.; Bandyopadhyay, J. N.; Sinha, P. K.

    1992-07-01

    A generalized formulation for the doubly curved laminated composite shell is attempted using eight-noded curved quadratic isoparametric finite elements with all three radii of curvature. The formulation is also applied to the isotropic material as a special case. In the present investigation, only the paraboloid of revolution is taken up for computing the deflections and stress resultants. Various parametric studies are carried out and the current results for both isotropic and laminated composite shells are compared with those available in the published literature. The shape functions are obtained from interpolation polynomial and the element stiffness matrices are formed on the basis of macromechanical analysis of laminates using the principle of minimum potential energy.

  2. A perturbation solution for interlaminar stresses in bidirectional laminates

    NASA Technical Reports Server (NTRS)

    Hsu, P. W.; Herakovich, C. T.

    1977-01-01

    The paper considers a thin elastic bidirectional symmetric composite laminate subjected to a uniform axial strain. All interlaminar stresses are determined by a zeroth-order perturbation analysis of the governing equations. The method of solution considers the laminate to be composed of an interior region (removed from the free edge) and a boundary layer region. The interior region is analyzed by dropping terms related to powers of the thickness-to-width ratio in the dimensionless elasticity equations. The boundary layer region is studied by introducing a stretching transformation to the governing equations. A uniform solution is then formed by satisfying Prandtl's matching principle of perturbation theory. Results for a four-layer bidirectional graphite-epoxy laminate are compared with existing finite-difference results. It is shown that the perturbation analysis provides more insight into the stress distribution near the free edge.

  3. Predicting viscoelastic response and delayed failures in general laminated composites

    NASA Technical Reports Server (NTRS)

    Dillard, D. A.; Morris, D. H.; Brinson, H. F.

    1982-01-01

    Although graphite fibers behave in an essentially elastic manner, the polymeric matrix of graphite/epoxy composites is a viscoelastic material which exhibits creep and delayed failures. The creep process is quite slow at room temperature, but may be accelerated by higher temperatures, moisture absorption, and other factors. Techniques are being studied to predict long-term behavior of general laminates based on short-term observations of the unidirectional material at elevated temperatures. A preliminary numerical procedure based on lamination theory is developed for predicting creep and delayed failures in laminated composites. A modification of the Findley nonlinear power law is used to model the constitutive behavior of a lamina. An adaptation of the Tsai-Hill failure criterion is used to predict the time-dependent strength of a lamina. Predicted creep and delayed failure results are compared with typical experimental data.

  4. Compression and compression fatigue testing of composite laminates

    NASA Technical Reports Server (NTRS)

    Porter, T. R.

    1982-01-01

    The effects of moisture and temperature on the fatigue and fracture response of composite laminates under compression loads were investigated. The structural laminates studied were an intermediate stiffness graphite-epoxy composite (a typical angle ply laimna liminate had a typical fan blade laminate). Full and half penetration slits and impact delaminations were the defects examined. Results are presented which show the effects of moisture on the fracture and fatigue strength at room temperature, 394 K (250 F), and 422 K (300 F). Static tests results show the effects of defect size and type on the compression-fracture strength under moisture and thermal environments. The cyclic tests results compare the fatigue lives and residual compression strength under compression only and under tension-compression fatigue loading.

  5. Fracture behavior of unidirectional boron/aluminum composite laminates

    NASA Technical Reports Server (NTRS)

    Jones, F. W.; Goree, J. G.

    1983-01-01

    An experimental investigation of the fracture behavior of unidirectional boron/aluminum composite laminates was conducted in order to verify the results of mathematical models. These models predict the fiber stresses and displacements and the amount of damage growth in a center-notched lamina as a function of the applied remote stress and the matrix and fiber material properties. A brittle lacquer coating was used to detect the yielding in the matrix while X-ray techniques were used to determine the number of broken fibers in the laminate. The notched strengths and the amounts of damage found in the specimens agreed well with those predicted by the models. It was shown that for thin laminates the amount of damage and the fiber displacements do not depend strongly on the number of plies for a given notch width.

  6. Low velocity impact of inclined CSM composite laminates

    SciTech Connect

    Arnold, W.S.; Madjidi, S.; Marshall, I.H.; Robb, M.D.

    1993-12-31

    The damage tolerance of composite laminates subject to low velocity impact is an important aspect of current design philosophies required to ensure the integrity of primary load bearing structures. To the authors knowledge, no work published in the open literature has addressed the damage tolerance of composites subject to impacts at non-perpendicular inclinations, which in practical situations is the most common form of impact. This paper describes an experimental study, devised to assess the influence of inclined impact on the residual strength characteristics of CSM laminates. Preliminary experimental results and comparisons with previous work on flat plate impact tests are presented. The influence of the degree of inclination and impact energy are correlated with the laminates damage area and residual tensile properties.

  7. Multiscale modeling of damage in multidirectional composite laminates

    NASA Astrophysics Data System (ADS)

    Singh, Chandra Veer

    The problem of damage accumulation in laminated composite materials has received much attention due to their widespread application in the aerospace, automotive, civil, and sports industries. In the aerospace industry, composites are used to make light weight and efficient structural components. In the Boeing 787, for example, more than 50% of the structure is made of composite materials. Although there have been significant developments in analyzing cross-ply laminates, none of the present approaches provides reasonable predictions for multidirectional laminates in which intralaminar cracks may form in multiple orientations. Nevertheless, the prediction of damage accumulation and its effect on structural performance is a very difficult problem due to complexity of the cracking processes. This study presents a synergistic damage mechanics (SDM) methodology to analyze damage behavior in multidirectional composite laminates with intralaminar cracks in plies of multiple orientations. SDM combines the strengths of micro-damage mechanics (MDM) and continuum damage mechanics (CDM) in predicting the stiffness degradation due to these cracks. The micromechanics is performed on a representative unit cell using a three-dimensional finite element analysis to calculate the crack opening displacement accounting for the influence of the surrounding plies, the so-called constraint effect. This information is then incorporated in the CDM formulation dealing with laminates containing cracks in different ply orientations through a 'constraint parameter'. Following CDM, a separate damage mode is defined for each type of crack and the expressions for engineering moduli of the damaged laminate are then derived in terms of crack density and the constraint parameter. The SDM methodology is implemented for [0 m/+/- thetan/0 m/2]s laminates containing cracks in +/-theta plies. It is then extended to [0m /+/- thetan/90 r]s and [0m/90 r/+/- thetan] s laminates with cracks additionally in the

  8. Some engineering properties of cotton-phenolic laminates

    NASA Astrophysics Data System (ADS)

    Walsh, R. P.; Toplosky, V. J.

    2002-05-01

    Although cotton/phenolic laminates are commonly used at cryogenic temperatures as structural and insulating materials, the available low temperature materials properties data is limited. We have reviewed the existing low temperature database for cotton/phenolic and have identified areas of need. We have conducted a materials test program on the two common types (linen and canvas) of cotton/phenolic laminates to add to the existing database and to generate new data in areas where needed. Also included is a comparison of cotton/phenolic engineering properties to the properties of NEMA G-10 CR glass-cloth reinforced laminate. The properties studied here are tensile and compressive strength, elastic modulus, shear properties and thermal expansion characteristics over the temperature range from 295 K to 4 K.

  9. 40 CFR 426.70 - Applicability; description of the automotive glass laminating subcategory.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... automotive glass laminating subcategory. 426.70 Section 426.70 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GLASS MANUFACTURING POINT SOURCE CATEGORY Automotive Glass Laminating Subcategory § 426.70 Applicability; description of the automotive...

  10. 40 CFR 426.70 - Applicability; description of the automotive glass laminating subcategory.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... automotive glass laminating subcategory. 426.70 Section 426.70 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) GLASS MANUFACTURING POINT SOURCE CATEGORY Automotive Glass Laminating Subcategory § 426.70 Applicability; description of the...

  11. 40 CFR 426.70 - Applicability; description of the automotive glass laminating subcategory.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... automotive glass laminating subcategory. 426.70 Section 426.70 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) GLASS MANUFACTURING POINT SOURCE CATEGORY Automotive Glass Laminating Subcategory § 426.70 Applicability; description of the...

  12. 40 CFR 426.70 - Applicability; description of the automotive glass laminating subcategory.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... automotive glass laminating subcategory. 426.70 Section 426.70 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GLASS MANUFACTURING POINT SOURCE CATEGORY Automotive Glass Laminating Subcategory § 426.70 Applicability; description of the automotive...

  13. 40 CFR 426.70 - Applicability; description of the automotive glass laminating subcategory.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... automotive glass laminating subcategory. 426.70 Section 426.70 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) GLASS MANUFACTURING POINT SOURCE CATEGORY Automotive Glass Laminating Subcategory § 426.70 Applicability; description of the...

  14. Development of laminated fiber-reinforced nanocomposites for bone regeneration

    NASA Astrophysics Data System (ADS)

    Xu, Weijie

    There have been numerous efforts to develop synthetic and/or natural tissue engineering scaffolds that are suitable for bone regeneration applications to replace autograft and allograft bones. Current biomaterials as a scaffold for bone regeneration are limited by the extent of degradation concurrent with bone formation, mechanical strength, and the extent of osteogenic differentiation of marrow stromal cells migrating from the surrounding tissues. In this project, a novel laminated nanocomposite scaffold is fabricated, consisting of poly (L-lactide ethylene oxide fumarate) (PLEOF) hydrogel reinforced with poly (L-lactic acid) (PLLA) electrospun nanofibers and hydroxyapatite (HA) nanoparticles. PLEOF is a novel in situ crosslinkable macromer synthesized from biocompatible building units which can be functionalized with bioactive peptides like the cell-adhesive Arg--Gly--Asp (RGD) amino acid sequence. The hydrophilicity and degradation rate of the macromer can be tailored to a particular application by controlling the ratio of PEG to PLA blocks in the macromer and the unsaturated fumarate units can be used for in-situ crosslinking. The PLLA nanofibers were electrospun from high molecular weight PLLA. The laminated nanocomposites were fabricated by dry-hand lay up technique followed by compression molding and thermal crosslinking. The laminated nanocomposites were evaluated with respect to degradation, water uptake, mechanical strength, and the extent of osteogenic differentiation of bone marrow stromal (BMS) cells. Laminates with or without HA nanoparticles showed modulus values much higher than that of trabecular bone (50-100 MPa). The effect of laminated nanocomposites on osteogenic differentiation of BMS cells was determined in terms of cell number, ALPase activity and calcium content. Our results demonstrate that grafting RGD peptide and HA nanoparticles to a PLEOF hydrogel reinforced with PLLA nanofibers synergistically enhance osteogenic differentiation of BMS

  15. Recycling of waste automotive laminated glass and valorization of polyvinyl butyral through mechanochemical separation.

    PubMed

    Swain, Basudev; Ryang Park, Jae; Yoon Shin, Dong; Park, Kyung-Soo; Hwan Hong, Myung; Gi Lee, Chan

    2015-10-01

    Due to strong binding, optical clarity, adhesion to many surfaces, toughness and flexibility polyvinyl butyral (PVB) resin films are commonly used in the automotive and architectural application as a protective interlayer in the laminated glass. Worldwide million tons of PVB waste generated from end-of-life automotive associated with various environmental issues. Stringent environmental directive, higher land cost eliminates land filling option, needs a study, we have developed a mechanochemical separation process to separate PVB resins from glass and characterized the separated PVB through various techniques, i.e., scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), infrared spectroscopy (IR) and nuclear magnetic resonance spectroscopy (NMR). Commercial nonionic surfactants D201 used for the mechanochemical separation purpose. Through parameter optimization following conditions are considered to be the optimum condition; 30v ol% D201, stirring speed of 400 rpm, 35 °C temperature, operation time 1h, and dilute D201 volume to waste automotive laminated glass weight ratio of ≈25. The technology developed in our laboratory is sustainable, environmentally friendly, techno-economical feasible process, capable of mass production (recycling). PMID:26318256

  16. N-cadherin is essential for retinal lamination in the zebrafish.

    PubMed

    Erdmann, Bettina; Kirsch, Frank-P; Rathjen, Fritz G; Moré, Margret I

    2003-03-01

    N-cadherin is one of the major Ca(2+)-dependent cell adhesion proteins in the developing nervous system. Here, we analyze eye development in the zebrafish N-cadherin loss-of-function mutant parachute(paR2.10) (pac(paR2.10)). The zebrafish visual system is fully developed by the time pac(paR2.10) mutants show lethality at day 5. Already at 24 hr postfertilization (hpf), mutant retinal cells are more disorganized and more rounded than in wild-type. At later stages, mutant retinae display a severe lamination defect with rosette formation (mostly islands of plexiform layer tissue surrounded by inner nuclear layer or photoreceptor cells), even though all major classes of cell types appear to be present as determined by histology. Of interest, electron microscopy reveals that the islands of plexiform layer tissue contain a normal amount of synapses with normal morphology. Although mutant photoreceptor cells are sometimes deformed, all typical structural components are present, including the membranous discs for rhodopsin storage. The lens fibers of the pac(paR2.10) mutants develop completely normally, but in some cases, lens epithelial cells round up and become multilayered. We conclude that cell adhesion mediated by N-cadherin is of major importance for retinal lamination and involved in maintenance of the lens epithelial sheet, but is not essential for the formation of photoreceptor ultrastructure or for synaptogenesis. PMID:12619142

  17. Optimum single modal and bimodal buckling design of symmetric laminates

    NASA Technical Reports Server (NTRS)

    Qian, B.; Reiss, R.; Aung, W.

    1989-01-01

    Variational calculus is used to determine the design that maximizes the resistance of classical symmetric laminates against buckling. The orientations of the constituent orthotropic laminae with respect to the principal axes of the laminate are the design variables. It is shown that the optimal design may not be a point of analyticity of the buckling load. Local analytic extrema are obtained from the design derivatives of the buckling load. Nonanalytic extrema occur whenever the buckling load is a repeated eigenvalue. A novel approach, using a directional design derivative, is employed to determine nonanalytic extrema. Specific examples are presented for biaxial buckling for several different boundary conditions.

  18. Laminated active matrix organic light-emitting devices

    NASA Astrophysics Data System (ADS)

    Liu, Hongyu; Sun, Runguang

    2008-02-01

    Laminated active matrix organic light-emitting device (AMOLED) realizing top emission by using bottom-emitting organic light-emitting diode (OLED) structure was proposed. The multilayer structure of OLED deposited in the conventional sequence is not on the thin film transistor (TFT) backplane but on the OLED plane. The contact between the indium tin oxide (ITO) electrode of TFT backplane and metal cathode of OLED plane is implemented by using transfer electrode. The stringent pixel design for aperture ratio of the bottom-emitting AMOLED, as well as special technology for the top ITO electrode of top-emitting AMOLED, is unnecessary in the laminated AMOLED.

  19. Complex response of a bistable laminated plate: Multiscale entropy analysis

    NASA Astrophysics Data System (ADS)

    Borowiec, M.; Rysak, A.; Betts, D. N.; Bowen, C. R.; Kim, H. A.; Litak, G.

    2014-10-01

    The use of bistable laminates is a potential approach to realize more broadband piezoelectric based energy harvesting systems. Based on the experimental time series of a bistable laminate plate we have examined its dynamic response. The system was subjected to harmonic excitations showing the existence of single well and snap-through vibrations of periodic and chaotic character. To identify the dynamics of the system response we examine the frequency spectrum, phase portraits and multi-scaled entropy. It is observed that the composite multiscale entropy analysis can be used to identify complexity within the dynamic response successfully.

  20. A higher order theory of laminated composite cylindrical shells

    NASA Technical Reports Server (NTRS)

    Krishna Murthy, A. V.; Reddy, T. S. R.

    1986-01-01

    A new higher order theory has been proposed for the analysis of composite cylindrical shells. The formulation allows for arbitrary variation of inplane displacements. Governing equations are presented in the form of a hierarchy of sets of partial differential equations. Each set describes the shell behavior to a certain degree of approximation. The natural frequencies of simply-supported isotropic and laminated shells and stresses in a ring loaded composite shell have been determined to various orders of approximation and compared with three dimensional solutions. These numerical studies indicate the improvements achievable in estimating the natural frequencies and the interlaminar shear stresses in laminated composite cylinders.

  1. Postbuckling analysis of composite laminated cylindrical panels under axial compression

    NASA Astrophysics Data System (ADS)

    Kweon, J. H.; Hong, C. S.

    1993-08-01

    The nonlinear finite element method is used to analyze the postbuckling behavior of composite laminated cylindrical panels with various stacking sequences under compression. The analysis is based on the updated Lagrangian formulation, an eight-node degenerated shell element, and an improved load-increment method based on the arc-length scheme. Results reveal that the postbuckling loads carrying capacities of laminated cylindrical panels under compression are largely dependent on the bending stiffness component. Not only the buckling loads but also the postbuckling load-carrying capacities should be considered in designing the structure.

  2. Metal Matrix Laminate Tailoring (MMLT) code: User's manual

    NASA Technical Reports Server (NTRS)

    Murthy, P. L. N.; Morel, M. R.; Saravanos, D. A.

    1993-01-01

    The User's Manual for the Metal Matrix Laminate Tailoring (MMLT) program is presented. The code is capable of tailoring the fabrication process, constituent characteristics, and laminate parameters (individually or concurrently) for a wide variety of metal matrix composite (MMC) materials, to improve the performance and identify trends or behavior of MMC's under different thermo-mechanical loading conditions. This document is meant to serve as a guide in the use of the MMLT code. Detailed explanations of the composite mechanics and tailoring analysis are beyond the scope of this document, and may be found in the references. MMLT was developed by the Structural Mechanics Branch at NASA Lewis Research Center (LeRC).

  3. Laminated rubber articulated joint for the Deep Water Gravity Tower

    SciTech Connect

    Sedillot, F.; Stevenson, A.

    1983-12-01

    The Deep Water Gravity Tower is an articulated structure resting on a fixed base through an articulated joint which is composed of curved laminated rubber pads, made from alternate layers of rubber and metallic shims. The paper first outlines the main design concept with the articulated joint. Some analysis is then provided of the response to imposed rotation and vertical load. This includes a brief description of the results of a finite element analysis. The paper then reviews the test performed on laminated rubber during 1980 and 1981 to assess the feasibility of the articulation: fatigue tests; environmental tests (effect of sea water, temperature, pressure).

  4. Transient thermal stress analysis of a laminated composite beam

    SciTech Connect

    Tanigawa, Y.; Murakami, H.; Ootao, Y. California Univ., La Jolla Osaka Prefectural Industrial Technology Research Institute )

    1989-01-01

    This paper considers a transient thermal stress analysis of a laminated beam made of different materials in multilayers. To simplify the problem, the heat conduction problem is treated as a one-dimensional case in the direction of thickness; then, the transient temperature solution is evaluated using the Laplace transform method. For the thermoelastic fields, thermal stress distributions are obtained using the elementary beam theory and Airy's thermal stress function method. As an example, numerical calculations are carried out for a laminated beam made of five layers, and the numerical results are examined.

  5. Laminated structures and methods and compositions for producing same

    DOEpatents

    Fumei, Giancarlo J.; Karabedian, James A.

    1977-04-05

    Methods for bonding two substrates, one of which is polymeric, which comprise coating the surface of at least one substrate with an adhesive composition comprising a major component which is an adhesive for the first substrate and a minor disperse phase which is a solution of a polymer in a solvent for the polymeric substrate and contacting the coated surface of the one substrate with the surface of the other substrate, together with adhesive compositions useful for joining such substrates, laminates so formed, and articles comprised of such laminates.

  6. Nuclear envelope structural defects cause chromosomal numerical instability and aneuploidy in ovarian cancer

    PubMed Central

    2011-01-01

    Background Despite our substantial understanding of molecular mechanisms and gene mutations involved in cancer, the technical approaches for diagnosis and prognosis of cancer are limited. In routine clinical diagnosis of cancer, the procedure is very basic: nuclear morphology is used as a common assessment of the degree of malignancy, and hence acts as a prognostic and predictive indicator of the disease. Furthermore, though the atypical nuclear morphology of cancer cells is believed to be a consequence of oncogenic signaling, the molecular basis remains unclear. Another common characteristic of human cancer is aneuploidy, but the causes and its role in carcinogenesis are not well established. Methods We investigated the expression of the nuclear envelope proteins lamin A/C in ovarian cancer by immunohistochemistry and studied the consequence of lamin A/C suppression using siRNA in primary human ovarian surface epithelial cells in culture. We used immunofluorescence microscopy to analyze nuclear morphology, flow cytometry to analyze cellular DNA content, and fluorescence in situ hybridization to examine cell ploidy of the lamin A/C-suppressed cells. Results We found that nuclear lamina proteins lamin A/C are often absent (47%) in ovarian cancer cells and tissues. Even in lamin A/C-positive ovarian cancer, the expression is heterogeneous within the population of tumor cells. In most cancer cell lines, a significant fraction of the lamin A/C-negative population was observed to intermix with the lamin A/C-positive cells. Down regulation of lamin A/C in non-cancerous primary ovarian surface epithelial cells led to morphological deformation and development of aneuploidy. The aneuploid cells became growth retarded due to a p53-dependent induction of the cell cycle inhibitor p21. Conclusions We conclude that the loss of nuclear envelope structural proteins, such as lamin A/C, may underlie two of the hallmarks of cancer - aberrations in nuclear morphology and aneuploidy

  7. Analysis of interlaminar stresses in thick composite laminates with and without edge delamination

    NASA Technical Reports Server (NTRS)

    Whitcomb, J. D.; Raju, I. S.

    1985-01-01

    The effect of laminate thickness on the interlaminar stresses in rectangular quasi-isotropic laminates under uniform axial strain was studied. Laminates from 8-ply to infinitely thick were analyzed. Thick laminates were synthesized by stacking (45/0/-45/90) ply groups, rather than grouping like plies. Laminates with and without delaminations were studied. In laminates without delaminations, the free-edge interlaminar normal stress distribution in the outer ply groups was insensitive to total laminate thickness. The interlaminar normal stress distribution for the interior ply groups was nearly the same as for an infinitely thick laminate. In contrast, the free-edge inter-laminar shear stress distribution was nearly the same for inner and outer ply groups and was insensitive to laminate thickness. In laminates with delaminations those delaminations near the top and bottom surfaces of a thick laminate have much larger total strain-energy-release rates (G sub t) and mode I-to-total (G sub t/G sub t) ratios than delaminations deep in the interior. Therefore, delaminations can be expected to grow more easily near the surfaces of a laminate than in the interior.

  8. Analysis of interlaminar stresses in thick composite laminates with and without edge delamination

    NASA Technical Reports Server (NTRS)

    Whitcomb, J. D.; Raju, I. S.

    1984-01-01

    The effect of laminate thickness on the interlaminar stresses in rectangular quasi-isotropic laminates under uniform axial strain was studied. Laminates from 8-ply to infinitely thick were analyzed. Thick laminates were synthesized by stacking (45/0/-45/90) ply groups, rather than grouping like plies. Laminates with and without delaminations were studied. In laminates without delaminations, the free-edge interlaminar normal stress distribution in the outer ply groups was insensitive to total laminate thickness. The interlaminar normal stress distribution for the interior ply groups was nearly the same as for an infinitely thick laminate. In contrast, the free-edge inter-laminar shear stress distribution was nearly the same for inner and outer ply groups and was insensitive to laminate thickness. In laminates with delaminations those delaminations near the top and bottom surfaces of a thick laminate have much larger total strain-energy-release rates (G sub t) and mode I-to-total (G sub t/G sub t) ratios than delaminations deep in the interior. Therefore, delaminations can be expected to grow more easily near the surfaces of a laminate than in the interior.

  9. Accelerated telomere shortening and replicative senescence in human fibroblasts overexpressing mutant and wild-type lamin A

    SciTech Connect

    Huang Shurong; Risques, Rosa Ana; Martin, George M.; Rabinovitch, Peter S.; Oshima, Junko

    2008-01-01

    LMNA mutations are responsible for a variety of genetic disorders, including muscular dystrophy, lipodystrophy, and certain progeroid syndromes, notably Hutchinson-Gilford Progeria. Although a number of clinical features of these disorders are suggestive of accelerated aging, it is not known whether cells derived from these patients exhibit cellular phenotypes associated with accelerated aging. We examined a series of isogenic skin fibroblast lines transfected with LMNA constructs bearing known pathogenic point mutations or deletion mutations found in progeroid syndromes. Fibroblasts overexpressing mutant lamin A exhibited accelerated rates of loss of telomeres and shortened replicative lifespans, in addition to abnormal nuclear morphology. To our surprise, these abnormalities were also observed in lines overexpressing wild-type lamin A. Copy number variants are common in human populations; those involving LMNA, whether arising meiotically or mitotically, might lead to progeroid phenotypes. In an initial pilot study of 23 progeroid cases without detectable WRN or LMNA mutations, however, no cases of altered LMNA copy number were detected. Nevertheless, our findings raise a hypothesis that changes in lamina organization may cause accelerated telomere attrition, with different kinetics for overexpession of wild-type and mutant lamin A, which leads to rapid replicative senescence and progroid phenotypes.

  10. A study of diamond laminated surfaces in evaporative spray cooling

    NASA Astrophysics Data System (ADS)

    Sehmbey, M. S.; Pais, M. R.; Chow, L. C.

    This effort is directed towards studying the performance of diamond laminated surfaces under conditions of evaporative spray cooling of high-heat-flux electronic components. The experimental results presented illustrate the robustness of the surface, as well as its heat transfer characteristics, wettability and roughness. Exceptional heat flux rates of over 1100 W/sq cm were obtained within superheats of 40 C.

  11. Damage in woven CFRP laminates subjected to low velocity impacts

    NASA Astrophysics Data System (ADS)

    Ullah, H.; Abdel-Wahab, A. A.; Harland, A. R.; Silberschmidt, V. V.

    2012-08-01

    Carbon fabric-reinforced polymer (CFRP) composites used in sports products can be exposed to different in-service conditions such as large dynamic bending deformations caused by impact loading. Composite materials subjected to such loads demonstrate various damage modes such as matrix cracking, delamination and, ultimately, fabric fracture. Damage evolution in these materials affects both their in-service properties and performance that can deteriorate with time. These processes need adequate means of analysis and investigation, the major approaches being experimental characterisation and non-destructive examination of internal damage in composite laminates. This research deals with a deformation behaviour and damage in woven composite laminates due to low-velocity dynamic out-of-plane bending. Experimental tests are carried out to characterise the behaviour of such laminates under large-deflection dynamic bending in un-notched specimens in Izod tests using a Resil Impactor. A series of low-velocity impact tests is carried out at various levels of impact energy to assess the energy absorbed and force-time response of CFRP laminates. X-ray micro computed tomography (micro-CT) is used to investigate material damage modes in the impacted specimens. X-ray tomographs revealed that through-thickness matrix cracking, inter-ply delamination and intra-ply delamination, such as tow debonding and fabric fracture, were the prominent damage modes.

  12. Polarized light reveals stress in machined laminated plastics

    NASA Technical Reports Server (NTRS)

    Frankowski, J.

    1967-01-01

    Polarized light applied to drilled laminated plastic components exposes to the human eye the locked-in stresses that will result in fractures and delaminations when the soldering procedure takes place. This technique detects stresses early in the production cycle before appreciable man-hours are invested in an item destined for rejection.

  13. An empirical modified fatigue damage model for impacted GFRP laminates

    NASA Astrophysics Data System (ADS)

    Naderi, S.; Hassan, M. A.; Bushroa, A. R.

    2014-10-01

    The aim of the present paper is to evaluate the residual strength of GFRP laminates following a low-velocity impact event under cyclic loading. The residual strength is calculated using a linear fatigue damage model. According to an investigation into the effect of low-velocity impact on the fatigue behavior of laminates, it seems laminate fatigue life decreases after impact. By normalizing the fatigue stress against undamaged static strength, the Fatigue Damage parameter “FD” is presented with a linear relationship as its slope which is a linear function of the initial impact energy; meanwhile, the constants were attained from experimental data. FD is implemented into a plane-stress continuum damage mechanics based model for GFRP composite laminates, in order to predict damage threshold in composite structures. An S-N curve is implemented to indicate the fatigue behavior for 2 mm thickness encompassing both undamaged and impacted samples. A decline in lifespan is evident when the impact energy level increases. Finally, the FD is intended to capture the unique GFRP composite characteristics.

  14. Liquid crystals detect voids in fiber glass laminates

    NASA Technical Reports Server (NTRS)

    Hollar, W. T.

    1967-01-01

    Liquid crystal solution nondestructively detects voids or poor bond lines in fiber glass laminates. A thin coating of the solution is applied by spray or brush to the test article surface, and when heated indicates the exact location of defects by differences in color.

  15. Analyzing the methods and merits of recycling fiber metal laminates

    NASA Astrophysics Data System (ADS)

    Tempelman, E.; Dalmijn, W. L.; Vlot, A.

    1996-04-01

    It is technically possible to recycle fiber metal laminates (FMLs) by retrieving the aluminum fraction from FML scrap; this reprocessing becomes economically feasible at a throughput of 50 tonnes or more per year. Until then, FML scrap can be dealt with in conventional ways.

  16. Residual strength of metal-matrix laminated panels

    SciTech Connect

    Wu, M.; Wilson, D.

    1997-12-31

    The primary objective of this study was to investigate the residual strength of ARALL-3 and GLARE-2 center-notched panels without stiffeners. The R-curve approach in linear elastic fracture mechanics (LEFM) was used for the residual strength predictions. The applicability of LEFM was verified through a series of tests of ARALL-3 and GLARE-2 center-notched panels with different layups. They demonstrated limited crack-tip plastic deformation. The R-curves calculated from the tests of different size panels with various initial crack extensions showed that they were independent of initial crack length and specimen width, which is true for the monolithic aluminum alloy. Polynomial curve fitting was used to obtain the R-curves for each laminate and laminate layup to be used for the R-curve residual strength predictions. The predictions were made by superimposing the crack driving force curves onto these R-curves to locate the tangent points. The results of prediction of unidirectional fiber/metal laminates proved that the R-curve approach was not only a suitable but simple method that has a great potential in the damage tolerance characterization of certain unstiffened and stiffened laminate materials.

  17. A survey of strength analysis methods for laminates with holes

    NASA Technical Reports Server (NTRS)

    Crews, J. H., Jr.

    1984-01-01

    The methods for predicting the strength of composite laminates with fastener holes are reviewed for the cases of unloaded as well as loaded holes. Three categories of methods are discussed: (1) the hole-boundary stress (HBS) methods which compare the peak stresses and the laminate strength; (2) the linear elastic fracture (LEFM) methods which assume cracks emanating from the hole and predict failure when the stress intensity factor for a crack equals the laminate fracture toughness; and (3) two different two-parameter (TP) methods: the average-stress (ASTP) method, which predicts failure when the average stress over a distance from the hole equals the laminate strength; and the point-stress (PSTP) Whitney-Nuismer (1974) approach, which predicts failure when the stress near the hole equals the material strength. The PSTP is relatively accurate and is by far the most widely used of all the prediction methods. However, for large ranges of variables and cases, the current strength predictions may not always be accurate.

  18. Dynamic delamination crack propagation in a graphite/epoxy laminate

    NASA Technical Reports Server (NTRS)

    Grady, J. E.; Sun, C. T.

    1991-01-01

    Dynamic delamination crack propagation in a (90/0) 5s Graphite/Epoxy laminate with an embedded interfacial crack was investigated experimentally using high speed photography. The dynamic motion was produced by impacting the beamlike laminate specimen with a silicon rubber ball. The threshold impact velocities required to initiate dynamic crack propagation in laminates with varying initial crack positions were determined. The crack propagation speeds were estimated from the photographs. Results show that the through the thickness position of the embedded crack can significantly affect the dominant mechanism and the threshold impact velocity for the onset of crack movement. If the initial delamination is placed near the top of bottom surface of the laminate, local buckling of the delaminated plies may cause instability of the crack. If the initial delamination lies on the midplane, local buckling does not occur and the initiation of crack propagation appears to be dominated by Mode II fracture. The crack propagation and arrest observed was seen to be affected by wave motion within the delamination region.

  19. Direct deposit laminate nanocomposites with enhanced propellent properties.

    PubMed

    Li, Xiangyu; Guerieri, Philip; Zhou, Wenbo; Huang, Chuan; Zachariah, Michael R

    2015-05-01

    One of the challenges in the use of energetic nanoparticles within a polymer matrix for propellant applications is obtaining high particle loading (high energy density) while maintaining mechanical integrity and reactivity. In this study, we explore a new strategy that utilizes laminate structures. Here, a laminate of alternating layers of aluminum nanoparticle (Al-NPs)/copper oxide nanoparticle (CuO-NPs) thermites in a polyvinylidene fluoride (PVDF) reactive binder, with a spacer layer of PVDF was fabricated by a electrospray layer-by-layer deposition method. The deposited layers containing up to 60 wt % Al-NPs/CuO-NPs thermite are found to be uniform and mechanically flexible. Both the reactive and mechanical properties of laminate significantly outperformed the single-layer structure with the same material composition. These results suggest that deploying a multilayer laminate structure enables the incorporation of high loadings of energetic materials and, in some cases, enhances the reactive properties over the corresponding homogeneous structure. These results imply that an additive manufacturing approach may yield significant advantages in developing a tailored architecture for advanced propulsion systems. PMID:25815706

  20. Laminated plastic microfluidic components for biological and chemical systems

    SciTech Connect

    Martin, P.M.; Matson, D.W.; Bennett, W.D.; Lin, Y.; Hammerstrom, D.J.

    1999-07-01

    Laminated plastic microfluidic components are being developed for biological testing systems and chemical sensors. Applications include a DNA thermal cycler, DNA analytical systems, electrophoretic flow systems, dialysis systems, and metal sensors for ground water. This article describes fabrication processes developed for these plastic microfluidic components, and the fabrication of a chromium metal sensor and a microdialysis device. Most of the components have a stacked architecture. Using this architecture, the fluid flows, or is pumped through, as many as nine laminated functional levels. Functions include pumping, mixing, reaction, detection, reservoirs, separations, and electronics. Polyimide, poly(methylmethacrylate) (PMMA), and polycarbonate materials with thicknesses between 25 and 125 {mu}m are used to construct the components. This makes the components low cost, inert to many biological fluids and chemicals, and disposable. The components are fabricated by excimer laser micromachining the microchannel patterns and microstructures in the various laminates. In some cases, micropumps are integrated into these components to move the fluids. Vias and interconnects are also cut by the laser and integrated with micropumps. The laminates are sealed and bonded by adhesive and thermal processes and are leak tight. The parts withstand pressures as high as 790 kPa. Typical channel widths are 50 to 100 {mu}m, with aspect ratios near 5. {copyright} {ital 1999 American Vacuum Society.}

  1. Making Ceramic Parts by Laminating and Sintering Thin Sheets

    NASA Technical Reports Server (NTRS)

    Cawley, J. D.

    1987-01-01

    Chemical composition varies as function of depth. Technique developed to fabricate monolithic ceramic component by sintering laminated body made from thin sheets of green ceramic. Method allows discrete changes in chemistry effected across monolith. Component having one-dimensional variation in material composition fabricated in this manner.

  2. Photodegradation in ballistic laminates: Spectroscopy and lifetime extension

    SciTech Connect

    Renschler, C.L.; Stallard, B.R.; White, C.A.; Garcia, M.J.; Morse, H.E.

    1996-06-01

    Several years ago, the Materials and Process Sciences Center (Org. 1800) was asked by Dept. 9613 to study the materials aging issues which had led to the loss of ballistic protection by Armored Tractor (AT) windshields and windows. The authors speculated that this loss of impact strength was due to photodegradation of the polycarbonate (PC) inboard ply. They developed a spectroscopic method to identify changes in the outboard surface of the PC, and showed that the changes in the surface which occurred upon natural aging in the field could be reproduced by exposing the laminates to a simulated solar flux. Based on these results, they recommended changes in the adhesive interlayers to filter out the ultraviolet (UV) light causing the aging problem. Working with the laminate vendor, PPG, they re-designed the laminates to implement these changes and block essentially all UV light from the inboard ply. The most recent phase of this work involved accelerated solar aging of laminates made with the new design to verify that photoaging effects have been blocked by the new materials. They report here the results of that study, and recommended follow-on work.

  3. Delamination failure in a unidirectional curved composite laminate

    NASA Technical Reports Server (NTRS)

    Martin, Roderick H.

    1992-01-01

    Delamination failure in a unidirectional curved composite laminate was investigated. The curved laminate failed unstably by delaminations developing around the curved region of the laminate at different depths through the thickness until virtually all bending stiffness was lost. Delamination was assumed to initiate at the location of the highest radial stress in the curved region. A closed form curved beam elasticity solution and a 2D finite element analysis (FEA) were conducted to determine this location. The variation in the strain energy release rate, G, with delamination growth was then determined using the FEA. A strength-based failure criteria adequately predicted the interlaminar tension failure which caused initial delamination onset. Using the G analysis the delamination was predicted to extend into the arm and leg of the laminate, predominantly in mode I. As the initial delamination grew around the curved region, the maximum radial stress in the newly formed inner sublaminate increased to a level sufficient to cause a new delamination to initiate in the sublaminate with no increase in applied load. This failure progression was observed experimentally.

  4. Delamination failure in a unidirectional curved composite laminate

    NASA Technical Reports Server (NTRS)

    Martin, Roderick H.

    1990-01-01

    Delamination failure in a unidirectional curved composite laminate was investigated. The curved laminate failed unstably by delaminations developing around the curved region of the laminate at different depths through the thickness until virtually all bending stiffness was lost. Delamination was assumed to initiate at the location of the highest radial stress in the curved region. A closed form curved beam elasticity solution and a 2-D finite element analysis (FEA) were conducted to determine this location. The variation in the strain energy release rate, G, with delamination growth was then determined using the FEA. A strength-based failure criteria adequately predicted the interlaminar tension failure which caused initial delamination onset. Using the G analysis the delamination was predicted to extend into the arm and leg of the laminate, predominantly in mode I. As the initial delamination grew arould the curved region, the maximum radial stress in the newly formed inner sublaminate increased to a level sufficient to cause a new delamination to initiate in the sublaminate with no increase in applied load. This failure progression was observed experimentally.

  5. Analysis of dynamic instability for arbitrarily laminated skew plates

    NASA Astrophysics Data System (ADS)

    Wu, G. Y.; Shih, Y. S.

    2006-04-01

    The dynamic instability and nonlinear response of rectangular and skew laminated plates subjected to periodic in-plane load are studied. Based on von Karman plate theory, the large amplitude dynamic equations of thin laminated plates are derived by applying the approach of generalized double Fourier series. On the assumed mode shape, the governing equations are reduced to the Mathieu equation using Galerkin's method. The incremental harmonic balance (IHB) method is applied to solve the nonlinear temporal equation of motion, and the region of dynamic instability is determined in this work. Calculations are carried out for isotropic, angle-ply and arbitrarily laminated plates under two cases of boundary conditions. The principal region of dynamic instability associated with the effect of the stacking sequence of lamination and the skew angle of plate are also investigated and discussed. The results obtained indicated that the instability behavior of the system is determined by the several parameters, such as the boundary condition, number of the layers, stacking sequence, in-plane load, aspect ratio, amplitude and the skew angle of plate.

  6. Process-induced viscoelastic stress in composite laminates

    SciTech Connect

    Stango, R.J.

    1985-01-01

    In recent years, considerable interest has developed in evaluating the stress response of composite laminates which is associated with cooling the material system from the cure temperature to room temperature. This research examines the fundamental nature of time-dependent residual-thermal stresses in composite laminates which are caused by the extreme temperature reduction encountered during the fabrication process. Viscoelastic stress in finite-width, symmetric composite laminates is examined on the basis of a formulation that employs an incremental hereditary integral approach in conjunction with a quasi-three dimensional finite element analysis. A consistent methodology is developed and employed for the characterization of lamina material properties. Special attention is given to the time-dependent stress response at ply-interface locations near the free-edge. In addition, the influence of cooling path on stress history is examined. Recently published material property data for graphite-epoxy lamina is employed in the analysis. Results of the investigation generally indicate that nominal differences between the thermoelastic and viscoelastic solutions are obtained. Slight changes of the final stress state are observed to result when different cooling paths are selected for the temperature history. The methodology employed is demonstrated to result in an accurate, efficient, and consistent approach for the viscoelastic analysis of advanced composite laminates.

  7. The Lamin B receptor is essential for cholesterol synthesis and perturbed by disease-causing mutations

    PubMed Central

    Tsai, Pei-Ling; Zhao, Chenguang; Turner, Elizabeth; Schlieker, Christian

    2016-01-01

    Lamin B receptor (LBR) is a polytopic membrane protein residing in the inner nuclear membrane in association with the nuclear lamina. We demonstrate that human LBR is essential for cholesterol synthesis. LBR mutant derivatives implicated in Greenberg skeletal dysplasia or Pelger-Huët anomaly fail to rescue the cholesterol auxotrophy of a LBR-deficient human cell line, consistent with a loss-of-function mechanism for these congenital disorders. These disease-causing variants fall into two classes: point mutations in the sterol reductase domain perturb enzymatic activity by reducing the affinity for the essential cofactor NADPH, while LBR truncations render the mutant protein metabolically unstable, leading to its rapid degradation at the inner nuclear membrane. Thus, metabolically unstable LBR variants may serve as long-sought-after model substrates enabling previously impossible investigations of poorly understood protein turnover mechanisms at the inner nuclear membrane of higher eukaryotes. DOI: http://dx.doi.org/10.7554/eLife.16011.001 PMID:27336722

  8. An experimental investigation on the three-point bending behavior of composite laminate

    NASA Astrophysics Data System (ADS)

    A, Azzam; W, Li

    2014-08-01

    The response of composite laminate structure to three-point bending load was investigated by subjecting two types of stacking sequences of composite laminate structure by using electronic universal tester (Type: WDW-20) machine. Optical microscope was selected in order to characterize bending damage, delamination, and damage shapes in composite laminate structures. The results showed that the [0/90/-45/45]2s exhibits a brittle behavior, while other laminates exhibit a progressive failure mode consisting of fiber failure, debonding (splitting), and delamination. The [45/45/90/0]2s laminate has a highly nonlinear load- displacement curve due to compressive yielding.

  9. A geometrically nonlinear analysis of interlaminar stresses in unsymmetrically laminated plates subjected to inplane mechanical loading

    NASA Technical Reports Server (NTRS)

    Norwood, D. Scott; Shuart, Mark J.; Herakovich, Carl T.

    1991-01-01

    The present analysis of interlaminar stresses in unsymmetrically laminates plates gives attention to the linear elastic large-deflection response of square laminated composite plates subjected to either uniaxial tension or compression loading. The effects of Poisson-ratio and mutual-influence coefficient mismatching between adjacent layers is evaluated in both cross-ply and angle-ply, and symmetric and asymmetric laminates. A global/local analysis procedure is used to obtain improved free-edge depictions; the results obtained indicate that the out-of-plane deflections of the unsymmetric laminates reduce interlaminar shear stresses, while reducing interlaminar normal stresses in some laminates and increasing them in others.

  10. A Micromechanics-Based Damage Model for [+/- Theta/90n]s Composite Laminates

    NASA Technical Reports Server (NTRS)

    Mayugo, Joan-Andreu; Camanho, Pedro P.; Maimi, Pere; Davila, Carlos G.

    2006-01-01

    A new damage model based on a micromechanical analysis of cracked [+/- Theta/90n]s laminates subjected to multiaxial loads is proposed. The model predicts the onset and accumulation of transverse matrix cracks in uniformly stressed laminates, the effect of matrix cracks on the stiffness of the laminate, as well as the ultimate failure of the laminate. The model also accounts for the effect of the ply thickness on the ply strength. Predictions relating the elastic properties of several laminates and multiaxial loads are presented.

  11. Lamination of organic solar cells and organic light emitting devices: Models and experiments

    SciTech Connect

    Oyewole, O. K.; Yu, D.; Du, J.; Asare, J.; Fashina, A.; Anye, V. C.; Zebaze Kana, M. G.; Soboyejo, W. O.

    2015-08-21

    In this paper, a combined experimental, computational, and analytical approach is used to provide new insights into the lamination of organic solar cells and light emitting devices at macro- and micro-scales. First, the effects of applied lamination force (on contact between the laminated layers) are studied. The crack driving forces associated with the interfacial cracks (at the bi-material interfaces) are estimated along with the critical interfacial crack driving forces associated with the separation of thin films, after layer transfer. The conditions for successful lamination are predicted using a combination of experiments and computational models. Guidelines are developed for the lamination of low-cost organic electronic structures.

  12. A numerical procedure for predicting creep and delayed failures in laminated composites

    NASA Technical Reports Server (NTRS)

    Dillard, D. A.; Brinson, H. F.

    1983-01-01

    A numerical procedure is described for predicting the viscoelastic response of general laminates. A nonlinear compliance model is used to predict the creep response of the individual laminae. A biaxial delayed failure model predicts ply failure. The numerical procedure, based on lamination theory, increases by increments through time to predict creep compliance and delayed failures in laminates. Numerical stability problems and experimental verification are discussed. Although the program has been quite successful in predicting creep of general laminates, the assumptions associated with lamination theory have resulted in erroneous bounds on the predicted material response. Delayed failure predictions have been conservative. Several improvements are suggested to increase the accuracy of the procedure.

  13. Effects of Interlayer Interfacial Stiffness on Ultrasonic Wave Propagation in Composite Laminates at Oblique Incidence

    NASA Astrophysics Data System (ADS)

    Ishii, Yosuke; Biwa, Shiro

    The transmission characteristics of ultrasonic wave impinging obliquely on composite laminates are analyzed. Incorporating the influence of thin resin-rich regions between adjacent plies by spring-type interfaces, the amplitude transmission coefficient of a unidirectional composite laminate immersed in water is calculated by the stiffness-matrix method. Using Floquet's theorem, the dispersion relation for the infinitely laminated structure is also calculated. Comparison between two results reveals that the frequency band-gaps in the dispersion relation agree well with the low-transmission frequency ranges of the finite laminated case. Comparing with the experimental transmission coefficients for an 11-ply carbon-epoxy composite laminate, the theoretical results are verified.

  14. A Micromechanics-Based Damage Model For The Strength Prediction of Composite Laminates

    NASA Technical Reports Server (NTRS)

    Camanho, Pedro P.; Mayugo, Joan A.; Maimi, Pere; Davila, Carlos G.

    2006-01-01

    A new damage model based on a micromechanical analysis of cracked [+/-0deg/90deg(sub n)]s laminates subjected to multiaxial loads is proposed. The model predicts the onset and accumulation of transverse matrix cracks in uniformly stressed laminates, the effect of matrix cracks on the stiffness of the laminate, as well as the ultimate failure of the laminate. The model also accounts for the effect of the ply thickness on the ply strength. Predictions relating the elastic properties of several laminates and multiaxial loads are presented.

  15. Preliminary investigation of crack arrest in composite laminates containing buffer strips

    NASA Technical Reports Server (NTRS)

    Goree, J. G.

    1978-01-01

    The mechanical properties of some hybrid buffer strip laminates and the crack arrest potential of laminates containing buffer strips were determined. The hybrid laminates consisted of graphite with either S-glass, E-glass, or Kevlar. Unnotched tensile coupons and center-cracked fracture coupons were tested. Elastic properties, complete stress/strain curves, and critical stress intensity values are given. The measured elastic properties compare well with those calculated by classical lamination theory for laminates with linear stress/strain behavior. The glass hybrids had more delamination and higher fracture toughness than the all-graphite or the Kevlar hybrid.

  16. Concurrent material-fabrication optimization of metal-matrix laminates under thermo-mechanical loading

    NASA Technical Reports Server (NTRS)

    Saravanos, D. A.; Morel, M. R.; Chamis, C. C.

    1991-01-01

    A methodology is developed to tailor fabrication and material parameters of metal-matrix laminates for maximum loading capacity under thermomechanical loads. The stresses during the thermomechanical response are minimized subject to failure constrains and bounds on the laminate properties. The thermomechanical response of the laminate is simulated using nonlinear composite mechanics. Evaluations of the method on a graphite/copper symmetric cross-ply laminate were performed. The cross-ply laminate required different optimum fabrication procedures than a unidirectional composite. Also, the consideration of the thermomechanical cycle had a significant effect on the predicted optimal process.

  17. A limiting analysis for edge effects in angle-ply laminates

    NASA Technical Reports Server (NTRS)

    Hsu, P. W.; Herakovich, C. T.

    1976-01-01

    A zeroth order solution for edge effects in angle ply composite laminates using perturbation techniques and a limiting free body approach was developed. The general method of solution for laminates is developed and then applied to the special case of a graphite/epoxy laminate. Interlaminar stress distributions are obtained as a function of the laminate thickness to width ratio h/b and compared to existing numerical results. The solution predicts stable, continuous stress distributions, determines finite maximum tensile interlaminar normal stress for two laminates, and provides mathematical evidence for singular interlaminar shear stresses.

  18. Mechanics of damping for fiber composite laminates including hygro-thermal effects

    NASA Technical Reports Server (NTRS)

    Saravanos, D. A.; Chamis, Christos C.

    1989-01-01

    An integrated mechanics theory was developed for the modeling of composite damping from the micromechanics to the laminate level. Simplified, design oriented equations based on hysteretic damping are presented for on-axis plies, off-axis plies, and laminates including the effect of temperature, moisture, and interply hysteretic damping. The temperature rise within vibrating composite laminates resulting from strain energy dissipation is also modeled, and their coupled hygro-thermo-mechanical response is predicted. The method correlates well with reported damping measurements. Application examples illustrate the effect of various ply, laminate, and hygro-thermal parameters on the overall damping performance of composite laminates.

  19. Mechanics of damping for fiber composite laminates including hygro-thermal effects

    NASA Technical Reports Server (NTRS)

    Saravanos, D. A.; Chamis, C. C.

    1989-01-01

    An integrated mechanics theory has been developed for the modeling of composite damping from the micromechanics to the laminate level. Simplified, design oriented equations based on hysteretic damping are presented for on-axis plies, off-axis plies, and laminates including the effect of temperature, moisture, and interply hysteretic damping. The temperature rise within vibrating composite laminates resulting from strain energy dissipation is also modeled, and their coupled hygro-thermo-mechanical response is predicted. The method correlates well with reported damping measurements. Application examples illustrate the effect of various ply, laminate, and hygro-thermal parameters on the overall damping performance of composite laminates.

  20. Shear degradation in fiber reinforced laminates due to matrix damage

    NASA Astrophysics Data System (ADS)

    Salavatian, Mohammedmahdi

    The objective of this study was to develop and implement a shear modulus degradation model to improve the failure analysis of the fiber reinforced composite structures. Matrix damage, involving transverse and shear cracks, is a common failure mode for composite structures, yet little is known concerning their interaction. To understand the material behavior after matrix failure, the nonlinear response of the composite laminate was studied using pressure vessels made from a [+/-o] bias orientation, which tend to exhibit a matrix dominated failure. The result of this work showed laminate matrix hardening in shear and softening in the transverse direction. A modified Iosipescu coupon was proposed to study the evolution of shear and transverse damage and their mutual effects. The proposed method showed good agreement with tubular results and has advantages of simplified specimen fabrication using standard test fixtures. The proposed method was extended by introducing a novel experimental technique to study the shear degradation model under biaxial loading. Experimental results of the transverse modulus reduction were in good agreement with material degradation models, while the predicted shear modulus reduction was higher than experiment. The discrepancy between available models and observations was due to the presence of a traction between the crack surfaces. Accordingly, a closed form solution was proposed for the shear stress-strain field of a cracked laminate by replacing the cracks with cohesive zones. The constitutive equations of the crack laminate were derived including the effects of internal tractions and transverse stress on the shear modulus. The proposed analytical model was shown to be the most comprehensive model for shear modulus degradation reduction of the fiber reinforced laminates. A numerical implementation of the shear degradation model was done using continuum damage mechanics. Through this work it was shown the common assumption of a linear

  1. Amyloid domains in the cell nucleus controlled by nucleoskeletal protein lamin B1 reveal a new pathway of mercury neurotoxicity

    PubMed Central

    Arnhold, Florian; Gührs, Karl-Heinz

    2015-01-01

    Mercury (Hg) is a bioaccumulating trace metal that globally circulates the atmosphere and waters in its elemental, inorganic and organic chemical forms. While Hg represents a notorious neurotoxicant, the underlying cellular pathways are insufficiently understood. We identify amyloid protein aggregation in the cell nucleus as a novel pathway of Hg-bio-interactions. By mass spectrometry of purified protein aggregates, a subset of spliceosomal components and nucleoskeletal protein lamin B1 were detected as constituent parts of an Hg-induced nuclear aggregome network. The aggregome network was located by confocal imaging of amyloid-specific antibodies and dyes to amyloid cores within splicing-speckles that additionally recruit components of the ubiquitin-proteasome system. Hg significantly enhances global proteasomal activity in the nucleus, suggesting that formation of amyloid speckles plays a role in maintenance of protein homeostasis. RNAi knock down showed that lamin B1 for its part regulates amyloid speckle formation and thus likewise participates in nuclear protein homeostasis. As the Hg-induced cascade of interactions between the nucleoskeleton and protein homeostasis reduces neuronal signalling, amyloid fibrillation in the cell nucleus is introduced as a feature of Hg-neurotoxicity that opens new avenues of future research. Similar to protein aggregation events in the cytoplasm that are controlled by the cytoskeleton, amyloid fibrillation of nuclear proteins may be driven by the nucleoskeleton. PMID:25699204

  2. Interfacial binding and aggregation of lamin A tail domains associated with Hutchinson-Gilford progeria syndrome

    PubMed Central

    Kalinowski, Agnieszka; Yaron, Peter N.; Qin, Zhao; Shenoy, Siddharth; Buehler, Markus J.; Lösche, Mathias; Dahl, Kris Noel

    2014-01-01

    Hutchinson-Gilford progeria syndrome is a premature aging disorder associated with the expression of Δ50 lamin A (Δ50LA), a mutant form of the nuclear structural protein lamin A (LA). Δ50LA is missing 50 amino acids from the tail domain and retains a C-terminal farnesyl group that is cleaved from the wild-type LA. Many of the cellular pathologies of HGPS are thought to be a consequence of protein-membrane association mediated by the retained farnesyl group. To better characterize the protein-membrane interface, we quantified binding of purified recombinant Δ50LA tail domain (Δ50LA-TD) to tethered bilayer membranes composed of phosphatidylserine and phosphocholine using surface plasmon resonance. Farnesylated Δ50LATD binds to the membrane interface only in the presence of Ca2+ or Mg2+ at physiological ionic strength. At extremely low ionic strength, both the farnesylated and non-farnesylated forms of Δ50LA-TD bind to the membrane surface in amounts that exceed those expected for a densely packed protein monolayer. Interestingly, the wild-type LA-TD with no farnesylation also associates with membranes at low ionic strength but forms only a single layer. We suggest that electrostatic interactions are mediated by charge clusters with a net positive charge that we calculate on the surface of the LA-TDs. These studies suggest that the accumulation of Δ50LA at the inner nuclear membrane observed in cells is due to a combination of aggregation and membrane association rather than simple membrane binding; electrostatics plays an important role in mediating this association. PMID:25194277

  3. Analysis and experiments for composite laminates with holes and subjected to 4-point bending

    NASA Technical Reports Server (NTRS)

    Shuart, M. J.; Prasad, C. B.

    1990-01-01

    Analytical and experimental results are presented for composite laminates with a hole and subjected to four-point bending. A finite-plate analysis is used to predict moment and strain distributions for six-layer quasi-isotropic laminates and transverse-ply laminates. Experimental data are compared with the analytical results. Experimental and analytical strain results show good agreement for the quasi-isotropic laminates. Failure of the two types of composite laminates is described, and failure strain results are presented as a function of normalized hole diameter. The failure results suggest that the initial failure mechanism for laminates subjected to four-point bending are similar to the initial failure mechanisms for corresponding laminates subjected to uniaxial inplane loadings.

  4. Lamin A/C-dependent interaction with 53BP1 promotes cellular responses to DNA damage

    PubMed Central

    Gibbs-Seymour, Ian; Markiewicz, Ewa; Bekker-Jensen, Simon; Mailand, Niels; Hutchison, Christopher J

    2015-01-01

    Lamins A/C have been implicated in DNA damage response pathways. We show that the DNA repair protein 53BP1 is a lamin A/C binding protein. In undamaged human dermal fibroblasts (HDF), 53BP1 is a nucleoskeleton protein. 53BP1 binds to lamins A/C via its Tudor domain, and this is abrogated by DNA damage. Lamins A/C regulate 53BP1 levels and consequently lamin A/C-null HDF display a 53BP1 null-like phenotype. Our data favour a model in which lamins A/C maintain a nucleoplasmic pool of 53BP1 in order to facilitate its rapid recruitment to sites of DNA damage and could explain why an absence of lamin A/C accelerates aging. PMID:25645366

  5. Dermal fibroblasts in Hutchinson-Gilford progeria syndrome with the lamin A G608G mutation have dysmorphic nuclei and are hypersensitive to heat stress

    PubMed Central

    Paradisi, Mauro; McClintock, Dayle; Boguslavsky, Revekka L; Pedicelli, Christina; Worman, Howard J; Djabali, Karima

    2005-01-01

    Background Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670) is a rare sporadic disorder with an incidence of approximately 1 per 8 million live births. The phenotypic appearance consists of short stature, sculptured nose, alopecia, prominent scalp veins, small face, loss of subcutaneous fat, faint mid-facial cyanosis, and dystrophic nails. HGPS is caused by mutations in LMNA, the gene that encodes nuclear lamins A and C. The most common mutation in subjects with HGPS is a de novo single-base pair substitution, G608G (GGC>GGT), within exon 11 of LMNA. This creates an abnormal splice donor site, leading to expression of a truncated protein. Results We studied a new case of a 5 year-old girl with HGPS and found a heterozygous point mutation, G608G, in LMNA. Complementary DNA sequencing of RNA showed that this mutation resulted in the deletion of 50 amino acids in the carboxyl-terminal tail domain of prelamin A. We characterized a primary dermal fibroblast cell line derived from the subject's skin. These cells expressed the mutant protein and exhibited a normal growth rate at early passage in primary culture but showed alterations in nuclear morphology. Expression levels and overall distributions of nuclear lamins and emerin, an integral protein of the inner nuclear membrane, were not dramatically altered. Ultrastructural analysis of the nuclear envelope using electron microscopy showed that chromatin is in close association to the nuclear lamina, even in areas with abnormal nuclear envelope morphology. The fibroblasts were hypersensitive to heat shock, and demonstrated a delayed response to heat stress. Conclusion Dermal fibroblasts from a subject with HGPS expressing a mutant truncated lamin A have dysmorphic nuclei, hypersensitivity to heat shock, and delayed response to heat stress. This suggests that the mutant protein, even when expressed at low levels, causes defective cell stability, which may be responsible for phenotypic abnormalities in the disease

  6. Seismic lamination and anisotropy of the Lower Continental Crust

    NASA Astrophysics Data System (ADS)

    Meissner, Rolf; Rabbel, Wolfgang; Kern, Hartmut

    2006-04-01

    Seismic lamination in the lower crust associated with marked anisotropy has been observed at various locations. Three of these locations were investigated by specially designed experiments in the near vertical and in the wide-angle range, that is the Urach and the Black Forrest area, both belonging to the Moldanubian, a collapsed Variscan terrane in southern Germany, and in the Donbas Basin, a rift inside the East European (Ukrainian) craton. In these three cases, a firm relationship between lower crust seismic lamination and anisotropy is found. There are more cases of lower-crustal lamination and anisotropy, e.g. from the Basin and Range province (western US) and from central Tibet, not revealed by seismic wide-angle measurements, but by teleseismic receiver function studies with a P-S conversion at the Moho. Other cases of lamination and anisotropy are from exhumed lower crustal rocks in Calabria (southern Italy), and Val Sesia and Val Strona (Ivrea area, Northern Italy). We demonstrate that rocks in the lower continental crust, apart from differing in composition, differ from the upper mantle both in terms of seismic lamination (observed in the near-vertical range) and in the type of anisotropy. Compared to upper mantle rocks exhibiting mainly orthorhombic symmetry, the symmetry of the rocks constituting the lower crust is either axial or orthorhombic and basically a result of preferred crystallographic orientation of major minerals (biotite, muscovite, hornblende). We argue that the generation of seismic lamination and anisotropy in the lower crust is a consequence of the same tectonic process, that is, ductile deformation in a warm and low-viscosity lower crust. This process takes place preferably in areas of extension. Heterogeneous rock units are formed that are generally felsic in composition, but that contain intercalations of mafic intrusions. The latter have acted as heat sources and provide the necessary seismic impedance contrasts. The observed

  7. Defects of Lipid Synthesis Are Linked to the Age-Dependent Demyelination Caused by Lamin B1 Overexpression

    PubMed Central

    Rolyan, Harshvardhan; Tyurina, Yulia Y.; Hernandez, Marylens; Amoscato, Andrew A.; Sparvero, Louis J.; Nmezi, Bruce C.; Lu, Yue; Estécio, Marcos R. H.; Lin, Kevin; Chen, Junda; He, Rong-Rong; Gong, Pin; Rigatti, Lora H.; Dupree, Jeffrey; Bayır, Hülya; Kagan, Valerian E.; Casaccia, Patrizia

    2015-01-01

    Lamin B1 is a component of the nuclear lamina and plays a critical role in maintaining nuclear architecture, regulating gene expression and modulating chromatin positioning. We have previously shown that LMNB1 gene duplications cause autosomal dominant leukodystrophy (ADLD), a fatal adult onset demyelinating disease. The mechanisms by which increased LMNB1 levels cause ADLD are unclear. To address this, we used a transgenic mouse model where Lamin B1 overexpression is targeted to oligodendrocytes. These mice showed severe vacuolar degeneration of the spinal cord white matter together with marked astrogliosis, microglial infiltration, and secondary axonal damage. Oligodendrocytes in the transgenic mice revealed alterations in histone modifications favoring a transcriptionally repressed state. Chromatin changes were accompanied by reduced expression of genes involved in lipid synthesis pathways, many of which are known to play important roles in myelin regulation and are preferentially expressed in oligodendrocytes. Decreased lipogenic gene expression resulted in a significant reduction in multiple classes of lipids involved in myelin formation. Many of these gene expression changes and lipid alterations were observed even before the onset of the phenotype, suggesting a causal role. Our findings establish, for the first time, a link between LMNB1 and lipid synthesis in oligodendrocytes, and provide a mechanistic framework to explain the age dependence and white matter involvement of the disease phenotype. These results have implications for disease pathogenesis and may also shed light on the regulation of lipid synthesis pathways in myelin maintenance and turnover. SIGNIFICANCE STATEMENT Autosomal dominant leukodystrophy (ADLD) is fatal neurological disorder caused by increased levels of the nuclear protein, Lamin B1. The disease is characterized by an age-dependent loss of myelin, the fatty sheath that covers nerve fibers. We have studied a mouse model where Lamin B

  8. The Novel Nuclear Envelope Protein KAKU4 Modulates Nuclear Morphology in Arabidopsis[W

    PubMed Central

    Goto, Chieko; Tamura, Kentaro; Fukao, Yoichiro; Shimada, Tomoo; Hara-Nishimura, Ikuko

    2014-01-01

    In animals, the nuclear lamina is a fibrillar meshwork on the inner surface of the nuclear envelope, composed of coiled-coil lamin proteins and lamin binding membrane proteins. Plants also have a meshwork on the inner surface of the nuclear envelope, but little is known about its composition other than the presence of members of the CROWDED NUCLEI (CRWN) protein family, possible plant lamin analogs. Here, we describe a candidate lamina component, based on two Arabidopsis thaliana mutants (kaku2 and kaku4) with aberrant nuclear morphology. The responsible gene in kaku2 encodes CRWN1, and the responsible gene in kaku4 encodes a plant-specific protein of unknown function (KAKU4) that physically interacts with CRWN1 and its homolog CRWN4. Immunogold labeling revealed that KAKU4 localizes at the inner nuclear membrane. KAKU4 deforms the nuclear envelope in a dose-dependent manner, in association with nuclear membrane invagination and stack formation. The KAKU4-dependent nuclear envelope deformation was enhanced by overaccumulation of CRWN1, although KAKU4 can deform the nuclear envelope even in the absence of CRWN1 and/or CRWN4. Together, these results suggest that plants have evolved a unique lamina-like structure to modulate nuclear shape and size. PMID:24824484

  9. Ancient and Modern Laminated Composites - From the Great Pyramid of Gizeh to Y2K

    SciTech Connect

    Wadsworth, J.; Lesuer, D.R.

    2000-03-14

    Laminated metal composites have been cited in antiquity; for example, a steel laminate that may date as far back as 2750 B.C., was found in the Great Pyramid in Gizeh in 1837. A laminated shield containing bronze, tin, and gold layers, is described in detail by Homer. Well-known examples of steel laminates, such as an Adze blade, dating to 400 B.C. can be found in the literature. The Japanese sword is a laminated composite at several different levels and Merovingian blades were composed of laminated steels. Other examples are also available, including composites from China, Thailand, Indonesia, Germany, Britain, Belgium, France, and Persia. The concept of lamination to provide improved properties has also found expression in modern materials. Of particular interest is the development of laminates including high carbon and low carbon layers. These materials have unusual properties that are of engineering interest; they are similar to ancient welded Damascus steels. The manufacture of collectable knives, labeled ''welded Damascus'', has also been a focus of contemporary knifemakers. Additionally, in the Former Soviet Union, laminated composite designs have been used in engineering applications. Each of the above areas will be briefly reviewed, and some of the metallurgical principles will be described that underlie improvement in properties by lamination. Where appropriate, links are made between these property improvements and those that may have been present in ancient artifacts.

  10. An investigation of the interfacial bond strength of polymeric laminates

    SciTech Connect

    Eby, R.K. )

    1991-08-01

    This report summarizes the results of an investigation of the bond strength of paper - polypropylene - paper (PPP) laminates. The strength has been measured with a peel test for the as--received laminates of different manufacturers, after thermal aging in air and nitrogen, after static thermal age in oil at room temperature and 90{degrees}C as well as after cyclic thermal aging in oil. Differential swelling of the paper and polypropylene at 90{degrees}C leads to a strong decrease in peel strength. Differential thermal expansion at 90{degrees}C is not as important. Cyclic thermal aging in oil leads to the greatest decrease in peel strength. The results further our knowledge of information that should be considered in preparing a PPP specification. 19 refs., 7 figs., 12 tabs.

  11. Geometrically nonlinear bending analysis of laminated composite plate

    NASA Astrophysics Data System (ADS)

    Dash, Padmanav; Singh, B. N.

    2010-10-01

    In this work, a transverse bending of shear deformable laminated composite plates in Green-Lagrange sense accounting for the transverse shear and large rotations are presented. Governing equations are developed in the framework of higher order shear deformation theory. All higher order terms arising from nonlinear strain-displacement relations are included in the formulation. The present plate theory satisfies zero transverse shear strains conditions at the top and bottom surfaces of the plate in von-Karman sense. A C0 isoparametric finite element is developed for the present nonlinear model. Numerical results for the laminated composite plates of orthotropic materials with different system parameters and boundary conditions are found out. The results are also compared with those available in the literature. Some new results with different parameters are also presented.

  12. Axisymmetric buckling of laminated thick annular spherical cap

    NASA Astrophysics Data System (ADS)

    Dumir, P. C.; Dube, G. P.; Mallick, A.

    2005-03-01

    Axisymmetric buckling analysis is presented for moderately thick laminated shallow annular spherical cap under transverse load. Buckling under central ring load and uniformly distributed transverse load, applied statically or as a step function load is considered. The central circular opening is either free or plugged by a rigid central mass or reinforced by a rigid ring. Annular spherical caps have been analysed for clamped and simple supports with movable and immovable inplane edge conditions. The governing equations of the Marguerre-type, first order shear deformation shallow shell theory (FSDT), formulated in terms of transverse deflection w, the rotation ψ of the normal to the midsurface and the stress function Φ, are solved by the orthogonal point collocation method. Typical numerical results for static and dynamic buckling loads for FSDT are compared with the classical lamination theory and the dependence of the effect of the shear deformation on the thickness parameter for various boundary conditions is investigated.

  13. Non-Linear Vibration Characteristics of Clamped Laminated Shallow Shells

    NASA Astrophysics Data System (ADS)

    ABE, A.; KOBAYASHI, Y.; YAMADA, G.

    2000-07-01

    This paper examines non-linear free vibration characteristics of first and second vibration modes of laminated shallow shells with rigidly clamped edges. Non-linear equations of motion for the shells based on the first order shear deformation and classical shell theories are derived by means of Hamilton's principle. We apply Galerkin's procedure to the equations of motion in which eigenvectors for first and second modes of linear vibration obtained by the Ritz method are employed as trial functions. Then simultaneous non-linear ordinary differential equations are derived in terms of amplitudes of the first and second vibration modes. Backbone curves for the first and second vibration modes are solved numerically by the Gauss-Legendre integration method and the shooting method respectively. The effects of lamination sequences and transverse shear deformation on the behavior are discussed. It is also shown that the motion of the first vibration mode affects the response for the second vibration mode.

  14. Air Blast-Induced Vibration of a Laminated Spherical Shell

    NASA Astrophysics Data System (ADS)

    Yzgüksel, Hzgüseyin Murat; Türkmen, Halit S.

    The scope of this study is to investigate the dynamic behavior of a laminated spherical shell subjected to air blast load. The shell structure considered here is a hemisphere in shape and made of a glass/epoxy laminated composite material. The blast experiments are performed on the spherical shell. The strain-time history of the center of the spherical shell panel is obtained experimentally. The blast loaded spherical shell is also modeled and analyzed using ANSYS finite element software. The static analysis is performed to characterize the material. The dynamic response of the spherical shell panel obtained numerically is compared to the experimental results. It is observed that the response frequency corresponds to the higher vibration modes of the panel. The qualitative agreement is found between the numerical and experimental results.

  15. Hygrothermal influence on delamination behavior of graphite/epoxy laminates

    NASA Technical Reports Server (NTRS)

    Garg, A.; Ishai, O.

    1984-01-01

    The hygrothermal effect on the fracture behavior of graphite-epoxy laminates was investigated to develop a methodology for damage tolerance predictions in advanced composite materials. Several T300/934 laminates were tested using a number of specimen configurations to evaluate the effects of temperature and humidity on delamination fracture toughness under mode 1 and mode 2 loading. It is indicated that moisture has a slightly beneficial influence on fracture toughness or critical strain energy release rate during mode 1 delamination, but has a slightly deleterious effect on mode 2 delamination and mode 1 transverse cracking. The failed specimens are examined by SEM and topographical differences due to fracture modes are identified. It is concluded that the effect of moisture on fracture topography can not be distinguished.

  16. Developments in impact damage modeling for laminated composite structures

    NASA Technical Reports Server (NTRS)

    Dost, Ernest F.; Avery, William B.; Swanson, Gary D.; Lin, Kuen Y.

    1991-01-01

    Damage tolerance is the most critical technical issue for composite fuselage structures studied in the Advanced Technology Composite Aircraft Structures (ATCAS) program. The objective here is to understand both the impact damage resistance and residual strength of the laminated composite fuselage structure. An understanding of the different damage mechanisms which occur during an impact event will support the selection of materials and structural configurations used in different fuselage quadrants and guide the development of analysis tools for predicting the residual strength of impacted laminates. Prediction of the damage state along with the knowledge of post-impact response to applied loads will allow for engineered stacking sequencies and structural configurations; intelligent decisions on repair requirements will also result.

  17. A new local high-order laminate theory

    NASA Astrophysics Data System (ADS)

    Wu, Chih-Ping; Hsu, Chih-Shun

    A new local high-order deformable theory of laminated composite/sandwich plates is presented here. The displacement fields of each discrete layer were assumed in the present theory to be of a high-order polynomial series through layer-thickness. The displacement and traction continuity conditions at the interface between layers and the traction conditions at the outer surfaces were imposed as the constraint conditions, and introduced into the potential energy functional by the Lagrange multiplier method. The equations of motion and admissible boundary conditions were given on the basis of the present theory by using the generalized variational principle. Pagano's 3-D elasticity solutions of generally rectangular laminated composite/sandwich plates, fully simply supported, subjected to transverse sinusoidal loading were used for assessment of the present theory and other theories discussed in previous literature. The present theory was found to agree very closely with 3-D elasticity solutions.

  18. Analysis of composite laminates with a generalized zigzag theory

    SciTech Connect

    Liu, D.; Li, X.

    1994-12-31

    This study presents a generalized expression for laminate theories, namely a generalized zigzag theory. It unifies shear deformation theories, layerwise theories, and zigzag theories. To begin with, two layer-dependent variables are assumed for each in-plane displacement components. The layer-dependent variables can be converted into layer-independent variables through the enforcement of continuity conditions for both interlaminar displacements and interlaminar shear stresses. The total number of degrees-of-freedom of the theory then becomes layer-number independent and the computational efficiency is thus guaranteed. Since the properties of individual layers are considered in the analysis, the generalized zigzag theory gives excellent in-plane displacements and stresses in the cases examined by Pagano. Satisfactory transverse shear stresses can also be obtained directly from the constitutive equations. Although the interlaminar normal stresses are not forced to be continuous on the laminate interfaces, the discrepancy seems to be very insignificant.

  19. Passively Damped Laminated Piezoelectric Shell Structures with Integrated Electric Networks

    NASA Technical Reports Server (NTRS)

    Saravanos, Dimitris A.

    1999-01-01

    Multi-field mechanics are presented for curvilinear piezoelectric laminates interfaced with distributed passive electric components. The equations of motion for laminated piezoelectric shell structures with embedded passive electric networks are directly formulated and solved using a finite element methodology. The modal damping and frequencies of the piezoelectric shell are calculated from the poles of the system. Experimental and numerical results are presented for the modal damping and frequency of composite beams with a resistively shunted piezoceramic patch. The modal damping and frequency of plates, cylindrical shells and cylindrical composite blades with piezoelectric-resistor layers are predicted. Both analytical and experimental studies illustrate a unique dependence of modal damping and frequencies on the shunting resistance and show the effect of structural shape and curvature on piezoelectric damping.

  20. Contact law and impact responses of laminated composites

    NASA Technical Reports Server (NTRS)

    Sun, C. T.; Yang, S. H.

    1980-01-01

    Static identation tests were performed to determine the law of contact between a steel ball and glass/epoxy and graphite/epoxy laminated composites. For both composites the power law with an index of 1.5 was found to be adequate for the loading curve. Substantial permanent deformations were noted after the unloading. A high order beam finite element was used to compute the dynamic contact force and response of the laminated composite subjected to the impact of an elastic sphere. This program can be used with either the classical Hertzian contact law or the measured contact law. A simple method is introduced for estimating the contact force and contact duration in elastic impacts.

  1. Development of lightweight reinforced plastic laminates for spacecraft interior applications

    NASA Technical Reports Server (NTRS)

    Hertz, J.

    1975-01-01

    Lightweight, Kevlar - reinforced laminating systems that are non-burning, generate little smoke in the space shuttle environment, and are physically equivalent to the fiberglass/polyimide system used in the Apollo program for non-structural cabin panels, racks, etc. Resin systems representing five generic classes were screened as matrices for Kevlar 49 reinforced laminates. Of the systems evaluated, the polyimides were the most promising with the phenolics a close second. Skybond 703 was selected as the most promising resin candidate. With the exception of compression strength, all program goals of physical and mechanical properties were exceeded. Several prototype space shuttle mobility and translation handrail segments were manufactured using Kevlar/epoxy and Kevlar-graphite/epoxy. This application shows significant weight savings over the baseline aluminum configuration used previous. The hybrid Kevlar-graphite/epoxy is more suitable from a processing standpoint.

  2. Probabilistic Simulation of Stress Concentration in Composite Laminates

    NASA Technical Reports Server (NTRS)

    Chamis, C. C.; Murthy, P. L. N.; Liaw, D. G.

    1994-01-01

    A computational methodology is described to probabilistically simulate the stress concentration factors (SCF's) in composite laminates. This new approach consists of coupling probabilistic composite mechanics with probabilistic finite element structural analysis. The composite mechanics is used to probabilistically describe all the uncertainties inherent in composite material properties, whereas the finite element is used to probabilistically describe the uncertainties associated with methods to experimentally evaluate SCF's, such as loads, geometry, and supports. The effectiveness of the methodology is demonstrated by using is to simulate the SCF's in three different composite laminates. Simulated results match experimental data for probability density and for cumulative distribution functions. The sensitivity factors indicate that the SCF's are influenced by local stiffness variables, by load eccentricities, and by initial stress fields.

  3. Fiberglass epoxy laminate fatigue properties at 300 and 20 K

    NASA Technical Reports Server (NTRS)

    Toth, J. M., Jr.; Bailey, W. J.; Boyce, D. A.

    1985-01-01

    A subcritical liquid hydrogen orbital storage and supply experiment is being designed for flight in the Space Shuttle cargo bay. The Cryogenic Fluid Management Experiment (CFME) includes a liquid hydrogen tank supported in a vacuum jacket by two fiberglass epoxy composite trunnion mounts. The ability of the CFME to last for the required seven missions depends primarily on the fatigue life of the composite trunnions at cryogenic temperatures. To verify the trunnion design and test the performance of the composite material, fatigue property data at 300 and 20 K were obtained for the specific E-glass fabric/S-glass unidirectional laminate that will be used for the CFME trunnions. The fatigue life of this laminate was greater at 20 K than at 300 K, and was satisfactory for the intended application.

  4. Failure criterion of glass fabric reinforced plastic laminates

    NASA Technical Reports Server (NTRS)

    Haga, O.; Hayashi, N.; Kasuya, K.

    1986-01-01

    Failure criteria are derived for several modes of failure (in unaxial tensile or compressive loading, or biaxial combined tensile-compressive loading) in the case of closely woven plain fabric, coarsely-woven plain fabric, or roving glass cloth reinforcements. The shear strength in the interaction formula is replaced by an equation dealing with tensile or compressive strength in the direction making a 45 degree angle with one of the anisotropic axes, for the uniaxial failure criteria. The interaction formula is useful as the failure criterion in combined tension-compression biaxial failure for the case of closely woven plain fabric laminates, but poor agreement is obtained in the case of coarsely woven fabric laminates.

  5. An experimental investigation of glare and restructured fiber metal laminates

    NASA Astrophysics Data System (ADS)

    Benedict, Adelina Vanessa

    Fiber Metal Laminates (FMLs) are a group of materials fabricated by bonding glass/epoxy layers within metal layers. This class of materials can provide good mechanical properties, as well as weight savings. An FML known as Glass Laminate Aluminum Reinforced Epoxy (GLARE) was studied. An experimental investigation comprising of microscopy and tensile testing was carried out using different grades of GLARE. Microscopy revealed the construction details of GLARE, while tensile testing provided means of measuring and analyzing its stress-strain responses. Next, different metal surface pretreatment methods were explored. These included sandblasting, Phosphoric Acid Anodizing (PAA), and AC-130 Sol-Gel treatment. Woven S-2 glass, an epoxy adhesive, and aluminum alloy sheet metal were used to fabricate restructured FMLs using time and cost effective procedures. Additional microscopy and tensile testing allowed for comparisons with GLARE and aircraft grade aluminum alloys. The restructured FMLs showed similar behaviors to GLARE with potential significant improvements in fabrication efficiency.

  6. High thermal conductivity of hexagonal boron nitride laminates

    NASA Astrophysics Data System (ADS)

    Zheng, Jin-Cheng; Zhang, Liang; Kretinin, A. V.; Morozov, S. V.; Wang, Yi Bo; Wang, Tun; Li, Xiaojun; Ren, Fei; Zhang, Jingyu; Lu, Ching-Yu; Chen, Jia-Cing; Lu, Miao; Wang, Hui-Qiong; Geim, A. K.; Novoselov, K. S.

    2016-03-01

    Two-dimensional materials are characterised by a number of unique physical properties which can potentially make them useful to a wide diversity of applications. In particular, the large thermal conductivity of graphene and hexagonal boron nitride (hBN) has already been acknowledged and these materials have been suggested as novel core materials for thermal management in electronics. However, it was not clear if mass produced flakes of hBN would allow one to achieve an industrially-relevant value of thermal conductivity. Here we demonstrate that laminates of hBN exhibit thermal conductivity of up to 20 W/m·K, which is significantly larger than that currently used in thermal management. We also show that the thermal conductivity of laminates increases with the increasing volumetric mass density, which creates a way of fine tuning its thermal properties.

  7. Iosipescu shear properties of graphite fabric/epoxy composite laminates

    NASA Technical Reports Server (NTRS)

    Walrath, D. E.; Adams, D. F.

    1985-01-01

    The Iosipescu shear test method is used to measure the in-plane and interlaminar shear properties of four T300 graphite fabric/934 epoxy composite materials. Different weave geometries tested include an Oxford weave, a 5-harness satin weave, an 8-harness satin weave, and a plain weave with auxiliary warp yarns. Both orthogonal and quasi-isotropic layup laminates were tested. In-plane and interlaminar shear properties are obtained for laminates of all four fabric types. Overall, little difference in shear properties attributable to the fabric weave pattern is observed. The auxiliary warp material is significantly weaker and less stiff in interlaminar shear parallel to its fill direction. A conventional strain gage extensometer is modified to measure shear strains for use with the Iosipescu shear test. While preliminary results are encouraging, several design iterations failed to produce a reliable shear transducer prototype. Strain gages are still the most reliable shear strain transducers for use with this test method.

  8. Tensile stress-strain behavior of graphite/epoxy laminates

    NASA Technical Reports Server (NTRS)

    Garber, D. P.

    1982-01-01

    The tensile stress-strain behavior of a variety of graphite/epoxy laminates was examined. Longitudinal and transverse specimens from eleven different layups were monotonically loaded in tension to failure. Ultimate strength, ultimate strain, and strss-strain curves wee obtained from four replicate tests in each case. Polynominal equations were fitted by the method of least squares to the stress-strain data to determine average curves. Values of Young's modulus and Poisson's ratio, derived from polynomial coefficients, were compared with laminate analysis results. While the polynomials appeared to accurately fit the stress-strain data in most cases, the use of polynomial coefficients to calculate elastic moduli appeared to be of questionable value in cases involving sharp changes in the slope of the stress-strain data or extensive scatter.

  9. Design of multiple-ply laminated composite tapered beams

    NASA Technical Reports Server (NTRS)

    Rodriguez, P.

    1993-01-01

    A study of a special case of symmetric laminated composite cantilever beams is presented. The approach models beams that are tapered both in depth and width and investigates the effect of the ply layup angle and the ply taper on bending and interlaminar shearing stresses. For the determination of stresses and deflections, the beam stiffness matrices are expressed as linear functions of the beam length. Using classical lamination theory (CLT) the stiffness matrices are determined and assembled at strategic locations along the length of the beam. They are then inverted and necessary stiffness parameters are obtained numerically and extracted for determination of design information at each location chosen. Several ply layup configurations are investigated, and design considerations are presented based on the findings. Finally, recommendations for the design of these beams are presented, and a means for anticipating the location of highest stresses is offered.

  10. On the enhancement of impact damage tolerance of composite laminates

    NASA Technical Reports Server (NTRS)

    Nettles, A. T.; Lance, D. G.

    1993-01-01

    This paper examines the use of a thin layer of Ultra High Molecular Weight Polyethylene (UHMWPE) on the outer surface of carbon/epoxy composite materials as a method of improving impact resistance and damage tolerance through hybridization. Flat 16-ply laminates as well as honeycomb sandwich structures with eight-ply facesheets were tested in this study. Instrumented drop-weight impact testing was used to inflict damage upon the specimens. Evaluation of damage resistance included instrumented impact data, visual examination, C-scanning and compression after impact (CAI) testing. The results show that only one lamina of UHMWPE did not improve the damage tolerance (strength retention) of the 16-ply flat laminate specimens or the honeycomb sandwich beams, however, a modest gain in impact resistance (detectable damage) was found for the honeycomb sandwich specimens that contained an outer layer of UHMWPE.

  11. Failure analysis of composite laminates including biaxial compression

    NASA Technical Reports Server (NTRS)

    Tennyson, R. C.; Elliott, W. G.

    1983-01-01

    This report describes a continued effort on the development and application of the tensor polynomial failure criterion for composite laminate analysis. In particular, emphasis is given to the design, construction and testing of a cross-beam laminate configuration to obtain "pure' biaxial compression failure. The purpose of this test case was to provide to permit "closure' of the cubic form of the failure surface in the 1-2 compression-compression quadrant. This resulted in a revised set of interaction strength parameters and the construction of a failure surface which can be used with confidence for strength predictions, assuming a plane stress state exists. Furthermore, the problem of complex conjugate roots which can occur in some failure regions is addressed and an "engineering' interpretation is provided. Results are presented illustrating this behavior and the methodology for overcoming this problem is discussed.

  12. Status of high-temperature laminating resins and adhesives

    NASA Technical Reports Server (NTRS)

    Hergenrother, P. M.; Johnston, N. J.

    1980-01-01

    High-temperature polymers now being developed as adhesives and composite matrices are reviewed, including aromatic polyimides, polybenzimidazoles, polyphenylquinoxalines, nadic end-capped imide oligomers, maleimide end-capped oligomers, and acetylene-terminated imide oligomers. The mechanical properties of laminates based on these resins are reported together with preliminary test results on the adhesive properties for titanium-to-titanium and composite-to-composite lap shear specimens.

  13. An overview of laminate materials with enhanced dielectric properties

    NASA Astrophysics Data System (ADS)

    Mumby, Stephen J.

    1989-03-01

    This report focuses on laminate materials (resins and reinforcements) having potential applications in the manufacture of multi-layer printed wiring boards (PWBs) that are required to efficiently transmit high-speed digital pulses. It is intended to be a primer and a reference for selection of candidate materials for such high-performance PWBs. Included are dielectric and physical properties, and where available chemical composition and/or structure, commercial availability, compatibility with typical PWB processing schemes and approximate relative cost. Recommendations are made as to the most viable candidate materials for this type of PWB application, based on a comparison of electrical and physical properties together with processing and cost considerations. The cyanate ester resin system appears promising. Such a resin may be reinforced with regular E-glass, or the more newly available S-glass, to produce a laminate useful for intermediate performance applications. For more demanding applications the E-glass will have to be replaced by a material of much lower relative permittivity. The expanded-PTFE reinforced laminates from W. L. Gore appear to be a good choice for these applications. The processing of the Gore materials can be expected to deviate from that used with FR-4 type materials, but is likely to be less problematic than laminates comprised of a fluorinated resin. Processing is a key obstacle to the implementation of any of the new materials herein. If implementation is to be successful, programs must be established to develop and optimize processing procedures. Cost will remain an important issue. However, the higher cost of the new materials may be justified in high-end products by the performance they deliver.

  14. A life prediction model for laminated composite structural components

    NASA Technical Reports Server (NTRS)

    Allen, David H.

    1990-01-01

    A life prediction methodology for laminated continuous fiber composites subjected to fatigue loading conditions was developed. A summary is presented of research completed. A phenomenological damage evolution law was formulated for matrix cracking which is independent of stacking sequence. Mechanistic and physical support was developed for the phenomenological evolution law proposed above. The damage evolution law proposed above was implemented to a finite element computer program. And preliminary predictions were obtained for a structural component undergoing fatigue loading induced damage.

  15. Method for alleviating thermal stress damage in laminates

    NASA Technical Reports Server (NTRS)

    Hoffman, C. A.; Weeton, J. W.; Orth, N. W. (Inventor)

    1981-01-01

    The method is for metallic matrix composites, such as laminated sheet or foil composites. Non-intersecting discrete discontinuities are positively introduced into the interface between the layers so as to reduce the thermal stress produced by unequal expansion of the materials making up the composite. The discontinuities are preferably produced by drilling holes in the metallic matrix layer. However, a plurality of discrete elements may be used between the layers to carry out this purpose.

  16. Finite element analysis of vibration and damping of laminated composites

    NASA Astrophysics Data System (ADS)

    Rikards, Rolands

    Simple finite elements are used to form a special laminated beam and plate superelements excluding all degrees of freedom in the nodes of the middle layer, and the finite element analysis of this structure is performed. To estimate damping of structures, modal loss factors are calculated, using two methods: the 'exact' method of complex eigenvalues and the approximate energy method. It was found that both methods give satisfactory results. However, the energy method needs less computer time than the exact method.

  17. Flux distraction effect on magnetoelectric laminate sensors and gradiometer

    NASA Astrophysics Data System (ADS)

    Shen, Ying; Gao, Junqi; Wang, Yaojin; Hasanyan, Davresh; Finkel, Peter; Li, Jiefang; Viehland, D.

    2013-10-01

    A magnetic flux distraction effect caused by a nearby metallic material was investigated for Metglas/Pb(Mg1/3Nb2/3)O3-PbTiO3 laminated magnetoelectric (ME) sensors. Using flux distraction, a ME sensor can perform an accurate search for metallic targets of different dimensions at various distances. Detection results and simulations were in good agreement. The findings demonstrate an effective means to employ stationary ME sensors and gradiometers for magnetic search applications.

  18. A Shear Deformable Shell Element for Laminated Composites

    NASA Technical Reports Server (NTRS)

    Chao, W. C.; Reddy, J. N.

    1984-01-01

    A three-dimensional element based on the total Lagrangian description of the motion of a layered anisotropic composite medium is developed, validated, and used to analyze layered composite shells. The element contains the following features: geometric nonlinearity, dynamic (transient) behavior, and arbitrary lamination scheme and lamina properties. Numerical results of nonlinear bending, natural vibration, and transient response are presented to illustrate the capabilities of the element.

  19. Fatigue delamination onset prediction in unidirectional tapered laminates

    NASA Technical Reports Server (NTRS)

    Murri, Gretchen B.; Salpekar, Satish A.; O'Brien, T. K.

    1991-01-01

    Tapered (0 deg) laminates of S2/CE9000 and S2/SP250 glass/epoxies, and IM6/1827I graphite/epoxy were tested in cyclic tension. The specimens usually showed some initial stable delaminations in the tapered region, but these did not affect the stiffness of the specimens, and loading was continued until the specimens either delaminated unstably, or reached 10(exp 6) to 2 x 10 (exp 7) million cycles with no unstable delamination. The final unstable delamination originated at the junction of the thin and tapered regions. A finite-element model was developed for the tapered laminate with and without the initial stable delaminations observed in the tests. The analysis showed that for both cases the most likely place for an opening (Mode I) delamination to originate is at the junction of the taper and thin regions. For each material type, the models were used to calculate the strain energy release rate, G, associated with delaminations originating at that junction and growing either into the thin region or tapered region. For the materials tested, cyclic G(sub Imax) values from DCB tests were used with the maximum strain energy release rates calculated from the finite-element analysis to predict the onset of unstable delamination at the junction as a function of fatigue cycles. The predictions were compared to experimental values of maximum cyclic load as a function of cycles to unstable delamination from fatigue tests in tapered laminates. For the IM6/1827I and S2/SP250 laminates, the predictions agreed very well with the test data. Predicted values for the S2/CE9000 were conservative compared to the test data.

  20. Fatigue delamination onset prediction in tapered composite laminates

    NASA Technical Reports Server (NTRS)

    Murri, Gretchen Bostaph; Salpekar, Satish A.; Obrien, T. Kevin

    1989-01-01

    Tapered (0 deg) laminates of S2/CE9000 and S2/SP250 glass/epoxies, and IM6/1827I graphite/epoxy were tested in cyclic tension. The specimens usually showed some initial stable delaminations in the tapered region, but these did not affect the stiffness of the specimens, and loading was continued until the specimens either delaminated unstably, or reached 10(exp 6) to 2 x 10(exp 7) million cycles with no unstable delamination. The final unstable delamination originated at the junction of the thin and tapered regions. A finite-element model was developed for the tapered laminate with and without the initial stable delaminations observed in the tests. The analysis showed that for both cases the most likely place for an opening (Mode 1) delamination to originate is at the junction of the taper and thin regions. For each material type, the models were used to calculate the strain energy release rate, G, associated with delaminations originating at that junction and growing either into the thin region or tapered region. For the materials tested, cyclic G(sub Imax) values from DCB tests were used with the maximum strain energy release rates calculated from the finite-element analysis to predict the onset of unstable delamination at the junction as a function of fatigue cycles. The predictions were compared to experimental values of maximum cyclic load as a function of cycles to unstable delamination from fatigue tests in tapered laminates. For the IM6/1827I and S2/SP250 laminates, the predictions agreed very well with the test data. Predicted values for the S2/CE9000 were conservative compared to the test data.