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

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Furukawa, Kazuhiro, E-mail: furukawa@chem.sc.niigata-u.ac.jp [Department of Chemistry, Faculty of Science, Niigata University, Niigata 950-2181 (Japan); Ishida, Kazuya; Tsunoyama, Taka-aki; Toda, Suguru; Osoda, Shinichi; Horigome, Tsuneyoshi [Department of Chemistry, Faculty of Science, Niigata University, Niigata 950-2181 (Japan); Fisher, Paul A. [Department of Pharmacological Sciences, School of Medicine, University Medical Center, State University of New York at Stony Brook, Stony Brook, NY 11794-8651 (United States); Sugiyama, Shin [Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya 464-8602 (Japan)

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.

Normal and mutant HTT interact to affect clinical severity and progression in Huntington disease

DEFF Research Database (Denmark)

Aziz, N A; Jurgens, C K; Landwehrmeyer, G B

2009-01-01

OBJECTIVE: Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in the HD gene (HTT). We aimed to assess whether interaction between CAG repeat sizes in the mutant and normal allele could affect disease severity and progression. METHODS: Using...... with less severe symptoms and pathology. CONCLUSIONS: Increasing CAG repeat size in normal HTT diminishes the association between mutant CAG repeat size and disease severity and progression in Huntington disease. The underlying mechanism may involve interaction of the polyglutamine domains of normal...

Loss of anti-Bax function in Gerstmann-Sträussler-Scheinker syndrome-associated prion protein mutants.

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Julie Jodoin

2009-08-01

Full Text Available Previously, we have shown the loss of anti-Bax function in Creutzfeldt Jakob disease (CJD-associated prion protein (PrP mutants that are unable to generate cytosolic PrP (CyPrP. To determine if the anti-Bax function of PrP modulates the manifestation of prion diseases, we further investigated the anti-Bax function of eight familial Gerstmann-Sträussler-Scheinker Syndrome (GSS-associated PrP mutants. These PrP mutants contained their respective methionine ((M or valine ((V at codon 129. All of the mutants lost their ability to prevent Bax-mediated chromatin condensation or DNA fragmentation in primary human neurons. In the breast carcinoma MCF-7 cells, the F198S(V, D202N(V, P102L(V and Q217R(V retained, whereas the P102L(M, P105L(V, Y145stop(M and Q212P(M PrP mutants lost their ability to inhibit Bax-mediated condensed chromatin. The inhibition of Bax-mediated condensed chromatin depended on the ability of the mutants to generate cytosolic PrP. However, except for the P102L(V, none of the mutants significantly inhibited Bax-mediated caspase activation. These results show that the cytosolic PrP generated from the GSS mutants is not as efficient as wild type PrP in inhibiting Bax-mediated cell death. Furthermore, these results indicate that the anti-Bax function is also disrupted in GSS-associated PrP mutants and is not associated with the difference between CJD and GSS.

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

International Nuclear Information System (INIS)

Wang Hu; Wang Jizheng; Zheng Weiyue; Wang Xiaojian; Wang Shuxia; Song Lei; Zou Yubao; Yao Yan; Hui Rutai

2006-01-01

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

Bovine laminitis: clinical aspects, pathology and pathogenesis with reference to acute equine laminitis.

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Boosman, R; Németh, F; Gruys, E

1991-07-01

This review deals with the features of clinical and subclinical laminitis in cattle. Prominent clinical signs of acute laminitis are a tender gait and arched back. The sole horn reveals red and yellowish discolourations within five days. In subacute and chronic cases clinical signs are less severe. In chronic laminitis the shape of the claws is altered. Laminitis is frequently followed by sole ulceration and white zone lesions. Blood tests showed no significant changes for laminitic animals. Arteriographic studies of claws affected by laminitis indicated that blood vessels had narrowed lumens. Gross pathology revealed congestion of the corium and rotation of the distal phalanx. Histopathologic studies indicate that laminitis is associated with changes of the vasculature. Peripartum management and nutrition are important factors in its aetiology. It is hypothesised that laminitis is evoked by disturbed digital circulation. In the pathogenesis of acute laminitis three factors are considered important: the occurrence of thrombosis, haemodynamic aspects of the corium, and endotoxins which trigger these pathologic events.

Laminitis and the equine metabolic syndrome.

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Johnson, Philip J; Wiedmeyer, Charles E; LaCarrubba, Alison; Ganjam, V K Seshu; Messer, Nat T

2010-08-01

Although much has been written about laminitis in the context of its association with inflammatory processes, recognition is growing that most cases of laminitis examined by veterinarians in private practice are those associated with pasture grazing, obesity, and insulin resistance (IR). The term 'endocrinopathic laminitis' has been adopted to classify the instances of laminitis in which the origin seems to be more strongly associated with an underlying endocrinopathy, such as either IR or the influence of corticosteroids. Results of a recent study suggest that obesity and IR represent the most common metabolic and endocrinopathic predispositions for laminitis in horses. IR also plays an important role in the pathogenesis of laminitis that develops when some horses or ponies are allowed to graze pastures at certain times of the year. The term equine metabolic syndrome (EMS) has been proposed as a label for horses whose clinical examination results (including both physical examination and laboratory testing) suggest heightened risk for developing laminitis as a result of underlying IR. Copyright (c) 2010 Elsevier Inc. All rights reserved.

"Subclinical" laminitis in dairy cattle.

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Vermunt, J J

1992-12-01

In dairying countries worldwide, the economic importance of lameness in cattle is now recognised. Laminitis is regarded as a major predisposing factor in lameness caused by claw disorders such as white zone lesions, sole ulcer, and heel horn erosion. The existence of subclinical laminitis was first suggested in the late 1970s by Dutch workers describing the symptoms of sole haemorrhages and yellowish-coloured, soft sole horn. In an attempt to clarify some of the confusing and often conflicting terminology, the literature on laminitis is reviewed. Disturbed haemodynamics, in particular repeated or prolonged dilation of arteriovenous anastomoses, have been implicated in the pathogenesis of both equine and bovine laminitis. Some characteristics of the vascular system of the bovine claw which may be of importance in the pathophysiology of the subclinical laminitis syndrome are therefore discussed. Clinical observations suggest that subclinical laminitis is a multifactorial disease. The different factors that are or may be involved in its aetiology vary in complexity and severity according to the management protocol of the animals. The possible involvement of subclinical laminitis in claw lesions is assessed.

PATHOLOGICAL AND MOLECULAR GENETIC STUDIES ON SOME SOYBEAN MUTANTS INDUCED BY GAMMA RAYS IN RELATION TO CHARCOAL ROT DISEASE

International Nuclear Information System (INIS)

ASHRY, N.A.; EL-DEMERDASH, H.M.; ABD EL-RAHMAN, S.S.

2008-01-01

The Egyptian soybean cultivar Giza-22 was used to induce resistant mutants for charcoal rot disease using gamma rays. Sixteen mutants and their parental cultivar were evaluated in M3 generation for their agronomic traits and for resistance to charcoal rot disease. Four mutants showed superiority in their agronomic traits as compared with their parental cultivar. Three mutants were significantly resistant to the disease than their parental cultivar (Giza-22). These three resistant mutants showed non-significant improvement in their agronomic traits as compared with Giza-22 cultivar. DNA extractions from the three resistant mutants and their parent were used to test the differences on the molecular level. Seven random amplified polymorphic DNA (RAPD) primers were used to detect RAPD markers related to charcoal rot resistance in soybean, and to differentiate these mutants. Six RAPD-primers showed molecular markers associated with resistance to charcoal rot in soybean, where five RAPD-primers could differentiate each of the three mutants from each other and from their parental cultivar

FireProt: Energy- and Evolution-Based Computational Design of Thermostable Multiple-Point Mutants.

Science.gov (United States)

Bednar, David; Beerens, Koen; Sebestova, Eva; Bendl, Jaroslav; Khare, Sagar; Chaloupkova, Radka; Prokop, Zbynek; Brezovsky, Jan; Baker, David; Damborsky, Jiri

2015-11-01

There is great interest in increasing proteins' stability to enhance their utility as biocatalysts, therapeutics, diagnostics and nanomaterials. Directed evolution is a powerful, but experimentally strenuous approach. Computational methods offer attractive alternatives. However, due to the limited reliability of predictions and potentially antagonistic effects of substitutions, only single-point mutations are usually predicted in silico, experimentally verified and then recombined in multiple-point mutants. Thus, substantial screening is still required. Here we present FireProt, a robust computational strategy for predicting highly stable multiple-point mutants that combines energy- and evolution-based approaches with smart filtering to identify additive stabilizing mutations. FireProt's reliability and applicability was demonstrated by validating its predictions against 656 mutations from the ProTherm database. We demonstrate that thermostability of the model enzymes haloalkane dehalogenase DhaA and γ-hexachlorocyclohexane dehydrochlorinase LinA can be substantially increased (ΔTm = 24°C and 21°C) by constructing and characterizing only a handful of multiple-point mutants. FireProt can be applied to any protein for which a tertiary structure and homologous sequences are available, and will facilitate the rapid development of robust proteins for biomedical and biotechnological applications.

FireProt: Energy- and Evolution-Based Computational Design of Thermostable Multiple-Point Mutants.

Directory of Open Access Journals (Sweden)

David Bednar

2015-11-01

Full Text Available There is great interest in increasing proteins' stability to enhance their utility as biocatalysts, therapeutics, diagnostics and nanomaterials. Directed evolution is a powerful, but experimentally strenuous approach. Computational methods offer attractive alternatives. However, due to the limited reliability of predictions and potentially antagonistic effects of substitutions, only single-point mutations are usually predicted in silico, experimentally verified and then recombined in multiple-point mutants. Thus, substantial screening is still required. Here we present FireProt, a robust computational strategy for predicting highly stable multiple-point mutants that combines energy- and evolution-based approaches with smart filtering to identify additive stabilizing mutations. FireProt's reliability and applicability was demonstrated by validating its predictions against 656 mutations from the ProTherm database. We demonstrate that thermostability of the model enzymes haloalkane dehalogenase DhaA and γ-hexachlorocyclohexane dehydrochlorinase LinA can be substantially increased (ΔTm = 24°C and 21°C by constructing and characterizing only a handful of multiple-point mutants. FireProt can be applied to any protein for which a tertiary structure and homologous sequences are available, and will facilitate the rapid development of robust proteins for biomedical and biotechnological applications.

Mutant power: using mutant allele collections for yeast functional genomics.

Science.gov (United States)

Norman, Kaitlyn L; Kumar, Anuj

2016-03-01

The budding yeast has long served as a model eukaryote for the functional genomic analysis of highly conserved signaling pathways, cellular processes and mechanisms underlying human disease. The collection of reagents available for genomics in yeast is extensive, encompassing a growing diversity of mutant collections beyond gene deletion sets in the standard wild-type S288C genetic background. We review here three main types of mutant allele collections: transposon mutagen collections, essential gene collections and overexpression libraries. Each collection provides unique and identifiable alleles that can be utilized in genome-wide, high-throughput studies. These genomic reagents are particularly informative in identifying synthetic phenotypes and functions associated with essential genes, including those modeled most effectively in complex genetic backgrounds. Several examples of genomic studies in filamentous/pseudohyphal backgrounds are provided here to illustrate this point. Additionally, the limitations of each approach are examined. Collectively, these mutant allele collections in Saccharomyces cerevisiae and the related pathogenic yeast Candida albicans promise insights toward an advanced understanding of eukaryotic molecular and cellular biology. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Laminated structure in internally oxidized Ru-Ta coatings

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Chen, Yung-I, E-mail: yichen@mail.ntou.edu.tw

2012-12-01

During the development of refractory alloy coatings for protective purposes at high temperature under oxygen-containing atmospheres, previous studies noted and examined the internal oxidation phenomenon for Mo-Ru and Ru-Ta coatings. The internally oxidized zone shows a laminated structure, consisting of alternating oxygen-rich and deficient layers stacked with a general orientation. Previous studies proposed a forming mechanism. To investigate in detail, Ru-Ta coatings were prepared with various rotating speeds of a substrate-holder. The coatings were annealed at 600 Degree-Sign C in an atmosphere continuously purged with 1% O{sub 2}-99% Ar mixed gas for 30 min. Transmission electron microscopy was used to examine the laminated-layer periods. Auger electron spectroscopy depth profiles certified the periodical variation of the related constituents. X-ray photoelectron spectroscopy proved the valence variation of Ta in the near surface, accompanied by the introduction of oxygen ions. The inward diffusion of oxygen was dominated by lattice diffusion. - Highlights: Black-Right-Pointing-Pointer Laminated Ru-Ta coatings consisted of a cyclical gradient concentration. Black-Right-Pointing-Pointer The as-deposited coatings showed a laminated structure with a period of 4-34 nm. Black-Right-Pointing-Pointer Internal oxidation of Ru-Ta coatings executed after annealing in 1% O{sub 2}-Ar atmosphere. Black-Right-Pointing-Pointer Oxygen inward diffusion was dominated by lattice diffusion.

Mutant lines of currant tomato, valuable germplasm with multiple disease resistance

International Nuclear Information System (INIS)

Govorova, G.F.; Khrustaleva, V.V.; Shcherbakov, V.K.

1987-01-01

Studies were carried out for two years on eight mutant lines of currant tomato at the Krymsk Experimental Breeding Station of the N.I. Vavilov All-Union Scientific Research Institute of Plant-Growing (VIR). The station is situated in an area of commercial field tomato growing (Krasnodar region). The mutant lines of currant tomato (VIR specimen No. k-4053) were obtained through chronic gamma-irradiation. A disease resistance evaluation of the mutants was carried out for Verticillium wilt (Verticillium albo-atrum Rein. and Berth.), for black bacterial spotting (Xanthomonas vesicatoria Dows.), for tobacco mosaic virus Nicotiana 1 Smith), for streak virus (Nicotiana 1), for the combination TMV with X and Y potato viruses, for cucumber virus (Cucumis 1), and also for top rot. Fifty plants of each mutant line were evaluated and checks were made three times in each season. A comparison of the currant tomato mutants with the standard tomato varieties demonstrates the better resistance shown by the mutant germplasm to the main pathogens. The degree to which some currant tomato mutants were affected by Verticillium was lower than that of the most VerticiIlium-resistant samples of tomato evaluated between 1975 and 1981. The mutants of currant tomato should therefore be of interest as germplasm in breeding tomatoes for improved multiple disease resistance

Evaluation of induced mutants of wheat for resistance to fungal diseases

International Nuclear Information System (INIS)

Barriga B, P.; Fuentes P, R.; Andrade S, N.; Seeman F, P.

1990-01-01

Evaluation of induced mutants of wheat for resistance to fungal diseases. Seeds of spring wheat cultivars Austral and Huenufen were exposed to gamma radiation in doses of 0.10 and 0.25 KGy with the objective of producing genotypes resistant to the main fungal diseases, with a high protein content and grain yield, for the southern region of Chile (39 sup(o)-44 sup(o) Latitude south). The selection process and evaluation up to the generation M sub(8) has made possible to identify mutants with a higher protein content and grain yield. Progress made in improving resistance to Puccinia striiformis and tolerance to Septoria spp., has also been important. Some selected mutants, conditioned to their future performance, could be directly used as commercial varieties and other mutants, on crosses with regionally adapted cultivars. (author)

'CM 88' - A multiple disease resistant chickpea mutant variety

International Nuclear Information System (INIS)

Haq, M.A.; Hassan, Mahmudul; Sadiq, M.

2001-01-01

Full text: Chickpea is the most important grain legume crop of Pakistan. Ascochyta blight (Ascochyta rabiei) and Fusarium wilt (Fusarium oxysporum F. sp cicer) are most serious diseases, having the potential to devastate a crop. A multiple disease resistant and high yielding mutant CM 88 has been developed through 100 Gy gamma irradiation treatment of variety 'C 727'. This was once a widely grown and popular variety, which lost its resistance to Ascochyta and was replaced. The selection of mutants was performed in the M2 generation grown in the Ascochyta blight nursery and sixteen mutants were selected. In the subsequent generations CM 88 proved resistant to both Ascochyta blight and Fusarium wilt, and exhibited superiority in agronomic characteristics. CM 88 was also tested for many years in the various yield trials on research stations and farmers fields throughout the country. In these trials it out yielded both the parent and standard varieties. The mutant CM 88 has been approved by the Punjab Seed Council on 27 October 1994 for general cultivation in the Punjab Province, especially the Thal area which accounts for more than 70% of the area under chickpea cultivation. (author)

Histopathology of dairy cows' hooves with signs of naturally acquired laminitis

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Heloisa M.F. Mendes

2013-05-01

Full Text Available The purpose of this study was to investigate histological changes in dairy cows' hooves with or without injuries from naturally acquired laminitis. Cull cows with no clinical signs of hoof abnormalities (G1, n=9 and those with macroscopic lesions associated with laminitis without (G2, n=23 or with lameness (G3, n=7 were used in the study. After slaughter, samples of dermo-epidermal junctions of sole, axial and dorsal regions of the hoof were obtained and histologically processed using HE and PAS staining. Congestion, hemorrhage and inflammatory infiltrate in the dermis of sole, axial and dorsal regions were blindly and semiquantitatively evaluated by the same researcher. Inflammatory infiltrate was evaluated in the dermal laminae of axial and dorsal regions. The morphology of epidermal cells and the presence of irregularities in three regions of the basement membrane (BM length were examined using PAS staining. Scores of lesions in different regions of the hoof in the same group and in different groups for each region of the hoof were compared using non-parametric analyses. Inflammatory infiltrate in the dermis of all regions of the hoof was detected in all groups with no significant statistical difference. Cows with no clinical signs of hoof abnormalities secondary to laminitis (G1 have inflammation scores and epidermal cell changes similar to those of groups with laminitis injuries, suggesting the existence of a prodromal phase for this disease in bovines. BM had irregularities with a variable intensity along its length, however, with no difference among groups. The pattern of BM irregularities found has not been reported so far and does not resemble the BM collapse described in horses and cattle with induced acute laminitis. Is it concluded that even in the absence of macroscopic hoof signs associated to laminitis, dairy cows have histological injuries compatible with inflammation of the dermo-epidermal junction as in affected animals

Mutant of Japanese pear resistant to Black Spot Disease

International Nuclear Information System (INIS)

Sanada, T.; Nishida, T.; Ikeda, F.

1987-01-01

Full text: Nijisseike is one of the leading cultivars of Japanese pear (Pyrus serotinea Rehd.), but susceptible to black spot disease. Farmers try to prevent this disease by wrapping the fruit with a paper bag and by repeated spraying of fungicides. The disease is caused by a Japanese pear pathotype of Alternaria alternata (Fr.) Keissler. Susceptibility is controlled by a single dominant gene. In 1962, grafted trees of this cultivar were planted at a distance between 53 and 93 m from the 60 Co source in the gamma-field (daily dose 15-4 rad). One branch on a tree planted at 53 m was detected as resistant in 1981. Under field conditions, black spots were observed on many fruits and leaves of the original trees by natural infection in early July, however, they were not observed on the mutant. To examine the resistance of the mutant, artificial inoculations were made using spores of the pathogen and the host specific toxin produced by germinating spores. When some drops of the spore suspension are placed on leaves, the formation of black spots depends upon the leaf age. In a resistant cv. as Chojuro, black spot symptoms are formed only when inoculated on young leaves. An intermediate reaction was observed in the mutant, whereas the original Nijisseiki showed severe symptoms. When inoculation was made on matured fruit skins, no black spot was formed on the mutant just like on the resistant cv. Chojuro, while many small black spots were formed and grew into large spots overlapping each other on the susceptible cv. Nijisseiki. In case of the crude toxin inoculation (4-0.04 ppm) of cv. Nijisseiki black spots were formed on the surface of the susceptible fruit skin, and necrotic lesions at the cut end of detached small pieces of leaves, although reaction on fruit skins was weaker compared with inoculation by spores. However, no symptoms were observed from the toxin application on the mutant and the resistant cv. Chojuro. That the resistance of the mutant is classified as

Chromatin and lamin A determine two different mechanical response regimes of the cell nucleus.

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Stephens, Andrew D; Banigan, Edward J; Adam, Stephen A; Goldman, Robert D; Marko, John F

2017-07-07

The cell nucleus must continually resist and respond to intercellular and intracellular mechanical forces to transduce mechanical signals and maintain proper genome organization and expression. Altered nuclear mechanics is associated with many human diseases, including heart disease, progeria, and cancer. Chromatin and nuclear envelope A-type lamin proteins are known to be key nuclear mechanical components perturbed in these diseases, but their distinct mechanical contributions are not known. Here we directly establish the separate roles of chromatin and lamin A/C and show that they determine two distinct mechanical regimes via micromanipulation of single isolated nuclei. Chromatin governs response to small extensions (<3 μm), and euchromatin/heterochromatin levels modulate the stiffness. In contrast, lamin A/C levels control nuclear strain stiffening at large extensions. These results can be understood through simulations of a polymeric shell and cross-linked polymer interior. Our results provide a framework for understanding the differential effects of chromatin and lamin A/C in cell nuclear mechanics and their alterations in disease. © 2017 Stephens et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Evaluation of Behaviours of Laminated Glass

Science.gov (United States)

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.

Laminates

Science.gov (United States)

Lepedat, Karin; Wagner, Robert; Lang, Jürgen

The use of phenolic resin for the impregnation of a carrier material such as paper or fabric based on either organic or inorganic fibers was and still is one of the most important application areas for liquid phenolic resins. Substrates like paper, cotton, or glass fabric impregnated with phenolic resins are used as core layers for decorative and technical laminates and for many other different industrial applications. Nowadays, phenolic resins for decorative laminates used for furniture, flooring, or in the construction and transportation industry have gained significant market share. The Laminates chapter mainly describes the manufacture of decorative laminates especially the impregnation and pressing process with special emphasis to new technological developments and recent trends. Moreover, the different types of laminates are introduced, combined with some brief comments as they relate to the market for decorative surfaces.

Minimality of invariant laminations for partially hyperbolic attractors

International Nuclear Information System (INIS)

Nobili, Felipe

2015-01-01

Let f : M → M be a C 1 -diffeomorphism over a compact boundaryless Riemannian manifold M, and Λ a compact f-invariant subset of M admitting a partially hyperbolic spliting T f Λ = E s  ⊕ E c  ⊕ E u over the tangent bundle T f Λ. It's known from the Hirsch–Pugh–Shub theory that Λ admits two invariant laminations associated to the extremal bundles E s and E u . These laminations are families of dynamically defined immersed submanifolds of the M tangent, respectively, to the bundles E s and E u at every point in Λ. In this work, we prove that at least one of the invariant laminations of a transitive partially hyperbolic attractor with a one-dimensional center bundle is minimal: the orbit of every leaf intersects Λ densely. This result extends those in Bonatti et al (2002 J. Inst. Math. Jussieu 1 513–41) and Hertz et al (2007 Fields Institute Communications vol 51 (Providence, RI: American Mathematical Society) pp 103–9) about minimal foliations for robustly transitive diffeomorphisms. (paper)

NH exchange in point mutants of human ubiquitin.

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Jahr, Nicole; Fiedler, Erik; Günther, Robert; Hofmann, Hans-Jörg; Berger, Stefan

2011-08-01

Several point mutants of human ubiquitin (Ub(T9V), Ub(F45W), Ub(F45G), and Ub(A46S)) were prepared by recombinant techniques. The NH exchange rate constants were measured by the NMR diffusion and the MEXICO methods and compared with those in the wild type to examine the influence of structural changes and to improve the understanding of this important reaction in studies of protein folding and denaturation. The observed changes follow qualitatively the polarity and steric alterations caused by the introduced amino acids. Attempts to reproduce quantitatively the observed changes by modeling studies and molecular dynamics simulations were not satisfactory. Copyright © 2011 Elsevier B.V. All rights reserved.

Differential effects of lesion mimic mutants in barley on disease development by facultative pathogens

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McGrann, Graham R. D.; Steed, , Andrew; Burt, Christopher; Nicholson, Paul; Brown, James K. M.

2015-01-01

Lesion mimic mutants display spontaneous necrotic spots and chlorotic leaves as a result of mis-regulated cell death programmes. Typically these mutants have increased resistance to biotrophic pathogens but their response to facultative fungi that cause necrotrophic diseases is less well studied. The effect of altered cell death regulation on the development of disease caused by Ramularia collo-cygni, Fusarium culmorum and Oculimacula yallundae was explored using a collection of barley necrotic (nec) lesion mimic mutants. nec8 mutants displayed lower levels of all three diseases compared to nec9 mutants, which had increased R. collo-cygni but decreased F. culmorum disease symptoms. nec1 mutants reduced disease development caused by both R. collo-cygni and F. culmorum. The severity of the nec1-induced lesion mimic phenotype and F. culmorum symptom development was reduced by mutation of the negative cell death regulator MLO. The significant reduction in R. collo-cygni symptoms caused by nec1 was completely abolished in the presence of the mlo-5 allele and both symptoms and fungal biomass were greater than in the wild-type. These results indicate that physiological pathways involved in regulation of cell death interact with one another in their effects on different fungal pathogens. PMID:25873675

Plasma proteomics shows an elevation of the anti-inflammatory protein APOA-IV in chronic equine laminitis

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Steelman Samantha M

2012-09-01

Full Text Available Abstract Background Equine laminitis is a devastating disease that causes severe pain in afflicted horses and places a major economic burden on the horse industry. In acute laminitis, the disintegration of the dermal-epidermal junction can cause the third phalanx to detach from the hoof wall, leaving the horse unable to bear weight on the affected limbs. Horses that survive the acute phase transition into a chronic form of laminitis, which is often termed “founder”. Some evidence suggests that chronic laminar inflammation might be associated with alterations in the endocrine and immune systems. We investigated this broad hypothesis by using DIGE to assess global differences in the plasma proteome between horses with chronic laminitis and controls. Results We identified 16 differentially expressed proteins; the majority of these were involved in the interrelated coagulation, clotting, and kininogen cascades. Clinical testing of functional coagulation parameters in foundered horses revealed a slight delay in prothrombin (PT clotting time, although most other indices were within normal ranges. Upregulation of the intestinal apolipoprotein APOA-IV in horses with chronic laminitis was confirmed by western blot. Conclusions Our results support the hypothesis that localized laminar inflammation may be linked to systemic alterations in immune regulation, particularly in the gastrointestinal system. Gastrointestinal inflammation has been implicated in the development of acute laminitis but has not previously been associated with chronic laminitis.

Lamination cooling system

Science.gov (United States)

Rippel, Wally E.; Kobayashi, Daryl M.

2005-10-11

An electric motor, transformer or inductor having a lamination cooling system including a stack of laminations, each defining a plurality of apertures at least partially coincident with apertures of adjacent laminations. The apertures define a plurality of cooling-fluid passageways through the lamination stack, and gaps between the adjacent laminations are sealed to prevent a liquid cooling fluid in the passageways from escaping between the laminations. The gaps are sealed by injecting a heat-cured sealant into the passageways, expelling excess sealant, and heat-curing the lamination stack. The apertures of each lamination can be coincident with the same-sized apertures of adjacent laminations to form straight passageways, or they can vary in size, shape and/or position to form non-axial passageways, angled passageways, bidirectional passageways, and manifold sections of passageways that connect a plurality of different passageway sections. Manifold members adjoin opposite ends of the lamination stack, and each is configured with one or more cavities to act as a manifold to adjacent passageway ends. Complex manifold arrangements can create bidirectional flow in a variety of patterns.

A knock-in/knock-out mouse model of HSPB8-associated distal hereditary motor neuropathy and myopathy reveals toxic gain-of-function of mutant Hspb8.

Science.gov (United States)

Bouhy, Delphine; Juneja, Manisha; Katona, Istvan; Holmgren, Anne; Asselbergh, Bob; De Winter, Vicky; Hochepied, Tino; Goossens, Steven; Haigh, Jody J; Libert, Claude; Ceuterick-de Groote, Chantal; Irobi, Joy; Weis, Joachim; Timmerman, Vincent

2018-01-01

Mutations in the small heat shock protein B8 gene (HSPB8/HSP22) have been associated with distal hereditary motor neuropathy, Charcot-Marie-Tooth disease, and recently distal myopathy. It is so far not clear how mutant HSPB8 induces the neuronal and muscular phenotypes and if a common pathogenesis lies behind these diseases. Growing evidence points towards a role of HSPB8 in chaperone-associated autophagy, which has been shown to be a determinant for the clearance of poly-glutamine aggregates in neurodegenerative diseases but also for the maintenance of skeletal muscle myofibrils. To test this hypothesis and better dissect the pathomechanism of mutant HSPB8, we generated a new transgenic mouse model leading to the expression of the mutant protein (knock-in lines) or the loss-of-function (functional knock-out lines) of the endogenous protein Hspb8. While the homozygous knock-in mice developed motor deficits associated with degeneration of peripheral nerves and severe muscle atrophy corroborating patient data, homozygous knock-out mice had locomotor performances equivalent to those of wild-type animals. The distal skeletal muscles of the post-symptomatic homozygous knock-in displayed Z-disk disorganisation, granulofilamentous material accumulation along with Hspb8, αB-crystallin (HSPB5/CRYAB), and desmin aggregates. The presence of the aggregates correlated with reduced markers of effective autophagy. The sciatic nerve of the homozygous knock-in mice was characterized by low autophagy potential in pre-symptomatic and Hspb8 aggregates in post-symptomatic animals. On the other hand, the sciatic nerve of the homozygous knock-out mice presented a normal morphology and their distal muscle displayed accumulation of abnormal mitochondria but intact myofiber and Z-line organisation. Our data, therefore, suggest that toxic gain-of-function of mutant Hspb8 aggregates is a major contributor to the peripheral neuropathy and the myopathy. In addition, mutant Hspb8 induces

Endoplasmic Reticulum-Targeted Subunit Toxins Provide a New Approach to Rescue Misfolded Mutant Proteins and Revert Cell Models of Genetic Diseases

OpenAIRE

Adnan, Humaira; Zhang, Zhenbo; Park, Hyun-Joo; Tailor, Chetankumar; Che, Clare; Kamani, Mustafa; Spitalny, George; Binnington, Beth; Lingwood, Clifford

2016-01-01

Many germ line diseases stem from a relatively minor disturbance in mutant protein endoplasmic reticulum (ER) 3D assembly. Chaperones are recruited which, on failure to correct folding, sort the mutant for retrotranslocation and cytosolic proteasomal degradation (ER-associated degradation-ERAD), to initiate/exacerbate deficiency-disease symptoms. Several bacterial (and plant) subunit toxins, retrograde transport to the ER after initial cell surface receptor binding/internalization. The A subu...

LAMINATES

Directory of Open Access Journals (Sweden)

Gökay Nemli

2004-04-01

Full Text Available Wood based panel producers afford to present their products either in sized semi-finished form or as covered in general by the in additional investments realized. The fact that the laminated material has a certain market share as well as the increase in demand for furniture types finished in various profiles have put the laminated sheets which provide very comprehensive design facilities at the top place and caused such boards to spread over the market rather more quickly. In line with this development, great developments have also been recorded during recent years in laminate utilization in furniture factoring sector and fast steps taken towards a more rational working environment. In this study, laminates types and manufacturing technologies were investigated.

Mechanical performance of laminated composites incorporated with nanofibrous membranes

International Nuclear Information System (INIS)

Liu, L.; Huang, Z.-M.; He, C.L.; Han, X.J.

2006-01-01

The effect of non-woven nanofibrous membranes as interlaminar interfaces on the mechanical performance of laminated composites was investigated experimentally. The nanofibrous membranes are porous, thin and lightweight, and exhibit toughness and strength to some extent. They give little increase in weight and thickness when incorporated into a laminate. More important, they can be used as a functional agent carrier for the laminate. The nanofiber membranes used in this paper were prepared by electrospinning of Nylon-6 (PA6), Epoxy 609 (EPO 1691-410) and thermoplastic polyurethane (TPU), with a thickness ranging from 20 to 150 μm. The non-woven fabrics were attached to one side of a glass/epoxy fabric lamina prior to lamination and each fabric was arranged in between two adjacent plies of the laminate. The nanofibrous membranes were characterized through scanning electron microscopy (SEM) and tensile testing, whereas the mechanical properties of the laminate were understood in terms of three-point bending and short-beam shear tests. Results have shown that the nanofibrous membranes in the ply interfaces with a proper thickness did not affect the mechanical performance of the composite laminates significantly

Purification, crystallization and preliminary X-ray diffraction analysis of disease-related mutants of p97

International Nuclear Information System (INIS)

Tang, Wai-Kwan; Li, Dongyang; Esser, Lothar; Xia, Di

2009-01-01

Mutations in the human AAA+ protein p97 cause a disease in humans called IBMPFD. How these mutations affect the structure and function of p97 is unknown. Here, the crystallization of three disease-related mutants of p97 in the presence of ATPγS are reported. The human type II AAA+ protein p97 participates in various cellular activities, presumably through its involvement in the ubiquitin–proteasome degradation pathway. Mutations in p97 have been implicated in patients with inclusion-body myopathy associated with Paget’s disease of the bone and frontotemporal dementia (IBMPFD). In this work, three mutant p97 N-D1 fragments, R86A, R95G and R155H, were crystallized in the presence of ATPγS with PEG 3350 as a main precipitant, yielding two different crystal forms. The R155H mutant crystal belonged to space group R3, with unit-cell parameters in the hexagonal setting of a = b = 134.2, c = 182.9 Å, and was merohedrally twinned, with an estimated twin fraction of 0.34. The crystals of the R86A and R95G mutants belonged to space group P1, with similar unit-cell parameters of a = 90.89, b = 102.6, c = 107.2 Å, α = 97.5, β = 90.6, γ = 91.5° and a = 92.76, b = 103.7, c = 107.7 Å, α = 97.7, β = 91.9, γ = 89.7°, respectively

β-Catenin is critical for cerebellar foliation and lamination.

Directory of Open Access Journals (Sweden)

Jing Wen

Full Text Available The cerebellum has a conserved foliation pattern and a well-organized layered structure. The process of foliation and lamination begins around birth. β-catenin is a downstream molecule of Wnt signaling pathway, which plays a critical role in tissue organization. Lack of β-catenin at early embryonic stages leads to either prenatal or neonatal death, therefore it has been difficult to resolve its role in cerebellar foliation and lamination. Here we used GFAP-Cre to ablate β-catenin in neuronal cells of the cerebellum after embryonic day 12.5, and found an unexpected role of β-catenin in determination of the foliation pattern. In the mutant mice, the positions of fissure formation were changed, and the meninges were improperly incorporated into fissures. At later stages, some lobules were formed by Purkinje cells remaining in deep regions of the cerebellum and the laminar structure was dramatically altered. Our results suggest that β-catenin is critical for cerebellar foliation and lamination. We also found a non cell-autonomous role of β-catenin in some developmental properties of major cerebellar cell types during specific stages.

Laminated articles

International Nuclear Information System (INIS)

Ridgway, P.C.; Case, D.F.

1979-01-01

In a method of bonding laminations of a magnetic core, photo-resist material consisting of a co-polymer is applied as a film to a sheet of magnetic material to define lamination shapes to enable the laminations to be formed by etching. The film of photo-resist material on the laminations is then utilised to bond the laminations together in a stack. In order to permit the core to operate at temperatures higher than the softening temperature of the photo-resist material, the bonded stack is irradiated with 1 - 2 Mer gamma radiation to a dose of 1 - 5 Mrads in 2 - 10 hrs to cause changes to the bonding material such that the material does not soften at the operating temperature of the core. (U.K.)

Moisture Absorption/Desorption Effects on Flexural Property of Glass-Fiber-Reinforced Polyester Laminates: Three-Point Bending Test and Coupled Hygro-Mechanical Finite Element Analysis

Directory of Open Access Journals (Sweden)

Xu Jiang

2016-08-01

Full Text Available Influence of moisture absorption/desorption on the flexural properties of Glass-fibre-reinforced polymer (GFRP laminates was experimentally investigated under hot/wet aging environments. To characterize mechanical degradation, three-point bending tests were performed following the ASTM test standard (ASTM D790-10A. The flexural properties of dry (0% Mt/M∞, moisture unsaturated (30% Mt/M∞ and 50% Mt/M∞ and moisture saturated (100% Mt/M∞ specimens at both 20 and 40 °C test temperatures were compared. One cycle of moisture absorption-desorption process was considered in this study to investigate the mechanical degradation scale and the permanent damage of GFRP laminates induced by moisture diffusion. Experimental results confirm that the combination of moisture and temperature effects sincerely deteriorates the flexural properties of GFRP laminates, on both strength and stiffness. Furthermore, the reducing percentage of flexural strength is found much larger than that of E-modulus. Unrecoverable losses of E-modulus (15.0% and flexural strength (16.4% for the GFRP laminates experiencing one cycle of moisture absorption/desorption process are evident at the test temperature of 40 °C, but not for the case of 20 °C test temperature. Moreover, a coupled hygro-mechanical Finite Element (FE model was developed to characterize the mechanical behaviors of GFRP laminates at different moisture absorption/desorption stages, and the modeling method was subsequently validated with flexural test results.

Engineered disulfide bonds restore chaperone-like function of DJ-1 mutants linked to familial Parkinson's disease.

Science.gov (United States)

Logan, Todd; Clark, Lindsay; Ray, Soumya S

2010-07-13

Loss-of-function mutations such as L166P, A104T, and M26I in the DJ-1 gene (PARK7) have been linked to autosomal-recessive early onset Parkinson's disease (PD). Cellular and structural studies of the familial mutants suggest that these mutations may destabilize the dimeric structure. To look for common dynamical signatures among the DJ-1 mutants, short MD simulations of up to 1000 ps were conducted to identify the weakest region of the protein (residues 38-70). In an attempt to stabilize the protein, we mutated residue Val 51 to cysteine (V51C) to make a symmetry-related disulfide bridge with the preexisting Cys 53 on the opposite subunit. We found that the introduction of this disulfide linkage stabilized the mutants A104T and M26I against thermal denaturation, improved their ability to scavenge reactive oxygen species (ROS), and restored a chaperone-like function of blocking alpha-synuclein aggregation. The L166P mutant was far too unstable to be rescued by introduction of the V51C mutation. The results presented here point to the possible development of pharmacological chaperones, which may eventually lead to PD therapeutics.

Geometry effect on the behaviour of single and glue-laminated glass fibre reinforced polymer composite sandwich beams loaded in four-point bending

International Nuclear Information System (INIS)

Awad, Ziad K.; Aravinthan, Thiru; Manalo, Allan

2012-01-01

Highlights: ► Investigated the behaviour of single and glue-laminated GFRP sandwich beam. ► Effect of shear span to depth was a key factor affecting the overall behaviour. ► Comparison with prediction models gave reasonable results in specific regions. ► A failure map was developed to identify the shear and flexural failures of panels. -- Abstract: The research investigated the behaviour of single and glue laminated glass fibre reinforced polymer (GFRP) composite sandwich beams considering different spans and beam cross sections. The composite sandwich beams with different thicknesses (1, 2, 3, 4, and 5 sandwich layers) have been tested in four-point static flexural test with different shear span to depth ratio (a/d). The a/d ratios showed a direct effect on the flexural and shear behaviour. The capacity of the beam decreased with increasing a/d. Various failure modes were observed including core crushing, core shear, and top skin compression failure. The failure mode map developed based on the experimental finding and analytical prediction indicated that the failure mode is affected by the a/d with the number of glue laminated panels.

Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and muscular dystrophy

NARCIS (Netherlands)

van der Kooi, A. J.; Bonne, G.; Eymard, B.; Duboc, D.; Talim, B.; van der Valk, M.; Reiss, P.; Richard, P.; Demay, L.; Merlini, L.; Schwartz, K.; Busch, H. F. M.; de Visser, M.

2002-01-01

Mutations in the lamin A/C gene are found in Emery-Dreifuss muscular dystrophy, limb girdle muscular dystrophy with cardiac conduction disturbances, dilated cardiomyopathy with conduction system disease, and familial partial lipodystrophy. Cases with lamin A/C mutations presenting with lipodystrophy

Invertebrate lamins

International Nuclear Information System (INIS)

Melcer, Shai; Gruenbaum, Yosef; Krohne, Georg

2007-01-01

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

Subclinical laminitis and its association with pO2 and faecal alterations: Isikli, Aydin experience

OpenAIRE

Ibrahim Akin; Deniz Alic Ural; Mehmet Gultekin; Kerem Ural

2015-01-01

ABSTRACTObjective. The aim of this field trial was to investigate the relationships among subclinical laminitis, hematological, ruminal and faecal alterations. Materials and Methods. To this extent dairy cows presenting subclinical laminitis (n=11) and to those of other healthy cows without laminitis (n=10) were enrolled and assigned into two groups. All animals were receiving the same daily ration formulated to contain 47% cornsilage and 18% hay, mainly. Effects of subclinical laminitis chal...

Climbing ripple structure and associated storm-lamination from a ...

Indian Academy of Sciences (India)

Pranhita–Godavari Valley, south India, displays well developed climbing ripple lamination and ... sedimentary environments, such as river flood .... Sediment, sequence and facies ..... tic Archaean Witwatersrand Supergroup, South Africa;.

Oncogenic Signaling by Leukemia-Associated Mutant Cbl Proteins

Science.gov (United States)

Nadeau, Scott; An, Wei; Palermo, Nick; Feng, Dan; Ahmad, Gulzar; Dong, Lin; Borgstahl, Gloria E. O.; Natarajan, Amarnath; Naramura, Mayumi; Band, Vimla; Band, Hamid

2013-01-01

Members of the Cbl protein family (Cbl, Cbl-b, and Cbl-c) are E3 ubiquitin ligases that have emerged as critical negative regulators of protein tyrosine kinase (PTK) signaling. This function reflects their ability to directly interact with activated PTKs and to target them as well as their associated signaling components for ubiquitination. Given the critical roles of PTK signaling in driving oncogenesis, recent studies in animal models and genetic analyses in human cancer have firmly established that Cbl proteins function as tumor suppressors. Missense mutations or small in-frame deletions within the regions of Cbl protein that are essential for its E3 activity have been identified in nearly 5% of leukemia patients with myelodysplastic/myeloproliferative disorders. Based on evidence from cell culture studies, in vivo models and clinical data, we discuss the potential signaling mechanisms of mutant Cbl-driven oncogenesis. Mechanistic insights into oncogenic Cbl mutants and associated animal models are likely to enhance our understanding of normal hematopoietic stem cell homeostasis and provide avenues for targeted therapy of mutant Cbl-driven cancers. PMID:23997989

Endoplasmic Reticulum-Targeted Subunit Toxins Provide a New Approach to Rescue Misfolded Mutant Proteins and Revert Cell Models of Genetic Diseases.

Science.gov (United States)

Adnan, Humaira; Zhang, Zhenbo; Park, Hyun-Joo; Tailor, Chetankumar; Che, Clare; Kamani, Mustafa; Spitalny, George; Binnington, Beth; Lingwood, Clifford

2016-01-01

Many germ line diseases stem from a relatively minor disturbance in mutant protein endoplasmic reticulum (ER) 3D assembly. Chaperones are recruited which, on failure to correct folding, sort the mutant for retrotranslocation and cytosolic proteasomal degradation (ER-associated degradation-ERAD), to initiate/exacerbate deficiency-disease symptoms. Several bacterial (and plant) subunit toxins, retrograde transport to the ER after initial cell surface receptor binding/internalization. The A subunit has evolved to mimic a misfolded protein and hijack the ERAD membrane translocon (dislocon), to effect cytosolic access and cytopathology. We show such toxins compete for ERAD to rescue endogenous misfolded proteins. Cholera toxin or verotoxin (Shiga toxin) containing genetically inactivated (± an N-terminal polyleucine tail) A subunit can, within 2-4 hrs, temporarily increase F508delCFTR protein, the major cystic fibrosis (CF) mutant (5-10x), F508delCFTR Golgi maturation (glucocerobrosidase (GCC) in N370SGCC Gaucher Disease fibroblasts (3x), another ERAD-exacerbated misfiling disease. We identify a new, potentially benign approach to the treatment of certain genetic protein misfolding diseases.

Association between time to disease progression end points and overall survival in patients with neuroendocrine tumors

Directory of Open Access Journals (Sweden)

Singh S

2014-08-01

Full Text Available Simron Singh,1 Xufang Wang,2 Calvin HL Law1 1Sunnybrook Odette Cancer Center, University of Toronto, Toronto, ON, Canada; 2Novartis Oncology, Florham Park, NJ, USA Abstract: Overall survival can be difficult to determine for slowly progressing malignancies, such as neuroendocrine tumors. We investigated whether time to disease progression is positively associated with overall survival in patients with such tumors. A literature review identified 22 clinical trials in patients with neuroendocrine tumors that reported survival probabilities for both time to disease progression (progression-free survival and time to progression and overall survival. Associations between median time to disease progression and median overall survival and between treatment effects on time to disease progression and treatment effects on overall survival were analyzed using weighted least-squares regression. Median time to disease progression was significantly associated with median overall survival (coefficient 0.595; P=0.022. In the seven randomized studies identified, the risk reduction for time to disease progression was positively associated with the risk reduction for overall survival (coefficient on −ln[HR] 0.151; 95% confidence interval −0.843, 1.145; P=0.713. The significant association between median time to disease progression and median overall survival supports the assertion that time to disease progression is an alternative end point to overall survival in patients with neuroendocrine tumors. An apparent albeit not significant trend correlates treatment effects on time to disease progression and treatment effects on overall survival. Informal surveys of physicians’ perceptions are consistent with these concepts, although additional randomized trials are needed. Keywords: neuroendocrine tumors, progression-free survival, disease progression, mortality

Reduced anti-oxidative stress activities of DJ-1 mutants found in Parkinson's disease patients

International Nuclear Information System (INIS)

Takahashi-Niki, Kazuko; Niki, Takeshi; Taira, Takahiro; Iguchi-Ariga, Sanae M.M.; Ariga, Hiroyoshi

2004-01-01

DJ-1 is a multi-functional protein that plays roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to result in onset of Parkinson's disease. We have previously reported that L166P, a mutant DJ-1 found in Parkinson's disease patients, had no activity to prevent hydrogen peroxide (H 2 O 2 )-induced cell death. In this study, we analyzed other mutants of DJ-1 found in Parkinson's disease patients, including M26I, R98Q, and D149A, as well as L166P. We first found that all of the mutants made heterodimers with wild-type DJ-1, while all of the mutants except for L166P made homodimers. We then found that M26I and L166P, both of which are derived from homozygous mutations of the DJ-1 gene, were unstable and that their stabilities were recovered, in part, in the presence of proteasome inhibitor, MG132. NIH3T3 cell lines stably expressing these mutants of DJ-1 showed that cell lines of L166P and C106S, a mutant for protease activity (-) of DJ-1, had no activity to scavenge even endogenously producing reactive oxygen species. These cell lines also showed that all of the mutants had reduced activities to eliminate exogenously added H 2 O 2 and that these activities, except for that of D149A, were parallel to those preventing H 2 O 2 -induced cell death

Lamin A/C might be involved in the EMT signalling pathway.

Science.gov (United States)

Zuo, Lingkun; Zhao, Huanying; Yang, Ronghui; Wang, Liyong; Ma, Hui; Xu, Xiaoxue; Zhou, Ping; Kong, Lu

2018-07-15

We have previously reported a heterogeneous expression pattern of the nuclear membrane protein lamin A/C in low- and high-Gleason score (GS) prostate cancer (PC) tissues, and we have now found that this change is not associated with LMNA mutations. This expression pattern appears to be similar to the process of epithelial to mesenchymal transition (EMT) or to that of mesenchymal to epithelial transition (MET). The role of lamin A/C in EMT or MET in PC remains unclear. Therefore, we first investigated the expression levels of and the associations between lamin A/C and several common EMT markers, such as E-cadherin, N-cadherin, β-catenin, snail, slug and vimentin in PC tissues with different GS values and in different cell lines with varying invasion abilities. Our results suggest that lamin A/C might constitute a type of epithelial marker that better signifies EMT and MET in PC tissue, since a decrease in lamin A/C expression in GS 4 + 5 cases is likely associated with the EMT process, while the re-expression of lamin A/C in GS 5 + 4 cases is likely linked with MET. The detailed GS better exhibited the changes in lamin A/C and the EMT markers examined. Lamin A/C overexpression or knockdown had an impact on EMT biomarkers in a cell model by direct regulation of β-catenin. Hence, we suggest that lamin A/C might serve as a reliable epithelial biomarker for the distinction of PC cell differentiation and might also be a fundamental factor in the occurrence of EMT or MET in PC. Copyright © 2018. Published by Elsevier B.V.

Mutant TDP-43 within motor neurons drives disease onset but not progression in amyotrophic lateral sclerosis.

Science.gov (United States)

Ditsworth, Dara; Maldonado, Marcus; McAlonis-Downes, Melissa; Sun, Shuying; Seelman, Amanda; Drenner, Kevin; Arnold, Eveline; Ling, Shuo-Chien; Pizzo, Donald; Ravits, John; Cleveland, Don W; Da Cruz, Sandrine

2017-06-01

Mutations in TDP-43 cause amyotrophic lateral sclerosis (ALS), a fatal paralytic disease characterized by degeneration and premature death of motor neurons. The contribution of mutant TDP-43-mediated damage within motor neurons was evaluated using mice expressing a conditional allele of an ALS-causing TDP-43 mutant (Q331K) whose broad expression throughout the central nervous system mimics endogenous TDP-43. TDP-43 Q331K mice develop age- and mutant-dependent motor deficits from degeneration and death of motor neurons. Cre-recombinase-mediated excision of the TDP-43 Q331K gene from motor neurons is shown to delay onset of motor symptoms and appearance of TDP-43-mediated aberrant nuclear morphology, and abrogate subsequent death of motor neurons. However, reduction of mutant TDP-43 selectively in motor neurons did not prevent age-dependent degeneration of axons and neuromuscular junction loss, nor did it attenuate astrogliosis or microgliosis. Thus, disease mechanism is non-cell autonomous with mutant TDP-43 expressed in motor neurons determining disease onset but progression defined by mutant acting within other cell types.

Foot-and-Mouth Disease (FMD) Virus 3C Protease Mutant L127P: Implications for FMD Vaccine Development.

Science.gov (United States)

Puckette, Michael; Clark, Benjamin A; Smith, Justin D; Turecek, Traci; Martel, Erica; Gabbert, Lindsay; Pisano, Melia; Hurtle, William; Pacheco, Juan M; Barrera, José; Neilan, John G; Rasmussen, Max

2017-11-15

The foot-and-mouth disease virus (FMDV) afflicts livestock in more than 80 countries, limiting food production and global trade. Production of foot-and-mouth disease (FMD) vaccines requires cytosolic expression of the FMDV 3C protease to cleave the P1 polyprotein into mature capsid proteins, but the FMDV 3C protease is toxic to host cells. To identify less-toxic isoforms of the FMDV 3C protease, we screened 3C mutants for increased transgene output in comparison to wild-type 3C using a Gaussia luciferase reporter system. The novel point mutation 3C(L127P) increased yields of recombinant FMDV subunit proteins in mammalian and bacterial cells expressing P1-3C transgenes and retained the ability to process P1 polyproteins from multiple FMDV serotypes. The 3C(L127P) mutant produced crystalline arrays of FMDV-like particles in mammalian and bacterial cells, potentially providing a practical method of rapid, inexpensive FMD vaccine production in bacteria. IMPORTANCE The mutant FMDV 3C protease L127P significantly increased yields of recombinant FMDV subunit antigens and produced virus-like particles in mammalian and bacterial cells. The L127P mutation represents a novel advancement for economical FMD vaccine production. Copyright © 2017 Puckette et al.

Lamination of organic solar cells and organic light emitting devices: Models and experiments

International Nuclear Information System (INIS)

Oyewole, O. K.; Yu, D.; Du, J.; Asare, J.; Fashina, A.; Anye, V. C.; Zebaze Kana, M. G.; Soboyejo, W. O.

2015-01-01

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

Delamination Resistance Of Laminate Made With VBO MTM46/HTS Prepreg

Directory of Open Access Journals (Sweden)

Czarnocki Piotr

2015-09-01

Full Text Available A laminate made with the Vacuum Bag Only (VBO prepregs can be cured out of autoclave. Because of low curing pressure such a process can result in deterioration of laminate mechanical properties. They can be significantly lower than those displayed by the autoclave cured ones. The resistance against delamination can be among the most affected. Since this property is a week point of all the laminates it was of particular interest. Delamination resistance of unidirectional laminate made from VBO MTM46/HTS(12K prepreg was in the scope of the presented research and the critical values of the Strain Energy Release Rates and the Paris-type equations corresponding to Mode I, Mode II and Mixed-Mode I/II static and cyclic loadings, respectively, were determined.

Tropicalized Lambda Lengths, Measured Laminations and Convexity

DEFF Research Database (Denmark)

C. Penner, R.

This work uncovers the tropical analogue for measured laminations of the convex hull construction of decorated Teichmueller theory, namely, it is a study in coordinates of geometric degeneration to a point of Thurston's boundary for Teichmueller space. This may offer a paradigm for the extension ...

Instantaneous mechanical fastening of quasi-isotropic CFRP laminates by a self-piercing rivet

OpenAIRE

上田, 政人; 三宅, 崇太郎; 長谷川, 寛幸; 平野, 義鎭; Ueda, Masahito; Miyake, Sotaro; Hasegawa, Hiroyuki; Hirano, Yoshiyasu

2012-01-01

A modified self-piercing rivet (SPR) has been proposed to mechanically fasten CFRP laminates. The modified SPR consists of a rivet body and two flat washers. The two flat washers were used to suppress delamination in the CFRP laminates at the point of piercing. The advantages of the modified SPR for fastening CFRP laminates are instantaneous process time and low cost. Any pretreatments such as surface treatments or hole drilling are not required. In this study, the viability of the modified S...

Disturbed secretion of mutant adiponectin associated with the metabolic syndrome.

Science.gov (United States)

Kishida, Ken; Nagaretani, Hiroyuki; Kondo, Hidehiko; Kobayashi, Hideki; Tanaka, Sachiyo; Maeda, Norikazu; Nagasawa, Azumi; Hibuse, Toshiyuki; Ohashi, Koji; Kumada, Masahiro; Nishizawa, Hitoshi; Okamoto, Yoshihisa; Ouchi, Noriyuki; Maeda, Kazuhisa; Kihara, Shinji; Funahashi, Tohru; Matsuzawa, Yuji

2003-06-20

Adiponectin, an adipocyte-derived protein, consists of collagen-like fibrous and complement C1q-like globular domains, and circulates in human plasma in a multimeric form. The protein exhibits anti-diabetic and anti-atherogenic activities. However, adiponectin plasma concentrations are low in obese subjects, and hypoadiponectinemia is associated with the metabolic syndrome, which is a cluster of insulin resistance, type 2 diabetes mellitus, hypertension, and dyslipidemia. We have recently reported a missense mutation in the adiponectin gene, in which isoleucine at position 164 in the globular domain is substituted with threonine (I164T). Subjects with this mutation showed markedly low level of plasma adiponectin and clinical features of the metabolic syndrome. Here, we examined the molecular characteristics of the mutant protein associated with a genetic cause of hypoadiponectinemia. The current study revealed (1) the mutant protein showed an oligomerization state similar to the wild-type as determined by gel filtration chromatography and, (2) the mutant protein exhibited normal insulin-sensitizing activity, but (3) pulse-chase study showed abnormal secretion of the mutant protein from adipose tissues. Our results suggest that I164T mutation is associated with hypoadiponectinemia through disturbed secretion into plasma, which may contribute to the development of the metabolic syndrome.

Lamination cooling system formation method

Science.gov (United States)

Rippel, Wally E [Altadena, CA; Kobayashi, Daryl M [Monrovia, CA

2009-05-12

An electric motor, transformer or inductor having a cooling system. A stack of laminations have apertures at least partially coincident with apertures of adjacent laminations. The apertures define straight or angled cooling-fluid passageways through the lamination stack. Gaps between the adjacent laminations are sealed by injecting a heat-cured sealant into the passageways, expelling excess sealant, and heat-curing the lamination stack. Manifold members adjoin opposite ends of the lamination stack, and each is configured with one or more cavities to act as a manifold to adjacent passageway ends. Complex manifold arrangements can create bidirectional flow in a variety of patterns.

Dual Teichmüller and lamination spaces

DEFF Research Database (Denmark)

Fock, Vladimir V.; Goncharov, Alexander B.

2007-01-01

We survey explicit coordinate descriptions for two versions of Teichmüller and lamination spaces for open surfaces, and extend them to the more general set-up of surfaces with distinguished collections of points on the boundary. Main features, such as mapping class group action, Poisson and sympl...

Differential disease resistance response in the barley necrotic mutant nec1

Directory of Open Access Journals (Sweden)

Kunga Laura

2011-04-01

Full Text Available Abstract Background Although ion fluxes are considered to be an integral part of signal transduction during responses to pathogens, only a few ion channels are known to participate in the plant response to infection. CNGC4 is a disease resistance-related cyclic nucleotide-gated ion channel. Arabidopsis thaliana CNGC4 mutants hlm1 and dnd2 display an impaired hypersensitive response (HR, retarded growth, a constitutively active salicylic acid (SA-mediated pathogenesis-related response and elevated resistance against bacterial pathogens. Barley CNGC4 shares 67% aa identity with AtCNGC4. The barley mutant nec1 comprising of a frame-shift mutation of CNGC4 displays a necrotic phenotype and constitutively over-expresses PR-1, yet it is not known what effect the nec1 mutation has on barley resistance against different types of pathogens. Results nec1 mutant accumulated high amount of SA and hydrogen peroxide compared to parental cv. Parkland. Experiments investigating nec1 disease resistance demonstrated positive effect of nec1 mutation on non-host resistance against Pseudomonas syringae pv. tomato (Pst at high inoculum density, whereas at normal Pst inoculum concentration nec1 resistance did not differ from wt. In contrast to augmented P. syringae resistance, penetration resistance against biotrophic fungus Blumeria graminis f. sp. hordei (Bgh, the causal agent of powdery mildew, was not altered in nec1. The nec1 mutant significantly over-expressed race non-specific Bgh resistance-related genes BI-1 and MLO. Induction of BI-1 and MLO suggested putative involvement of nec1 in race non-specific Bgh resistance, therefore the effect of nec1on mlo-5-mediated Bgh resistance was assessed. The nec1/mlo-5 double mutant was as resistant to Bgh as Nec1/mlo-5 plants, suggesting that nec1 did not impair mlo-5 race non-specific Bgh resistance. Conclusions Together, the results suggest that nec1 mutation alters activation of systemic acquired resistance

Subclinical laminitis and its association with pO2 and faecal alterations: Isikli, Aydin experience

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Ibrahim Akin

2015-05-01

Full Text Available ABSTRACT Objective. The aim of this field trial was to investigate the relationships among subclinical laminitis, hematological, ruminal and faecal alterations. Materials and Methods. To this extent dairy cows presenting subclinical laminitis (n=11 and to those of other healthy cows without laminitis (n=10 were enrolled and assigned into two groups. All animals were receiving the same daily ration formulated to contain 47% cornsilage and 18% hay, mainly. Effects of subclinical laminitis challenges on measurements of feces, and blood samples, were investigated to determine which of these measurements may aid in the diagnosis. pH changes in ruminal fluid collected via rumenocentesis were measured. Besides the following parameters were also measured; blood pH, faecal pH and faecal scoring. Blinded investigators performed the sample collection. Results. No statistical differences between the groups were detected for blood gas values studied regarding pCO2, HCO3, BE, indeed mean that pO2 values decreased statistically (p<0.05 and faecal pH was significantly decreased (p<0.05 in cows with subclinical laminitis in contrast to healthy controls. Conclusions. pO2 values and faecal pH may be valuable as indirect indicators of subclinical laminitis in cattle.

Lamins of the sea lamprey (Petromyzon marinus) and the evolution of the vertebrate lamin protein family.

Science.gov (United States)

Schilf, Paul; Peter, Annette; Hurek, Thomas; Stick, Reimer

2014-07-01

Lamin proteins are found in all metazoans. Most non-vertebrate genomes including those of the closest relatives of vertebrates, the cephalochordates and tunicates, encode only a single lamin. In teleosts and tetrapods the number of lamin genes has quadrupled. They can be divided into four sub-types, lmnb1, lmnb2, LIII, and lmna, each characterized by particular features and functional differentiations. Little is known when during vertebrate evolution these features have emerged. Lampreys belong to the Agnatha, the sister group of the Gnathostomata. They split off first within the vertebrate lineage. Analysis of the sea lamprey (Petromyzon marinus) lamin complement presented here, identified three functional lamin genes, one encoding a lamin LIII, indicating that the characteristic gene structure of this subtype had been established prior to the agnathan/gnathostome split. Two other genes encode lamins for which orthology to gnathostome lamins cannot be designated. Search for lamin gene sequences in all vertebrate taxa for which sufficient sequence data are available reveals the evolutionary time frame in which specific features of the vertebrate lamins were established. Structural features characteristic for A-type lamins are not found in the lamprey genome. In contrast, lmna genes are present in all gnathostome lineages suggesting that this gene evolved with the emergence of the gnathostomes. The analysis of lamin gene neighborhoods reveals noticeable similarities between the different vertebrate lamin genes supporting the hypothesis that they emerged due to two rounds of whole genome duplication and makes clear that an orthologous relationship between a particular vertebrate paralog and lamins outside the vertebrate lineage cannot be established. Copyright © 2014 Elsevier GmbH. All rights reserved.

Influence of bress laminate volume fraction on electromechanical properties of externally laminated coated conductor tapes

Energy Technology Data Exchange (ETDEWEB)

Bautista, Zhierwinjay M.; Shin, Hyung Seop [Dept. of Mechanical Design Engineering, Andong National University, Andong (Korea, Republic of); Lee, Jae Hun; Lee, Hun Ju; Moon, Seung Hyun [SuNAM Co Ltd., Anseong (Korea, Republic of)

2016-09-15

The enhancement of mechanical properties of coated conductor (CC) tapes in practical application are usually achieved by reinforcing through lamination or electroplating metal layers on either sides of the CC tape. Mechanical or electromechanical properties of the CC tapes have been largely affected by the lamination structure under various loading modes such as tension, bending or even cyclic. In this study, the influence of brass laminate volume fraction on electromechanical properties of RCE-DR processed Gadolinium-barium-copper-oxide (GdBCO) CC tapes was investigated. The samples used were composed of single-side and both-side laminate of brass layer to the Cu-stabilized CC tape and their Ic behaviors were compared to those of the Cu-stabilized CC tape without external lamination. The stress/strain dependences of Ic in laminated CC tapes under uniaxial tension were analyzed and the irreversible stress/strain limits were determined. As a result, the increase of brass laminate volume fraction initially increased the irreversible strain limit and became gradual. The corresponding irreversible stress limit, however, showed no difference even though the brass laminate volume fraction increased to 3.4. But the irreversible load limit linearly increased with the brass laminate volume fraction.

BILAM: a composite laminate failure-analysis code using bilinear stress-strain approximations

Energy Technology Data Exchange (ETDEWEB)

McLaughlin, P.V. Jr.; Dasgupta, A.; Chun, Y.W.

1980-10-01

The BILAM code which uses constant strain laminate analysis to generate in-plane load/deformation or stress/strain history of composite laminates to the point of laminate failure is described. The program uses bilinear stress-strain curves to model layer stress-strain behavior. Composite laminates are used for flywheels. The use of this computer code will help to develop data on the behavior of fiber composite materials which can be used by flywheel designers. In this program the stress-strain curves are modelled by assuming linear response in axial tension while using bilinear approximations (2 linear segments) for stress-strain response to axial compressive, transverse tensile, transverse compressive and axial shear loadings. It should be noted that the program attempts to empirically simulate the effects of the phenomena which cause nonlinear stress-strain behavior, instead of mathematically modelling the micromechanics involved. This code, therefore, performs a bilinear laminate analysis, and, in conjunction with several user-defined failure interaction criteria, is designed to provide sequential information on all layer failures up to and including the first fiber failure. The modus operandi is described. Code BILAM can be used to: predict the load-deformation/stress-strain behavior of a composite laminate subjected to a given combination of in-plane loads, and make analytical predictions of laminate strength.

Endoplasmic Reticulum-Targeted Subunit Toxins Provide a New Approach to Rescue Misfolded Mutant Proteins and Revert Cell Models of Genetic Diseases.

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Humaira Adnan

Full Text Available Many germ line diseases stem from a relatively minor disturbance in mutant protein endoplasmic reticulum (ER 3D assembly. Chaperones are recruited which, on failure to correct folding, sort the mutant for retrotranslocation and cytosolic proteasomal degradation (ER-associated degradation-ERAD, to initiate/exacerbate deficiency-disease symptoms. Several bacterial (and plant subunit toxins, retrograde transport to the ER after initial cell surface receptor binding/internalization. The A subunit has evolved to mimic a misfolded protein and hijack the ERAD membrane translocon (dislocon, to effect cytosolic access and cytopathology. We show such toxins compete for ERAD to rescue endogenous misfolded proteins. Cholera toxin or verotoxin (Shiga toxin containing genetically inactivated (± an N-terminal polyleucine tail A subunit can, within 2-4 hrs, temporarily increase F508delCFTR protein, the major cystic fibrosis (CF mutant (5-10x, F508delCFTR Golgi maturation (<10x, cell surface expression (20x and chloride transport (2x in F508del CFTR transfected cells and patient-derived F508delCFTR bronchiolar epithelia, without apparent cytopathology. These toxoids also increase glucocerobrosidase (GCC in N370SGCC Gaucher Disease fibroblasts (3x, another ERAD-exacerbated misfiling disease. We identify a new, potentially benign approach to the treatment of certain genetic protein misfolding diseases.

Effect of laminate edge conditions on the formation of microvoids in composite laminates

Science.gov (United States)

Anderson, J. P.; Altan, M. C.

2015-05-01

Manufacturing defects such as microvoids are common in thermoset composite components and are known to negatively affect their strength. The resin pressure developed in and the resin flow out from the laminates during cure have been reported to be the primary factors influencing the final void content of a composite component. In this work, the effect of laminate edge conditions during the cure process on the formation of microvoids was experimentally investigated. This was achieved by fabricating eight-ply laminates from TenCate® BT250/7781 prepreg in a hot-press at a constant cure pressure of 170 kPa while limiting the laminate perimeter available for resin flow by 0%, 25%, 50%, 75%, and 100%. The individual plies of these five laminates were conditioned at 99% relative humidity before curing to maximize the moisture present in the lay-up before fabrication. The presence of moisture in the lay-ups was expected to promote void formation and allow the effect of restricting flow at the edges of a laminate to be better identified. The restriction of resin outflow was found to cause the average characteristic void diameter to decrease by 17% and void content to rise by 33%. This phenomenon was identified to be a result of the outflow restriction increasing the number of voids trapped within the laminate and indicates that for laminates cured at low pressures resin outflow is the dominant mechanism for void reduction.

Data supporting mitochondrial morphological changes by SPG13-associated HSPD1 mutants

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Yuki Miyamoto

2016-03-01

Full Text Available The data is related to the research article entitled “Hypomyelinating leukodystrophy-associated missense mutation in HSPD1 blunts mitochondrial dynamics” [1]. In addition to hypomyelinating leukodystrophy (HLD 4 (OMIM no. 612233, it is known that spastic paraplegia (SPG 13 (OMIM no. 605280 is caused by HSPD1’s amino acid mutation. Two amino acid mutations Val-98-to-Ile (V98I and Gln-461-to-Glu (Q461E are associated with SPG13 [2]. In order to investigate the effects of HSPD1’s V98I or Q461E mutant on mitochondrial morphological changes, we transfected each of the respective mutant-encoding genes into Cos-7 cells. Either of V98I or Q461E mutant exhibited increased number of mitochondria and short length mitochondrial morphologies. Using MitoTracker dye-incorporating assay, decreased mitochondrial membrane potential was also observed in both cases. The data described here supports that SPG13-associated HSPD1 mutant participates in causing aberrant mitochondrial morphological changes with decreased activities. Keywords: SPG13, HSPD1, Mitochondrion, Morphological change

IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation

Science.gov (United States)

Oktay, Yavuz; Ülgen, Ege; Can, Özge; Akyerli, Cemaliye B.; Yüksel, Şirin; Erdemgil, Yiğit; Durası, İ. Melis; Henegariu, Octavian Ioan; Nanni, E. Paolo; Selevsek, Nathalie; Grossmann, Jonas; Erson-Omay, E. Zeynep; Bai, Hanwen; Gupta, Manu; Lee, William; Turcan, Şevin; Özpınar, Aysel; Huse, Jason T.; Sav, M. Aydın; Flanagan, Adrienne; Günel, Murat; Sezerman, O. Uğur; Yakıcıer, M. Cengiz; Pamir, M. Necmettin; Özduman, Koray

2016-01-01

The single nucleotide polymorphism rs55705857, located in a non-coding but evolutionarily conserved region at 8q24.21, is strongly associated with IDH-mutant glioma development and was suggested to be a causal variant. However, the molecular mechanism underlying this association has remained unknown. With a case control study in 285 gliomas, 316 healthy controls, 380 systemic cancers, 31 other CNS-tumors, and 120 IDH-mutant cartilaginous tumors, we identified that the association was specific to IDH-mutant gliomas. Odds-ratios were 9.25 (5.17–16.52; 95% CI) for IDH-mutated gliomas and 12.85 (5.94–27.83; 95% CI) for IDH-mutated, 1p/19q co-deleted gliomas. Decreasing strength with increasing anaplasia implied a modulatory effect. No somatic mutations were noted at this locus in 114 blood-tumor pairs, nor was there a copy number difference between risk-allele and only-ancestral allele carriers. CCDC26 RNA-expression was rare and not different between the two groups. There were only minor subtype-specific differences in common glioma driver genes. RNA sequencing and LC-MS/MS comparisons pointed to significantly altered MYC-signaling. Baseline enhancer activity of the conserved region specifically on the MYC promoter and its further positive modulation by the SNP risk-allele was shown in vitro. Our findings implicate MYC deregulation as the underlying cause of the observed association. PMID:27282637

The potential role of Clostridium botulinum toxin in the treatment of equine laminitis

NARCIS (Netherlands)

Hardeman, L C

2016-01-01

Laminitis is a severe and painful disease in the horse that may lead to loosening of the attachment of the distal phalanx to the horny hoof capsule. Although a large variety of treatment options has come and gone since the first descriptions of laminitis, there is certainly a thus far unmet need for

Cln6 mutants associated with neuronal ceroid lipofuscinosis are degraded in a proteasome-dependent manner.

Science.gov (United States)

Oresic, Kristina; Mueller, Britta; Tortorella, Domenico

2009-06-01

NCLs (neuronal ceroid lipofuscinoses), a group of inherited neurodegenerative lysosomal storage diseases that predominantly affect children, are the result of autosomal recessive mutations within one of the nine cln genes. The wild-type cln gene products are composed of membrane and soluble proteins that localize to the lysosome or the ER (endoplasmic reticulum). However, the destiny of the Cln variants has not been fully characterized. To explore a possible link between ER quality control and processing of Cln mutants, we investigated the fate of two NCL-related Cln6 mutants found in patient samples (Cln6(G123D) and Cln6(M241T)) in neuronal-derived human cells. The point mutations are predicted to be in the putative transmembrane domains and most probably generate misfolded membrane proteins that are subjected to ER quality control. Consistent with this paradigm, both mutants underwent rapid proteasome-mediated degradation and complexed with components of the ER extraction apparatus, Derlin-1 and p97. In addition, knockdown of SEL1L [sel-1 suppressor of lin-12-like (Caenorhabditis elegans)], a member of an E3 ubiquitin ligase complex involved in ER protein extraction, rescued significant amounts of Cln6(G123D) and Cln6(M241T) polypeptides. The results implicate ER quality control in the instability of the Cln variants that probably contributes to the development of NCL.

Isoprenylation is required for the processing of the lamin A precursor

International Nuclear Information System (INIS)

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

1990-01-01

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

Partial restoration of mutant enzyme homeostasis in three distinct lysosomal storage disease cell lines by altering calcium homeostasis.

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Ting-Wei Mu

2008-02-01

Full Text Available A lysosomal storage disease (LSD results from deficient lysosomal enzyme activity, thus the substrate of the mutant enzyme accumulates in the lysosome, leading to pathology. In many but not all LSDs, the clinically most important mutations compromise the cellular folding of the enzyme, subjecting it to endoplasmic reticulum-associated degradation instead of proper folding and lysosomal trafficking. A small molecule that restores partial mutant enzyme folding, trafficking, and activity would be highly desirable, particularly if one molecule could ameliorate multiple distinct LSDs by virtue of its mechanism of action. Inhibition of L-type Ca2+ channels, using either diltiazem or verapamil-both US Food and Drug Administration-approved hypertension drugs-partially restores N370S and L444P glucocerebrosidase homeostasis in Gaucher patient-derived fibroblasts; the latter mutation is associated with refractory neuropathic disease. Diltiazem structure-activity studies suggest that it is its Ca2+ channel blocker activity that enhances the capacity of the endoplasmic reticulum to fold misfolding-prone proteins, likely by modest up-regulation of a subset of molecular chaperones, including BiP and Hsp40. Importantly, diltiazem and verapamil also partially restore mutant enzyme homeostasis in two other distinct LSDs involving enzymes essential for glycoprotein and heparan sulfate degradation, namely alpha-mannosidosis and type IIIA mucopolysaccharidosis, respectively. Manipulation of calcium homeostasis may represent a general strategy to restore protein homeostasis in multiple LSDs. However, further efforts are required to demonstrate clinical utility and safety.

MMS exposure promotes increased MtDNA mutagenesis in the presence of replication-defective disease-associated DNA polymerase γ variants.

Science.gov (United States)

Stumpf, Jeffrey D; Copeland, William C

2014-10-01

Mitochondrial DNA (mtDNA) encodes proteins essential for ATP production. Mutant variants of the mtDNA polymerase cause mutagenesis that contributes to aging, genetic diseases, and sensitivity to environmental agents. We interrogated mtDNA replication in Saccharomyces cerevisiae strains with disease-associated mutations affecting conserved regions of the mtDNA polymerase, Mip1, in the presence of the wild type Mip1. Mutant frequency arising from mtDNA base substitutions that confer erythromycin resistance and deletions between 21-nucleotide direct repeats was determined. Previously, increased mutagenesis was observed in strains encoding mutant variants that were insufficient to maintain mtDNA and that were not expected to reduce polymerase fidelity or exonuclease proofreading. Increased mutagenesis could be explained by mutant variants stalling the replication fork, thereby predisposing the template DNA to irreparable damage that is bypassed with poor fidelity. This hypothesis suggests that the exogenous base-alkylating agent, methyl methanesulfonate (MMS), would further increase mtDNA mutagenesis. Mitochondrial mutagenesis associated with MMS exposure was increased up to 30-fold in mip1 mutants containing disease-associated alterations that affect polymerase activity. Disrupting exonuclease activity of mutant variants was not associated with increased spontaneous mutagenesis compared with exonuclease-proficient alleles, suggesting that most or all of the mtDNA was replicated by wild type Mip1. A novel subset of C to G transversions was responsible for about half of the mutants arising after MMS exposure implicating error-prone bypass of methylated cytosines as the predominant mutational mechanism. Exposure to MMS does not disrupt exonuclease activity that suppresses deletions between 21-nucleotide direct repeats, suggesting the MMS-induce mutagenesis is not explained by inactivated exonuclease activity. Further, trace amounts of CdCl2 inhibit mtDNA replication but

Mutants with Enhanced Nitrogenase Activity in Hydroponic Azospirillum brasilense-Wheat Associations

Science.gov (United States)

Pereg Gerk, Lily; Gilchrist, Kate; Kennedy, Ivan R.

2000-01-01

The effect of a mutation affecting flocculation, differentiation into cyst-like forms, and root colonization on nitrogenase expression by Azospirillum brasilense is described. The gene flcA of strain Sp7 restored these phenotypes in spontaneous mutants of both strains Sp7 and Sp245. Employing both constitutive pLA-lacZ and nifH-lacZ reporter fusions expressed in situ, the colony morphology, colonization pattern, and potential for nitrogenase activity of spontaneous mutants and flcA Tn5-induced mutants were established. The results of this study show that the ability of Sp7 and Sp245 mutant strains to remain in a vegetative form improved their ability to express nitrogenase activity in association with wheat in a hydroponic system. Restoring the cyst formation and colonization pattern to the spontaneous mutant Sp7-S reduced nitrogenase activity rates in association with plants to that of the wild-type Sp7. Although Tn5-induced flcA mutants showed higher potentials for nitrogenase expression than Sp7, their potentials were lower than that of Sp7-S, indicating that other factors in this strain contribute to its exceptional nitrogenase activity rates on plants. The lack of lateral flagella is not one of these factors, as Sp7-PM23, a spontaneous mutant impaired in swarming and lateral-flagellum production but not in flocculation, showed wild-type nitrogenase activity and expression. The results also suggest factors of importance in evolving an effective symbiosis between Azospirillum and wheat, such as increasing the availability of microaerobic niches along the root, increased supply of carbon sources by the plant, and the retention of the bacterial cells in vegetative form for faster metabolism. PMID:10788397

A Progressive Damage Model for Predicting Permanent Indentation and Impact Damage in Composite Laminates

Science.gov (United States)

Ji, Zhaojie; Guan, Zhidong; Li, Zengshan

2017-10-01

In this paper, a progressive damage model was established on the basis of ABAQUS software for predicting permanent indentation and impact damage in composite laminates. Intralaminar and interlaminar damage was modelled based on the continuum damage mechanics (CDM) in the finite element model. For the verification of the model, low-velocity impact tests of quasi-isotropic laminates with material system of T300/5228A were conducted. Permanent indentation and impact damage of the laminates were simulated and the numerical results agree well with the experiments. It can be concluded that an obvious knee point can be identified on the curve of the indentation depth versus impact energy. Matrix cracking and delamination develops rapidly with the increasing impact energy, while considerable amount of fiber breakage only occurs when the impact energy exceeds the energy corresponding to the knee point. Predicted indentation depth after the knee point is very sensitive to the parameter μ which is proposed in this paper, and the acceptable value of this parameter is in range from 0.9 to 1.0.

Bending analyses for 3D engineered structural panels made from laminated paper and carbon fabric

Science.gov (United States)

Jinghao Li; John F. Hunt; Zhiyong Cai; Xianyan Zhou

2013-01-01

This paper presents analysis of a 3-dimensional engineered structural panel (3DESP) having a tri-axial core structure made from phenolic impregnated laminated-paper composites with and without high strength composite carbon-fiber fabric laminated to the outside of both faces. Both I-beam equations and finite element method were used to analyze four-point bending of the...

Laminated Root Rot of Western Conifers

Science.gov (United States)

E.E. Nelson; N.E. Martin; R.E. Williams

1981-01-01

Laminated root rot is caused by the native fungus Phellinus weirii (Murr.) Gilb. It occurs throughout the Northwestern United States and in southern British Columbia, Canada. The disease has also been reported in Japan and Manchuria. In the United States, the pathogen is most destructive in pure Douglas-fir stands west of the crest of the Cascade Range in Washington...

Lamin A expression in circulating osteoprogenitors as a potential biomarker for frailty: The Nepean Osteoporosis and Frailty (NOF) Study.

Science.gov (United States)

Al Saedi, Ahmed; Gunawardene, Piumali; Bermeo, Sandra; Vogrin, Sara; Boersma, Derek; Phu, Steven; Singh, Lakshman; Suriyaarachchi, Pushpa; Duque, Gustavo

2018-02-01

Lamin A is a protein of the nuclear lamina. Low levels of lamin A expression are associated with osteosarcopenia in mice. In this study, we hypothesized that low lamin A expression is also associated with frailty in humans. We aimed to develop a non-invasive method to quantify lamin A expression in epithelial and circulating osteoprogenitor (COP) cells, and to determine the relationship between lamin A expression and frailty in older individuals. COP cells and buccal swabs were obtained from 66 subjects (median age 74; 60% female; 26 non-frail, 23 pre-frail, and 17 frail) participating at the Nepean Osteoporosis and Frailty (NOF) Study. We quantified physical performance and disability, and stratified frailty in this population. Lamin A expression in epithelial and COP cells was quantified by flow cytometry. Linear regression models estimated the relationship between lamin A expression in buccal and COP cells, and prevalent disability and frailty. Lamin A expression in buccal cells showed no association with either disability or frailty. Low lamin A expression values in COP cells were associated with frailty. Frail individuals showed 60% lower levels of lamin A compared to non-frail (95% CI -36 to -74%, p<0.001) and 62% lower levels compared to pre-frail (95%CI -40 to -76%, p<0.001). In summary, we have identified lamin A expression in COP cells as a strong indicator of frailty. Further work is needed to understand lamin A expression as a risk stratifier, biomarker, or therapeutic target in frail older persons. Copyright © 2017 Elsevier Inc. All rights reserved.

DESIGN ALTERNATIVES ON THE LAMINATES

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Gökay Nemli

2004-04-01

Full Text Available Wood based panel manufacturers use increasing volumes of laminates. Laminates are resistant to the water, humidity, scratch, abrasion, burning and chemicals. These products consist of printed decor papers that have been saturated with thermosetting resin. In this study, laminate types, composition form and design alternatives were investigated.

Assessment of horse owners' ability to recognise equine laminitis: A cross-sectional study of 93 veterinary diagnosed cases in Great Britain.

Science.gov (United States)

Pollard, D; Wylie, C E; Verheyen, K L P; Newton, J R

2017-11-01

Use of owner-reported data could further epidemiological knowledge of equine laminitis. However, owner recognition of laminitis has not previously been assessed. The primary objective was to establish whether cases of owner-suspected laminitis would be confirmed as laminitis by the attending veterinary surgeon. Secondary objectives were to compare owner- and veterinary-reported information from veterinary-confirmed cases of equine laminitis. Cross-sectional study. Twenty-five British veterinary practices were invited to submit laminitis reporting forms (LRFs) for active laminitis cases attended between January 2014 and October 2015; detailing 27 clinical signs, 5 underlying conditions and 7 risk factors associated with laminitis. Owners were invited to independently complete a modified LRF if reason for the veterinary visit was suspicion of laminitis. Differences between paired veterinary and owner LRFs, and between cases where owners did and did not recognise laminitis, were assessed using McNemar's and Fisher's Exact tests, respectively. Veterinary LRFs were received for 93 veterinary-diagnosed laminitis cases. All 51 owner-suspected cases were confirmed by veterinary diagnosis, with the remaining 42 (45.2%) not recognised as laminitis by owners. Undefined lameness, foot abscesses, colic and stiffness were common reasons for owner-requested veterinary visits in owner-unrecognised cases. 'Divergent growth rings' (prevalence difference: +27.3%, P = 0.01) and 'breed type' (prevalence difference: +21.2%, P = 0.04) were more commonly reported by veterinary surgeons in owner-recognised compared to owner-unrecognised cases. 'Difficulty turning', 'shifting weight' and risk factor 'body condition' were more frequently reported by veterinary surgeons whilst 'increased hoof temperature' was reported more frequently by owners. The limited clinical data restricted statistical inferences regarding the secondary objectives. All owner-suspected laminitis cases were confirmed

A theory of piezoelectric laminates

International Nuclear Information System (INIS)

Giangreco, E.

1997-01-01

A theory of piezoelectric laminates is rationally derived from the three-dimensional Voigt theory of piezoelectricity. The present theory is a generalization to piezoelectric laminates of the Reissner-Mindlin-type layer-wise theory of elastic laminates. Both a differential formulation and a variational formulation of the piezoelectric laminate problem are presented. The proposed theory is adopted in the analysis of simple problems, in order to verify its effectiveness. The results it provides turn out to be in good agreement with the results supplied by the Voigt theory of piezoelectricity

Subclinical Laminitis in Dairy Cattle: 205 Selected Cases

OpenAIRE

BAKIR, Ali BELGE Bahtiyar

2005-01-01

The economic importance of lameness in dairy cattle has newly been recognized in Turkey. Lameness incidence in Turkey has been reported to be between 13% and 58%, which is similar to that of other countries where 4% and 55% incidence rates have been reported. The objective of this study was to determine the prevalence of sole lesions associated with subclinical laminitis in the hooves of dairy cattle in Van, Turkey. The risk factors for subclinical laminitis are proposed and discussed. The so...

Non-linked inhibitory gene controls a disease mimicking mutant in rice [Oryza sativa L.

International Nuclear Information System (INIS)

Jambhulkar, S.J.; Joshua, D.C.; Goswamy, D.G.

2001-01-01

A gamma ray induced disease mimicking mutant called luchai lesion was isolated in the rice variety White Luchai 112. The appearance of small light red lesions and their development continued from seedling to flowering. The lesions appeared gradually on older leaves and their uncontrolled spread eventually lead to leaf senescence. They resembled the disease spots caused by Magnaporthe grisea. However, pathological studies ruled out the possibility of pathogen mediated disease symptoms. Genetic studies revealed that lesions were governed by a dominant gene; however, their expression was suppressed in presence of a non-linked inhibitory gene. It is hypothesised that the plant cells of the mutant are able to sense inbuilt spontaneous signals leading to lesion development, but in presence of an inhibitory gene the signals are suppressed by perturbation in the signal transduction pathway [it

Tauopathic changes in the striatum of A53T α-synuclein mutant mouse model of Parkinson's disease.

Directory of Open Access Journals (Sweden)

Jonathan Wills

2011-03-01

Full Text Available Tauopathic pathways lead to degenerative changes in Alzheimer's disease and there is evidence that they are also involved in the neurodegenerative pathology of Parkinson's disease [PD]. We have examined tauopathic changes in striatum of the α-synuclein (α-Syn A53T mutant mouse. Elevated levels of α-Syn were observed in striatum of the adult A53T α-Syn mice. This was accompanied by increases in hyperphosphorylated Tau [p-Tau], phosphorylated at Ser202, Ser262 and Ser396/404, which are the same toxic sites also seen in Alzheimer's disease. There was an increase in active p-GSK-3β, hyperphosphorylated at Tyr216, a major and primary kinase known to phosphorylate Tau at multiple sites. The sites of hyperphosphorylation of Tau in the A53T mutant mice were similar to those seen in post-mortem striata from PD patients, attesting to their pathophysiological relevance. Increases in p-Tau were not due to alterations on protein phosphatases in either A53T mice or in human PD, suggesting lack of involvement of these proteins in tauopathy. Extraction of striata with Triton X-100 showed large increases in oligomeric forms of α-Syn suggesting that α-Syn had formed aggregates the mutant mice. In addition, increased levels of p-GSK-3β and pSer396/404 were also found associated with aggregated α-Syn. Differential solubilization to measure protein binding to cytoskeletal proteins demonstrated that p-Tau in the A53T mutant mouse were unbound to cytoskeletal proteins, consistent with dissociation of p-Tau from the microtubules upon hyperphosphorylation. Interestingly, α-Syn remained tightly bound to the cytoskeleton, while p-GSK-3β was seen in the cytoskeleton-free fractions. Immunohistochemical studies showed that α-Syn, pSer396/404 Tau and p-GSK-3β co-localized with one another and was aggregated and accumulated into large inclusion bodies, leading to cell death of Substantia nigral neurons. Together, these data demonstrate an elevated state of

A historical perspective of laminitis.

Science.gov (United States)

Heymering, Henry W

2010-04-01

The causes of laminitis are many-often interrelated, sometimes direct opposites. The history of laminitis has been a search for the cause or causes of laminitis and for effective treatment. Going in and out of fashion, many treatments have lasted for centuries, some for millennia, but very few have been proven. Copyright 2010 Elsevier Inc. All rights reserved.

Composite lamination method

Science.gov (United States)

Dickerson, G. E. (Inventor)

1977-01-01

A process was developed for preparing relatively thick composite laminate structure wherein thin layers of prepreg tapes are assembled, these thin layers are cut into strips that are partially cured, and stacked into the desired thickness with uncured prepreg disposed between each layer of strips. The formed laminate is finally cured and thereafter machined to the desired final dimensions.

Evaluation of some garlic (Allium Sativum L.) mutants resistant to white rot disease by RAPD analysis

International Nuclear Information System (INIS)

Nabulsi, I.; Al-Safadi, B.; Mir ali, N.; Arabi, M.I.E.

2002-01-01

Random amplified polymorphic DNA (RAPD) analysis was used to evaluate genetic diversity among eight garlic mutants resistant to white rot disease (Sclerotium cepivorum) and two controls. Twelve of 13 synthetic random primers were found to identify polymorphism in amplification products. Mutants characterised with moderate resistance to white rot were closely related to the control using cluster and correlation analyses. On the other hand, highly resistant mutants were quite distant from the control with low correlation coefficients. The banding patterns produced by primer OPB-15 (GGAAGGGTGTT) with highly resistant mutants may be used as genetic markers for early selection of resistant plants. (author)

Larger aggregates of mutant seipin in Celia's Encephalopathy, a new protein misfolding neurodegenerative disease.

Science.gov (United States)

Ruiz-Riquelme, Alejandro; Sánchez-Iglesias, Sofía; Rábano, Alberto; Guillén-Navarro, Encarna; Domingo-Jiménez, Rosario; Ramos, Adriana; Rosa, Isaac; Senra, Ana; Nilsson, Peter; García, Ángel; Araújo-Vilar, David; Requena, Jesús R

2015-11-01

Celia's Encephalopathy (MIM #615924) is a recently discovered fatal neurodegenerative syndrome associated with a new BSCL2 mutation (c.985C>T) that results in an aberrant isoform of seipin (Celia seipin). This mutation is lethal in both homozygosity and compounded heterozygosity with a lipodystrophic BSCL2 mutation, resulting in a progressive encephalopathy with fatal outcomes at ages 6-8. Strikingly, heterozygous carriers are asymptomatic, conflicting with the gain of toxic function attributed to this mutation. Here we report new key insights about the molecular pathogenic mechanism of this new syndrome. Intranuclear inclusions containing mutant seipin were found in brain tissue from a homozygous patient suggesting a pathogenic mechanism similar to other neurodegenerative diseases featuring brain accumulation of aggregated, misfolded proteins. Sucrose gradient distribution showed that mutant seipin forms much larger aggregates as compared with wild type (wt) seipin, indicating an impaired oligomerization. On the other hand, the interaction between wt and Celia seipin confirmed by coimmunoprecipitation (CoIP) assays, together with the identification of mixed oligomers in sucrose gradient fractionation experiments can explain the lack of symptoms in heterozygous carriers. We propose that the increased aggregation and subsequent impaired oligomerization of Celia seipin leads to cell death. In heterozygous carriers, wt seipin might prevent the damage caused by mutant seipin through its sequestration into harmless mixed oligomers. Copyright © 2015 Elsevier Inc. All rights reserved.

Ectopic norrin induces growth of ocular capillaries and restores normal retinal angiogenesis in Norrie disease mutant mice.

Science.gov (United States)

Ohlmann, Andreas; Scholz, Michael; Goldwich, Andreas; Chauhan, Bharesh K; Hudl, Kristiane; Ohlmann, Anne V; Zrenner, Eberhart; Berger, Wolfgang; Cvekl, Ales; Seeliger, Mathias W; Tamm, Ernst R

2005-02-16

Norrie disease is an X-linked retinal dysplasia that presents with congenital blindness, sensorineural deafness, and mental retardation. Norrin, the protein product of the Norrie disease gene (NDP), is a secreted protein of unknown biochemical function. Norrie disease (Ndp(y/-)) mutant mice that are deficient in norrin develop blindness, show a distinct failure in retinal angiogenesis, and completely lack the deep capillary layers of the retina. We show here that the transgenic expression of ectopic norrin under control of a lens-specific promoter restores the formation of a normal retinal vascular network in Ndp(y/-) mutant mice. The improvement in structure correlates with restoration of neuronal function in the retina. In addition, lenses of transgenic mice with ectopic expression of norrin show significantly more capillaries in the hyaloid vasculature that surrounds the lens during development. In vitro, lenses of transgenic mice in coculture with microvascular endothelial cells induce proliferation of the cells. Transgenic mice with ectopic expression of norrin show more bromodeoxyuridine-labeled retinal progenitor cells at embryonic day 14.5 and thicker retinas at postnatal life than wild-type littermates, indicating a putative direct neurotrophic effect of norrin. These data provide direct evidence that norrin induces growth of ocular capillaries and that pharmacologic modulation of norrin might be used for treatment of the vascular abnormalities associated with Norrie disease or other vascular disorders of the retina.

Argonaute2 and LaminB modulate gene expression by controlling chromatin topology.

Directory of Open Access Journals (Sweden)

Ezequiel Nazer

2018-03-01

Full Text Available Drosophila Argonaute2 (AGO2 has been shown to regulate expression of certain loci in an RNA interference (RNAi-independent manner, but its genome-wide function on chromatin remains unknown. Here, we identified the nuclear scaffolding protein LaminB as a novel interactor of AGO2. When either AGO2 or LaminB are depleted in Kc cells, similar transcription changes are observed genome-wide. In particular, changes in expression occur mainly in active or potentially active chromatin, both inside and outside LaminB-associated domains (LADs. Furthermore, we identified a somatic target of AGO2 transcriptional repression, no hitter (nht, which is immersed in a LAD located within a repressive topologically-associated domain (TAD. Null mutation but not catalytic inactivation of AGO2 leads to ectopic expression of nht and downstream spermatogenesis genes. Depletion of either AGO2 or LaminB results in reduced looping interactions within the nht TAD as well as ectopic inter-TAD interactions, as detected by 4C-seq analysis. Overall, our findings reveal coordination of AGO2 and LaminB function to dictate genome architecture and thereby regulate gene expression.

Normal aging modulates the neurotoxicity of mutant huntingtin.

Directory of Open Access Journals (Sweden)

Elsa Diguet

Full Text Available Aging likely plays a role in neurodegenerative disorders. In Huntington's disease (HD, a disorder caused by an abnormal expansion of a polyglutamine tract in the protein huntingtin (Htt, the role of aging is unclear. For a given tract length, the probability of disease onset increases with age. There are mainly two hypotheses that could explain adult onset in HD: Either mutant Htt progressively produces cumulative defects over time or "normal" aging renders neurons more vulnerable to mutant Htt toxicity. In the present study, we directly explored whether aging affected the toxicity of mutant Htt in vivo. We studied the impact of aging on the effects produced by overexpression of an N-terminal fragment of mutant Htt, of wild-type Htt or of a beta-Galactosidase (beta-Gal reporter gene in the rat striatum. Stereotaxic injections of lentiviral vectors were performed simultaneously in young (3 week and old (15 month rats. Histological evaluation at different time points after infection demonstrated that the expression of mutant Htt led to pathological changes that were more severe in old rats, including an increase in the number of small Htt-containing aggregates in the neuropil, a greater loss of DARPP-32 immunoreactivity and striatal neurons as assessed by unbiased stereological counts.The present results support the hypothesis that "normal" aging is involved in HD pathogenesis, and suggest that age-related cellular defects might constitute potential therapeutic targets for HD.

Process-induced viscoelastic stress in composite laminates

International Nuclear Information System (INIS)

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

Development of a quantitative multivariable radiographic method to evaluate anatomic changes associated with laminitis in the forefeet of donkeys.

Science.gov (United States)

Collins, Simon N; Dyson, Sue J; Murray, Rachel C; Newton, J Richard; Burden, Faith; Trawford, Andrew F

2012-08-01

To establish and validate an objective method of radiographic diagnosis of anatomic changes in laminitic forefeet of donkeys on the basis of data from a comprehensive series of radiographic measurements. 85 donkeys with and 85 without forelimb laminitis for baseline data determination; a cohort of 44 donkeys with and 18 without forelimb laminitis was used for validation analyses. For each donkey, lateromedial radiographic views of 1 weight-bearing forelimb were obtained; images from 11 laminitic and 2 nonlaminitic donkeys were excluded (motion artifact) from baseline data determination. Data from an a priori selection of 19 measurements of anatomic features of laminitic and nonlaminitic donkey feet were analyzed by use of a novel application of multivariate statistical techniques. The resultant diagnostic models were validated in a blinded manner with data from the separate cohort of laminitic and nonlaminitic donkeys. Data were modeled, and robust statistical rules were established for the diagnosis of anatomic changes within laminitic donkey forefeet. Component 1 scores ≤ -3.5 were indicative of extreme anatomic change, and scores from -2.0 to 0.0 denoted modest change. Nonlaminitic donkeys with a score from 0.5 to 1.0 should be considered as at risk for laminitis. Results indicated that the radiographic procedures evaluated can be used for the identification, assessment, and monitoring of anatomic changes associated with laminitis. Screening assessments by use of this method may enable early detection of mild anatomic change and identification of at-risk donkeys.

Photovoltaic-Panel Laminator

Science.gov (United States)

Keenan, R.

1985-01-01

Two-piece unit heats and presses protective layers to form laminate. Rubber diaphragm between upper and lower vacuum chambers alternates between neutral position and one that presses against solar-cell array, supplying distributed force necessary to press layers of laminate together. Encapsulation helps to protect cells from environment and to ensure long panel life while allowing efficient generation of electricity from Sunlight.

A dwarf wheat mutant is associated with increased drought ...

African Journals Online (AJOL)

... was significantly higher than Jingdong 6. Most of the s-dwarf seedlings survived in recovering experiement after water loss. The stalk of s-dwarf seedling also showed reduced gravitropism. This is the first report about a new dwarf wheat mutant associated with increased drought resistance and altered stalk gravitropism.

Continuous jute fibre reinforced laminated paper composite

Indian Academy of Sciences (India)

Jute fibre; laminated paper composite; plastic bag pollution. Abstract. Plastic bags create a serious environmental problem. The proposed jute fibre reinforced laminated paper composite and reinforcement-fibre free paper laminate may help to combat the war against this pollutant to certain extent. The paper laminate ...

Bovine pododermatitis aseptica diffusa (laminitis) aetiology, pathogenesis, treatment and control.

Science.gov (United States)

Mgasa, M N

1987-01-01

Pododermatitis aseptica diffusa (laminitis) is a major cause of lameness and discomfort to cattle with resultant economic losses. The disease is a result of multifactorial aetiology most of which is not clearly understood. Feeding readily fermentable carbohydrates to unaccustomed cattle predisposes to the disease. Histamine, lactic acid and endotoxins are believed to be involved. Systemic acidosis, histaminosis and endotoxaemia are thought to produce the pathophysiological characteristics of laminitis. The diagnosis is primarily based on the observation of symmetrical and bilateral lesions in hooves and characteristic lameness affecting all feet. Gross lesions include concavity of the dorsal wall, discolorations in the sole and rotation of the pedal bone. Degenerative changes and arteriosclerosis are constant histological findings in the corium, with chronic thrombi and chronic granulation tissue. The disease may be treated conservatively and by application of cyclo-oxygenase inhibiting non-steroidal anti-inflammatory drugs and prevented or controlled by proper feeding and management practices.

Prevalence of lesions associated with subclinical laminitis in first-lactation cows from herds with high milk production.

Science.gov (United States)

Smilie, R H; Hoblet, K H; Weiss, W P; Eastridge, M L; Rings, D M; Schnitkey, G L

1996-05-01

To determine prevalence of lesions associated with subclinical laminitis in first-lactation Holstein cows during early lactation and pregnant Holstein heifers during late gestation in herds with high milk production. Cross-sectional study. 203 cattle in 13 herbs. Cattle were placed in lateral recumbency to allow visual examination and photography of their hooves. Claws on a forelimb and hind limb were examined on all cattle. Observable categories of lesions considered to be associated with subclinical laminitis in our study included yellow waxy discoloration of the sole, hemorrhage of the sole, separation of the white line, and erosion of the heel. Lesions in at least 1 of the categories were found in all herds. Lesions in all categories were found in 11 of 13 herds. Among claws, hemorrhage of the sole was observed most frequently in the lateral claw of the hoof of the hind limb. When days in milk was treated as a covariate, significant (P < 0.01) differences were detected in the prevalence of lesions between herds. Because the prevalence of lesions differed significantly among herds, it is logical to believe that causative factors and corrective measures also may have differed among herds.

Wettability of graphene-laminated micropillar structures

International Nuclear Information System (INIS)

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

2014-01-01

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

An ALS-linked mutant SOD1 produces a locomotor defect associated with aggregation and synaptic dysfunction when expressed in neurons of Caenorhabditis elegans.

Directory of Open Access Journals (Sweden)

Jiou Wang

2009-01-01

Full Text Available The nature of toxic effects exerted on neurons by misfolded proteins, occurring in a number of neurodegenerative diseases, is poorly understood. One approach to this problem is to measure effects when such proteins are expressed in heterologous neurons. We report on effects of an ALS-associated, misfolding-prone mutant human SOD1, G85R, when expressed in the neurons of Caenorhabditis elegans. Stable mutant transgenic animals, but not wild-type human SOD1 transgenics, exhibited a strong locomotor defect associated with the presence, specifically in mutant animals, of both soluble oligomers and insoluble aggregates of G85R protein. A whole-genome RNAi screen identified chaperones and other components whose deficiency increased aggregation and further diminished locomotion. The nature of the locomotor defect was investigated. Mutant animals were resistant to paralysis by the cholinesterase inhibitor aldicarb, while exhibiting normal sensitivity to the cholinergic agonist levamisole and normal muscle morphology. When fluorescently labeled presynaptic components were examined in the dorsal nerve cord, decreased numbers of puncta corresponding to neuromuscular junctions were observed in mutant animals and brightness was also diminished. At the EM level, mutant animals exhibited a reduced number of synaptic vesicles. Neurotoxicity in this system thus appears to be mediated by misfolded SOD1 and is exerted on synaptic vesicle biogenesis and/or trafficking.

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

Science.gov (United States)

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.

A-type nuclear lamins act as transcriptional repressors when targeted to promoters

International Nuclear Information System (INIS)

Lee, Damian C.; Welton, K. Linnea; Smith, Erica D.; Kennedy, Brian K.

2009-01-01

Regions of heterochromatin are often found at the periphery of the mammalian nucleus, juxtaposed to the nuclear lamina. Genes in these regions are likely maintained in a transcriptionally silent state, although other locations at the nuclear periphery associated with nuclear pores are sites of active transcription. As primary components of the nuclear lamina, A- and B-type nuclear lamins are intermediate filament proteins that interact with DNA, histones and known transcriptional repressors, leading to speculation that they may promote establishment of repressive domains. However, no direct evidence of a role for nuclear lamins in transcriptional repression has been reported. Here we find that human lamin A, when expressed in yeast and cultured human cells as a fusion protein to the Gal4 DNA-binding domain (DBD), can mediate robust transcriptional repression of promoters with Gal4 binding sites. Full repression by lamin A requires both the coiled-coil rod domain and the C-terminal tail domain. In human cells, other intermediate filament proteins such as lamin B and vimentin are unable to confer robust repression as Gal4-DBD fusions, indicating that this property is specific to A-type nuclear lamins. These findings indicate that A-type lamins can promote transcriptional repression when in proximity of a promoter

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

Science.gov (United States)

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

Sharing mutants and experimental information prepublication using FgMutantDb (https://scabusa.org/FgMutantDb).

Science.gov (United States)

Baldwin, Thomas T; Basenko, Evelina; Harb, Omar; Brown, Neil A; Urban, Martin; Hammond-Kosack, Kim E; Bregitzer, Phil P

2018-06-01

There is no comprehensive storage for generated mutants of Fusarium graminearum or data associated with these mutants. Instead, researchers relied on several independent and non-integrated databases. FgMutantDb was designed as a simple spreadsheet that is accessible globally on the web that will function as a centralized source of information on F. graminearum mutants. FgMutantDb aids in the maintenance and sharing of mutants within a research community. It will serve also as a platform for disseminating prepublication results as well as negative results that often go unreported. Additionally, the highly curated information on mutants in FgMutantDb will be shared with other databases (FungiDB, Ensembl, PhytoPath, and PHI-base) through updating reports. Here we describe the creation and potential usefulness of FgMutantDb to the F. graminearum research community, and provide a tutorial on its use. This type of database could be easily emulated for other fungal species. Published by Elsevier Inc.

Modeling Treatment Response for Lamin A/C Related Dilated Cardiomyopathy in Human Induced Pluripotent Stem Cells.

Science.gov (United States)

Lee, Yee-Ki; Lau, Yee-Man; Cai, Zhu-Jun; Lai, Wing-Hon; Wong, Lai-Yung; Tse, Hung-Fat; Ng, Kwong-Man; Siu, Chung-Wah

2017-07-28

Precision medicine is an emerging approach to disease treatment and prevention that takes into account individual variability in the environment, lifestyle, and genetic makeup of patients. Patient-specific human induced pluripotent stem cells hold promise to transform precision medicine into real-life clinical practice. Lamin A/C (LMNA)-related cardiomyopathy is the most common inherited cardiomyopathy in which a substantial proportion of mutations in the LMNA gene are of nonsense mutation. PTC124 induces translational read-through over the premature stop codon and restores production of the full-length proteins from the affected genes. In this study we generated human induced pluripotent stem cells-derived cardiomyocytes from patients who harbored different LMNA mutations (nonsense and frameshift) to evaluate the potential therapeutic effects of PTC124 in LMNA -related cardiomyopathy. We generated human induced pluripotent stem cells lines from 3 patients who carried distinctive mutations (R225X, Q354X, and T518fs) in the LMNA gene. The cardiomyocytes derived from these human induced pluripotent stem cells lines reproduced the pathophysiological hallmarks of LMNA -related cardiomyopathy. Interestingly, PTC124 treatment increased the production of full-length LMNA proteins in only the R225X mutant, not in other mutations. Functional evaluation experiments on the R225X mutant further demonstrated that PTC124 treatment not only reduced nuclear blebbing and electrical stress-induced apoptosis but also improved the excitation-contraction coupling of the affected cardiomyocytes. Using cardiomyocytes derived from human induced pluripotent stem cells carrying different LMNA mutations, we demonstrated that the effect of PTC124 is codon selective. A premature stop codon UGA appeared to be most responsive to PTC124 treatment. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Dose-Dependent Lowering of Mutant Huntingtin Using Antisense Oligonucleotides in Huntington Disease Patients.

Science.gov (United States)

van Roon-Mom, Willeke M C; Roos, Raymund A C; de Bot, Susanne T

2018-04-01

On December 11 of 2017, Ionis Pharmaceuticals published a press release announcing dose-dependent reductions of mutant huntingtin protein in their HTTRx Phase 1/2a study in Huntington disease (HD) patients. The results from this Ionis trial have gained much attention from the patient community and the oligonucleotide therapeutics field, since it is the first trial targeting the cause of HD, namely the mutant huntingtin protein, using antisense oligonucleotides (ASOs). The press release also states that the primary endpoints of the study (safety and tolerability) were met, but does not contain data. This news follows the approval of another therapeutic ASO nusinersen (trade name Spinraza) for a neurological disease, spinal muscular atrophy, by the U.S. Food and Drug Administration and European Medicines Agency, in 2016 and 2017, respectively. Combined, this offers hope for the development of the HTTRx therapy for HD patients.

ALS-associated mutant FUS induces selective motor neuron degeneration through toxic gain of function.

Science.gov (United States)

Sharma, Aarti; Lyashchenko, Alexander K; Lu, Lei; Nasrabady, Sara Ebrahimi; Elmaleh, Margot; Mendelsohn, Monica; Nemes, Adriana; Tapia, Juan Carlos; Mentis, George Z; Shneider, Neil A

2016-02-04

Mutations in FUS cause amyotrophic lateral sclerosis (ALS), including some of the most aggressive, juvenile-onset forms of the disease. FUS loss-of-function and toxic gain-of-function mechanisms have been proposed to explain how mutant FUS leads to motor neuron degeneration, but neither has been firmly established in the pathogenesis of ALS. Here we characterize a series of transgenic FUS mouse lines that manifest progressive, mutant-dependent motor neuron degeneration preceded by early, structural and functional abnormalities at the neuromuscular junction. A novel, conditional FUS knockout mutant reveals that postnatal elimination of FUS has no effect on motor neuron survival or function. Moreover, endogenous FUS does not contribute to the onset of the ALS phenotype induced by mutant FUS. These findings demonstrate that FUS-dependent motor degeneration is not due to loss of FUS function, but to the gain of toxic properties conferred by ALS mutations.

Laser desorption mass spectrometry for point mutation detection

Energy Technology Data Exchange (ETDEWEB)

Taranenko, N.I.; Chung, C.N.; Zhu, Y.F. [Oak Ridge National Lab., TN (United States)] [and others

1996-12-31

A point mutation can be associated with the pathogenesis of inherited or acquired diseases. Laser desorption mass spectrometry coupled with allele specific polymerase chain reaction (PCR) was first used for point mutation detection. G551D is one of several mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene present in 1-3% of the mutant CFTR alleles in most European populations. In this work, two different approaches were pursued to detect G551D point mutation in the cystic fibrosis gene. The strategy is to amplify the desired region of DNA template by PCR using two primers that overlap one base at the site of the point mutation and which vary in size. If the two primers based on the normal sequence match the target DNA sequence, a normal PCR product will be produced. However, if the alternately sized primers that match the mutant sequence recognize the target DNA, an abnormal PCR product will be produced. Thus, the mass spectrometer can be used to identify patients that are homozygous normal, heterozygous for a mutation or homozygous abnormal at a mutation site. Another approach to identify similar mutations is the use of sequence specific restriction enzymes which respond to changes in the DNA sequence. Mass spectrometry is used to detect the length of the restriction fragments by digestion of a PCR generated target fragment. 21 refs., 10 figs., 2 tabs.

Lamination effects on a 3D model of the magnetic core of power transformers

Directory of Open Access Journals (Sweden)

Poveda-Lerma Antonio

2017-12-01

Full Text Available In this paper the lamination effect on the model of a power transformer’s core with stacked E-I structure is analyzed. The distribution of the magnetic flux in the laminations depends on the stacking method. In this work it is shown, using a 3D FEM model and an experimental prototype, that the non-uniform distribution of the flux in a laminated E-I core with alternate-lap joint stack increases substantially the average value of the magnetic flux density in the core, compared with a butt joint stack. Both the simulated model and the experimental tests show that the presence of constructive air-gaps in the E-I junctions gives rise to a zig-zag flux in the depth direction. This inter-lamination flux reduces the magnetic flux density in the I-pieces and increases substantially the magnetic flux density in the E-pieces, with highly saturated points that traditional 2D analysis cannot reproduce. The relation between the number of laminations included in the model, and the computational resourses needed to build it, is also evaluated in this work.

Energy Saving Glass Lamination via Selective Radio Frequency Heating

Energy Technology Data Exchange (ETDEWEB)

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

Energy Saving Glass Lamination via Selective Radio Frequency Heating

Energy Technology Data Exchange (ETDEWEB)

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

Lipid-mediated interactions tune the association of glycophorin A helix and its disruptive mutants in membranes

NARCIS (Netherlands)

Sengupta, Durba; Marrink, Siewert J.

2010-01-01

The specific and non-specific driving forces of helix association within membranes are still poorly understood. Here, we use coarse-grain molecular dynamics simulations to study the association behavior of glycophorin A and two disruptive mutants, T87F and a triple mutant of the GxxxG motif

The role of nonlinear viscoelasticity on the functionality of laminating shortenings

Energy Technology Data Exchange (ETDEWEB)

Macias-Rodriguez, Braulio A.; Peyronel, Fernanda; Marangoni, Alejandro G.

2017-11-01

The rheology of fats is essential for the development of homogeneous and continuous layered structures of doughs. Here, we define laminating shortenings in terms of rheological behavior displayed during linear-to-nonlinear shear deformations, investigated by large amplitude oscillatory shear rheology. Likewise, we associate the rheological behavior of the shortenings with structural length scales elucidated by ultra-small angle x-ray scattering and cryo-electron microscopy. Shortenings exhibited solid-like viscoelastic and viscoelastoplastic behaviors in the linear and nonlinear regimes respectively. In the nonlinear region, laminating shortenings dissipated more viscous energy (larger normalized dynamic viscosities) than a cake bakery shortening. The fat solid-like network of laminating shortening displayed a three-hierarchy structure and layered crystal aggregates, in comparison to two-hierarchy structure and spherical-like crystal aggregates of a cake shortening. We argue that the observed rheology, correlated to the structural network, is crucial for optimal laminating performance of shortenings.

Morphological Characterization and Assessment of Genetic Variability, Character Association, and Divergence in Soybean Mutants

Directory of Open Access Journals (Sweden)

M. A. Malek

2014-01-01

Full Text Available Genetic diversity is important for crop improvement. An experiment was conducted during 2011 to study genetic variability, character association, and genetic diversity among 27 soybean mutants and four mother genotypes. Analysis of variance revealed significant differences among the mutants and mothers for nine morphological traits. Eighteen mutants performed superiorly to their mothers in respect to seed yield and some morphological traits including yield attributes. Narrow differences between phenotypic and genotypic coefficients of variation (PCV and GCV for most of the characters revealed less environmental influence on their expression. High values of heritability and genetic advance with high GCV for branch number, plant height, pod number, and seed weight can be considered as favorable attributes for soybean improvement through phenotypic selection and high expected genetic gain can be achieved. Pod and seed number and maturity period appeared to be the first order traits for higher yield and priority should be given in selection due to their strong associations and high magnitudes of direct effects on yield. Cluster analysis grouped 31 genotypes into five groups at the coefficient value of 235. The mutants/genotypes from cluster I and cluster II could be used for hybridization program with the mutants of clusters IV and V in order to develop high yielding mutant-derived soybean varieties for further improvement.

Impact damages modeling in laminated composite structures

Directory of Open Access Journals (Sweden)

Kreculj Dragan D.

2014-01-01

Full Text Available Laminated composites have an important application in modern engineering structures. They are characterized by extraordinary properties, such as: high strength and stiffness and lightweight. Nevertheless, a serious obstacle to more widespread use of those materials is their sensitivity to the impact loads. Impacts cause initiation and development of certain types of damages. Failures that occur in laminated composite structures can be intralaminar and interlaminar. To date it was developed a lot of simulation models for impact damages analysis in laminates. Those models can replace real and expensive testing in laminated structures with a certain accuracy. By using specialized software the damage parameters and distributions can be determined (at certain conditions on laminate structures. With performing numerical simulation of impact on composite laminates there are corresponding results valid for the analysis of these structures.

Self-Healing Laminate System

Science.gov (United States)

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.

Metabolic syndrome in healthy ponies facilitates nutritional countermeasures against pasture laminitis.

Science.gov (United States)

Kronfeld, David S; Treiber, Kibby H; Hess, Tanja M; Splan, Rebecca K; Byrd, Bridgett M; Staniar, W Burton; White, Nathanial W

2006-07-01

Treatment of clinical laminitis usually fails to prevent some degree of persistent disability; thus, intervention should aim at avoiding risk factors and preventing the disease. Efficiency of intervention would be improved by identifying predisposed horses and ponies. A herd of 160 healthy ponies included 54 previously laminitic (PL) and 106 never laminitic (NL). Pedigree analysis was consistent with dominant inheritance partially suppressed in males. Blood analysis revealed higher plasma concentrations of insulin and triglycerides but not cortisol, glucose, or free fatty acids in the PL group. Proxies for insulin sensitivity and beta-cell responsiveness, which were calculated from plasma insulin and glucose, indicated compensated insulin resistance in the PL group. A prelaminitic metabolic syndrome (PLMS) was derived statistically to have cut-off points for the 2 proxies, hypertriglyceridemia, and body condition score. It had a total predictive power of 78%. It identified 62 ponies with PLMS, and 98 as PLMS-free. Two months later, pasture starch concentration doubled, and 13 clinical cases of laminitis developed, 11 in the PLMS group and 2 in the PLMS-free group, giving an odds ratio of 10.4 (P = 0.0006). The PLMS can be used to identify predisposed ponies in need of special care; the efficiency of intervention would increase nearly 3-fold in the present case. It enables the design of new interventions suitable for testing. The PLMS also might influence market values.

Problem-Solving Test: Tryptophan Operon Mutants

Science.gov (United States)

Szeberenyi, Jozsef

2010-01-01

This paper presents a problem-solving test that deals with the regulation of the "trp" operon of "Escherichia coli." Two mutants of this operon are described: in mutant A, the operator region of the operon carries a point mutation so that it is unable to carry out its function; mutant B expresses a "trp" repressor protein unable to bind…

Properties of Chitosan-Laminated Collagen Film

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Vera Lazić

2012-01-01

Full Text Available The objective of this study is to determine physical, mechanical and barrier properties of chitosan-laminated collagen film. Commercial collagen film, which is used for making collagen casings for dry fermented sausage production, was laminated with chitosan film layer in order to improve the collagen film barrier properties. Different volumes of oregano essential oil per 100 mL of filmogenic solution were added to chitosan film layer: 0, 0.2, 0.4, 0.6 and 0.8 mL to optimize water vapour barrier properties. Chitosan layer with 0.6 or 0.8 % of oregano essential oil lowered the water vapour transmission rate to (1.85±0.10·10–6 and (1.78±0.03·10–6 g/(m2·s·Pa respectively, compared to collagen film ((2.51±0.05·10–6 g/(m2·s·Pa. However, chitosan-laminated collagen film did not show improved mechanical properties compared to the collagen one. Tensile strength decreased from (54.0±3.8 MPa of the uncoated collagen film to (36.3±4.0 MPa when the film was laminated with 0.8 % oregano essential oil chitosan layer. Elongation at break values of laminated films did not differ from those of collagen film ((18.4±2.7 %. Oxygen barrier properties were considerably improved by lamination. Oxygen permeability of collagen film was (1806.8±628.0·10–14 cm3/(m·s·Pa and values of laminated films were below 35·10–14 cm3/(m·s·Pa. Regarding film appearance and colour, lamination with chitosan reduced lightness (L and yellowness (+b of collagen film, while film redness (+a increased. These changes were not visible to the naked eye.

Familial CJD Associated PrP Mutants within Transmembrane Region Induced Ctm-PrP Retention in ER and Triggered Apoptosis by ER Stress in SH-SY5Y Cells

Science.gov (United States)

Wang, Xin; Shi, Qi; Xu, Kun; Gao, Chen; Chen, Cao; Li, Xiao-Li; Wang, Gui-Rong; Tian, Chan; Han, Jun; Dong, Xiao-Ping

2011-01-01

Background Genetic prion diseases are linked to point and inserted mutations in the prion protein (PrP) gene that are presumed to favor conversion of the cellular isoform of PrP (PrPC) to the pathogenic one (PrPSc). The pathogenic mechanisms and the subcellular sites of the conversion are not completely understood. Here we introduce several PRNP gene mutations (such as, PrP-KDEL, PrP-3AV, PrP-A117V, PrP-G114V, PrP-P102L and PrP-E200K) into the cultured cells in order to explore the pathogenic mechanism of familial prion disease. Methodology/Principal Findings To address the roles of aberrant retention of PrP in endoplasmic reticulum (ER), the recombinant plasmids expressing full-length human PrP tailed with an ER signal peptide at the COOH-terminal (PrP-KDEL) and PrP with three amino acids exchange in transmembrane region (PrP-3AV) were constructed. In the preparations of transient transfections, 18-kD COOH-terminal proteolytic resistant fragments (Ctm-PrP) were detected in the cells expressing PrP-KDEL and PrP-3AV. Analyses of the cell viabilities in the presences of tunicamycin and brefeldin A revealed that expressions of PrP-KDEL and PrP-3AV sensitized the transfected cells to ER stress stimuli. Western blots and RT-PCR identified the clear alternations of ER stress associated events in the cells expressing PrP-KDEL and PrP-3AV that induced ER mediated apoptosis by CHOP and capase-12 apoptosis pathway. Moreover, several familial CJD related PrP mutants were transiently introduced into the cultured cells. Only the mutants within the transmembrane region (G114V and A117V) induced the formation of Ctm-PrP and caused the ER stress, while the mutants outside the transmembrane region (P102L and E200K) failed. Conclusions/Significance The data indicate that the retention of PrP in ER through formation of Ctm-PrP results in ER stress and cell apoptosis. The cytopathic activities caused by different familial CJD associated PrP mutants may vary, among them the mutants

Familial CJD associated PrP mutants within transmembrane region induced Ctm-PrP retention in ER and triggered apoptosis by ER stress in SH-SY5Y cells.

Directory of Open Access Journals (Sweden)

Xin Wang

Full Text Available BACKGROUND: Genetic prion diseases are linked to point and inserted mutations in the prion protein (PrP gene that are presumed to favor conversion of the cellular isoform of PrP (PrP(C to the pathogenic one (PrP(Sc. The pathogenic mechanisms and the subcellular sites of the conversion are not completely understood. Here we introduce several PRNP gene mutations (such as, PrP-KDEL, PrP-3AV, PrP-A117V, PrP-G114V, PrP-P102L and PrP-E200K into the cultured cells in order to explore the pathogenic mechanism of familial prion disease. METHODOLOGY/PRINCIPAL FINDINGS: To address the roles of aberrant retention of PrP in endoplasmic reticulum (ER, the recombinant plasmids expressing full-length human PrP tailed with an ER signal peptide at the COOH-terminal (PrP-KDEL and PrP with three amino acids exchange in transmembrane region (PrP-3AV were constructed. In the preparations of transient transfections, 18-kD COOH-terminal proteolytic resistant fragments (Ctm-PrP were detected in the cells expressing PrP-KDEL and PrP-3AV. Analyses of the cell viabilities in the presences of tunicamycin and brefeldin A revealed that expressions of PrP-KDEL and PrP-3AV sensitized the transfected cells to ER stress stimuli. Western blots and RT-PCR identified the clear alternations of ER stress associated events in the cells expressing PrP-KDEL and PrP-3AV that induced ER mediated apoptosis by CHOP and caspase-12 apoptosis pathway. Moreover, several familial CJD related PrP mutants were transiently introduced into the cultured cells. Only the mutants within the transmembrane region (G114V and A117V induced the formation of Ctm-PrP and caused the ER stress, while the mutants outside the transmembrane region (P102L and E200K failed. CONCLUSIONS/SIGNIFICANCE: The data indicate that the retention of PrP in ER through formation of Ctm-PrP results in ER stress and cell apoptosis. The cytopathic activities caused by different familial CJD associated PrP mutants may vary, among them

A genetic algorithm for the optimization of fiber angles in composite laminates

International Nuclear Information System (INIS)

Hwang, Shun Fa; Hsu, Ya Chu; Chen, Yuder

2014-01-01

A genetic algorithm for the optimization of composite laminates is proposed in this work. The well-known roulette selection criterion, one-point crossover operator, and uniform mutation operator are used in this genetic algorithm to create the next population. To improve the hill-climbing capability of the algorithm, adaptive mechanisms designed to adjust the probabilities of the crossover and mutation operators are included, and the elite strategy is enforced to ensure the quality of the optimum solution. The proposed algorithm includes a new operator called the elite comparison, which compares and uses the differences in the design variables of the two best solutions to find possible combinations. This genetic algorithm is tested in four optimization problems of composite laminates. Specifically, the effect of the elite comparison operator is evaluated. Results indicate that the elite comparison operator significantly accelerates the convergence of the algorithm, which thus becomes a good candidate for the optimization of composite laminates.

Heart-specific expression of laminopathic mutations in transgenic zebrafish.

Science.gov (United States)

Verma, Ajay D; Parnaik, Veena K

2017-07-01

Lamins are key determinants of nuclear organization and function in the metazoan nucleus. Mutations in human lamin A cause a spectrum of genetic diseases that affect cardiac muscle and skeletal muscle as well as other tissues. A few laminopathies have been modeled using the mouse. As zebrafish is a well established model for the study of cardiac development and disease, we have investigated the effects of heart-specific lamin A mutations in transgenic zebrafish. We have developed transgenic lines of zebrafish expressing conserved lamin A mutations that cause cardiac dysfunction in humans. Expression of zlamin A mutations Q291P and M368K in the heart was driven by the zebrafish cardiac troponin T2 promoter. Homozygous mutant embryos displayed nuclear abnormalities in cardiomyocyte nuclei. Expression analysis showed the upregulation of genes involved in heart regeneration in transgenic mutant embryos and a cell proliferation marker was increased in adult heart tissue. At the physiological level, there was deviation of up to 20% from normal heart rate in transgenic embryos expressing mutant lamins. Adult homozygous zebrafish were fertile and did not show signs of early mortality. Our results suggest that transgenic zebrafish models of heart-specific laminopathies show cardiac regeneration and moderate deviations in heart rate during embryonic development. © 2017 International Federation for Cell Biology.

Criterion of damage beginning: experimental identification for laminate composite

International Nuclear Information System (INIS)

Thiebaud, F.; Perreux, D.; Varchon, D.; Lebras, J.

1996-01-01

The aim of this study is to propose a criterion of damage beginning for laminate composite. The materials is a glass-epoxy laminate [+55 deg.,-55 deg.[ n performed by winding filament process. First of all a description of the damage is performed and allows to define a damage variable. Thanks to the potential of free energy, an associated variable is defined. The damage criterion is written by using this last one. The parameter of the criterion is identified using mechanical and acoustical methods. The result is compared and exhibit a good agreement. (authors). 13 refs., 5 figs

Effect of stacking angles on mechanical properties and damage propagation of plain woven carbon fiber laminates

Science.gov (United States)

Zhuang, Weimin; Ao, Wenhong

2018-03-01

Damage propagation induced failure is a predominant damage mechanism. This study is aimed at assessing the damage state and damage propagation induced failure with different stacking angles, of woven carbon fiber/epoxy laminates subjected to quasi-static tensile and bending load. Different stages of damage processing and damage behavior under the bending load are investigated by Scanning Electron Microscopy (SEM). The woven carbon fiber/epoxy laminates which are stacked at six different angles (0°, 15°, 30°, 45°, 60°, 75°) with eight plies have been analyzed: [0]8, [15]8, [30]8, [45]8, [60]8, [75]8. Three-point bending test and quasi-static tensile test are used in validating the woven carbon fiber/epoxy laminates’ mechanical properties. Furthermore, the damage propagation and failure modes observed under flexural loading is correlated with flexural force and load-displacement behaviour respectively for the laminates. The experimental results have indicated that [45]8 laminate exhibits the best flexural performance in terms of energy absorption duo to its pseudo-ductile behaviour but the tensile strength and flexural strength drastically decreased compared to [0]8 laminate. Finally, SEM micrographs of specimens and fracture surfaces are used to reveal the different types of damage of the laminates with different stacking angles.

Modeling Bistable Composite Laminates for Piezoelectric Morphing Structures

OpenAIRE

Darryl V. Murray; Oliver J. Myers

2013-01-01

A sequential modeling effort for bistable composite laminates for piezoelectric morphing structures is presented. Thin unsymmetric carbon fiber composite laminates are examined for use of morphing structures using piezoelectric actuation. When cooling from the elevated cure temperature to room temperature, these unsymmetric composite laminates will deform. These postcure room temperature deformation shapes can be used as morphing structures. Applying a force to these deformed laminates will c...

Determination of CTOD C in Fibre Metal Laminates by ASTM and Schwalbe Methods

Directory of Open Access Journals (Sweden)

E.M. Castrodeza

2002-06-01

Full Text Available Fibre Metal Laminates (FMLs have arisen as a demand of the aeronautical industry to use thin sheets with high resistance to fatigue crack growth, high damage tolerance, corrosion resistance and high specific strength. Considering these requirements, FMLs are an advantageous choice when compared to metal alloys currently used. In order to employ FMLs in aircraft structures, designers must hold a deep knowledge of a wide set of their properties including fracture toughness. The aim of this work was to evaluate the available methodologies to measure fracture toughness at instability (CTOD C in unidirectional fibre metal laminates reinforced with aramid fibres (ARALL®. To achieve this, tests were performed to obtain traditional and Schwalbe CTODs by using experimental ASTM based techniques, especially adapted to these laminates. Results achieved point out that Schwalbe method is more appropriate and also that there are differences between both CTOD parameters.

Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome.

Science.gov (United States)

Liu, Guang-Hui; Barkho, Basam Z; Ruiz, Sergio; Diep, Dinh; Qu, Jing; Yang, Sheng-Lian; Panopoulos, Athanasia D; Suzuki, Keiichiro; Kurian, Leo; Walsh, Christopher; Thompson, James; Boue, Stephanie; Fung, Ho Lim; Sancho-Martinez, Ignacio; Zhang, Kun; Yates, John; Izpisua Belmonte, Juan Carlos

2011-04-14

Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal human premature ageing disease, characterized by premature arteriosclerosis and degeneration of vascular smooth muscle cells (SMCs). HGPS is caused by a single point mutation in the lamin A (LMNA) gene, resulting in the generation of progerin, a truncated splicing mutant of lamin A. Accumulation of progerin leads to various ageing-associated nuclear defects including disorganization of nuclear lamina and loss of heterochromatin. Here we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS. HGPS-iPSCs show absence of progerin, and more importantly, lack the nuclear envelope and epigenetic alterations normally associated with premature ageing. Upon differentiation of HGPS-iPSCs, progerin and its ageing-associated phenotypic consequences are restored. Specifically, directed differentiation of HGPS-iPSCs to SMCs leads to the appearance of premature senescence phenotypes associated with vascular ageing. Additionally, our studies identify DNA-dependent protein kinase catalytic subunit (DNAPKcs, also known as PRKDC) as a downstream target of progerin. The absence of nuclear DNAPK holoenzyme correlates with premature as well as physiological ageing. Because progerin also accumulates during physiological ageing, our results provide an in vitro iPSC-based model to study the pathogenesis of human premature and physiological vascular ageing.

Laser desorption mass spectrometry for point mutation detection

Energy Technology Data Exchange (ETDEWEB)

Taranenko, N.I.; Chung, C.N.; Zhu, Y.F. [Oak Ridge National Lab., TN (United States)] [and others

1996-10-01

A point mutation can be associated with the pathogenesis of inherited or acquired diseases. Laser desorption mass spectrometry coupled with allele specific polymerase chain reaction (PCR) was first used for point mutation detection. G551D is one of several mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene present in 1-3% of the mutant CFTR alleles in most European populations. In this work, two different approaches were pursued to detect G551D point mutation in the cystic fibrosis gene. The strategy is to amplify the desired region of DNA template by PCR using two primers that overlap one base at the site of the point mutation and which vary in size. If the two primers based on the normal sequence match the target DNA sequence, a normal PCR product will be produced. However, if the alternately sized primers that match the mutant sequence recognize the target DNA, an abnormal PCR product will be produced. Thus, the mass spectrometer can be used to identify patients that are homozygous normal, heterozygous for a mutation or homozygous abnormal at a mutation site. Another approach to identify similar mutations is the use of sequence specific restriction enzymes which respond to changes in the DNA sequence. Mass spectrometry is used to detect the length of the restriction fragments generated by digestion of a PCR generated target fragment. 21 refs., 10 figs., 2 tabs.

Subclinical laminitis in dairy heifers.

Science.gov (United States)

Bradley, H K; Shannon, D; Neilson, D R

1989-08-19

By causing poorer horn quality, subclinical laminitis is considered to be a major predisposing cause of other hoof problems, particularly sole ulcers in newly calved heifers. In this study the hind hooves of 136 female Friesian/Holstein cattle aged between four months and two years were examined to discover at what age the signs of subclinical laminitis appeared. Sole haemorrhages were found in the hoof horn of calves as young as five months. The consistent finding of these lesions in heifers of all ages indicated that subclinical laminitis of varying degree was a common condition during the early growing period of young dairy heifers.

Increased intracellular proteolysis reduces disease severity in an ER stress-associated dwarfism.

Science.gov (United States)

Mullan, Lorna A; Mularczyk, Ewa J; Kung, Louise H; Forouhan, Mitra; Wragg, Jordan Ma; Goodacre, Royston; Bateman, John F; Swanton, Eileithyia; Briggs, Michael D; Boot-Handford, Raymond P

2017-10-02

The short-limbed dwarfism metaphyseal chondrodysplasia type Schmid (MCDS) is linked to mutations in type X collagen, which increase ER stress by inducing misfolding of the mutant protein and subsequently disrupting hypertrophic chondrocyte differentiation. Here, we show that carbamazepine (CBZ), an autophagy-stimulating drug that is clinically approved for the treatment of seizures and bipolar disease, reduced the ER stress induced by 4 different MCDS-causing mutant forms of collagen X in human cell culture. Depending on the nature of the mutation, CBZ application stimulated proteolysis of misfolded collagen X by either autophagy or proteasomal degradation, thereby reducing intracellular accumulation of mutant collagen. In MCDS mice expressing the Col10a1.pN617K mutation, CBZ reduced the MCDS-associated expansion of the growth plate hypertrophic zone, attenuated enhanced expression of ER stress markers such as Bip and Atf4, increased bone growth, and reduced skeletal dysplasia. CBZ produced these beneficial effects by reducing the MCDS-associated abnormalities in hypertrophic chondrocyte differentiation. Stimulation of intracellular proteolysis using CBZ treatment may therefore be a clinically viable way of treating the ER stress-associated dwarfism MCDS.

Ectopic Mineralization and Conductive Hearing Loss in Enpp1asj Mutant Mice, a New Model for Otitis Media and Tympanosclerosis.

Science.gov (United States)

Tian, Cong; Harris, Belinda S; Johnson, Kenneth R

2016-01-01

Otitis media (OM), inflammation of the middle ear, is a common cause of hearing loss in children and in patients with many different syndromic diseases. Studies of the human population and mouse models have revealed that OM is a multifactorial disease with many environmental and genetic contributing factors. Here, we report on otitis media-related hearing loss in asj (ages with stiffened joints) mutant mice, which bear a point mutation in the Enpp1 gene. Auditory-evoked brainstem response (ABR) measurements revealed that around 90% of the mutant mice (Enpp1asj/asj) tested had moderate to severe hearing impairment in at least one ear. The ABR thresholds were variable and generally elevated with age. We found otitis media with effusion (OME) in all of the hearing-impaired Enpp1asj/asj mice by anatomic and histological examinations. The volume and inflammatory cell content of the effusion varied among the asj mutant mice, but all mutants exhibited a thickened middle ear epithelium with fibrous polyps and more mucin-secreting goblet cells than controls. Other abnormalities observed in the Enpp1 mutant mice include over-ossification at the round window ridge, thickened and over-calcified stapedial artery, fusion of malleus and incus, and white patches on the inside of tympanic membrane, some of which are typical symptoms of tympanosclerosis. An excessive yellow discharge was detected in the outer ear canal of older asj mutant mice, with 100% penetrance by 5 months of age, and contributes to the progressive nature of the hearing loss. This is the first report of hearing loss and ear pathology associated with an Enpp1 mutation in mice. The Enpp1asj mutant mouse provides a new animal model for studying tympanosclerotic otitis and otitis media with effusion, and also provides a specific model for the hearing loss recently reported to be associated with human ENPP1 mutations causing generalized arterial calcification of infancy and hypophosphatemic rickets.

Livestock disease threats associated with intensification of pastoral dairy farming.

Science.gov (United States)

Lean, Ij; Westwood, Ct; Playford, Mc

2008-12-01

This paper provides an overview of the changes in the pasture-based dairy systems of New Zealand and Australia that may influence the health of cattle. There are relatively few available data that can be used to quantify the effects of increased intensification of milk production on the health of cattle. There is evidence that increased production increases the risk of mastitis and culling for udder health. Increased risks of mastitis with treatment with somatotropin support these findings; however, the risk of mastitis may decrease with increased milking frequency. Larger herds with greater stocking density should increase the risk for infectious disease, but evidence to support this contention is sparse. Very intensive grazing patterns associated with higher grass yields achieved using better cultivars and greater use of fertilisers favour nematode parasites. There is some evidence of anthelmintic resistance in both nematodes and liver fluke. Veterinarians will need to be aware of the potential for these to reduce the productivity of cattle. There have been benefits of improved nutrition on the efficiency of energy use for dairy production. Diseases such as bloat and ketosis appear to be of lower prevalence. It also appears that mineral nutrition of pasture-fed cattle is being better addressed, with gains in the control of milk fever, hypomagnesaemia and trace-element deficiencies. However, acidosis is a condition with a high point prevalence in pasture-based dairy systems where cows are fed supplements; one study in Australia found a point prevalence of approximately 11% of cows with acidosis. There is evidence from this study that the neutral detergent fibre (NDF) in pasture-based diets may need to be higher than 30% of the diet to maintain rumen stability. Laminitis and acidosis are different conditions with a similar pathogenesis, specifically highly fermentable diets. The prevalence of lameness was 28% in herds in Australia, suggesting that this condition

Embedded adhesive connection for laminated glass plates

DEFF Research Database (Denmark)

Hansen, Jens Zangenberg; Poulsen, S.H.; Bagger, A.

2012-01-01

The structural behavior of a new connection design, the embedded adhesive connection, used for laminated glass plates is investigated. The connection consists of an aluminum plate encapsulated in-between two adjacent triple layered laminated glass plates. Fastening between glass and aluminum...... usage in a design situation. The embedded connection shows promising potential as a future fastening system for load-carrying laminated glass plates....

Site-specific perturbations of alpha-synuclein fibril structure by the Parkinson's disease associated mutations A53T and E46K.

Directory of Open Access Journals (Sweden)

Luisel R Lemkau

Full Text Available Parkinson's disease (PD is pathologically characterized by the presence of Lewy bodies (LBs in dopaminergic neurons of the substantia nigra. These intracellular inclusions are largely composed of misfolded α-synuclein (AS, a neuronal protein that is abundant in the vertebrate brain. Point mutations in AS are associated with rare, early-onset forms of PD, although aggregation of the wild-type (WT protein is observed in the more common sporadic forms of the disease. Here, we employed multidimensional solid-state NMR experiments to assess A53T and E46K mutant fibrils, in comparison to our recent description of WT AS fibrils. We made de novo chemical shift assignments for the mutants, and used these chemical shifts to empirically determine secondary structures. We observe significant perturbations in secondary structure throughout the fibril core for the E46K fibril, while the A53T fibril exhibits more localized perturbations near the mutation site. Overall, these results demonstrate that the secondary structure of A53T has some small differences from the WT and the secondary structure of E46K has significant differences, which may alter the overall structural arrangement of the fibrils.

Behaviour of Mechanically Laminated CLT Members

Science.gov (United States)

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.

Identification of genes associated with growth cessation and bud dormancy entrance using a dormancy-incapable tree mutant.

Science.gov (United States)

Jiménez, Sergio; Li, Zhigang; Reighard, Gregory L; Bielenberg, Douglas G

2010-02-09

In many tree species the perception of short days (SD) can trigger growth cessation, dormancy entrance, and the establishment of a chilling requirement for bud break. The molecular mechanisms connecting photoperiod perception, growth cessation and dormancy entrance in perennials are not clearly understood. The peach [Prunus persica (L.) Batsch] evergrowing (evg) mutant fails to cease growth and therefore cannot enter dormancy under SD. We used the evg mutant to filter gene expression associated with growth cessation after exposure to SD. Wild-type and evg plants were grown under controlled conditions of long days (16 h/8 h) followed by transfer to SD (8 h/16 h) for eight weeks. Apical tissues were sampled at zero, one, two, four, and eight weeks of SD and suppression subtractive hybridization was performed between genotypes at the same time points. We identified 23 up-regulated genes in the wild-type with respect to the mutant during SD exposure. We used quantitative real-time PCR to verify the expression of the differentially expressed genes in wild-type tissues following the transition to SD treatment. Three general expression patterns were evident: one group of genes decreased at the time of growth cessation (after 2 weeks in SD), another that increased immediately after the SD exposure and then remained steady, and another that increased throughout SD exposure. The use of the dormancy-incapable mutant evg has allowed us to reduce the number of genes typically detected by differential display techniques for SD experiments. These genes are candidates for involvement in the signalling pathway leading from photoperiod perception to growth cessation and dormancy entrance and will be the target of future investigations.

Histopathology of dairy cows' hooves with signs of naturally acquired laminitis

OpenAIRE

Mendes, Heloisa M.F.; Casagrande, Fernando P.; Lima, Ingrid R.; Souza, Cairo H.; Gontijo, Lílian D'.; Alves, Geraldo E.S.; Vasconcelos, Anilton C.; Faleiros, Rafael R.

2013-01-01

The purpose of this study was to investigate histological changes in dairy cows' hooves with or without injuries from naturally acquired laminitis. Cull cows with no clinical signs of hoof abnormalities (G1, n=9) and those with macroscopic lesions associated with laminitis without (G2, n=23) or with lameness (G3, n=7) were used in the study. After slaughter, samples of dermo-epidermal junctions of sole, axial and dorsal regions of the hoof were obtained and histologically processed using HE a...

Cotton leaf curl Burewala virus with intact or mutant transcriptional activator proteins: complexity of cotton leaf curl disease.

Science.gov (United States)

Kumar, Jitendra; Gunapati, Samatha; Alok, Anshu; Lalit, Adarsh; Gadre, Rekha; Sharma, Naresh C; Roy, Joy K; Singh, Sudhir P

2015-05-01

Cotton leaf curl disease (CLCuD) is a serious disease of cotton on the Indian subcontinent. In the present study, three cotton leaf curl viruses, cotton leaf curl Burewala virus (CLCuBuV), cotton leaf curl Kokhran virus (CLCuKoV) and cotton leaf curl Multan virus (CLCuMV), and their associated satellites, cotton leaf curl Multan betasatellite (CLCuMB) and cotton leaf curl Multan alphasatellite (CLCuMA), were detected. CLCuBuV with either intact (CLCuBuV-1) or mutant (CLCuBuV-2) transcriptional activator protein (TrAP) were detected in different plants. Agroinoculation with CLCuBuV-1 or CLCuBuV-2 together with CLCuMB and CLCuMA, resulted in typical leaf curling and stunting of tobacco plants. Inoculation with CLCuKoV or an isolate of CLCuMV (CLCuMV-2), together with CLCuMB and CLCuMA, induced severe leaf curling, while the other isolate of CLCuMV (CLCuMV-1), which was recombinant in origin, showed mild leaf curling in tobacco. To investigate the effect of intact or mutant TrAP and also the recombination events, CLCuBuV-1, CLCuBuV-2, CLCuMV-1 or CLCuMV-2 together with the satellites (CLCuMA and CLCuMB) were transferred to cotton via whitefly-mediated transmission. Cotton plants containing CLCuBuV-1, CLCuBuV-2 or CLCuMV-2 together with satellites showed curling and stunting, whereas the plants having CLCuMV-1 and the satellites showed only mild and indistinguishable symptoms. CLCuBuV-1 (intact TrAP) showed severe symptoms in comparison to CLCuBuV-2 (mutant TrAP). The present study reveals that two types of CLCuBuV, one with an intact TrAP and the other with a mutant TrAP, exist in natural infection of cotton in India. Additionally, CLCuMuV-1, which has a recombinant origin, induces mild symptoms in comparison to the other CLCuMV isolates.

Thermally induced self-healing epoxy/glass laminates with porous layers containing crystallized healing agent

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T. Szmechtyk

2018-07-01

Full Text Available Porous glass fiber and paper layers were tested for application in thermally induced self healing epoxy laminates as healing porous layers. Both types of layers were impregnated using high purity bisphenol A diglycidyl ether (BADGE epoxy with ability to crystallize during storage under 25 °C. Absorption capacity of porous layers was evaluated. Differential scanning calorimetry was used to investigate BADGE healing agent recrystallization process. Healing porous glass layers (HPGL were selected for further tests. Liquid chromatography and Fourier transform infrared (FT IR spectroscopy provided information about average molecular mass of embedded healing agent and functional groups in HPGL layers. Self-healing efficiency of three different laminates with HPGL layers was calculated based on the results of three-point bending test and Charpy impact test. Also, flexural properties and impact strength of laminates were evaluated. The obtained results confirm competitive self healing ability of composites with HPGL.

Hygrothermal effects on the mechanical behaviour of graphite fibre-reinforced epoxy laminates beyond initial failure

Science.gov (United States)

Ishai, O.; Garg, A.; Nelson, H. G.

1986-01-01

The critical load levels and associated cracking beyond which a multidirectional laminate can be considered as structurally failed has been determined by loading graphite fiber-reinforced epoxy laminates to different strain levels up to ultimate failure. Transverse matrix cracking was monitored by acoustic and optical methods. The residual stiffness and strength parallel and perpendicular to the cracks were determined and related to the environmental/loading history. Within the range of experimental conditions studied, it is concluded that the transverse cracking process does not have a crucial effect on the structural performance of multidirectional composite laminates.

Incidence of laminitis and survey of dietary and management practices in pleasure horses and ponies in south-eastern Australia.

Science.gov (United States)

Potter, S J; Bamford, N J; Harris, P A; Bailey, S R

2017-10-01

The aims of this study were to (1) report the incidence of laminitis among a population of horses and ponies attending Pony Clubs in Victoria, Australia, and (2) describe the dietary and management practices of the sample population. Researchers visited 10 Pony Clubs over a 10-month period. Horse and pony owners completed a questionnaire to provide information on management relating to diet and exercise. Owners were also asked to report their animal's history of laminitis, if any. From a survey population of 233 horses and ponies, 15.0% of animals (35 individuals) were reported to have suffered from at least one episode of laminitis. Of the animals that had suffered from laminitis, more than half had experienced multiple episodes. The majority of previously laminitic horses and ponies (71.4%) had not experienced an episode of laminitis within the past 12 months; however, 14.2% had experienced an incident within the past month. The proportion of ponies affected by laminitis (31/142; 21.8%) was significantly higher (P horses affected by laminitis (4/91; 4.4%). The incidence of laminitis within the pony group sampled was 6.5 cases per 100 pony years, while the incidence in horses was 0.55 cases per 100 horse years. This study provided information on the incidence of laminitis in the general population of pleasure horses and ponies in south-eastern Australia. It also provided an overview of dietary and management practices. Given the high incidence of animals that had been affected by laminitis (and the associated welfare implications), this study highlights the importance of owner education regarding appropriate feeding and management strategies to reduce the risk of laminitis. © 2017 Australian Veterinary Association.

Mechanical characterisation of hybrid composite laminates based on basalt fibres in combination with flax, hemp and glass fibres manufactured by vacuum infusion

International Nuclear Information System (INIS)

Petrucci, R.; Santulli, C.; Puglia, D.; Sarasini, F.; Torre, L.; Kenny, J.M.

2013-01-01

Highlights: ► For the first time, hybrid laminates with three different fibres were produced. ► Concerns are confirmed on the brittleness of hybrid laminates with basalt fibre core. ► An optimal configuration (FHB) for flexural properties was singled out. ► Differences between tensile and flexural properties of hybrids were identified. ► In general, the specific mechanical properties of the hybrids are quite high. - Abstract: This work concerns the production by vacuum infusion and the comparison of the properties of different hybrid composite laminates, based on basalt fibre composites as the inner core, and using also glass, flax and hemp fibre laminates to produce symmetrical configurations, all of them with a 21–23% fibre volume, in an epoxy resin. The laminates have been subjected to tensile, three-point flexural and interlaminar shear strength tests and their fracture surfaces have been characterised by scanning electron microscopy. The mechanical performance of all the hybrid laminates appears superior to pure hemp and flax fibre reinforced laminates and inferior to basalt fibre laminates. Among the hybrids, the best properties are offered by those obtained by adding glass and flax to basalt fibre reinforced laminates. Scanning electron microscopy (SEM) observation of hybrid laminates showed the diffuse presence of fibre pull-out in hemp and flax fibre reinforced layers and a general trend of brittle failure

Analysis on and Optimization of a Circular Piezoelectric Composite Laminate for a Micro-Pump Driver

International Nuclear Information System (INIS)

Jia, Jianyuan; Wang, Weidong; Huang, Xinbo

2002-01-01

Among the various micro-pump actuation devices, piezoelectric composite laminate actuation has become an effective method. Due to lacking of analysis treatments, the design of this type micro-pump is in a great limitation. In this paper, an electromechanical-coupled mechanics model is established for the circle-flake micro-actuator. A kind of analysis and design method is presented that piezoelectric plate's radial strain induced by inverse piezoelectric effect is equivalently substituted with transverse stress on piezoelectric composite laminates. It is pointed out that the equivalent transverse load depends on the edge electric field distribution of parallel plate capacitor. The question has been solved that where the neutral plane in the piezoelectric composite laminates lies. Finally, an optimization design is developed on the radius ratio of piezoelectric-to-silicon plate radius by utilizing of FEA modeling

Process monitoring of glass reinforced polypropylene laminates using fiber Bragg gratings

KAUST Repository

Mulle, Matthieu

2015-12-29

Hot-press molding of glass-fiber-reinforced polypropylene (GFPP) laminates was monitored using longitudinally and transversely embedded fiber Bragg gratings (FBGs) at different locations in unidirectional laminates. The optical sensors proved to efficiently characterize some material properties; for example, strain variations could be related physical change of the laminate, revealing key transition points such as the onset of melt or solidification. These results were confirmed through some comparison with traditional techniques such as differential scanning calorimetry. After the GFPP plate was released from the mold, residual strains were estimated. Because cooling rate is an important process parameter in thermoplastics, affecting crystallinity and ultimately residual strain, two different conditions (22 and 3 °C/min) were investigated. In the longitudinal direction, results were nearly identical while in the transverse direction results showed a 20% discrepancy. Coefficients of thermal expansion (CTE) were also identified during a post-process heating procedure using the embedded FBGs and compared to the results of a thermo-mechanical analysis. Again, dissimilarities were observed for the transverse direction. With regards to through the thickness properties, no differences were observed for residual strains or for CTEs.

Self-heating forecasting for thick laminate specimens in fatigue

Science.gov (United States)

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.

Selection of sugarcane mutants with resistance to red-rot disease, water-logging and delayed/non-flowering

Energy Technology Data Exchange (ETDEWEB)

Shaikh, M A.Q.; Shamsuzzaman, K M; Majid, M A; Howlider, M A.R.; Islam, M M [Institute of Nuclear Agriculture, Mymensingh (Bangladesh)

1997-07-01

Three batches of sugarcane cuttings were irradiated with gamma-rays in three different years for isolating mutants for delayed flowering, resistance to red-rot disease and water-logged conditions. In the first batch cuttings of cvs. `Isd-2/54`, `Latarijaba` and `Nagarbari` were irradiated with 20-40 Gy gamma-rays. In M{sub 1} V{sub 4} generation, 2,114 canes selected from inoculated M{sub 1}V{sub 3} generation, were re-inoculated with red-hot pathogen. Of these, four canes were resistant and 64 canes were moderately resistant to the disease. The M{sub 1}V{sub 5} generation of the selected clones was grown at two locations for selection. In the second batch, cuttings of cvs. `Isd-16`, `Isd-2/54`, `Nagarbari` and `Latarijaba` were irradiated with 20-60 Gy gamma-rays. The irradiated material was divided into three lots and each lot was put under different selection pressure. For isolating mutants with resistance to red-rot disease, 15,104 canes were artificially inoculated in the M{sub 1}V{sub 3}. Among these, one clone was resistant and 16 were moderately resistant. Of the 10,000 M{sub 1}V{sub 3} canes, grown under water-logged condition and selected for greenness of leaf at harvest, 38 canes were reasonably tolerant. For selecting late flowering mutants, about 8,500 canes were left in a field for a month after normal harvest; of these five showed late flowering. These mutants were grown for further selection in the M{sub 1}V{sub 4}. To screen out non-flowering canes, cvs. `I-291/87`, an early flowering types, and `I525/85`, a late flowering type were irradiated with 20-40 Gy gamma rays. M{sub 1}V{sub 3} generation has been grown in the field. (author). 13 refs, 6 tabs.

Investigation into the Quality of Thermally Treated Package Lamination

Directory of Open Access Journals (Sweden)

Darius Kazlauskas

2011-02-01

Full Text Available The article deals with the problem of delaminating the package after pasteurization at relatively high temperatures. The main parameters of the lamination process influencing lamination strength were determined. The role of the amount of lamination glue and tension in the rewinder for two glue types were experimentally examined defining lamination regimes at which the process of delamination is excluded.Article in Lithuanian

Energy Saving Glass Lamination via Selective Radio-Frequency Heating

Energy Technology Data Exchange (ETDEWEB)

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

Evaluation of Force-Time Changes During Impact of Hybrid Laminates Made of Titanium and Fibrous Composite

Directory of Open Access Journals (Sweden)

Jakubczak P.

2016-06-01

Full Text Available Fibre metal laminates (FML are the modern hybrid materials with potential wide range of applications in aerospace technology due to their excellent mechanical properties (particularly fatigue strength, resistance to impacts and also excellent corrosion resistance. The study describes the resistance to low velocity impacts in Ti/CFRP laminates. Tested laminates were produced in autoclave process. The laminates were characterized in terms of their response to impacts in specified energy range (5J, 10J, 20J. The tests were performed in accordance with ASTM D7137 standard. The laminates were subjected to impacts by means of hemispherical impactor with diameter of 12,7 mm. The following values have been determined: impact force vs. time, maximum force and the force at which the material destruction process commences (Pi. It has been found that fibre titanium laminates are characterized by high resistance to impacts. This feature is associated with elasto-plastic properties of metal and high rigidity of epoxy - fibre composite. It has been observed that Ti/CFRP laminates are characterized by more instable force during impact in stage of stabilization of impactor-laminate system and stage of force growth that glass fibre laminates. It has been observed more stable force decrease in stage of stress relaxation and withdrawal of the impactor. In energy range under test, the laminates based on titanium with glass and carbon fibres reinforcement demonstrate similar and high resistance to low-velocity impact, measured by means of failure initiation force and impact maximum force.

From one body mutant to one cell mutant. A progress of radiation breeding in crops

International Nuclear Information System (INIS)

Nagatomi, Shigeki

1996-01-01

An effective method was established to obtain non-chimeral mutants with wide spectrum of flower colors, regenerated from floral organs on which mutated sectors were come out on chronic irradiated plants. By this way, six mutant varieties of flower colors have been selected from one pink flower of chrysanthemum, and cultivated for cut-flower production. By the same method, 3 mutant varieties with small and spray type flowers were selected in Eustoma. Mutant varieties such as a rust disease resistant in sugarcane, 6 dwarfs in Cytisus and pure-white mushroom in velvet shank have been selected successively for short period. (J.P.N.)

Biological changes in Barley mutants resistant to powdery mildew disease

International Nuclear Information System (INIS)

Amer, I. M.; Fahim, M. M.; Moustafa, N. A.

2012-12-01

physiological studies showed that all kinds of chlorophyll (a), (b) and (a + b) content in infected plant were decreased while, the carotenes pigment were increased. Infection generally reduced total sugars content of all resistant mutants. Infected resistant mutant showed more phenols content and peroxidase, polyphenoloxidase activities than healthy ones of the mutants. (Author)

Development and Application of Optimization Techniques for Composite Laminates.

Science.gov (United States)

1983-09-01

Institute of Technolgy Air University in Partial Fulfillment of the Requirements for the Degree of Master of Science by Gerald V. Flanagan, S.B. Lt. USAF...global minima [9]. An informal definition of convexity is that any two points in the space can be connected by a straight line which does not pass out of...question. A quick look at gradient information suggests that too few angles (2 for example) will make the laminate sensitive to small changes in

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

Directory of Open Access Journals (Sweden)

Wenqiang Wei

2016-05-01

Full Text Available 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.

Thermoviscoelastic characterization and prediction of Kevlar/epoxy composite laminates

Science.gov (United States)

Gramoll, K. C.; Dillard, D. A.; Brinson, H. F.

1990-01-01

The thermoviscoelastic characterization of Kevlar 49/Fiberite 7714A epoxy composite lamina and the development of a numerical procedure to predict the viscoelastic response of any general laminate constructed from the same material were studied. The four orthotropic material properties, S sub 11, S sub 12, S sub 22, and S sub 66, were characterized by 20 minute static creep tests on unidirectional (0) sub 8, (10) sub 8, and (90) sub 16 lamina specimens. The Time-Temperature Superposition-Principle (TTSP) was used successfully to accelerate the characterization process. A nonlinear constitutive model was developed to describe the stress dependent viscoelastic response for each of the material properties. A numerical procedure to predict long term laminate properties from lamina properties (obtained experimentally) was developed. Numerical instabilities and time constraints associated with viscoelastic numerical techniques were discussed and solved. The numerical procedure was incorporated into a user friendly microcomputer program called Viscoelastic Composite Analysis Program (VCAP), which is available for IBM PC type computers. The program was designed for ease of use. The final phase involved testing actual laminates constructed from the characterized material, Kevlar/epoxy, at various temperatures and load level for 4 to 5 weeks. These results were compared with the VCAP program predictions to verify the testing procedure and to check the numerical procedure used in the program. The actual tests and predictions agreed for all test cases which included 1, 2, 3, and 4 fiber direction laminates.

Mutation in Rice Abscisic Acid2 Results in Cell Death, Enhanced Disease-Resistance, Altered Seed Dormancy and Development

Directory of Open Access Journals (Sweden)

Yongxiang Liao

2018-03-01

Full Text Available Lesion mimic mutants display spontaneous cell death, and thus are valuable for understanding the molecular mechanism of cell death and disease resistance. Although a lot of such mutants have been characterized in rice, the relationship between lesion formation and abscisic acid (ABA synthesis pathway is not reported. In the present study, we identified a rice mutant, lesion mimic mutant 9150 (lmm9150, exhibiting spontaneous cell death, pre-harvest sprouting, enhanced growth, and resistance to rice bacterial and blast diseases. Cell death in the mutant was accompanied with excessive accumulation of H2O2. Enhanced disease resistance was associated with cell death and upregulation of defense-related genes. Map-based cloning identified a G-to-A point mutation resulting in a D-to-N substitution at the amino acid position 110 of OsABA2 (LOC_Os03g59610 in lmm9150. Knock-out of OsABA2 through CRISPR/Cas9 led to phenotypes similar to those of lmm9150. Consistent with the function of OsABA2 in ABA biosynthesis, ABA level in the lmm9150 mutant was significantly reduced. Moreover, exogenous application of ABA could rescue all the mutant phenotypes of lmm9150. Taken together, our data linked ABA deficiency to cell death and provided insight into the role of ABA in rice disease resistance.

Mutation in Rice Abscisic Acid2 Results in Cell Death, Enhanced Disease-Resistance, Altered Seed Dormancy and Development.

Science.gov (United States)

Liao, Yongxiang; Bai, Que; Xu, Peizhou; Wu, Tingkai; Guo, Daiming; Peng, Yongbin; Zhang, Hongyu; Deng, Xiaoshu; Chen, Xiaoqiong; Luo, Ming; Ali, Asif; Wang, Wenming; Wu, Xianjun

2018-01-01

Lesion mimic mutants display spontaneous cell death, and thus are valuable for understanding the molecular mechanism of cell death and disease resistance. Although a lot of such mutants have been characterized in rice, the relationship between lesion formation and abscisic acid (ABA) synthesis pathway is not reported. In the present study, we identified a rice mutant, lesion mimic mutant 9150 ( lmm9150 ), exhibiting spontaneous cell death, pre-harvest sprouting, enhanced growth, and resistance to rice bacterial and blast diseases. Cell death in the mutant was accompanied with excessive accumulation of H 2 O 2 . Enhanced disease resistance was associated with cell death and upregulation of defense-related genes. Map-based cloning identified a G-to-A point mutation resulting in a D-to-N substitution at the amino acid position 110 of OsABA2 (LOC_Os03g59610) in lmm9150 . Knock-out of OsABA2 through CRISPR/Cas9 led to phenotypes similar to those of lmm9150 . Consistent with the function of OsABA2 in ABA biosynthesis, ABA level in the lmm9150 mutant was significantly reduced. Moreover, exogenous application of ABA could rescue all the mutant phenotypes of lmm9150 . Taken together, our data linked ABA deficiency to cell death and provided insight into the role of ABA in rice disease resistance.

Calreticulin mutants in mice induce an MPL-dependent thrombocytosis with frequent progression to myelofibrosis.

Science.gov (United States)

Marty, Caroline; Pecquet, Christian; Nivarthi, Harini; El-Khoury, Mira; Chachoua, Ilyas; Tulliez, Micheline; Villeval, Jean-Luc; Raslova, Hana; Kralovics, Robert; Constantinescu, Stefan N; Plo, Isabelle; Vainchenker, William

2016-03-10

Frameshift mutations in the calreticulin (CALR) gene are seen in about 30% of essential thrombocythemia and myelofibrosis patients. To address the contribution of the CALR mutants to the pathogenesis of myeloproliferative neoplasms, we engrafted lethally irradiated recipient mice with bone marrow cells transduced with retroviruses expressing these mutants. In contrast to wild-type CALR, CALRdel52 (type I) and, to a lesser extent, CALRins5 (type II) induced thrombocytosis due to a megakaryocyte (MK) hyperplasia. Disease was transplantable into secondary recipients. After 6 months, CALRdel52-, in contrast to rare CALRins5-, transduced mice developed a myelofibrosis associated with a splenomegaly and a marked osteosclerosis. Monitoring of virus-transduced populations indicated that CALRdel52 leads to expansion at earlier stages of hematopoiesis than CALRins5. However, both mutants still specifically amplified the MK lineage and platelet production. Moreover, a mutant deleted of the entire exon 9 (CALRdelex9) did not induce a disease, suggesting that the oncogenic property of CALR mutants was related to the new C-terminus peptide. To understand how the CALR mutants target the MK lineage, we used a cell-line model and demonstrated that the CALR mutants, but not CALRdelex9, specifically activate the thrombopoietin (TPO) receptor (MPL) to induce constitutive activation of Janus kinase 2 and signal transducer and activator of transcription 5/3/1. We confirmed in c-mpl- and tpo-deficient mice that expression of Mpl, but not of Tpo, was essential for the CALR mutants to induce thrombocytosis in vivo, although Tpo contributes to disease penetrance. Thus, CALR mutants are sufficient to induce thrombocytosis through MPL activation. © 2016 by The American Society of Hematology.

Compression of laminated composite beams with initial damage

Science.gov (United States)

Breivik, Nicole L.; Gurdal, Zafer; Griffin, O. H., Jr.

1993-01-01

The effect of isolated damage modes on the compressive strength and failure characteristics of laminated composite test specimens were evaluated experimentally and numerically. In addition to specimens without initial damage, specimens with three types of initial damage were considered: (1) specimens with short delaminations distributed evenly through the specimen thickness, (2) specimens with few long delaminations, and (3) specimens with local fiber damage in the surface plies under the three-point bend contact point. It was found that specimens with short multiple delamination experienced the greatest reduction in compression strength compared to the undamaged specimens. Single delaminations far from the specimen surface had little effect on the final compression strength, and moderate strength reduction was observed for specimens with localized surface ply damage.

Geometrically Nonlinear Transient Response of Laminated Plates with Nonlinear Elastic Restraints

Directory of Open Access Journals (Sweden)

Shaochong Yang

2017-01-01

Full Text Available To investigate the dynamic behavior of laminated plates with nonlinear elastic restraints, a varied constraint force model and a systematic numerical procedure are presented in this work. Several kinds of typical relationships of force-displacement for spring are established to simulate the nonlinear elastic restraints. In addition, considering the restraining moments of flexible pads, the pads are modeled by translational and rotational springs. The displacement- dependent constraint forces are added to the right-hand side of equations of motion and treated as additional applied loads. These loads can be explicitly defined, via an independent set of nonlinear load functions. The time histories of transverse displacements at typical points of the laminated plate are obtained through the transient analysis. Numerical examples show that the present method can effectively treat the geometrically nonlinear transient response of plates with nonlinear elastic restraints.

Computational screening and molecular dynamics simulation of disease associated nsSNPs in CENP-E

Energy Technology Data Exchange (ETDEWEB)

Kumar, Ambuj [Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore 632014, Tamil Nadu (India); Purohit, Rituraj, E-mail: riturajpurohit@gmail.com [Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore 632014, Tamil Nadu (India)

2012-10-15

Aneuploidy and chromosomal instability (CIN) are hallmarks of most solid tumors. Mutations in centroemere proteins have been observed in promoting aneuploidy and tumorigenesis. Recent studies reported that Centromere-associated protein-E (CENP-E) is involved in inducing cancers. In this study we investigated the pathogenic effect of 132 nsSNPs reported in CENP-E using computational platform. Y63H point mutation found to be associated with cancer using SIFT, Polyphen, PhD-SNP, MutPred, CanPredict and Dr. Cancer tools. Further we investigated the binding affinity of ATP molecule to the CENP-E motor domain. Complementarity scores obtained from docking studies showed significant loss in ATP binding affinity of mutant structure. Molecular dynamics simulation was carried to examine the structural consequences of Y63H mutation. Root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (R{sub g}), solvent accessibility surface area (SASA), energy value, hydrogen bond (NH Bond), eigenvector projection, trace of covariance matrix and atom density analysis results showed notable loss in stability for mutant structure. Y63H mutation was also shown to disrupt the native conformation of ATP binding region in CENP-E motor domain. Docking studies for remaining 18 mutations at 63rd residue position as well as other two computationally predicted disease associated mutations S22L and P69S were also carried to investigate their affect on ATP binding affinity of CENP-E motor domain. Our study provided a promising computational methodology to study the tumorigenic consequences of nsSNPs that have not been characterized and clear clue to the wet lab scientist.

Computational screening and molecular dynamics simulation of disease associated nsSNPs in CENP-E

International Nuclear Information System (INIS)

Kumar, Ambuj; Purohit, Rituraj

2012-01-01

Aneuploidy and chromosomal instability (CIN) are hallmarks of most solid tumors. Mutations in centroemere proteins have been observed in promoting aneuploidy and tumorigenesis. Recent studies reported that Centromere-associated protein-E (CENP-E) is involved in inducing cancers. In this study we investigated the pathogenic effect of 132 nsSNPs reported in CENP-E using computational platform. Y63H point mutation found to be associated with cancer using SIFT, Polyphen, PhD-SNP, MutPred, CanPredict and Dr. Cancer tools. Further we investigated the binding affinity of ATP molecule to the CENP-E motor domain. Complementarity scores obtained from docking studies showed significant loss in ATP binding affinity of mutant structure. Molecular dynamics simulation was carried to examine the structural consequences of Y63H mutation. Root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (R g ), solvent accessibility surface area (SASA), energy value, hydrogen bond (NH Bond), eigenvector projection, trace of covariance matrix and atom density analysis results showed notable loss in stability for mutant structure. Y63H mutation was also shown to disrupt the native conformation of ATP binding region in CENP-E motor domain. Docking studies for remaining 18 mutations at 63rd residue position as well as other two computationally predicted disease associated mutations S22L and P69S were also carried to investigate their affect on ATP binding affinity of CENP-E motor domain. Our study provided a promising computational methodology to study the tumorigenic consequences of nsSNPs that have not been characterized and clear clue to the wet lab scientist.

An update on equine laminitis

OpenAIRE

Laskoski, Luciane Maria; Valadão, Carlos Augusto Araújo; Dittrich, Rosangela Locatelli; Deconto, Ivan; Faleiros, Rafael Resende

2016-01-01

ABSTRACT: Laminitis is a severe podal affection, which pathophysiology remains partially renowned. Ischemic, enzymatic, metabolic and inflammatory mechanisms are connected to the development of laminar lesions. However, few therapeutic measures are effective to prevent or control the severity of acute laminitis and its prodromal stage, which often determines serious complications such as rotation and/or sinking of the distal phalanx and even the loss of hoof. The purpose of this study is to c...

Simulation of delamination crack growth in composite laminates: application of local and non-local interface damage models

International Nuclear Information System (INIS)

Ijaz, H.; Asad, M.

2015-01-01

The use of composite laminates is increasing in these days due to higher strength and low density values in comparison of metals. Delamination is a major source of failure in composite laminates. Damage mechanics based theories are employed to simulate the delamination phenomena between composite laminates. These damage models are inherently local and can cause the concentration of stresses around the crack tip. In the present study integral type non-local damage formulation is proposed to avoid the localization problem associated to damage formulation. A comprehensive study is carried out for the models and classical local damage model are performed and results are compared with available experimental data for un IMS/924 Carbon/fiber epoxy composite laminate. (author)

Combined tension and bending testing of tapered composite laminates

Science.gov (United States)

O'Brien, T. Kevin; Murri, Gretchen B.; Hagemeier, Rick; Rogers, Charles

1994-11-01

A simple beam element used at Bell Helicopter was incorporated in the Computational Mechanics Testbed (COMET) finite element code at the Langley Research Center (LaRC) to analyze the responce of tappered laminates typical of flexbeams in composite rotor hubs. This beam element incorporated the influence of membrane loads on the flexural response of the tapered laminate configurations modeled and tested in a combined axial tension and bending (ATB) hydraulic load frame designed and built at LaRC. The moments generated from the finite element model were used in a tapered laminated plate theory analysis to estimate axial stresses on the surface of the tapered laminates due to combined bending and tension loads. Surfaces strains were calculated and compared to surface strains measured using strain gages mounted along the laminate length. The strain distributions correlated reasonably well with the analysis. The analysis was then used to examine the surface strain distribution in a non-linear tapered laminate where a similarly good correlation was obtained. Results indicate that simple finite element beam models may be used to identify tapered laminate configurations best suited for simulating the response of a composite flexbeam in a full scale rotor hub.

EB curable laminating adhesives

International Nuclear Information System (INIS)

Matsuyama, Asao; Kobayashi, Masahide; Gotoh, Sakiko

1992-01-01

New developed solvent free EB curable laminating adhesives have two liquid components, A with hydroxy and acryloyl group, B with isocyanate and acryloyl group in a molecule. These EB laminating adhesives do not need any aging process, which is a big advantage, and are very suitable for environment, safety, and health because of no heating process and solvent free formulas. And we have made basic research about the relation of peel strength or heat seal strength versus Tg of cured film, elongation at break, elastic modulus, and so on. Basic specifications of the new developed adhesives are shown. (author)

SUN2 Modulates HIV-1 Infection and Latency through Association with Lamin A/C To Maintain the Repressive Chromatin.

Science.gov (United States)

Sun, Wei-Wei; Jiao, Shi; Sun, Li; Zhou, Zhaocai; Jin, Xia; Wang, Jian-Hua

2018-05-01

The postintegrational latency of HIV-1 is characterized by reversible silencing of long terminal repeat (LTR)-driven transcription of the HIV genome. It is known that the formation of repressive chromatin at the 5'-LTR of HIV-1 proviral DNA impedes viral transcription by blocking the recruitment of positive transcription factors. How the repressive chromatin is formed and modulated during HIV-1 infection remains elusive. Elucidation of which chromatin reassembly factor mediates the reorganization of chromatin is likely to facilitate the understanding of the host's modulation of HIV-1 transcription and latency. Here we revealed that "Sad1 and UNC84 domain containing 2" (SUN2), an inner nuclear membrane protein, maintained the repressive chromatin and inhibited HIV LTR-driven transcription of proviral DNA through an association with lamin A/C. Specifically, lamin A/C tethered SUN2 to the nucleosomes 1 and 2 of the HIV-1 5'-LTR to block the initiation and elongation of HIV-1 transcription. SUN2 knockdown converted chromatin to an active form and thus enhanced the phosphorylation of RNA polymerase II and its recruitment to the 5'-LTR HIV-1 proviral DNA, leading to reactivation of HIV-1 from latency. Conversely, the exogenous factors such as tumor necrosis factor alpha (TNF-α) induced reactivation, and the replication of HIV-1 led to the disassociation between SUN2 and lamin A/C, suggesting that disruption of the association between SUN2 and lamin A/C to convert the repressive chromatin to the active form might be a prerequisite for the initiation of HIV-1 transcription and replication. Together, our findings indicate that SUN2 is a novel chromatin reassembly factor that helps to maintain chromatin in a repressive state and consequently inhibits HIV-1 transcription. IMPORTANCE Despite the successful use of scores of antiretroviral drugs, HIV latency poses a major impediment to virus eradication. Elucidation of the mechanism of latency facilitates the discovery of new

The mechanical behavior of GLARE laminates for aircraft structures

Science.gov (United States)

Wu, Guocai; Yang, J.-M.

2005-01-01

GLARE (glass-reinforced aluminum laminate) is a new class of fiber metal laminates for advanced aerospace structural applications. It consists of thin aluminum sheets bonded together with unidirectional or biaxially reinforced adhesive prepreg of high-strength glass fibers. GLARE laminates offer a unique combination of properties such as outstanding fatigue resistance, high specific static properties, excellent impact resistance, good residual and blunt notch strength, flame resistance and corrosion properties, and ease of manufacture and repair. GLARE laminates can be tailored to suit a wide variety of applications by varying the fiber/resin system, the alloy type and thickness, stacking sequence, fiber orientation, surface pretreatment technique, etc. This article presents a comprehensive overview of the mechanical properties of various GLARE laminates under different loading conditions.

Regulation of 1, 4, 5-triphosphate receptor channel gating dynamics by mutant presenilin in Alzheimer's disease cells

Science.gov (United States)

Wei, Fang; Li, Xiang; Cai, Meichun; Liu, Yanping; Jung, Peter; Shuai, Jianwei

2017-06-01

In neurons of patients with Alzheimer's disease, the intracellular Ca2+ concentration is increased by its release from the endoplasmic reticulum via the inositol 1, 4, 5-triphosphate receptor (IP3R). In this paper, we discuss the IP3R gating dynamics in familial Alzheimer's disease (FAD) cells induced with presenilin mutation PS1. By fitting the parameters of an IP3R channel model to experimental data of the open probability, the mean open time and the mean closed time of IP3R channels, in control cells and FAD mutant cells, we suggest that the interaction of presenilin mutation PS1 with IP3R channels leads the decrease in the unbinding rates of IP3 and the activating Ca2+ from IP3Rs. As a result, the increased affinities of IP3 and activating Ca2+ for IP3R channels induce the increase in the Ca2+ signal in FAD mutant cells. Specifically, the PS1 mutation decreases the IP3 dissociation rate of IP3R channels significantly in FAD mutant cells. Our results suggest possible novel targets for FAD therapeutic intervention.

Endocrine Disease in Aged Horses.

Science.gov (United States)

Durham, Andy E

2016-08-01

Aging horses may be at particular risk of endocrine disease. Two major equine endocrinopathies, pituitary pars intermedia dysfunction and equine metabolic syndrome, are commonly encountered in an aging population and may present with several recognizable signs, including laminitis. Investigation, treatment, and management of these diseases are discussed. Additionally, aging may be associated with development of rarer endocrinopathic problems, often associated with neoplasia, including diabetes mellitus and other confounders of glucose homeostasis, as well as thyroid, parathyroid, and adrenal diseases. Brief details of the recognition and management of these conditions are presented. Copyright © 2016 Elsevier Inc. All rights reserved.

A MEMS lamination technology based on sequential multilayer electrodeposition

International Nuclear Information System (INIS)

Kim, Minsoo; Kim, Jooncheol; Herrault, Florian; Schafer, Richard; Allen, Mark G

2013-01-01

A MEMS lamination technology based on sequential multilayer electrodeposition is presented. The process comprises three main steps: (1) automated sequential electrodeposition of permalloy (Ni 80 Fe 20 ) 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 µm, 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. (paper)

Analytical and Experimental Characterization of Thick-Section Fiber-Metal Laminates

Science.gov (United States)

2013-06-01

laminate . The model individually models each layer of the laminate and predicts stiffness degradation as metal layers plastically deform and as prepreg ...eliminating four of the possible ECM laminates . Additionally, since at least four individual layers (two aluminum and two prepreg ) are used in FML an...AFRL-AFOSR-UK-TR-2013-0023 Analytical and Experimental Characterization of Thick- Section Fiber-Metal Laminates Dr. Rene

The yeast complex I equivalent NADH dehydrogenase rescues pink1 mutants.

Directory of Open Access Journals (Sweden)

Sven Vilain

2012-01-01

Full Text Available Pink1 is a mitochondrial kinase involved in Parkinson's disease, and loss of Pink1 function affects mitochondrial morphology via a pathway involving Parkin and components of the mitochondrial remodeling machinery. Pink1 loss also affects the enzymatic activity of isolated Complex I of the electron transport chain (ETC; however, the primary defect in pink1 mutants is unclear. We tested the hypothesis that ETC deficiency is upstream of other pink1-associated phenotypes. We expressed Saccaromyces cerevisiae Ndi1p, an enzyme that bypasses ETC Complex I, or sea squirt Ciona intestinalis AOX, an enzyme that bypasses ETC Complex III and IV, in pink1 mutant Drosophila and find that expression of Ndi1p, but not of AOX, rescues pink1-associated defects. Likewise, loss of function of subunits that encode for Complex I-associated proteins displays many of the pink1-associated phenotypes, and these defects are rescued by Ndi1p expression. Conversely, expression of Ndi1p fails to rescue any of the parkin mutant phenotypes. Additionally, unlike pink1 mutants, fly parkin mutants do not show reduced enzymatic activity of Complex I, indicating that Ndi1p acts downstream or parallel to Pink1, but upstream or independent of Parkin. Furthermore, while increasing mitochondrial fission or decreasing mitochondrial fusion rescues mitochondrial morphological defects in pink1 mutants, these manipulations fail to significantly rescue the reduced enzymatic activity of Complex I, indicating that functional defects observed at the level of Complex I enzymatic activity in pink1 mutant mitochondria do not arise from morphological defects. Our data indicate a central role for Complex I dysfunction in pink1-associated defects, and our genetic analyses with heterologous ETC enzymes suggest that Ndi1p-dependent NADH dehydrogenase activity largely acts downstream of, or in parallel to, Pink1 but upstream of Parkin and mitochondrial remodeling.

Experimental and Numerical Simulation Analysis of Typical Carbon Woven Fabric/Epoxy Laminates Subjected to Lightning Strike

Science.gov (United States)

Yin, J. J.; Chang, F.; Li, S. L.; Yao, X. L.; Sun, J. R.; Xiao, Y.

2017-12-01

To clarify the evolution of damage for typical carbon woven fabric/epoxy laminates exposed to lightning strike, artificial lightning testing on carbon woven fabric/epoxy laminates were conducted, damage was assessed using visual inspection and damage peeling approaches. Relationships between damage size and action integral were also elucidated. Results showed that damage appearance of carbon woven fabric/epoxy laminate presents circular distribution, and center of the circle located at the lightning attachment point approximately, there exist no damage projected area dislocations for different layers, visual damage territory represents maximum damage scope; visible damage can be categorized into five modes: resin ablation, fiber fracture and sublimation, delamination, ablation scallops and block-shaped ply-lift; delamination damage due to resin pyrolysis and internal pressure exist obvious distinguish; project area of total damage is linear with action integral for the same type specimens, that of resin ablation damage is linear with action integral, but no correlation with specimen type, for all specimens, damage depth is linear with logarithm of action integral. The coupled thermal-electrical model constructed is capable to simulate the ablation damage for carbon woven fabric/epoxy laminates exposed to simulated lightning current through experimental verification.

Minimum weight design of composite laminates for multiple loads

International Nuclear Information System (INIS)

Krikanov, A.A.; Soni, S.R.

1995-01-01

A new design method of constructing optimum weight composite laminates for multiple loads is proposed in this paper. A netting analysis approach is used to develop an optimization procedure. Three ply orientations permit development of optimum laminate design without using stress-strain relations. It is proved that stresses in minimum weight laminate reach allowable values in each ply with given load. The optimum ply thickness is defined at maximum value among tensile and compressive loads. Two examples are given to obtain optimum ply orientations, thicknesses and materials. For comparison purposes, calculations of stresses are done in orthotropic material using classical lamination theory. Based upon these calculations, matrix degrades at 30 to 50% of ultimate load. There is no fiber failure and therefore laminates withstand all applied loads in both examples

Fatigue Performance of Composite Laminates After Low-velocity Impact

Directory of Open Access Journals (Sweden)

LIANG Xiao-lin

2016-12-01

Full Text Available Compression-compression fatigue tests were carried out on T300/5405 composite laminates after low-velocity impact, compression performance of the laminates with different impact damages was studied together with its fatigue life and damage propagation under different stress levels, then the effects of impact energy, stress level and damage propagation on fatigue life of laminates were discussed. The results indicate that impact damage can greatly reduce the residual strength of laminates; under low fatigue load levels, the higher impact energy is, the shorter the fatigue life of laminates with impact damage will be; damage propagation undergoes two stages during the fatigue test, namely the steady propagation and the rapid propagation, accounting for 80% and 20% of the overall fatigue life, respectively; damage propagation rate decreases with the reduction of stress level.

Discovery of candidate disease genes in ENU-induced mouse mutants by large-scale sequencing, including a splice-site mutation in nucleoredoxin.

Directory of Open Access Journals (Sweden)

Melissa K Boles

2009-12-01

Full Text Available An accurate and precisely annotated genome assembly is a fundamental requirement for functional genomic analysis. Here, the complete DNA sequence and gene annotation of mouse Chromosome 11 was used to test the efficacy of large-scale sequencing for mutation identification. We re-sequenced the 14,000 annotated exons and boundaries from over 900 genes in 41 recessive mutant mouse lines that were isolated in an N-ethyl-N-nitrosourea (ENU mutation screen targeted to mouse Chromosome 11. Fifty-nine sequence variants were identified in 55 genes from 31 mutant lines. 39% of the lesions lie in coding sequences and create primarily missense mutations. The other 61% lie in noncoding regions, many of them in highly conserved sequences. A lesion in the perinatal lethal line l11Jus13 alters a consensus splice site of nucleoredoxin (Nxn, inserting 10 amino acids into the resulting protein. We conclude that point mutations can be accurately and sensitively recovered by large-scale sequencing, and that conserved noncoding regions should be included for disease mutation identification. Only seven of the candidate genes we report have been previously targeted by mutation in mice or rats, showing that despite ongoing efforts to functionally annotate genes in the mammalian genome, an enormous gap remains between phenotype and function. Our data show that the classical positional mapping approach of disease mutation identification can be extended to large target regions using high-throughput sequencing.

Mitochondrial Calcium Dysregulation Contributes to Dendrite Degeneration Mediated by PD/LBD-Associated LRRK2 Mutants.

Science.gov (United States)

Verma, Manish; Callio, Jason; Otero, P Anthony; Sekler, Israel; Wills, Zachary P; Chu, Charleen T

2017-11-15

Mutations in leucine-rich repeat kinase 2 (LRRK2) contribute to development of late-onset familial Parkinson's disease (PD), with clinical features of motor and cognitive dysfunction indistinguishable from sporadic PD. Calcium dysregulation plays an important role in PD pathogenesis, but the mechanisms of neurodegeneration remain unclear. Recent reports indicate enhanced excitatory neurotransmission in cortical neurons expressing mutant LRRK2, which occurs before the well-characterized phenotype of dendritic shortening. As mitochondria play a major role in the rapid buffering of cytosolic calcium, we hypothesized that altered mitochondrial calcium handling contributes to dendritic retraction elicited by the LRRK2-G2019S and -R1441C mutations. In primary mouse cortical neurons, we observed increased depolarization-induced mitochondrial calcium uptake. We found that expression of mutant LRRK2 elicited transcriptional upregulation of the mitochondrial calcium uniporter (MCU) and the mitochondrial calcium uptake 1 protein (MICU1) with no change in levels of the mitochondrial calcium antiporter NCLX. Elevated MCU and MICU1 were also observed in LRRK2-mutated patient fibroblasts, along with increased mitochondrial calcium uptake, and in postmortem brains of sporadic PD/PDD patients of both sexes. Transcriptional upregulation of MCU and MICU1 was caused by activation of the ERK1/2 (MAPK3/1) pathway. Inhibiting ERK1/2 conferred protection against mutant LRRK2-induced neurite shortening. Pharmacological inhibitors or RNAi knockdown of MCU attenuated mitochondrial calcium uptake and dendritic/neuritic shortening elicited by mutant LRRK2, whereas expression of a constitutively active mutant of NCLX that enhances calcium export from mitochondria was neuroprotective. These data suggest that an increased susceptibility to mitochondrial calcium dysregulation contributes to dendritic injury in mutant LRRK2 pathogenesis. SIGNIFICANCE STATEMENT Cognitive dysfunction and dementia are

Mutants of Escherichia coli K-12 with enhanced resistance to ionizing radiation. 4. Peculiarities of recombination in Gamsup(r) mutants

International Nuclear Information System (INIS)

Bresler, S.E.; Kalinin, V.L.; Laneeva, N.I.

1984-01-01

Radioresistant mutant Gam sup(r) 444 differs from a wild type and from Gam sup(r) 445 mutant in decreased frequency of long episome heritage ORF 1 (pur E + -tsx + -proC + -lac + ) and F 14 (ilv + -argE + ), containing hot points of RecRecF - depending recombination and in increased frequency of chromosome mobilization and integrative suppression of temperature sensitive dna A46 mutation by sexual factor F. In this respect Gam sup(r) 444 mutant resembles rec BC sbs B mutant with RecF - recombination type

Finite elements modeling of delaminations in composite laminates

DEFF Research Database (Denmark)

Gaiotti, m.; Rizzo, C.M.; Branner, Kim

2011-01-01

of the buckling strength of composite laminates containing delaminations. Namely, non-linear buckling and post-buckling analyses are carried out to predict the critical buckling load of elementary composite laminates affected by rectangular delaminations of different sizes and locations, which are modelled......The application of composite materials in many structures poses to engineers the problem to create reliable and relatively simple methods, able to estimate the strength of multilayer composite structures. Multilayer composites, like other laminated materials, suffer from layer separation, i.......e., delaminations, which may affect the stiffness and stability of structural components. Especially deep delaminations in the mid surface of laminates are expected to reduce the effective flexural stiffness and lead to collapse, often due to buckling behaviour. This paper deals with the numerical modelling...

Progressive delamination in polymer matrix composite laminates: A new approach

Science.gov (United States)

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.

Selection of mutants resistant to black spot disease by chronic irradiation of gamma-rays in Japanese pear 'Osanijisseiki'

International Nuclear Information System (INIS)

Masuda, Tetsuo; Yoshioka, Toji; Kotobuki, Kazuo; Sanada, Tetsuro; Inoue, Kosuke; Murata, Kenji; Kitagawa, Kenichi; Tabira, Hiroki; Yoshida, Akira

1997-01-01

'Osanijisseiki', a self-compatible, spontaneous bud sport of the Japanese pear 'Nijisseiki' is an excellent cultivar with a smooth skin. However, this cultivar is susceptible to Japanese pear black spot disease caused by Alternaria alternata Japanese pear pathotype. To obtain resistant mutants from 'Osanijisseiki', nursery plants of 'Osanijisseiki' have been irradiated chronically with gamma-rays in the Gamma Field of the Institute of Radiation Breeding, NAR, MAFF, since 1986. Screening tests using AK toxin, a host-specific toxin produced by A. alternata Japanese pear pathotype, were performed form 1988 to 1993. Four branches of young trees planted at a distance of 40 m from the 60 Co source were selected as being resistant mutants in 1991 (IRB 502-13T and IRB 502-14T) and 1993 (IRB 502-17T and IRB 502-18T). Sensitivity of the four resistant mutants to AK-toxin and susceptibility to the pathogen were compared with other of susceptible and resistant cultivars. The results showed that these four mutants possessed intermediate resistance. Furthermore, a mutant, IRB 502-13T, had the same characteristics as the original 'Osanijisseiki', except for the difference in toxin sensitivity. The characteristics of the other mutants, IRB 502 14-T, IRB 502-17T, and IRB 502-18T, care being examined. (author)

Current perpendicular to plane giant magnetoresistance in laminated nanostructures

International Nuclear Information System (INIS)

Vedyayev, A.; Zhukov, I.; Dieny, B.

2005-01-01

We theoretically studied spin-dependent electron transport perpendicular-to-plain (CPP) in magnetic laminated multilayered structures by using Kubo formalism. We took into account not only bulk scattering, but the interface resistance due to both specular and diffuse reflection and also spin conserving and spin-flip processes. It was shown that spin-flip scattering at interfaces substantially reduces the value of giant magnetoresistance (GMR). This can explain the experimental observations that the CPP GMR ratio for laminated structures only slightly increases as compared to non-laminated ones even though lamination induces a significant increase in CPP resistance

Effects of differently hardened brass foil laminate on the electromechanical property of externally laminated CC tapes

Energy Technology Data Exchange (ETDEWEB)

Bautista, Zhierwinjay; Shin, Hyung Seop [Dept. of Mechanical Design Engineering, Andong National University, Andong (Korea, Republic of); Mean, Byoung Jean; Lee, Jae Hun [SuNAM Co Ltd., Anseong (Korea, Republic of)

2016-12-15

The mechanical properties of REBCO coated conductor (CC) wires under uniaxial tension are largely determined by the thick component layers in the architecture, namely, the substrate and the stabilizer or even the reinforcement layer. Depending on device applications of the CC tapes, it is necessary to reinforce thin metallic foils externally to one-side or both sides of the CC tapes. Due to the external reinforcement of brass foils, it was found that this could increase the reversible strain limit from the Cu-stabilized CC tapes. In this study, the effects of differently hardened brass foil laminate on the electromechanical property of CC tapes were investigated under uniaxial tension loading. The tensile strain dependence of the critical current (I{sub c}) was measured at 77 K and self-field. Depending on whether the I{sub c} of CC tapes were measured during loading or after unloading, a reversible strain (or stress) limit could be determined, respectively. The both-sides of the Cu-stabilized CC tapes were laminated with brass foils with different hardness, namely 1/4H, 1H and EH. From the obtained results, it showed that the yield strength of the brass laminated CC tapes with EH brass foil laminate was comparable to the one of the Cu-stabilized CC tape due to its large yield strength even though its large volume fraction. It was found that the brass foil with different hardness was mainly sensitive on the stress dependence of I{sub c}, but not on the strain sensitivity due to the residual strain induced in the laminated CC tapes during unloading.

Comparison between the DNA Fingerprints Obtained from the Yellow Vein Mosaic Disease Tolerant Okra Mutants and Their Parental Variety

International Nuclear Information System (INIS)

Boonsirichai, Kanokporn; Puripunyavanich, Vichai; Phadvibulya, Valailak; Adthalungrong, Amnuai; Srithongchai, Wanphen

2006-01-01

The yellow vein mosaic disease (YVMD) is a widespread disease that is found among export orchards of okra. In this report, we studied gamma radiation-induced YVMD tolerant okra mutants and other commercial okra varieties at DNA level. We found that DNA extraction method that utilized sodium dodecyl sulfate and potassium acetate to precipitate other biomolecules was a suitable method to use for DNA finger printing of okra. The MFLP finger printing technique was superior to the AFLP technique in finding polymorphisms among different okra varieties. Also polymorphisms between the YVMD-tolerant mutant lines and their parental variety could be detected, indicating that gamma radiation could induce some changes at DNA level in these plants

Evaluation of Yield and Chemical Characteristics of some Peanut Mutants Induced by Gamma Irradiation

International Nuclear Information System (INIS)

Abd El-daem, G.A.; Anwar, M.M.

2013-01-01

nearly scores. The produced yoghurt of low milk fat by replacing peanut by 50% of milk fat avoid health problems associated with milk fat such as diabetes and heart disease. It can be concluded that peanut oil can be used as milk fat substitute at 50% according to its nutritional point of view where it contained a high percent of total unsaturated fatty acids 82% compared with milk fat 50%.

Optimal Design of Laminated Composite Beams

DEFF Research Database (Denmark)

Blasques, José Pedro Albergaria Amaral

model for the analysis of laminated composite beams is proposed. The structural analysis is performed in a beam finite element context. The development of a finite element based tool for the analysis of the cross section stiffness properties is described. The resulting beam finite element formulation...... is able to account for the effects of material anisotropy and inhomogeneity in the global response of the beam. Beam finite element models allow for a significant reduction in problem size and are therefore an efficient alternative in computationally intensive applications like optimization frameworks...... design of laminated composite beams. The devised framework is applied in the optimal design of laminated composite beams with different cross section geometries and subjected to different load cases. Design criteria such as beam stiffness, weight, magnitude of the natural frequencies of vibration...

A broad phenotypic screen identifies novel phenotypes driven by a single mutant allele in Huntington's disease CAG knock-in mice.

Directory of Open Access Journals (Sweden)

Sabine M Hölter

Full Text Available Huntington's disease (HD is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in the HTT gene encoding huntingtin. The disease has an insidious course, typically progressing over 10-15 years until death. Currently there is no effective disease-modifying therapy. To better understand the HD pathogenic process we have developed genetic HTT CAG knock-in mouse models that accurately recapitulate the HD mutation in man. Here, we describe results of a broad, standardized phenotypic screen in 10-46 week old heterozygous HdhQ111 knock-in mice, probing a wide range of physiological systems. The results of this screen revealed a number of behavioral abnormalities in HdhQ111/+ mice that include hypoactivity, decreased anxiety, motor learning and coordination deficits, and impaired olfactory discrimination. The screen also provided evidence supporting subtle cardiovascular, lung, and plasma metabolite alterations. Importantly, our results reveal that a single mutant HTT allele in the mouse is sufficient to elicit multiple phenotypic abnormalities, consistent with a dominant disease process in patients. These data provide a starting point for further investigation of several organ systems in HD, for the dissection of underlying pathogenic mechanisms and for the identification of reliable phenotypic endpoints for therapeutic testing.

Apoc2 loss-of-function zebrafish mutant as a genetic model of hyperlipidemia

Directory of Open Access Journals (Sweden)

Chao Liu

2015-08-01

Full Text Available Apolipoprotein C-II (APOC2 is an obligatory activator of lipoprotein lipase. Human patients with APOC2 deficiency display severe hypertriglyceridemia while consuming a normal diet, often manifesting xanthomas, lipemia retinalis and pancreatitis. Hypertriglyceridemia is also an important risk factor for development of cardiovascular disease. Animal models to study hypertriglyceridemia are limited, with no Apoc2-knockout mouse reported. To develop a genetic model of hypertriglyceridemia, we generated an apoc2 mutant zebrafish characterized by the loss of Apoc2 function. apoc2 mutants show decreased plasma lipase activity and display chylomicronemia and severe hypertriglyceridemia, which closely resemble the phenotype observed in human patients with APOC2 deficiency. The hypertriglyceridemia in apoc2 mutants is rescued by injection of plasma from wild-type zebrafish or by injection of a human APOC2 mimetic peptide. Consistent with a previous report of a transient apoc2 knockdown, apoc2 mutant larvae have a minor delay in yolk consumption and angiogenesis. Furthermore, apoc2 mutants fed a normal diet accumulate lipid and lipid-laden macrophages in the vasculature, which resemble early events in the development of human atherosclerotic lesions. In addition, apoc2 mutant embryos show ectopic overgrowth of pancreas. Taken together, our data suggest that the apoc2 mutant zebrafish is a robust and versatile animal model to study hypertriglyceridemia and the mechanisms involved in the pathogenesis of associated human diseases.

Effect of shallow angles on compressive strength of biaxial and triaxial laminates.

Science.gov (United States)

Jia, Hongli; Yang, Hyun-Ik

2016-01-01

Biaxial (BX) and triaxial (TX) composite laminates with ±45° angled plies have been widely used in wind turbine blades. As the scale of blades increases, BX and TX laminates with shallow-angled plies (i.e. off-axis ply angle shallow-angled BX and TX laminates are critical considering their locations in a wind turbine blade, and therefore in this study, the uniaxial static compression tests were conducted using BX and TX laminates with angled-plies of ±45°, ±35°, and ±25°, for the purpose of evaluation. On the other hand, Mori-Tanaka mean field homogenization method was employed to predict elastic constants of plies in BX and TX laminates involved in tests; linear regression analyses of experimentally measured ply strengths collected from various sources were then performed to estimate strengths of plies in BX and TX laminates; finally, Tsai-Wu, Hashin, and Puck failure criteria were chosen to predict compressive strengths of BX and TX laminates. Comparison between theoretical predictions and test results were carried out to illustrate the effectiveness of each criterion. The compressive strength of BX laminate decreases as ply angle increases, and the trend was successfully predicted by all three failure criteria. For TX laminates, ±35° angled plies rather than ±45° angled plies led to the lowest laminate compressive strength. Hashin and Puck criteria gave good predictions at certain ply angles for TX laminates, but Tsai-Wu criterion was able to capture the unexpected strength variation of TX laminates with ply angle. It was concluded that the transverse tensile stress in 0° plies of TX laminates, which attains its maximum when the off-axis ply angle is 35°, is the dominant factor in failure determination if using Tsai-Wu criterion. This explains the unexpected strength variation of TX laminates with ply angle, and also indicates that proper selection of ply angle is the key to fully utilizing the advantages of shallow-angled laminates.

Modeling of Nonlinear Mechanical Response in CFRP Angle-Ply Laminates

Science.gov (United States)

Ogihara, Shinji

2014-03-01

It is known that the failure process in angle-ply laminate involves matrix cracking and delamination and that they exhibit nonlinear stress-strain relation. There may be a significant effect of the constituent blocked ply thickness on the mechanical behavior of angle-ply laminates. These days, thin prepregs whose thickness is, for example 50 micron, are developed and commercially available. Therefore, we can design wide variety of laminates with various constituent ply thicknesses. In this study, effects of constituent ply thickness on the nonlinear mechanical behavior and the damage behavior of CFRP angle-ply laminates are investigated experimentally. Based on the experimental results, the mechanical response in CFRP angle-ply laminates is modeled by using the finite strain viscoplasticity model. We evaluated the mechanical behavior and damage behavior in CFRP angle-ply laminates with different constituent ply thickness under tensile loading experimentally. It was found that as the constituent ply thickness decreases, the strength and failure strain increases. We also observed difference in damage behavior. The preliminary results of finite strain viscoplasticity model considering the damage effect for laminated composites are shown. A qualitative agreement is obtained.

Associations between disease awareness and health-related quality of life in a multi-ethnic Asian population.

Science.gov (United States)

Venkataraman, Kavita; Khoo, ChinMeng; Wee, Hwee Lin; Tan, Chuen Seng; Ma, Stefan; Heng, Derrick; Lee, Jeannette; Tai, E Shyong; Thumboo, Julian

2014-01-01

Health related quality of life (HRQoL) is an important dimension of individuals' well-being, and especially in chronic diseases like diabetes and hypertension. The objective of this study was to evaluate the contributions of disease process, comorbidities, medication or awareness of the disease to HRQoL in diabetes mellitus, hypertension and dyslipidemia. This was a cross-sectional study of 3514 respondents from the general community in Singapore, assessed for HRQoL, disease and comorbid conditions through self-report, clinical and laboratory investigations. HRQoL was assessed using SF-36 health survey version 2. For each condition, participants were categorized as having 1) no disease, 2) undiagnosed, 3) diagnosed, not taking medication, and 4) diagnosed, taking medication. Analysis used one-way ANOVA and multiple linear regression. Diagnosed disease was associated with lower physical health component summary (PCS) scores across all three conditions. After adjustment for comorbidities, this association remained significant only for those not on medication in diabetes (-2.7±1.2 points, p = 0.03) and dyslipidemia (-1.3±0.4 points, p = 0.003). Diagnosed hypertension (no medication -2.6±0.9 points, p = 0.002; medication -1.4±0.5 points, p = 0.004) and dyslipidemia (no medication -0.9±0.4 points, p = 0.03; medication -1.9±0.5 points, pmental health component summary (MCS) scores. Undiagnosed disease was associated with higher MCS in diabetes (2.4±1.0 points, p = 0.01) and dyslipidemia (0.8±0.4 points, p = 0.045), and PCS in hypertension (1.2±0.4 points, p = 0.004). Disease awareness was associated with lower HRQoL across the diseases studied, with PCS associations partially mediated by comorbidities. Equally importantly, undiagnosed disease was not associated with HRQoL deficits, which may partly explain why these individuals do not seek medical care.

Experimental Assessment of Tensile Failure Characteristic for Advanced Composite Laminates

Energy Technology Data Exchange (ETDEWEB)

Lee, Myoung Keon [Agency for Defense Development, Daejeon (Korea, Republic of); Lee, Jeong Won; Yoon, Dong Hyun; Kim, Jae Hoon [Chungnam Nat’l Univ., Daejeon (Korea, Republic of)

2017-10-15

In recent years, major airplane manufacturers have been using the laminate failure theory to estimate the strain of composite structures for airplanes. The laminate failure theory uses the failure strain of the laminate to analyze composite structures. This paper describes a procedure for the experimental assessment of laminate tensile failure characteristics. Regression analysis was used as the experimental assessment method. The regression analysis was performed with the response variable being the laminate failure strain and with the regressor variables being two-ply orientation (0° and ±45°) variables. The composite material in this study is a carbon/epoxy unidirectional (UD) tape that was cured as a pre-preg at 177°C(350°F). A total of 149 tension tests were conducted on specimens from 14 distinct laminates that were laid up at standard angle layers (0°, 45°, -45°, and 90°). The ASTM-D-3039 standard was used as the test method.

Experimental Assessment of Tensile Failure Characteristic for Advanced Composite Laminates

International Nuclear Information System (INIS)

Lee, Myoung Keon; Lee, Jeong Won; Yoon, Dong Hyun; Kim, Jae Hoon

2017-01-01

In recent years, major airplane manufacturers have been using the laminate failure theory to estimate the strain of composite structures for airplanes. The laminate failure theory uses the failure strain of the laminate to analyze composite structures. This paper describes a procedure for the experimental assessment of laminate tensile failure characteristics. Regression analysis was used as the experimental assessment method. The regression analysis was performed with the response variable being the laminate failure strain and with the regressor variables being two-ply orientation (0° and ±45°) variables. The composite material in this study is a carbon/epoxy unidirectional (UD) tape that was cured as a pre-preg at 177°C(350°F). A total of 149 tension tests were conducted on specimens from 14 distinct laminates that were laid up at standard angle layers (0°, 45°, -45°, and 90°). The ASTM-D-3039 standard was used as the test method.

The Effect of Thermal Lamination Processes on Colorimetric Change in Spot Colours

Directory of Open Access Journals (Sweden)

Eduard Galić

2015-03-01

Full Text Available Understanding the effect of laminating processes on spot colours is of great importance in the offset printing process, especially given the application versatility of spot colours. Laminating process, as a very common process and one of the first in a sequence of finishing processes in graphics production, can affect print’s visual impression to varying degrees. Spot colours, as mixtures of different ratios of inks, are subject to a change due to matt or gloss lamination process. The research examined the impact of thermal lamination processes on printed spot colours on different printing substrates. The degree of change on prints caused by laminating films in the thermal process was determined using spectrophotometric and densitometric methods. Particular emphasis is placed on the spot colour because of its specific characteristics. Research results are shown in charts and they are showing clearly the modality and the extent laminating processes effect the colorimetric difference in laminated and non-laminated prints. This scientific research provides objective conclusions that help in predicting the possible variations within the usage of laminating processes.

A case of Lamin C gene-mutation with preserved systolic function and ventricular dysrrhythmia

Directory of Open Access Journals (Sweden)

Kevin Kit Ng

2013-02-01

Full Text Available Lamin A/C gene-related cardiomyopathy is associated with progressive heart failure and malignant arrhythmias. Current guidelines advise the use of implantable defibrillators to prevent arrhythmogenic sudden cardiac death only in situations where there is evidence of severe left ventricular dysfunction. We describe a case of a woman with genetically confirmed Lamin C deficiency with preserved left ventricular function in whom an implantable defibrillator was inserted and within a month of implantation was used to terminate symptomatic ventricular tachycardia.

Tay–Sachs disease mutations in HEXA target the α chain of hexosaminidase A to endoplasmic reticulum–associated degradation

Science.gov (United States)

Dersh, Devin; Iwamoto, Yuichiro; Argon, Yair

2016-01-01

Loss of function of the enzyme β-hexosaminidase A (HexA) causes the lysosomal storage disorder Tay–Sachs disease (TSD). It has been proposed that mutations in the α chain of HexA can impair folding, enzyme assembly, and/or trafficking, yet there is surprisingly little known about the mechanisms of these potential routes of pathogenesis. We therefore investigated the biosynthesis and trafficking of TSD-associated HexA α mutants, seeking to identify relevant cellular quality control mechanisms. The α mutants E482K and G269S are defective in enzymatic activity, unprocessed by lysosomal proteases, and exhibit altered folding pathways compared with wild-type α. E482K is more severely misfolded than G269S, as observed by its aggregation and inability to associate with the HexA β chain. Importantly, both mutants are retrotranslocated from the endoplasmic reticulum (ER) to the cytosol and are degraded by the proteasome, indicating that they are cleared via ER-associated degradation (ERAD). Leveraging these discoveries, we observed that manipulating the cellular folding environment or ERAD pathways can alter the kinetics of mutant α degradation. Additionally, growth of patient fibroblasts at a permissive temperature or with chemical chaperones increases cellular Hex activity by improving mutant α folding. Therefore modulation of the ER quality control systems may be a potential therapeutic route for improving some forms of TSD. PMID:27682588

Effect of nanomodified polyester resin on hybrid sandwich laminates

International Nuclear Information System (INIS)

Anbusagar, NRR.; Giridharan, P.K.; Palanikumar, K.

2014-01-01

Highlights: • Effect of nanomodified polyester resin on hybrid sandwich laminates is evaluated. • The hybrid sandwich laminates are fabricated with varying wt% of nanoclay. • Flexural, impact and moisture absorbtion properties are evaluated for hybrid composites. • Scanning electron microscopy is utilized to analyze the dispersion of clay and fractured surfaces of the nanocomposites. - Abstract: Effect of nanoclay modified polyester resin on flexural, impact, hardness and water absorption properties of untreated woven jute and glass fabric hybrid sandwich laminates have been investigated experimentally. The hybrid sandwich laminates are prepared by hand lay-up manufacturing technique (HL) for investigation. All hybrid sandwich laminates are fabricated with a total of 10 layers, by varying the extreme layers and wt% of nanoclay in polyester resin so as to obtain four different combinations of hybrid sandwich laminates. For comparison of the composite with hybrid composite, jute fiber reinforced composite laminate also fabricated. X-ray diffraction (XRD) results obtained from samples with nanoclay indicated that intergallery spacing of the layered clay increases with matrix. Scanning electron microscopy (SEM) gave a morphological picture of the cross-sections and energy dispersive X-ray spectroscopy (EDS) allowed investigating the elemental composition of matrix in composites. The testing results indicated that the flexural properties are greatly increased at 4% of nanoclay loading while impact, hardness and water absorption properties are increased at 6% of nanoclay loading. A plausible explanation for high increase of properties has also been discussed

Deficiency of toxin-binding protein activity in mutants of sugarcane clone H54-775 as it relates to disease resistance

International Nuclear Information System (INIS)

Strobel, G.A.; Steiner, G.W.; Byther, R.

1975-01-01

Three mutants selected from a population of sugarcane clone H54-775 that had been irradiated with 3 kR γ-radiation all lacked toxin-binding protein activity. This activity previously had been shown to be essential for eye spot disease susceptibility and was demonstrated in the susceptible parent clone H54-775. In one mutant, the biochemical, immunochemical, and electrophoretic mobilities of the toxin-binding protein were all modified

Xyloketal-derived small molecules show protective effect by decreasing mutant Huntingtin protein aggregates in Caenorhabditis elegans model of Huntington’s disease

Directory of Open Access Journals (Sweden)

Zeng YX

2016-04-01

Full Text Available Yixuan Zeng,1,2,* Wenyuan Guo,1,* Guangqing Xu,3 Qinmei Wang,4 Luyang Feng,1,2 Simei Long,1 Fengyin Liang,1 Yi Huang,1 Xilin Lu,1 Shichang Li,5 Jiebin Zhou,5 Jean-Marc Burgunder,6 Jiyan Pang,5 Zhong Pei1,2 1Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Disease, The First Affiliated Hospital, Sun Yat-sen University, 2Guangzhou Center, Chinese Huntington’s Disease Network, 3Department of Rehabilitation, The First Affiliated Hospital, 4Key laboratory on Assisted Circulation, Ministry of Health, Department of Cardiovascular Medicine of the First Affiliated Hospital, 5School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 6Swiss Huntington’s Disease Center, Department of Neurology, University of Bern, Bern, Switzerland *These authors contributed equally to this work Abstract: Huntington’s disease is an autosomal-dominant neurodegenerative disorder, with chorea as the most prominent manifestation. The disease is caused by abnormal expansion of CAG codon repeats in the IT15 gene, which leads to the expression of a glutamine-rich protein named mutant Huntingtin (Htt. Because of its devastating disease burden and lack of valid treatment, development of more effective therapeutics for Huntington’s disease is urgently required. Xyloketal B, a natural product from mangrove fungus, has shown protective effects against toxicity in other neurodegenerative disease models such as Parkinson’s and Alzheimer’s diseases. To identify potential neuroprotective molecules for Huntington’s disease, six derivatives of xyloketal B were screened in a Caenorhabditis elegans Huntington’s disease model; all six compounds showed a protective effect. Molecular docking studies indicated that compound 1 could bind to residues GLN369 and GLN393 of the mutant Htt protein, forming a

Tensile strength of glulam laminations of Nordic spruce

DEFF Research Database (Denmark)

Hoffmeyer, Preben; Bräuner, Lise; Boström, Lars

1999-01-01

Design of glulam according to the European timber code Eurocode 5 is based on the standard document prEN1194 , according to which glulam beam strength is to be established either by full scale testing or by calculation. The calculation must be based on a knowledge of lamination tensile strength....... This knowledge may be obtained either by adopting a general rule that the characteristic tensile strength is sixty percent of the characteristic bending strength, or by performing tensile tests on an adequate number of laminations representative of the whole population. The present paper presents...... an investigation aimed at establishing such an adequate experimental background for the assignment of strength classes for glulam made of visually strength graded laminations from Nordic sawmills. The investigation includes more than 1800 boards (laminations) of Norway spruce (Picea abies) sampled from eight...

Laminated Ti-Al composites: Processing, structure and strength

DEFF Research Database (Denmark)

Du, Yan; Fan, Guohua; Yu, Tianbo

2016-01-01

Laminated Ti-Al composite sheets with different layer thickness ratios have been fabricated through hot pressing followed by multi-pass hot rolling at 500 °C.The laminated sheets show strong bonding with intermetallic interface layers of nanoscale thickness between the layers of Ti and Al....... The mechanical properties of the composites with different volume fractions of Al from 10% to 67% show a good combination of strength and ductility. A constraint strain in the hot-rolled laminated structure between the hard and soft phases introduces an elastic-plastic deformation stage, which becomes more...

Tryptophan 32 potentiates aggregation and cytotoxicity of a copper/zinc superoxide dismutase mutant associated with familial amyotrophic lateral sclerosis.

Science.gov (United States)

Taylor, David M; Gibbs, Bernard F; Kabashi, Edor; Minotti, Sandra; Durham, Heather D; Agar, Jeffrey N

2007-06-01

One familial form of the neurodegenerative disease, amyotrophic lateral sclerosis, is caused by gain-of-function mutations in the gene encoding copper/zinc superoxide dismutase (SOD-1). This study provides in vivo evidence that normally occurring oxidative modification to SOD-1 promotes aggregation and toxicity of mutant proteins. The oxidation of Trp-32 was identified as a normal modification being present in both wild-type enzyme and SOD-1 with the disease-causing mutation, G93A, isolated from erythrocytes. Mutating Trp-32 to a residue with a slower rate of oxidative modification, phenylalanine, decreased both the cytotoxicity of mutant SOD-1 and its propensity to form cytoplasmic inclusions in motor neurons of dissociated mouse spinal cord cultures.

Investigation of Forming Performance of Laminated Steel Sheets Using Finite Element Analyses

International Nuclear Information System (INIS)

Liu Wenning; Sun Xin; Ruokolainen, Robert; Gayden Xiaohong

2007-01-01

Laminated steel sheets have been used in automotive structures for reducing in-cabin noise. However, due to the marked difference in material properties of the different laminated layers, integrating laminated steel parts into the manufacturing processes can be challenging. Especially, the behavior of laminated sheets during forming processes is very different from that of monolithic steel sheets. During the deep-draw forming process, large shear deformation and corresponding high interfacial stress may initiate and propagate interfacial cracks between the core polymer and the metal skin, hence degrading the performance of the laminated sheets. In this paper, the formability of the laminated steel sheets is investigated by means of numerical analysis. The goal of this work is to gain insight into the relationship between the individual properties of the laminated sheet layers and the corresponding formability of the laminated sheet as a whole, eventually leading to reliable design and successful forming process development of such materials. Finite element analyses of laminate sheet forming are presented. Effects of polymer core thickness and viscoelastic properties of the polymer core, as well as punching velocity, are also investigated

Functional testing of keratin 14 mutant proteins associated with the three major subtypes of epidermolysis bullosa simplex

DEFF Research Database (Denmark)

Sørensen, Charlotte B; Andresen, Brage S; Jensen, Uffe B

2003-01-01

vectors were transiently transfected into normal human primary keratinocytes (NHK), HaCaT or HeLa cells in order to analyze the ability of the mutant K14 proteins to integrate into the existing endogenous keratin filament network (KFN). No effect on the keratin cytoskeleton was observed upon transfection...... of NHK with the various K14 constructs neither with nor without a subsequently induced heat-stress. In contrast, all constructs, including wild-type K14, caused collapse of the endogenous KFN in a small fraction of the transfected HeLa and HaCaT cells. However, overexpression of the mutation associated...... with the most severe form of the disease, EBS Dowling-Meara, resulted in a higher number of transfected HaCaT cells with KFN collapse (P

Characterization of Thermo-Elastic Properties and Microcracking Behaviors of CFRP Laminates Using Cup-Stacked Carbon Nanotubes (CSCNT) Dispersed Resin

Science.gov (United States)

Yokozeki, Tomohiro; Iwahori, Yutaka; Ishiwata, Shin

This study investigated the thermo-elastic properties and microscopic ply cracking behaviors in carbon fiber reinforced nanotube-dispersed epoxy laminates. The nanocomposite laminates used in this study consisted of traditional carbon fibers and epoxy resin filled with cup-stacked carbon nanotubes (CSCNTs). Thermo-mechanical properties of unidirectional nanocomposite laminates were evaluated, and quasi-static and fatigue tension tests of cross-ply laminates were carried out in order to observe the damage accumulation behaviors of matrix cracks. Clear retardation of matrix crack onset and accumulation was found in composite laminates with CSCNT compared to those without CSCNT. Fracture toughness associated with matrix cracking was evaluated based on the analytical model using the experimental results. It was concluded that the dispersion of CSCNT resulted in fracture toughness improvement and residual thermal strain decrease, and specifically, the former was the main contribution to the retardation of matrix crack formation.

Association of CYP1A1 gene polymorphism with chronic kidney disease: a case control study.

Science.gov (United States)

Siddarth, Manushi; Datta, Sudip K; Ahmed, Rafat S; Banerjee, Basu D; Kalra, Om P; Tripathi, Ashok K

2013-07-01

CYP1A1 is an important xenobiotic metabolizing enzyme, present in liver and kidney. Expression of CYP1A1 enzyme increases manifold when kidney cells are exposed to nephrotoxins/chemicals leading to oxidative stress-induced cell damage. To study the association of CYP1A1 gene polymorphism in patients of chronic kidney disease with unknown etiology (CKDU), we recruited 334 CKDU patients and 334 age and sex matched healthy controls. CYP1A1*2A and *2C polymorphisms were studied by PCR-RFLP and allele specific-PCR respectively. Subjects carrying at least one mutant allele of CYP1A1*2A (TC, CC) and *2C (AG, GG) were shown to be associated with 1.4-2-fold increased risk of CKDU. Also, genotypic combinations of hetero-/homozygous mutants of CYP1A1*2A (TC, CC) with hetero-/homozygous mutant genotypes of CYP1A1*2C (AG, GG) i.e. TC/AG (pCKDU with an odd ratio ranging 1.8-3.3 times approximately. This study demonstrates association of CYP1A1 polymorphisms with CKDU. Copyright © 2013 Elsevier B.V. All rights reserved.

Deflection of Cross-Ply Composite Laminates Induced by Piezoelectric Actuators

Directory of Open Access Journals (Sweden)

Chi-Sheng Lin

2010-01-01

Full Text Available The coupling effects between the mechanical and electric properties of piezoelectric materials have drawn significant attention for their potential applications as sensors and actuators. In this investigation, two piezoelectric actuators are symmetrically surface bonded on a cross-ply composite laminate. Electric voltages with the same amplitude and opposite sign are applied to the two symmetric piezoelectric actuators, resulting in the bending effect on the laminated plate. The bending moment is derived by using the classical laminate theory and piezoelectricity. The analytical solution of the flexural displacement of the simply supported composite plate subjected to the bending moment is solved by using the plate theory. The analytical solution is compared with the finite element solution to show the validation of present approach. The effects of the size and location of the piezoelectric actuators on the response of the composite laminate are presented through a parametric study. A simple model incorporating the classical laminate theory and plate theory is presented to predict the deformed shape of the simply supported laminate plate.

Laser cutting of Kevlar laminates

Energy Technology Data Exchange (ETDEWEB)

VanCleave, R.A.

1977-09-01

An investigation has been conducted of the use of laser energy for cutting contours, diameters, and holes in flat and shaped Kevlar 49 fiber-reinforced epoxy laminates as an alternate to conventional machining. The investigation has shown that flat laminates 6.35 mm thick may be cut without backup by using a high-powered (1000-watt) continuous wave CO/sub 2/ laser at high feedrates (33.87 mm per second). The cut produced was free of the burrs and delaminations resulting from conventional machining methods without intimate contact backup. In addition, the process cycle time was greatly reduced.

A transparent, solvent-free laminated top electrode for perovskite solar cells

OpenAIRE

Makha, Mohammed; Fernandes, Silvia Let?cia; Jenatsch, Sandra; Offermans, Ton; Schleuniger, J?rg; Tisserant, Jean-Nicolas; V?ron, Anna C.; Hany, Roland

2016-01-01

Abstract A simple lamination process of the top electrode for perovskite solar cells is demonstrated. The laminate electrode consists of a transparent and conductive plastic/metal mesh substrate, coated with an adhesive mixture of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate), PEDOT:PSS, and sorbitol. The laminate electrode showed a high degree of transparency of 85%. Best cell performance was achieved for laminate electrodes prepared with a sorbitol concentration of ~30 wt% per mil...

A Theoretical Model for Estimation of Yield Strength of Fiber Metal Laminate

Science.gov (United States)

Bhat, Sunil; Nagesh, Suresh; Umesh, C. K.; Narayanan, S.

2017-08-01

The paper presents a theoretical model for estimation of yield strength of fiber metal laminate. Principles of elasticity and formulation of residual stress are employed to determine the stress state in metal layer of the laminate that is found to be higher than the stress applied over the laminate resulting in reduced yield strength of the laminate in comparison with that of the metal layer. The model is tested over 4A-3/2 Glare laminate comprising three thin aerospace 2014-T6 aluminum alloy layers alternately bonded adhesively with two prepregs, each prepreg built up of three uni-directional glass fiber layers laid in longitudinal and transverse directions. Laminates with prepregs of E-Glass and S-Glass fibers are investigated separately under uni-axial tension. Yield strengths of both the Glare variants are found to be less than that of aluminum alloy with use of S-Glass fiber resulting in higher laminate yield strength than with the use of E-Glass fiber. Results from finite element analysis and tensile tests conducted over the laminates substantiate the theoretical model.

Hygrothermal effects on the tensile strength of carbon/epoxy laminates with molded edges

Directory of Open Access Journals (Sweden)

Cândido Geraldo Maurício

2000-01-01

Full Text Available The interlaminar stresses are confined to a region near the free edge. Therefore, the laminate stacking sequence and the free edge finishing are some of the factors that affect the strength of the laminate and limit its life. The use of molded edges eliminates the need for trimming and machining the laminates edges thus improving productivity. However, this fabrication technique may have a detrimental effect on the laminate strength for certain stacking sequences. This effect in the presence of moisture has not been characterized. This work presents the results of a comparative study of the resistance to delamination of laminates with machined edges and molded edges. Additionally, two environmental conditions were considered: dry laminates and laminates saturated with moisture. The tensile strength of the laminates were measured and micrographs were used to analyze the microstructure of the laminates near the free edges. It is concluded that the mechanical properties of advanced composites depend on the environmental conditions and the fabrication techniques used to produce the laminates. Therefore, it is necessary to account for these factors when experimentally determining the design allowables.

[Construction of FANCA mutant protein from Fanconi anemia patient and analysis of its function].

Science.gov (United States)

Chen, Fei; Zhang, Ke-Jian; Zuo, Xue-Lan; Zeng, Xian-Chang

2007-11-01

To study FANCA protein expression in Fanconi anemia patient's (FA) cells and explore its function. FANCA protein expression was analyzed in 3 lymphoblast cell lines derived from 3 cases of type A FA (FA-A) patients using Western blot. Nucleus and cytoplasm localization of FANCA protein was analyzed in one case of FA-A which contained a truncated FANCA (exon 5 deletion). The FANCA mutant was constructed from the same patient and its interaction with FANCG was evaluated by mammalian two-hybrid (M2H) assay. FANCA protein was not detected in the 3 FA-A patients by rabbit anti-human MoAb, but a truncated FANCA protein was detected in 1 of them by mouse anti-human MoAb. The truncated FANCA could not transport from cytoplasm into nucleus. The disease-associated FANCA mutant was defective in binding to FANCG in M2H system. FANCA proteins are defective in the 3 FA-A patients. Disfunction of disease-associated FANCA mutant proved to be the pathogenic mutations in FANCA gene. Exon 5 of FANCA gene was involved in the interaction between FANCA and FANCG.

On Subsurface Crack Growth in Fibre Metal Laminate Materials

National Research Council Canada - National Science Library

Randall, Christian

2003-01-01

Fatigue crack growth in fibre metal laminates (FMLs) is significantly more complex than in monolithic materials due to the interaction of various physical mechanisms that govern the growth of cracks in laminates...

Fatigue damage mechanics of notched graphite-epoxy laminates

Science.gov (United States)

Spearing, Mark; Beaumont, Peter W. R.; Ashby, Michael F.

A modeling approach is presented that recognizes that the residual properties of composite laminates after any form of loading depend on the damage state. Therefore, in the case of cyclic loading, it is necessary to first derive a damage growth law and then relate the residual properties to the accumulated damage. The propagation of fatigue damage in notched laminates is investigated. A power law relationship between damage growth and the strain energy release rate is developed. The material constants used in the model have been determined in independent experiments and are invariant for all the layups investigated. The strain energy release rates are calculated using a simple finite element representation of the damaged specimen. The model is used to predict the effect of tension-tension cyclic loading on laminates of the T300/914C carbon-fiber epoxy system. The extent of damage propagation is successfully predicted in a number of cross-ply laminates.

Concurrent material-fabrication optimization of metal-matrix laminates under thermo-mechanical loading

Science.gov (United States)

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.

The modelling and control of failure in bi-material ceramic laminates

International Nuclear Information System (INIS)

Phillipps, A.J.; Howard, S.J.; Clegg, W.J.; Clyne, T.W.

1993-01-01

Recent experimental and theoretical work on simple, single phase, laminated systems has indicated that failure resistant ceramics can be produced using an elegant method that avoids many of the problems and limitations of comparable fibrous ceramic composites. Theoretical work on these laminated systems has shown good agreement with experiment and simulated the effects of material properties and laminate structure on the composite performance. This work has provided guidelines for optimised laminate performance. In the current study, theoretical work has been simply extended to predict the behaviour of bi-material laminates with alternating layers of weak and strong material with different stiffnesses. Expressions for the strain energy release rates of internal advancing cracks are derived and combined with existing criteria to predict the failure behaviour of these laminates during bending. The modelling indicates three modes of failure dictated by the relative proportions, thicknesses and interfacial properties of the weak and strong phases. A critical percentage of strong phase is necessary to improve failure behaviour, in an identical argument to that for fibre composites. Incorporation of compliant layers is also investigated and implications for laminate design discussed. (orig.)

A novel triple repeat mutant tau transgenic model that mimics aspects of pick's disease and fronto-temporal tauopathies.

Directory of Open Access Journals (Sweden)

Edward Rockenstein

Full Text Available Tauopathies are a group of disorders leading to cognitive and behavioral impairment in the aging population. While four-repeat (4R Tau is more abundant in corticobasal degeneration, progressive supranuclear palsy, and Alzheimer's disease, three-repeat (3R Tau is the most abundant splice, in Pick's disease. A number of transgenic models expressing wild-type and mutant forms of the 4R Tau have been developed. However, few models of three-repeat Tau are available. A transgenic mouse model expressing three-repeat Tau was developed bearing the mutations associated with familial forms of Pick's disease (L266V and G272V mutations. Two lines expressing high (Line 13 and low (Line 2 levels of the three-repeat mutant Tau were analyzed. By Western blot, using antibodies specific to three-repeat Tau, Line 13 expressed 5-times more Tau than Line 2. The Tau expressed by these mice was most abundant in the frontal-temporal cortex and limbic system and was phosphorylated at residues detected by the PHF-1, AT8, CP9 and CP13 antibodies. The higher-expressing mice displayed hyperactivity, memory deficits in the water maze and alterations in the round beam. The behavioral deficits started at 6-8 months of age and were associated with a progressive increase in the accumulation of 3R Tau. By immunocytochemistry, mice from Line 13 displayed extensive accumulation of 3R Tau in neuronal cells bodies in the pyramidal neurons of the neocortex, CA1-3 regions, and dentate gyrus of the hippocampus. Aggregates in the granular cells had a globus appearance and mimic Pick's-like inclusions. There were abundant dystrophic neurites, astrogliosis and synapto-dendritic damage in the neocortex and hippocampus of the higher expresser line. The hippocampal lesions were moderately argyrophilic and Thioflavin-S negative. By electron microscopy, discrete straight filament aggregates were detected in some neurons in the hippocampus. This model holds promise for better understanding the

On the plastic behaviour of multi directional epoxy-bolted CFRP laminates

DEFF Research Database (Denmark)

Jensen, Aage; Poulsen, Ervin

2004-01-01

The second generation of CFRP laminate has recently been developed. It is a multi directional CFRP laminate, i.e. a laminate with carbon fibres having several directions other than the first generation. The paper describes the laboratory tests carried out in order to develop anchorage devices for...

Selection individual on mutant genotype of soybean (Glycine maxl.merrill) in m5 generation based on resistance of stem rot disease Athelia rolfsii (curzi)

Science.gov (United States)

Rahmah, M.; Hanafiah, D. S.; Siregar, L. A. M.; Safni, I.

2018-02-01

This study was aimed to obtain selected individuals on soybean plant Glycine max L. (Merrill) in M5 generation based on high production character and tolerance of stem rot disease Athelia rolfsii (Curzi). This research was conducted in Plant Disease Laboratory and experimental field Faculty of Agriculture Universitas Sumatera Utara Medan, Indonesia. This research was conducted from December 2016 to June 2017. The treatments were 15 mutant lines genotypes and Anjasmoro variety. The results showed that some lines mutant genotypes can gave the good agronomic appearance character than Anjasmoro variety on inoculation treatment of stem rot disease. Selection performed on population M5 producesselected individuals with tolerance of stem rot disease from 100 and 200 Gy population.

Normalization of Impact Energy by Laminate Thickness for Compression After Impact Testing

Science.gov (United States)

Nettles, A. T.; Hromisin, S. M.

2013-01-01

The amount of impact energy used to damage a composite laminate is a critical parameter when assessing residual strength properties. The compression after impact (CAI) strength of impacted laminates is dependent upon how thick the laminate is and this has traditionally been accounted for by normalizing (dividing) the impact energy by the laminate's thickness. However, when comparing CAI strength values for a given lay-up sequence and fiber/resin system, dividing the impact energy by the specimen thickness has been noted by the author to give higher CAI strength values for thicker laminates. A study was thus undertaken to assess the comparability of CAI strength data by normalizing the impact energy by the specimen thickness raised to a power to account for the higher strength of thicker laminates. One set of data from the literature and two generated in this study were analyzed by dividing the impact energy by the specimen thickness to the 1, 1.5, 2, and 2.5 powers. Results show that as laminate thickness and damage severity decreased, the value which the laminate thickness needs to be raised to in order to yield more comparable CAI data increases.

Acoustic Pressure Waves in Vibrating 3-D Laminated Beam-Plate Enclosures

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Charles A. Osheku

2009-01-01

Full Text Available The effect of structural vibration on the propagation of acoustic pressure waves through a cantilevered 3-D laminated beam-plate enclosure is investigated analytically. For this problem, a set of well-posed partial differential equations governing the vibroacoustic wave interaction phenomenon are formulated and matched for the various vibrating boundary surfaces. By employing integral transforms, a closed form analytical expression is computed suitable for vibroacoustic modeling, design analysis, and general aerospace defensive applications. The closed-form expression takes the form of a kernel of polynomials for acoustic pressure waves showing the influence of linear interface pressure variation across the axes of vibrating boundary surfaces. Simulated results demonstrate how the mode shapes and the associated natural frequencies can be easily computed. It is shown in this paper that acoustic pressure waves propagation are dynamically stable through laminated enclosures with progressive decrement in interfacial pressure distribution under the influence of high excitation frequencies irrespective of whether the induced flow is subsonic, sonic , supersonic, or hypersonic. Hence, in practice, dynamic stability of hypersonic aircrafts or jet airplanes can be further enhanced by replacing their noise transmission systems with laminated enclosures.

Plated lamination structures for integrated magnetic devices

Science.gov (United States)

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.

Convoluted laminations in waterlain sediments:three examples from Eastern Canada and their relevance to neotectonics

International Nuclear Information System (INIS)

Macdougall, D.A.; Broster, B.E.

1995-10-01

The catastrophic disturbance of unconsolidated sediment produces a wide variety of deformation structures, particularly if the sediment is water-saturated at the time of disturbance. Layers, originally deposited as sub-horizontal, can become stretched or distended resulting in convoluted laminations. Faulted beds, slumped units, or dewatering structures may also occur in association with the disturbance. Convolutions were studied in five examples of Pleistocene glaciomarine deltas, at three locations in eastern Canada. Results from this study indicate that similar structures were produced in each of the sediment deposits, but some are especially common in specific facies (e.g. bottomset, foreset, topset). However, the particular cause of the convolutions varied within each deposit, and the origin could be better assessed when studied in relationship to other structures. None of the convolutions found could be attributed, categorically, to a seismic origin. However, neither could a seismic origin be dismissed for structures associated with convolutions occurring in deposits at: St. George, New Brunswick; Economy Point, Nova Scotia; and Lanark, Ontario. Of these deposits, the deformed structures at Economy Point are apparently post-glacial. (author). 24 refs., 58 figs

A transparent, solvent-free laminated top electrode for perovskite solar cells.

Science.gov (United States)

Makha, Mohammed; Fernandes, Silvia Letícia; Jenatsch, Sandra; Offermans, Ton; Schleuniger, Jürg; Tisserant, Jean-Nicolas; Véron, Anna C; Hany, Roland

2016-01-01

A simple lamination process of the top electrode for perovskite solar cells is demonstrated. The laminate electrode consists of a transparent and conductive plastic/metal mesh substrate, coated with an adhesive mixture of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate), PEDOT:PSS, and sorbitol. The laminate electrode showed a high degree of transparency of 85%. Best cell performance was achieved for laminate electrodes prepared with a sorbitol concentration of ~30 wt% per milliliter PEDOT:PSS dispersion, and using a pre-annealing temperature of 120°C for 10 min before lamination. Thereby, perovskite solar cells with stabilized power conversion efficiencies of (7.6 ± 1.0)% were obtained which corresponds to 80% of the reference devices with reflective opaque gold electrodes.

Study of the Formability of Laminated Lightweight Metallic Materials

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Girjob Claudia

2017-01-01

Full Text Available The main objective of this work was to test the formability of laminated materials. Laminated materials are considered a good choice when parts with reduced weight are considered. Thus, a laminated material, aluminum - polypropylene - aluminum (Al-PP-Al, as sheet 1.2 mm and 1.4 mm thickness was used. Before processing the material by means of unconventional plastic deformation, its formability was determined by running the Nakajima test. After obtaining the forming limit curves, the material was machined by means of incremental forming.

End points for adjuvant therapy trials: has the time come to accept disease-free survival as a surrogate end point for overall survival?

Science.gov (United States)

Gill, Sharlene; Sargent, Daniel

2006-06-01

The intent of adjuvant therapy is to eradicate micro-metastatic residual disease following curative resection with the goal of preventing or delaying recurrence. The time-honored standard for demonstrating efficacy of new adjuvant therapies is an improvement in overall survival (OS). This typically requires phase III trials of large sample size with lengthy follow-up. With the intent of reducing the cost and time of completing such trials, there is considerable interest in developing alternative or surrogate end points. A surrogate end point may be employed as a substitute to directly assess the effects of an intervention on an already accepted clinical end point such as mortality. When used judiciously, surrogate end points can accelerate the evaluation of new therapies, resulting in the more timely dissemination of effective therapies to patients. The current review provides a perspective on the suitability and validity of disease-free survival (DFS) as an alternative end point for OS. Criteria for establishing surrogacy and the advantages and limitations associated with the use of DFS as a primary end point in adjuvant clinical trials and as the basis for approval of new adjuvant therapies are discussed.

The analysis of composite laminated beams using a 2D interpolating meshless technique

Science.gov (United States)

Sadek, S. H. M.; Belinha, J.; Parente, M. P. L.; Natal Jorge, R. M.; de Sá, J. M. A. César; Ferreira, A. J. M.

2018-02-01

Laminated composite materials are widely implemented in several engineering constructions. For its relative light weight, these materials are suitable for aerospace, military, marine, and automotive structural applications. To obtain safe and economical structures, the modelling analysis accuracy is highly relevant. Since meshless methods in the recent years achieved a remarkable progress in computational mechanics, the present work uses one of the most flexible and stable interpolation meshless technique available in the literature—the Radial Point Interpolation Method (RPIM). Here, a 2D approach is considered to numerically analyse composite laminated beams. Both the meshless formulation and the equilibrium equations ruling the studied physical phenomenon are presented with detail. Several benchmark beam examples are studied and the results are compared with exact solutions available in the literature and the results obtained from a commercial finite element software. The results show the efficiency and accuracy of the proposed numeric technique.

A three-dimensional layerwise-differential quadrature free vibration analysis of laminated cylindrical shells

Energy Technology Data Exchange (ETDEWEB)

Malekzadeh, P. [Department of Mechanical Engineering, Persian Gulf University, Boushehr 75168 (Iran, Islamic Republic of); Center of Excellence for Computational Mechanics in Mechanical Engineering, Shiraz University, Shiraz (Iran, Islamic Republic of)], E-mail: malekzadeh@pgu.ac.ir; Farid, M. [Center of Excellence for Computational Mechanics in Mechanical Engineering, Shiraz University, Shiraz (Iran, Islamic Republic of); Department of Mechanical Engineering, Shiraz University, Shiraz (Iran, Islamic Republic of); Zahedinejad, P. [Department of Mechanical Engineering, Shiraz University, Shiraz (Iran, Islamic Republic of)

2008-07-15

A mixed layerwise theory and differential quadrature (DQ) method (LW-DQ) for three-dimensional free vibration analysis of arbitrary laminated circular cylindrical shells is introduced. Using the layerwise theory in conjunction with the three-dimensional form of Hamilton's principle, the transversely discretized equations of motion and the related boundary conditions are obtained. Then, the DQ method is employed to discretize the resulting equations in the axial directions. The fast convergence behavior of the method is demonstrated and its accuracy is verified by comparing the results with those of other shell theories obtained using conventional methods and also with those of ANSYS software. In the case of arbitrary laminated shells with simply supported ends, the exact solution is developed for comparison purposes. It is shown that using few DQ grid points, converged accurate solutions are obtained. Less computational efforts of the proposed approach with respect to ANSYS software is shown.

Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling

International Nuclear Information System (INIS)

Noda, Saori; Takahashi, Atsushi; Hayashi, Takeru; Tanuma, Sei-ichi; Hatakeyama, Masanori

2016-01-01

SHP2, encoded by the PTPN11 gene, is a protein tyrosine phosphatase that plays a key role in the proliferation of cells via RAS-ERK activation. SHP2 also promotes Wnt signaling by dephosphorylating parafibromin. Germline missense mutations of PTPN11 are found in more than half of patients with Noonan syndrome (NS) and LEOPARD syndrome (LS), both of which are congenital developmental disorders with multiple common symptoms. However, whereas NS-associated PTPN11 mutations give rise to gain-of-function SHP2 mutants, LS-associated SHP2 mutants are reportedly loss-of-function mutants. To determine the phosphatase activity of LS-associated SHP2 more appropriately, we performed an in vitro phosphatase assay using tyrosine-phosphorylated parafibromin, a biologically relevant substrate of SHP2 and the positive regulator of Wnt signaling that is activated through SHP2-mediated dephosphorylation. We found that LS-associated SHP2 mutants (Y279C, T468M, Q506P, and Q510E) exhibited a substantially reduced phosphatase activity toward parafibromin when compared with wild-type SHP2. Furthermore, each of the LS-associated mutants displayed a differential degree of decrease in phosphatase activity. Deviation of the SHP2 catalytic activity from a certain range, either too strong or too weak, may therefore lead to similar clinical outcomes in NS and LS, possibly through an imbalanced Wnt signal caused by inadequate dephosphorylation of parafibromin. - Highlights: • LS-associated SHP2 mutants dephosphorylate parafibromin on Y290, Y293, and Y315. • LS-associated SHP2 mutants display a reduced tyrosine phosphatase activity. • LS-specific SHP2-Y279C is catalytically less active than LS-specific SHP2-T468M. • NS/LS-associated SHP2-Q506P has both hyper- and hypomorphic enzymatic properties.

Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling

Energy Technology Data Exchange (ETDEWEB)

Noda, Saori [Division of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba (Japan); Takahashi, Atsushi; Hayashi, Takeru [Division of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Tanuma, Sei-ichi [Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba (Japan); Hatakeyama, Masanori, E-mail: mhata@m.u-tokyo.ac.jp [Division of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan)

2016-01-22

SHP2, encoded by the PTPN11 gene, is a protein tyrosine phosphatase that plays a key role in the proliferation of cells via RAS-ERK activation. SHP2 also promotes Wnt signaling by dephosphorylating parafibromin. Germline missense mutations of PTPN11 are found in more than half of patients with Noonan syndrome (NS) and LEOPARD syndrome (LS), both of which are congenital developmental disorders with multiple common symptoms. However, whereas NS-associated PTPN11 mutations give rise to gain-of-function SHP2 mutants, LS-associated SHP2 mutants are reportedly loss-of-function mutants. To determine the phosphatase activity of LS-associated SHP2 more appropriately, we performed an in vitro phosphatase assay using tyrosine-phosphorylated parafibromin, a biologically relevant substrate of SHP2 and the positive regulator of Wnt signaling that is activated through SHP2-mediated dephosphorylation. We found that LS-associated SHP2 mutants (Y279C, T468M, Q506P, and Q510E) exhibited a substantially reduced phosphatase activity toward parafibromin when compared with wild-type SHP2. Furthermore, each of the LS-associated mutants displayed a differential degree of decrease in phosphatase activity. Deviation of the SHP2 catalytic activity from a certain range, either too strong or too weak, may therefore lead to similar clinical outcomes in NS and LS, possibly through an imbalanced Wnt signal caused by inadequate dephosphorylation of parafibromin. - Highlights: • LS-associated SHP2 mutants dephosphorylate parafibromin on Y290, Y293, and Y315. • LS-associated SHP2 mutants display a reduced tyrosine phosphatase activity. • LS-specific SHP2-Y279C is catalytically less active than LS-specific SHP2-T468M. • NS/LS-associated SHP2-Q506P has both hyper- and hypomorphic enzymatic properties.

LamLum : a tool for evaluating the financial feasibility of laminated lumber plants

Science.gov (United States)

E.M. (Ted) Bilek; John F. Hunt

2006-01-01

A spreadsheet-based computer program called LamLum was created to analyze the economics of value- added laminated lumber manufacturing facilities. Such facilities manufacture laminations, typically from lower grades of structural lumber, then glue these laminations together to make various types of higher value laminated lumber products. This report provides the...

Neurodegeneration in drop-dead mutant drosophila melanogaster is associated with the respiratory system but not with Hypoxia.

Directory of Open Access Journals (Sweden)

Christine Lynn Sansone

Full Text Available Mutations in the gene drop-dead (drd cause diverse phenotypes in adult Drosophila melanogaster including early lethality, neurodegeneration, tracheal defects, gut dysfunction, reduced body mass, and female sterility. Despite the identification of the drd gene itself, the causes of early lethality and neurodegeneration in the mutant flies remain unknown. To determine the pattern of drd expression associated with the neurodegenerative phenotype, knockdown of drd with various Gal4 drivers was performed. Early adult lethality and neurodegeneration were observed upon knockdown of drd in the tracheal system with two independent insertions of the breathless-Gal4 driver and upon knockdown in the tracheal system and elsewhere with the DJ717-Gal4 driver. Surprisingly, rescue of drd expression exclusively in the tracheae in otherwise mutant flies rescued the neurodegenerative phenotype but not adult lethality. Gut dysfunction, as measured by defecation rate, was not rescued in these flies, and gut function appeared normal upon tracheal-specific knockdown of drd. Finally, the hypothesis that tracheal dysfunction in drd mutants results in hypoxia was tested. Hypoxia-sensitive reporter transgenes (LDH-Gal4 and LDH-LacZ were placed on a drd mutant background, but enhanced expression of these reporters was not observed. In addition, manipulation of drd expression in the tracheae did not affect expression of the hypoxia-induced genes LDH, tango, and similar. Overall, these results indicate that there are at least two causes of adult lethality in drd mutants, that gut dysfunction and neurodegeneration are independent phenotypes, and that neurodegeneration is associated with tracheal expression of drd but not with hypoxia.

Influence of bruxism on survival of porcelain laminate veneers.

Science.gov (United States)

Granell-Ruíz, Maria; Agustín-Panadero, Rubén; Fons-Font, Antonio; Román-Rodríguez, Juan-Luis; Solá-Ruíz, María-Fernanda

2014-09-01

This study aims to determine whether bruxism and the use of occlusal splints affect the survival of porcelain laminate veneers in patients treated with this technique. Restorations were made in 70 patients, including 30 patients with some type of parafunctional habit. A total of 323 veneers were placed, 170 in patients with bruxism activity, and the remaining 153 in patients without it. A clinical examination determined the presence or absence of ceramic failure (cracks, fractures and debonding) of the restorations; these incidents were analyzed for association with bruxism and the use of splints. Analysis of the ceramic failures showed that of the 13 fractures and 29 debonding that were present in our study, 8 fractures and 22 debonding were related to the presence of bruxism. Porcelain laminate veneers are a predictable treatment option that provides excellent results, recognizing a higher risk of failure in patients with bruxism activity. The use of occlusal splints reduces the risk of fractures.

Lamination and end plate design studies of SSC Low Energy Booster magnet prototypes

International Nuclear Information System (INIS)

Li, N.

1993-01-01

The LEB machine includes six kinds of laminated magnets and 4 kinds of laminations. The main quadrupole magnet and low field and high field corrector quadrupoles use the same lamination shape. The chromaticity sextupole, corrector dipole, and main dipole have different lamination designs. To test the physical design and production procedure for the magnets, it is necessary to build 2 or 3 prototypes for each kind of magnet. The ZVI plant in Moscow, manufactured all 4 kinds of lamination punching dies for the LEB magnets. Each die takes 3 to 5 months to fabricate. SSCL manufactured laser cut laminated magnet prototypes in the SSC shop at the same time. Since the LEB cycles at 10 Hz, the high frequency current and laminated end plate design causes a delamination problem on the magnet end. This problem is of concern and will be addressed

An ALS-Associated Mutant SOD1 Rapidly Suppresses KCNT1 (Slack) Na+-Activated K+ Channels in Aplysia Neurons.

Science.gov (United States)

Zhang, Yalan; Ni, Weiming; Horwich, Arthur L; Kaczmarek, Leonard K

2017-02-22

Mutations that alter levels of Slack (KCNT1) Na + -activated K + current produce devastating effects on neuronal development and neuronal function. We now find that Slack currents are rapidly suppressed by oligomers of mutant human Cu/Zn superoxide dismutase 1 (SOD1), which are associated with motor neuron toxicity in an inherited form of amyotrophic lateral sclerosis (ALS). We recorded from bag cell neurons of Aplysia californica , a model system to study neuronal excitability. We found that injection of fluorescent wild-type SOD1 (wt SOD1YFP) or monomeric mutant G85R SOD1YFP had no effect on net ionic currents measured under voltage clamp. In contrast, outward potassium currents were significantly reduced by microinjection of mutant G85R SOD1YFP that had been preincubated at 37°C or of cross-linked dimers of G85R SOD1YFP. Reduction of potassium current was also seen with multimeric G85R SOD1YFP of ∼300 kDa or >300 kDa that had been cross-linked. In current clamp recordings, microinjection of cross-linked 300 kDa increased excitability by depolarizing the resting membrane potential, and decreasing the latency of action potentials triggered by depolarization. The effect of cross-linked 300 kDa on potassium current was reduced by removing Na + from the bath solution, or by knocking down levels of Slack using siRNA. It was also prevented by pharmacological inhibition of ASK1 (apoptosis signal-regulating kinase 1) or of c-Jun N-terminal kinase, but not by an inhibitor of p38 mitogen-activated protein kinase. These results suggest that soluble mutant SOD1 oligomers rapidly trigger a kinase pathway that regulates the activity of Na + -activated K + channels in neurons. SIGNIFICANCE STATEMENT Slack Na + -activated K + channels (KCNT1, K Na 1.1) regulate neuronal excitability but are also linked to cytoplasmic signaling pathways that control neuronal protein translation. Mutations that alter the amplitude of these currents have devastating effects on neuronal

Sorting nexin 6 enhances lamin a synthesis and incorporation into the nuclear envelope.

Directory of Open Access Journals (Sweden)

Jose M González-Granado

Full Text Available Nuclear lamins are important structural and functional proteins in mammalian cells, but little is known about the mechanisms and cofactors that regulate their traffic into the nucleus. Here, we demonstrate that trafficking of lamin A, but not lamin B1, and its assembly into the nuclear envelope are regulated by sorting nexin 6 (SNX6, a major component of the retromer that targets proteins and other molecules to specific subcellular locations. SNX6 interacts with lamin A in vitro and in vivo and links it to the outer surface of the endoplasmic reticulum in human and mouse cells. SNX6 transports its lamin A cargo to the nuclear envelope in a process that takes several hours. Lamin A protein levels in the nucleus augment or decrease, respectively, upon gain or loss of SNX6 function. We further show that SNX6-dependent lamin A nuclear import occurs across the nuclear pore complex via a RAN-GTP-dependent mechanism. These results identify SNX6 as a key regulator of lamin A synthesis and incorporation into the nuclear envelope.

Sorting Nexin 6 Enhances Lamin A Synthesis and Incorporation into the Nuclear Envelope

Science.gov (United States)

González-Granado, Jose M.; Navarro-Puche, Ana; Molina-Sanchez, Pedro; Blanco-Berrocal, Marta; Viana, Rosa; de Mora, Jaime Font; Andrés, Vicente

2014-01-01

Nuclear lamins are important structural and functional proteins in mammalian cells, but little is known about the mechanisms and cofactors that regulate their traffic into the nucleus. Here, we demonstrate that trafficking of lamin A, but not lamin B1, and its assembly into the nuclear envelope are regulated by sorting nexin 6 (SNX6), a major component of the retromer that targets proteins and other molecules to specific subcellular locations. SNX6 interacts with lamin A in vitro and in vivo and links it to the outer surface of the endoplasmic reticulum in human and mouse cells. SNX6 transports its lamin A cargo to the nuclear envelope in a process that takes several hours. Lamin A protein levels in the nucleus augment or decrease, respectively, upon gain or loss of SNX6 function. We further show that SNX6-dependent lamin A nuclear import occurs across the nuclear pore complex via a RAN-GTP-dependent mechanism. These results identify SNX6 as a key regulator of lamin A synthesis and incorporation into the nuclear envelope. PMID:25535984

Identification of key uric acid synthesis pathway in a unique mutant silkworm Bombyx mori model of Parkinson's disease.

Directory of Open Access Journals (Sweden)

Hiroko Tabunoki

Full Text Available Plasma uric acid (UA levels decrease following clinical progression and stage development of Parkinson's disease (PD. However, the molecular mechanisms underlying decreases in plasma UA levels remain unclear, and the potential to apply mutagenesis to a PD model has not previously been discovered. We identified a unique mutant of the silkworm Bombyx mori (B.mori op. Initially, we investigated the causality of the phenotypic "op" by microarray analysis using our constructed KAIKO functional annotation pipeline. Consequently, we found a novel UA synthesis-modulating pathway, from DJ-1 to xanthine oxidase, and established methods for large-scale analysis of gene expression in B. mori. We found that the mRNA levels of genes in this pathway were significantly lower in B. mori op mutants, indicating that downstream events in the signal transduction cascade might be prevented. Additionally, levels of B.mori tyrosine hydroxylase (TH and DJ-1 mRNA were significantly lower in the brain of B. mori op mutants. UA content was significantly lower in the B. mori op mutant tissues and hemolymph. The possibility that the B. mori op mutant might be due to loss of DJ-1 function was supported by the observed vulnerability to oxidative stress. These results suggest that UA synthesis, transport, elimination and accumulation are decreased by environmental oxidative stress in the B. mori op mutant. In the case of B. mori op mutants, the relatively low availability of UA appears to be due both to the oxidation of DJ-1 and to its expenditure to mitigate the effects of environmental oxidative stress. Our findings are expected to provide information needed to elucidate the molecular mechanism of decreased plasma UA levels in the clinical stage progression of PD.

NiCoCrAl/YSZ laminate composites fabricated by EB-PVD

International Nuclear Information System (INIS)

Shi Guodong; Wang Zhi; Liang Jun; Wu Zhanjun

2011-01-01

Highlights: → The metal-ceramic laminate composites were fabricated by EB-PVD. → Both metal and ceramic layers consisted of straight columns with banded structures. → Columnar grain size was limited by the periodic layer interfaces in the laminates. → Effect of columns on fracture property was decreased by limiting layer thickness. → Laminates showed greater specific strength than monolithic metal foil. - Abstract: Two NiCoCrAl/YSZ laminate composites (A and B) with different metal-layer thickness (∼35 μm and 14 μm, respectively) were fabricated by electron beam physical vapor deposition (EB-PVD). Their microstructure was examined and their mechanical properties were compared with the 289 μm thick NiCoCrAl monolithic foil produced by EB-PVD. Both the YSZ and NiCoCrAl layers of the laminate composites had columnar grain structure. But the periodic layer interfaces limited the columnar grain size. Some pores between the columns were also observed. It was found that the strength of the laminate A was equal approximately to that of the NiCoCrAl monolithic foil, and that laminate B had the greater strength. Moreover, the density of the foils decreased with the increasing thickness ratio of YSZ/NiCoCrAl layers and the increasing the layer number. Thus, comparing with the NiCoCrAl monolithic foil, the NiCoCrAl/YSZ laminate composites not only had the equal or greater strength, but also had the much greater specific strength.

Fracture toughness of Ceramic-Fiber-Reinforced Metallic-Intermetallic-Laminate (CFR-MIL) composites

International Nuclear Information System (INIS)

Vecchio, Kenneth S.; Jiang, Fengchun

2016-01-01

Novel Ceramic-Fiber-Reinforced-Metal-Intermetallic-Laminate (CFR-MIL) composites, Ti–Al 3 Ti–Al 2 O 3 –Al, were synthesized by reactive foil sintering in air. Microstructure controlled material architectures were achieved with continuous Al 2 O 3 fibers oriented in 0° and 90° layers to form fully dense composites in which the volume fractions of all four component phases can be tailored. Bend fracture specimens were cut from the laminate plates in divider orientation, and bend tests were performed to study the fracture behavior of CFR-MIL composites under three-point and four-point bending loading conditions. The microstructures and fractured surfaces of the CFR-MIL composites were examined using optical microscopy and scanning electron microscopy to establish a correlation between the fracture toughness, fracture surface morphology and microstructures of CFR-MIL composites. The fracture and toughening mechanisms of the CFR-MIL composites are also addressed. The present experimental results indicate that the fracture toughness of CFR-MIL composites determined by three- and four-point bend loading configurations are quite similar, and increased significantly compared to MIL composites without ceramic fiber reinforcement. The interface cracking behavior is related to the volume fraction of the brittle Al 3 Ti phase and residual ductile Al, but the fracture toughness values appear to be insensitive to the ratio of these two phases. The toughness appears to be dominated by the ductility/strength of the Ti layers and the strength and crack bridging effect of the ceramic fibers.

Nuclear lamins: laminopathies and their role in premature ageing

NARCIS (Netherlands)

Broers, J.L.V.; Ramaekers, F.C.S.; Bonne, G.; Yaou, R.; Hutchison, C.J.

2006-01-01

It has been demonstrated that nuclear lamins are important proteins in maintaining cellular as well as nuclear integrity, and in maintaining chromatin organization in the nucleus. Moreover, there is growing evidence that lamins play a prominent role in transcriptional control. The family of

The effect of bulk-resin CNT-enrichment on damage and plasticity in shear-loaded laminated composites

KAUST Repository

Ventura, Isaac Aguilar

2013-07-01

One way to improve multi functionality of epoxy-based laminated composites is to dope the resin with carbon nanotubes. Many investigators have focused on the elastic and fracture behavior of such nano-modified polymers under tensile loading. Yet, in real structural applications, laminated composites can exhibit plasticity and progressive damage initiated mainly by shear loading. We investigated the damage and plasticity induced by the addition of carbon nanotubes to the matrix of a glass fiber/epoxy composite system. We characterized both the modified epoxy resin and the associated modified laminates using classical mesoscale analysis. We used dynamic mechanical analysis, scanning electron microscopy, atomic force microscopy and classical mechanical testing to characterize samples with different concentrations of nanofillers. Since the samples were prepared using the solvent evaporation technique, we also studied the influence of this process. We found that in addition to the global increase in elastic regime properties, the addition of carbon nanotubes also accelerates the damage process in both the bulk resin and its associated glass-fiber composite. © 2013 Elsevier Ltd.

Case-control study of risk factors for the development of laminitis in the contralateral limb in Equidae with unilateral lameness

International Nuclear Information System (INIS)

Peloso, J.G.; Cohen, N.D.; Walker, M.A.; Watkins, J.P.; Gayle, J.M.; Moyer, W.

1996-01-01

To identify risk factors associated with development of laminitis of the supporting limb in Equidae with unilateral laminitis and to determine the radiographic appearance of this type of laminitis. Retrospective analysis of medical records. 20 Equidae with unilateral lameness that developed laminitis of the contralateral limb. Case animals were compared with matched and unmatched populations of control animals that did not develop contralateral limb laminitis. Lateromedial radiographic projections of affected feet were evaluated for evidence of laminitis. Body weight of case animals was not significantly different from that of control animals, but number of days that control animals were lame prior to recovery was significantly less than number of days that case animals were lame prior to the onset of laminitis. Lateromedial radiographic projections of the foot of the support limb were available for 16 of the 20 case animals. For all 16, thickness of the soft tissue dorsal to the distal phalanx was > 29% of the palmar cortical length of the distal phalanx, but only 1 had evidence of rotation of the distal phalanx. The proportion of case animals that were euthanatized was significantly greater than the proportion of control animals that were euthanatized. Duration of lameness, but not body weight, was a risk factor for development of laminitis in the contralateral limb in Equidae with unilateral lameness, and animals that developed this complication were more likely to be euthanatized than were animals that did not

Disease-Causing Mutations in BEST1 Gene Are Associated with Altered Sorting of Bestrophin-1 Protein

Science.gov (United States)

Doumanov, Jordan A.; Zeitz, Christina; Gimenez, Paloma Dominguez; Audo, Isabelle; Krishna, Abhay; Alfano, Giovanna; Diaz, Maria Luz Bellido; Moskova-Doumanova, Veselina; Lancelot, Marie-Elise; Sahel, José-Alain; Nandrot, Emeline F.; Bhattacharya, Shomi S.

2013-01-01

Mutations in BEST1 gene, encoding the bestrophin-1 (Best1) protein are associated with macular dystrophies. Best1 is predominantly expressed in the retinal pigment epithelium (RPE), and is inserted in its basolateral membrane. We investigated the cellular localization in polarized MDCKII cells of disease-associated Best1 mutant proteins to study specific sorting motifs of Best1. Real-time PCR and western blots for endogenous expression of BEST1 in MDCK cells were performed. Best1 mutant constructs were generated using site-directed mutagenesis and transfected in MDCK cells. For protein sorting, confocal microscopy studies, biotinylation assays and statistical methods for quantification of mislocalization were used. Analysis of endogenous expression of BEST1 in MDCK cells revealed the presence of BEST1 transcript but no protein. Confocal microscopy and quantitative analyses indicate that transfected normal human Best1 displays a basolateral localization in MDCK cells, while cell sorting of several Best1 mutants (Y85H, Q96R, L100R, Y227N, Y227E) was altered. In contrast to constitutively active Y227E, constitutively inactive Y227F Best1 mutant localized basolaterally similar to the normal Best1 protein. Our data suggest that at least three basolateral sorting motifs might be implicated in proper Best1 basolateral localization. In addition, non-phosphorylated tyrosine 227 could play a role for basolateral delivery. PMID:23880862

Clinical spectrum of Castleman disease-associated neuropathy.

Science.gov (United States)

Naddaf, Elie; Dispenzieri, Angela; Mandrekar, Jay; Mauermann, Michelle L

2016-12-06

To define the peripheral neuropathy phenotypes associated with Castleman disease. We conducted a retrospective chart review for patients with biopsy-proven Castleman disease evaluated between January 2003 and December 2014. Patients with associated peripheral neuropathy were identified and divided into 2 groups: those with Castleman disease without POEMS syndrome (CD-PN) and those with Castleman disease with POEMS syndrome (CD-POEMS). We used a cohort of patients with POEMS as controls. Clinical, electrodiagnostic, and laboratory characteristics were collected and compared among patient subgroups. There were 7 patients with CD-PN, 20 with CD-POEMS, and 122 with POEMS. Patients with CD-PN had the mildest neuropathy characterized by predominant sensory symptoms with no pain and mild distal sensory deficits (median Neuropathy Impairment Score of 7 points). Although both patients with CD-POEMS and patients with POEMS had a severe sensory and motor neuropathy, patients with CD-POEMS were less affected (median Neuropathy Impairment Score of 33 and 66 points, respectively). The degree of severity was also reflected on electrodiagnostic testing in which patients with CD-PN demonstrated a mild degree of axonal loss, followed by patients with CD-POEMS and then those with POEMS. Demyelinating features, defined by European Federation of Neurologic Societies/Peripheral Nerve Society criteria, were present in 43% of the CD-PN, 78% of the CD-POEMS, and 86% of the POEMS group. There is a spectrum of demyelinating peripheral neuropathies associated with Castleman disease. CD-PN is sensory predominant and is the mildest phenotype, whereas CD-POEMS is a more severe sensory and motor neuropathy. Compared to the POEMS cohort, those with CD-POEMS neuropathy have a similar but less severe phenotype. Whether these patients respond differently to treatment deserves further study. © 2016 American Academy of Neurology.

Destabilizing protein polymorphisms in the genetic background direct phenotypic expression of mutant SOD1 toxicity.

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Tali Gidalevitz

2009-03-01

Full Text Available Genetic background exerts a strong modulatory effect on the toxicity of aggregation-prone proteins in conformational diseases. In addition to influencing the misfolding and aggregation behavior of the mutant proteins, polymorphisms in putative modifier genes may affect the molecular processes leading to the disease phenotype. Mutations in SOD1 in a subset of familial amyotrophic lateral sclerosis (ALS cases confer dominant but clinically variable toxicity, thought to be mediated by misfolding and aggregation of mutant SOD1 protein. While the mechanism of toxicity remains unknown, both the nature of the SOD1 mutation and the genetic background in which it is expressed appear important. To address this, we established a Caenorhabditis elegans model to systematically examine the aggregation behavior and genetic interactions of mutant forms of SOD1. Expression of three structurally distinct SOD1 mutants in C. elegans muscle cells resulted in the appearance of heterogeneous populations of aggregates and was associated with only mild cellular dysfunction. However, introduction of destabilizing temperature-sensitive mutations into the genetic background strongly enhanced the toxicity of SOD1 mutants, resulting in exposure of several deleterious phenotypes at permissive conditions in a manner dependent on the specific SOD1 mutation. The nature of the observed phenotype was dependent on the temperature-sensitive mutation present, while its penetrance reflected the specific combination of temperature-sensitive and SOD1 mutations. Thus, the specific toxic phenotypes of conformational disease may not be simply due to misfolding/aggregation toxicity of the causative mutant proteins, but may be defined by their genetic interactions with cellular pathways harboring mildly destabilizing missense alleles.

High throughput screening for small molecule therapy for Gaucher disease using patient tissue as the source of mutant glucocerebrosidase.

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Ehud Goldin

Full Text Available Gaucher disease (GD, the most common lysosomal storage disorder, results from the inherited deficiency of the lysosomal enzyme glucocerebrosidase (GCase. Previously, wildtype GCase was used for high throughput screening (HTS of large collections of compounds to identify small molecule chaperones that could be developed as new therapies for GD. However, the compounds identified from HTS usually showed reduced potency later in confirmatory cell-based assays. An alternate strategy is to perform HTS on mutant enzyme to identify different lead compounds, including those enhancing mutant enzyme activities. We developed a new screening assay using enzyme extract prepared from the spleen of a patient with Gaucher disease with genotype N370S/N370S. In tissue extracts, GCase is in a more native physiological environment, and is present with the native activator saposin C and other potential cofactors. Using this assay, we screened a library of 250,000 compounds and identified novel modulators of mutant GCase including 14 new lead inhibitors and 30 lead activators. The activities of some of the primary hits were confirmed in subsequent cell-based assays using patient-derived fibroblasts. These results suggest that primary screening assays using enzyme extracted from tissues is an alternative approach to identify high quality, physiologically relevant lead compounds for drug development.

Modal analysis of pre and post impacted nano composite laminates

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R. Velmurugan

Full Text Available Modal analysis is carried out on pre and post impacted nano composite laminates. The laminates are prepared using 3, 5 and 8 layers of 610gsm glass woven roving mats(WRM with epoxy resin and montmorillonite(MMT clay content is varied from 1% to 5%. Impulse hammer technique is used to find natural frequency and damping factor of laminates. Medium velocity impact tests are conducted by using a gas gun. The vibration responses of natural frequency and damping factor are obtained and are studied for laminates with all edges clamped boundary conditions. Results show considerable improvement in natural frequency and damping factor due to nano clay addition. It is also seen that the nano clay controls the delamination due to impact loading.

Free vibration of fully functionally graded carbon nanotube reinforced graphite/epoxy laminates

Science.gov (United States)

Kuo, Shih-Yao

2018-03-01

This study provides the first-known vibration analysis of fully functionally graded carbon nanotube reinforced hybrid composite (FFG-CNTRHC) laminates. CNTs are non-uniformly distributed to reinforce the graphite/epoxy laminates. Some CNT distribution functions in the plane and thickness directions are proposed to more efficiently increase the stiffening effect. The rule of mixtures is modified by considering the non-homogeneous material properties of FFG-CNTRHC laminates. The formulation of the location dependent stiffness matrix and mass matrix is derived. The effects of CNT volume fraction and distribution on the natural frequencies of FFG-CNTRHC laminates are discussed. The results reveal that the FFG layout may significantly increase the natural frequencies of FFG-CNTRHC laminate.

Arteriographical and pathological changes in chronic laminitis in dairy cattle.

Science.gov (United States)

Boosman, R; Nemeth, F; Gruys, E; Klarenbeek, A

1989-07-01

The arteriographic appearance of 76 bovine hind digits, obtained from a slaughterhouse, was related to the macroscopic signs of chronic laminitis in the digits. There were statistically significant correlations between the macroscopic and the arteriographic appearance of the claws. Subsequent histological examination of the radiographically abnormal arteries revealed features indicative of arteriosclerosis. The results of this study indicate that chronic laminitis develops following a subclinical attack of laminitis due to a continous hypoperfusion of the digit.

Ubiquitin ligase RNF123 mediates degradation of heterochromatin protein 1α and β in lamin A/C knock-down cells.

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Pankaj Chaturvedi

Full Text Available The nuclear lamina is a key determinant of nuclear architecture, integrity and functionality in metazoan nuclei. Mutations in the human lamin A gene lead to highly debilitating genetic diseases termed as laminopathies. Expression of lamin A mutations or reduction in levels of endogenous A-type lamins leads to nuclear defects such as abnormal nuclear morphology and disorganization of heterochromatin. This is accompanied by increased proteasomal degradation of certain nuclear proteins such as emerin, nesprin-1α, retinoblastoma protein and heterochromatin protein 1 (HP1. However, the pathways of proteasomal degradation have not been well characterized.To investigate the mechanisms underlying the degradation of HP1 proteins upon lamin misexpression, we analyzed the effects of shRNA-mediated knock-down of lamins A and C in HeLa cells. Cells with reduced levels of expression of lamins A and C exhibited proteasomal degradation of HP1α and HP1β but not HP1γ. Since specific ubiquitin ligases are upregulated in lamin A/C knock-down cells, further studies were carried out with one of these ligases, RNF123, which has a putative HP1-binding motif. Ectopic expression of GFP-tagged RNF123 directly resulted in degradation of HP1α and HP1β. Mutational analysis showed that the canonical HP1-binding pentapeptide motif PXVXL in the N-terminus of RNF123 was required for binding to HP1 proteins and targeting them for degradation. The role of endogenous RNF123 in the degradation of HP1 isoforms was confirmed by RNF123 RNAi experiments. Furthermore, FRAP analysis suggested that HP1β was displaced from chromatin in laminopathic cells.Our data support a role for RNF123 ubiquitin ligase in the degradation of HP1α and HP1β upon lamin A/C knock-down. Hence lamin misexpression can cause degradation of mislocalized proteins involved in key nuclear processes by induction of specific components of the ubiquitin-proteasome system.

Bayesian inference model for fatigue life of laminated composites

DEFF Research Database (Denmark)

Dimitrov, Nikolay Krasimirov; Kiureghian, Armen Der; Berggreen, Christian

2016-01-01

A probabilistic model for estimating the fatigue life of laminated composite plates is developed. The model is based on lamina-level input data, making it possible to predict fatigue properties for a wide range of laminate configurations. Model parameters are estimated by Bayesian inference. The ...

Steel skin - SMC laminate structures for lightweight automotive manufacturing

Science.gov (United States)

Quagliato, Luca; Jang, Changsoon; Murugesan, Mohanraj; Kim, Naksoo

2017-09-01

In the present research work an innovative material, made of steel skin and sheet molding compound core, is presented and is aimed to be utilized for the production of automotive body frames. For a precise description of the laminate structure, the material properties of all the components, including the adhesive utilized as an interlayer, have been carried out, along with the simple tension test of the composite material. The result have shown that the proposed laminate structure has a specific yield strength 114% higher than 6061 T6 aluminum, 34% higher than 7075 T6 aluminum, 186% higher than AISI 304 stainless steel (30HRC) and 42% than SK5 high-strength steel (52HRC), showing its reliability and convenience for the realization of automotive components. After calibrating the material properties of the laminate structure, and utilizing as reference the simple tension results of the laminate structure, the derived material properties have been utilized for the simulation of the mechanical behavior of an automotive B-pillar. The results have been compared with those of a standard B-pillar made of steel, showing that the MS-SMC laminate structure manifests load and impact carry capacity comparable with those of high strength steel, while granting, at least, an 11% weight reduction.

Characterization of Pustular Mats and Related Rivularia-Rich Laminations in Oncoids From the Laguna Negra Lake (Argentina

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Estela C. Mlewski

2018-05-01

Full Text Available Stromatolites are organo-sedimentary structures that represent some of the oldest records of the early biosphere on Earth. Cyanobacteria are considered as a main component of the microbial mats that are supposed to produce stromatolite-like structures. Understanding the role of cyanobacteria and associated microorganisms on the mineralization processes is critical to better understand what can be preserved in the laminated structure of stromatolites. Laguna Negra (Catamarca, Argentina, a high-altitude hypersaline lake where stromatolites are currently formed, is considered as an analog environment of early Earth. This study aimed at characterizing carbonate precipitation within microbial mats and associated oncoids in Laguna Negra. In particular, we focused on carbonated black pustular mats. By combining Confocal Laser Scanning Microscopy, Scanning Electron Microscopy, Laser Microdissection and Whole Genome Amplification, Cloning and Sanger sequencing, and Focused Ion Beam milling for Transmission Electron Microscopy, we showed that carbonate precipitation did not directly initiate on the sheaths of cyanobacterial Rivularia, which dominate in the mat. It occurred via organo-mineralization processes within a large EPS matrix excreted by the diverse microbial consortium associated with Rivularia where diatoms and anoxygenic phototrophic bacteria were particularly abundant. By structuring a large microbial consortium, Rivularia should then favor the formation of organic-rich laminations of carbonates that can be preserved in stromatolites. By using Fourier Transform Infrared spectroscopy and Synchrotron-based deep UV fluorescence imaging, we compared laminations rich in structures resembling Rivularia to putatively chemically-precipitated laminations in oncoids associated with the mats. We showed that they presented a different mineralogy jointly with a higher content in organic remnants, hence providing some criteria of biogenicity to be searched

Field performance of stress-laminated timber bridges on low-volume roads

Science.gov (United States)

M. A. Ritter; J. P. Wacker; S. R. Duwadi

1995-01-01

Stress-laminated timber bridges were first introduced in the United States in the late 1980s. Since that time, the concept of stress-laminating has received a great deal of attention and hundreds of bridges have been built. Most of these bridges are located on rural low-volume roads. To evaluate the performance of stress-laminated bridges, the United States Department...

Field performance of timber bridges. 13, Mohawk Canal stress-laminated bridge

Science.gov (United States)

P. D. Hilbrich Lee; X. Lauderdale

The Mohawk Canal bridge was constructed in August 1994, just outside Roll, Arizona. It is a simple-span, double-lane, stress-laminated deck superstructure, approximately 6.4 m (21 ft) long and 10.4 m (34 ft) wide and constructed with Combination 16F-V3 Douglas Fir glued-laminated timber beam laminations. The performance of the bridge was monitored continuously for 2...

Flecainide associated torsade de pointes: A potential case of reverse use dependence

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Kevin Hayes

2013-01-01

Full Text Available Flecainide has been known to cause torsades de pointes (TdP in patients with structural heart disease and its mechanism has been attributed to use-dependency. We present a patient with flecainide-induced TdP in the absence of any other precipitating factors. This case highlights potential reverse use dependence associated with flecainide resulting in TdP.

Hybrid Laminates for Application in North Conditions

Science.gov (United States)

Antipov, V. V.; Oreshko, E. I.; Erasov, V. S.; Serebrennikova, N. Yu.

2016-11-01

A hybrid aluminum-lithium alloy/SIAL laminate as a possible material for application in structures operated in North conditions is considered. The finite-element method is used for a buckling stability analysis of hybrid panels, bars, and plates. A technique allowing one to compare the buckling stability of multilayered hybrid plates is offered. Compression tests were run on a hybrid laminate wing panel as a prototype of the top panel of TU-204SM airplane made from a high-strength B95T2 aluminum alloy. It turned out that the lighter composite panel had a higher load-carrying capacity than the aluminum one. Results of investigation into the properties the hybrid aluminum-lithium alloy/SIAL laminate and an analysis of scientific-technical data on this subject showed that this composite material could be used in the elements of airframes, including those operated in north conditions.

Lateral testing of glued laminated timber tudor arch

Science.gov (United States)

Douglas R. Rammer; Philip Line

2016-01-01

Glued laminated timber Tudor arches have been in wide use in the United States since the 1930s, but detailed knowledge related to seismic design in modern U.S. building codes is lacking. FEMA P-695 (P-695) is a methodology to determine seismic performance factors for a seismic force resisting system. A limited P-695 study for glued laminated timber arch structures...

Hole-thru-laminate mounting supports for photovoltaic modules

Science.gov (United States)

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.

Photovoltaic module and laminate

Science.gov (United States)

Bunea, Gabriela E.; Kim, Sung Dug; Kavulak, David F.J.

2018-04-10

A photovoltaic module is disclosed. The photovoltaic module has a first side directed toward the sun during normal operation and a second, lower side. The photovoltaic module comprises a perimeter frame and a photovoltaic laminate at least partially enclosed by and supported by the perimeter frame. The photovoltaic laminate comprises a transparent cover layer positioned toward the first side of the photovoltaic module, an upper encapsulant layer beneath and adhering to the cover layer, a plurality of photovoltaic solar cells beneath the upper encapsulant layer, the photovoltaic solar cells electrically interconnected, a lower encapsulant layer beneath the plurality of photovoltaic solar cells, the upper and lower encapsulant layers enclosing the plurality of photovoltaic solar cells, and a homogenous rear environmental protection layer, the rear environmental protection layer adhering to the lower encapsulant layer, the rear environmental protection layer exposed to the ambient environment on the second side of the photovoltaic module.

Inhibition of Prenylation Promotes Caspase 3 Activation, Lamin B Degradation and Loss in Metabolic Cell Viability in Pancreatic β-Cells

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Khadija G. Syeda

2017-10-01

Full Text Available Background/Aims: Lamins are intermediate filament proteins that constitute the main components of the lamina underlying the inner-nuclear membrane and serve to organize chromatin. Lamins (e.g., lamin B undergo posttranslational modifications (e.g., isoprenylation at their C-terminal cysteine residues. Such modifications are thought to render optimal association of lamins with the nuclear envelop. Using human islets, rodent islets, and INS-1 832/13 cells, we recently reported significant metabolic defects under glucotoxic and endoplasmic reticulum (ER stress conditions, including caspase 3 activation and lamin B degradation. The current study is aimed at further understanding the regulatory roles of protein prenylation in the induction of the aforestated metabolic defects. Methods: Subcellular phase partitioning assay was done using Triton X-114. Cell morphology and metabolic cell viability assays were carried out using standard methodologies. Results: We report that exposure of pancreatic β-cells to Simvastatin, an inhibitor of mevalonic acid (MVA biosynthesis, and its downstream isoprenoid derivatives, or FTI-277, an inhibitor of farnesyltransferase that mediates farnesylation of lamins, leads to activation of caspase 3 and lamin B degradation. Furthermore, Simvastatin-treatment increased activation of p38MAPK (a stress kinase and inhibited ERK1/2 (regulator of cell proliferation. Inhibition of farnesylation also resulted in the release of degraded lamin B into the cytosolic fraction and promoted loss in metabolic cell viability. Conclusion: Based on these findings we conclude that protein prenylation plays key roles in islet β-cell function. These findings affirm further support to the hypothesis that defects in prenylation pathway induce caspase-3 activation and nuclear lamin degradation in pancreatic β-cells under the duress of metabolic stress (e.g., glucotoxicity.

Association of methionine requirement with methyl mercury resistant mutants of yeast

Energy Technology Data Exchange (ETDEWEB)

Singh, A.; Sherman, F.

1974-01-25

It has been known for several years that strains resistant to mercury can be obtained in several bacterial species. Soon after the correlation between resistance to antibiotics and to mercury was recognized, it was established that genetic elements conferring resistance to antibiotics, mercury and other heavy metals in Escherichia coli and Samonella typhimurium and Staphylococcus aureus reside on extrachromosomal resistance transfer factors or plasmids. Among fungi, mercury resistant strains of Botrytis cinerea, Penicillium notatum, Sclerotinia fructicola, Stemphylium sarcinaeforme, and Saccharomyces cerevisiae have been reported. In most cases, this was accomplished by training the normal strains for growth on media supplemented with successively increasing concentrations of mercury compounds, and in some cases the resistance was lost when subcultured on mercury-free media. It is noteworthy that in none of the mercury-adapted strains of fungi has the genetic basis of resistance been determined. In this report we describe a method of isolation and characterization of methyl mercury resistant mutants of S. cerevisiae. This study was undertaken with the view that the examination of physiological changes associated with genetically defined resistant mutants will be useful in studying the mechanisms of cellular detoxification of organic mercurials.

The deoxyhypusine synthase mutant dys1-1 reveals the association of eIF5A and Asc1 with cell wall integrity.

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Fabio Carrilho Galvão

Full Text Available The putative eukaryotic translation initiation factor 5A (eIF5A is a highly conserved protein among archaea and eukaryotes that has recently been implicated in the elongation step of translation. eIF5A undergoes an essential and conserved posttranslational modification at a specific lysine to generate the residue hypusine. The enzymes deoxyhypusine synthase (Dys1 and deoxyhypusine hydroxylase (Lia1 catalyze this two-step modification process. Although several Saccharomyces cerevisiae eIF5A mutants have importantly contributed to the study of eIF5A function, no conditional mutant of Dys1 has been described so far. In this study, we generated and characterized the dys1-1 mutant, which showed a strong depletion of mutated Dys1 protein, resulting in more than 2-fold decrease in hypusine levels relative to the wild type. The dys1-1 mutant demonstrated a defect in total protein synthesis, a defect in polysome profile indicative of a translation elongation defect and a reduced association of eIF5A with polysomes. The growth phenotype of dys1-1 mutant is severe, growing only in the presence of 1 M sorbitol, an osmotic stabilizer. Although this phenotype is characteristic of Pkc1 cell wall integrity mutants, the sorbitol requirement from dys1-1 is not associated with cell lysis. We observed that the dys1-1 genetically interacts with the sole yeast protein kinase C (Pkc1 and Asc1, a component of the 40S ribosomal subunit. The dys1-1 mutant was synthetically lethal in combination with asc1Δ and overexpression of TIF51A (eIF5A or DYS1 is toxic for an asc1Δ strain. Moreover, eIF5A is more associated with translating ribosomes in the absence of Asc1 in the cell. Finally, analysis of the sensitivity to cell wall-perturbing compounds revealed a more similar behavior of the dys1-1 and asc1Δ mutants in comparison with the pkc1Δ mutant. These data suggest a correlated role for eIF5A and Asc1 in coordinating the translational control of a subset of m

Abnormal A-type lamin organization in a human lung carcinoma cell line

NARCIS (Netherlands)

Machiels, BM; Broers, JL; Raymond, Y; de Leij, Louis; Kuijpers, HJH; Caberg, NEH; Ramaekers, Frans C. S.

We have studied the expression of lamins A and C (A-type lamins) in a lung carcinoma cell line using type-specific monoclonal antibodies, Using immunofluorescence and immunoblotting studies it was noted that several irregularities in lamin expression exist in the cell line GLC-A1, derived from an

Mutant uromodulin expression leads to altered homeostasis of the endoplasmic reticulum and activates the unfolded protein response.

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Céline Schaeffer

Full Text Available Uromodulin is the most abundant urinary protein in physiological conditions. It is exclusively produced by renal epithelial cells lining the thick ascending limb of Henle's loop (TAL and it plays key roles in kidney function and disease. Mutations in UMOD, the gene encoding uromodulin, cause autosomal dominant tubulointerstitial kidney disease uromodulin-related (ADTKD-UMOD, characterised by hyperuricemia, gout and progressive loss of renal function. While the primary effect of UMOD mutations, retention in the endoplasmic reticulum (ER, is well established, its downstream effects are still largely unknown. To gain insight into ADTKD-UMOD pathogenesis, we performed transcriptional profiling and biochemical characterisation of cellular models (immortalised mouse TAL cells of robust expression of wild type or mutant GFP-tagged uromodulin. In this model mutant uromodulin accumulation in the ER does not impact on cell viability and proliferation. Transcriptional profiling identified 109 genes that are differentially expressed in mutant cells relative to wild type ones. Up-regulated genes include several ER resident chaperones and protein disulphide isomerases. Consistently, pathway enrichment analysis indicates that mutant uromodulin expression affects ER function and protein homeostasis. Interestingly, mutant uromodulin expression induces the Unfolded Protein Response (UPR, and specifically the IRE1 branch, as shown by an increased splicing of XBP1. Consistent with UPR induction, we show increased interaction of mutant uromodulin with ER chaperones Bip, calnexin and PDI. Using metabolic labelling, we also demonstrate that while autophagy plays no role, mutant protein is partially degraded by the proteasome through ER-associated degradation. Our work demonstrates that ER stress could play a central role in ADTKD-UMOD pathogenesis. This sets the bases for future work to develop novel therapeutic strategies through modulation of ER homeostasis and

Structural consequences of disease-causing mutations in the ATRX-DNMT3-DNMT3L (ADD) domain of the chromatin-associated protein ATRX.

Science.gov (United States)

Argentaro, Anthony; Yang, Ji-Chun; Chapman, Lynda; Kowalczyk, Monika S; Gibbons, Richard J; Higgs, Douglas R; Neuhaus, David; Rhodes, Daniela

2007-07-17

The chromatin-associated protein ATRX was originally identified because mutations in the ATRX gene cause a severe form of syndromal X-linked mental retardation associated with alpha-thalassemia. Half of all of the disease-associated missense mutations cluster in a cysteine-rich region in the N terminus of ATRX. This region was named the ATRX-DNMT3-DNMT3L (ADD) domain, based on sequence homology with a family of DNA methyltransferases. Here, we report the solution structure of the ADD domain of ATRX, which consists of an N-terminal GATA-like zinc finger, a plant homeodomain finger, and a long C-terminal alpha-helix that pack together to form a single globular domain. Interestingly, the alpha-helix of the GATA-like finger is exposed and highly basic, suggesting a DNA-binding function for ATRX. The disease-causing mutations fall into two groups: the majority affect buried residues and hence affect the structural integrity of the ADD domain; another group affects a cluster of surface residues, and these are likely to perturb a potential protein interaction site. The effects of individual point mutations on the folding state and stability of the ADD domain correlate well with the levels of mutant ATRX protein in patients, providing insights into the molecular pathophysiology of ATR-X syndrome.

Analysis of interlaminar stresses in symmetric and unsymmetric laminates under various loadings

Science.gov (United States)

Leger, C. A.; Chan, W. S.

1993-04-01

A quasi-three-dimensional finite-element model is developed to investigate the interlaminar stresses in a composite laminate under combined loadings. An isoparametric quadrilateral element with eight nodes and three degrees of freedom per node is the finite element used in this study. The element is used to model a composite laminate cross section loaded by tension, torsion, transverse shear, and both beam and chord bending which are representative of loading in a helicopter rotor system. Symmetric and unsymmetric laminates are examined with comparisons made between the interlaminar stress distributions and magnitudes for each laminate. Unsymmetric results are compared favorably to limited results found in literature. The unsymmetric interlaminar normal stress distribution in a symmetric laminate containing a free edge delamination is also examined.

Predictions of Poisson's ratio in cross-ply laminates containing matrix cracks and delaminations

Science.gov (United States)

Harris, Charles E.; Allen, David H.; Nottorf, Eric W.

1989-01-01

A damage-dependent constitutive model for laminated composites has been developed for the combined damage modes of matrix cracks and delaminations. The model is based on the concept of continuum damage mechanics and uses second-order tensor valued internal state variables to represent each mode of damage. The internal state variables are defined as the local volume average of the relative crack face displacements. Since the local volume for delaminations is specified at the laminate level, the constitutive model takes the form of laminate analysis equations modified by the internal state variables. Model implementation is demonstrated for the laminate engineering modulus E(x) and Poisson's ratio nu(xy) of quasi-isotropic and cross-ply laminates. The model predictions are in close agreement to experimental results obtained for graphite/epoxy laminates.

Effect of resin system on the mechanical properties and water absorption of kenaf fibre reinforced laminates

International Nuclear Information System (INIS)

Rassmann, S.; Paskaramoorthy, R.; Reid, R.G.

2011-01-01

The objective of this study is to compare the mechanical and water absorption properties of kenaf (Hibiscus cannabinus L.) fibre reinforced laminates made of three different resin systems. The use of different resin systems is considered so that potentially complex and expensive fibre treatments are avoided. The resin systems used include a polyester, a vinyl ester and an epoxy. Laminates of 15%, 22.5% and 30% fibre volume fraction were manufactured by resin transfer moulding. The laminates were tested for strength and modulus under tensile and flexural loading. Additionally, tests were carried out on laminates to determine the impact energy, impact strength and water absorption. The results revealed that properties were affected in markedly different ways by the resin system and the fibre volume fraction. Polyester laminates showed good modulus and impact properties, epoxy laminates displayed good strength values and vinyl ester laminates exhibited good water absorption characteristics. Scanning electron microscope studies show that epoxy laminates fail by fibre fracture, polyester laminates by fibre pull-out and vinyl ester laminates by a combination of the two. A comparison between kenaf and glass laminates revealed that the specific tensile and flexural moduli of both laminates are comparable at the volume fraction of 15%. However, glass laminates have much better specific properties than the kenaf laminates at high fibre volume fractions for all three resins used.

Computational Fatigue Life Analysis of Carbon Fiber Laminate

Science.gov (United States)

Shastry, Shrimukhi G.; Chandrashekara, C. V., Dr.

2018-02-01

In the present scenario, many traditional materials are being replaced by composite materials for its light weight and high strength properties. Industries like automotive industry, aerospace industry etc., are some of the examples which uses composite materials for most of its components. Replacing of components which are subjected to static load or impact load are less challenging compared to components which are subjected to dynamic loading. Replacing the components made up of composite materials demands many stages of parametric study. One such parametric study is the fatigue analysis of composite material. This paper focuses on the fatigue life analysis of the composite material by using computational techniques. A composite plate is considered for the study which has a hole at the center. The analysis is carried on (0°/90°/90°/90°/90°)s laminate sequence and (45°/-45°)2s laminate sequence by using a computer script. The life cycles for both the lay-up sequence are compared with each other. It is observed that, for the same material and geometry of the component, cross ply laminates show better fatigue life than that of angled ply laminates.

Photodegradation in ballistic laminates: Spectroscopy and lifetime extension

Energy Technology Data Exchange (ETDEWEB)

Renschler, C.L.; Stallard, B.R.; White, C.A.; Garcia, M.J.; Morse, H.E. [Sandia National Labs., Albuquerque, NM (United States). Properties of Organic Materials Dept.

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.

Development of High Performance CFRP/Metal Active Laminates

Science.gov (United States)

Asanuma, Hiroshi; Haga, Osamu; Imori, Masataka

This paper describes development of high performance CFRP/metal active laminates mainly by investigating the kind and thickness of the metal. Various types of the laminates were made by hot-pressing of an aluminum, aluminum alloys, a stainless steel and a titanium for the metal layer as a high CTE material, a unidirectional CFRP prepreg as a low CTE/electric resistance heating material, a unidirectional KFRP prepreg as a low CTE/insulating material. The aluminum and its alloy type laminates have almost the same and the highest room temperature curvatures and they linearly change with increasing temperature up to their fabrication temperature. The curvature of the stainless steel type jumps from one to another around its fabrication temperature, whereas the titanium type causes a double curvature and its change becomes complicated. The output force of the stainless steel type attains the highest of the three under the same thickness. The aluminum type successfully increased its output force by increasing its thickness and using its alloys. The electric resistance of the CFRP layer can be used to monitor the temperature, that is, the curvature of the active laminate because the curvature is a function of temperature.

No amelioration of uromodulin maturation and trafficking defect by sodium 4-phenylbutyrate in vivo: studies in mouse models of uromodulin-associated kidney disease.

Science.gov (United States)

Kemter, Elisabeth; Sklenak, Stefanie; Rathkolb, Birgit; Hrabě de Angelis, Martin; Wolf, Eckhard; Aigner, Bernhard; Wanke, Ruediger

2014-04-11

Uromodulin (UMOD)-associated kidney disease (UAKD) belongs to the hereditary progressive ER storage diseases caused by maturation defects of mutant UMOD protein. Current treatments of UAKD patients are symptomatic and cannot prevent disease progression. Two in vitro studies reported a positive effect of the chemical chaperone sodium 4-phenylbutyrate (4-PBA) on mutant UMOD maturation. Thus, 4-PBA was suggested as a potential treatment for UAKD. This study evaluated the effects of 4-PBA in two mouse models of UAKD. In contrast to previous in vitro studies, treatment with 4-PBA did not increase HSP70 expression or improve maturation and trafficking of mutant UMOD in vivo. Kidney function of UAKD mice was actually deteriorated by 4-PBA treatment. In transfected tubular epithelial cells, 4-PBA did not improve maturation but increased the expression level of both mutant and wild-type UMOD protein. Activation of NF-κB pathway in thick ascending limb of Henle's loop cells of UAKD mice was detected by increased abundance of RelB and phospho-IκB kinase α/β, an indirect activator of NF-κB. Furthermore, the abundance of NF-κB1 p105/p50, NF-κB2 p100/p52, and TRAF2 was increased in UAKD. NF-κB activation was identified as a novel disease mechanism of UAKD and might be a target for therapeutic intervention.

High yielding and disease resistant mutants of sorghum in Venezuela

Energy Technology Data Exchange (ETDEWEB)

Reinoso, A; Murty, B R; Taborda, F [Faculty of Agronomy, University of Zulia, Maracaibo (Venezuela)

1987-07-01

The programme was assisted by IAEA under project VEN/5/005 since 1978. It aims at improvement of plant type, earliness and resistance to Macrophomina in the locally adapted varieties Criollo Rojo Pequeno (CRP) and Criollo Blanco Alto (CBA). The mutagenic treatment consisted of seed irradiation at 20, 30 and 40 kR of gamma rays and chemical mutagenesis using sodium azide followed by 5000 kR gamma radiation. The 16 best mutants were evaluated in multilocation trials during M{sub 6}-M{sub 9} 1981-1984: Mutants from CRP namely 1279, 1543, 1265, 2085, 1251 and 1359 and four mutant from CBA, 109, 467, 469 and 81-1227 were found to be superior to their parents and the existing commercial hybrids. CRP 1279, 1543 and 2085 are already under large scale cultivation by farmers and under process for cultivar certification by the Ministry of Agriculture.

High yielding and disease resistant mutants of sorghum in Venezuela

International Nuclear Information System (INIS)

Reinoso, A.; Murty, B.R.; Taborda, F.

1987-01-01

The programme was assisted by IAEA under project VEN/5/005 since 1978. It aims at improvement of plant type, earliness and resistance to Macrophomina in the locally adapted varieties Criollo Rojo Pequeno (CRP) and Criollo Blanco Alto (CBA). The mutagenic treatment consisted of seed irradiation at 20, 30 and 40 kR of gamma rays and chemical mutagenesis using sodium azide followed by 5000 kR gamma radiation. The 16 best mutants were evaluated in multilocation trials during M 6 -M 9 1981-1984: Mutants from CRP namely 1279, 1543, 1265, 2085, 1251 and 1359 and four mutant from CBA, 109, 467, 469 and 81-1227 were found to be superior to their parents and the existing commercial hybrids. CRP 1279, 1543 and 2085 are already under large scale cultivation by farmers and under process for cultivar certification by the Ministry of Agriculture

UV irradiation analysis of complementation between, and replication of, RNA-negative temperature-sensitivie mutants of Newcastle disease virus

International Nuclear Information System (INIS)

Peeples, M.E.; Bratt, M.A.

1982-01-01

Random uv irradiation-induced lesions destroy the infectivity of Newcastle disease virus (NDV) by blocking downstream transcription from the single viral promoter. The nucleocapsid-associated polypeptides most likely to be involved in RNA synthesis are located at the extreme ends of the genome: NP and P are promoter proximal genes, and L is the most distal gene. We attempted to order the two temperature-sensitive (ts) RNA-negative (RNA-) mutant groups of NDV by determining the uv target sizes for the complementing abilities of mutants A1 and E1. After uv irradiation, E1 was unable to complement A1, a result compatible with the A mutation lying in the L gene. In contrast, after uv irradiation A1 was able to complement E1 for both virus production and viral protein synthesis, with a target size most consistent with the E mutation lying in the P gene. UV-irradiated virus was unable to replicate as indicated by its absence in the yields of multiply infected cells, either as infectious virus or as particles with complementing activity. After irradiation, ts mutant B1ΔP, with a non-ts mutation affecting the electrophoretic mobility of the P protein, complemented E1 in a manner similar to A1, but it did not amplify the expression of ΔP in infected cells. This too is consistent with irradiated virus being unable to replicate despite the presence of the components needed for replication of E1. At high uv doses, A1 was able to complement E1 in a different, uv-resistant manner, probably by direct donation of input polypeptides. Multiplicity reactivation has previously been observed at high-multiplicity infection by uv-irradiated paramyxoviruses. In this case, virions which are noninfectious because they lack a protein component may be activated by a protein from irradiated virions

Isozyme patterns of powdery mildew resistant wheat mutants

International Nuclear Information System (INIS)

Xia Wengau; Li Zhengkui; Wang Kefeng

1989-01-01

Full Text: Wheat mutants induced by gamma irradiation and showing improved resistance to powdery mildew were analysed for isozymes. The peroxidase band 3A could be related to the disease reaction. The band 3A is absent in resistant mutants, the higher the activity of band 3A the greater the susceptibility. (author)

Analysis of a brittle-culm mutant of rice (Oryza sativa) induced bay gamma rays

International Nuclear Information System (INIS)

Doat, Jacqueline; Marie, R.

1977-01-01

An unexpected ''brittle-culm'' mutant has been screened in the progeny of the rice cultivar ''Balilla 28'' after a seed treatment by gamma rays from a Cobalt-60 source. This property proved hereditable and true-breeding. It does not affect the high resistance to lodging of rice plants. Important difference were pointed out between control and mutant lines in cellulose content and 1 p. cent NaOH extracts: ''brittle-culm'' straw contains less cellulose and shows a degradation of glucid coupounds. The brittleness of plant tissues appears to be correlated with a partial depolymerization of cellulose, associated with a possible transformation from alpha- to beta- or gamma-cellulose [fr

Primary coenzyme Q deficiency in Pdss2 mutant mice causes isolated renal disease.

Directory of Open Access Journals (Sweden)

Min Peng

2008-04-01

Full Text Available Coenzyme Q (CoQ is an essential electron carrier in the respiratory chain whose deficiency has been implicated in a wide variety of human mitochondrial disease manifestations. Its multi-step biosynthesis involves production of polyisoprenoid diphosphate in a reaction that requires the enzymes be encoded by PDSS1 and PDSS2. Homozygous mutations in either of these genes, in humans, lead to severe neuromuscular disease, with nephrotic syndrome seen in PDSS2 deficiency. We now show that a presumed autoimmune kidney disease in mice with the missense Pdss2(kd/kd genotype can be attributed to a mitochondrial CoQ biosynthetic defect. Levels of CoQ9 and CoQ10 in kidney homogenates from B6.Pdss2(kd/kd mutants were significantly lower than those in B6 control mice. Disease manifestations originate specifically in glomerular podocytes, as renal disease is seen in Podocin/cre,Pdss2(loxP/loxP knockout mice but not in conditional knockouts targeted to renal tubular epithelium, monocytes, or hepatocytes. Liver-conditional B6.Alb/cre,Pdss2(loxP/loxP knockout mice have no overt disease despite demonstration that their livers have undetectable CoQ9 levels, impaired respiratory capacity, and significantly altered intermediary metabolism as evidenced by transcriptional profiling and amino acid quantitation. These data suggest that disease manifestations of CoQ deficiency relate to tissue-specific respiratory capacity thresholds, with glomerular podocytes displaying the greatest sensitivity to Pdss2 impairment.

Modeling delamination of FRP laminates under low velocity impact

Science.gov (United States)

Jiang, Z.; Wen, H. M.; Ren, S. L.

2017-09-01

Fiber reinforced plastic laminates (FRP) have been increasingly used in various engineering such as aeronautics, astronautics, transportation, naval architecture and their impact response and failure are a major concern in academic community. A new numerical model is suggested for fiber reinforced plastic composites. The model considers that FRP laminates has been constituted by unidirectional laminated plates with adhesive layers. A modified adhesive layer damage model that considering strain rate effects is incorporated into the ABAQUS / EXPLICIT finite element program by the user-defined material subroutine VUMAT. It transpires that the present model predicted delamination is in good agreement with the experimental results for low velocity impact.

Numerical analysis of laminated elastomer by FEM

International Nuclear Information System (INIS)

Mazda, T.; Shiojiri, H.

1993-01-01

A Computer code based on mixed finite element method was developed for three dimensional large strain analyses of laminated elastomers including nonlinear bulk stress vs. bulk strain relationships. The adopted element is the variable node element with maximum node numbers of 27 for displacements and 4 for pressures. At first, the displacements and pressures were calculated by the code using single element under various loading conditions. The results were compared with theoretical solutions and the both results' exactly coincided with each other. Next, the analyses of laminated elastomers subjected to axial loadings were conducted using both the new code and ABAQUS code, and the results were compared with the test results. The agreement of the results of the present code were better than ABAQUS code mainly due to the capability of handling wider range of material properties. Lastly, the shearing tests of laminated elastomers were simulated by the new code. The results were shown to be in good agreement with the test results. (author)

The role of endotoxin in the pathogenesis of acute bovine laminitis.

Science.gov (United States)

Boosman, R; Mutsaers, C W; Klarenbeek, A

1991-07-01

To study the possible role of endotoxin in the pathogenesis of bovine laminitis, local and systemic injections of endotoxin (E. coli 0111 B4) with different doses were given to three groups of four cows each. Clinical and haematologic parameters indicated an acute-phase response, including positive plasma ethanol gelation (soluble fibrin), the occurrence of fibrin degradation products and decreased thrombocyte counts. Local Shwartzman reactions were not evoked. Clinical examination of the claws and the gait of the animals revealed no signs of laminitis. However, on histopathological examination of the claw corium signs of laminitis such as vacuolisation of the Stratum basale, lymphocyte and leucocyte infiltration and thrombosis were found. These results indicate that endotoxin indeed may be involved in the pathogenesis of laminitis. For the development of a clinical acute laminitis model in cattle either another dosage, other toxins or factors in addition to the endotoxin used in this experiment are needed.

Tungsten foil laminate for structural divertor applications - Joining of tungsten foils

Science.gov (United States)

Reiser, Jens; Rieth, Michael; Möslang, Anton; Dafferner, Bernhard; Hoffmann, Jan; Mrotzek, Tobias; Hoffmann, Andreas; Armstrong, D. E. J.; Yi, Xiaoou

2013-05-01

This paper is the fourth in our series on tungsten laminates. The aim of this paper is to discuss laminate synthesis, meaning the joining of tungsten foils. It is obvious that the properties of the tungsten laminate strongly depend on the combination of (i) interlayer and (ii) joining technology, as this combination defines (i) the condition of the tungsten foil after joining (as-received or recrystallised) as well as (ii) the characteristics of the interface between the tungsten foil and the interlayer (wettability or diffusion leading to a solid solution or the formation of intermetallics). From the example of tungsten laminates joined by brazing with (i) an eutectic silver copper brazing filler, (ii) copper, (iii) titanium, and (iv) zirconium, the microstructure will be discussed, with special focus on the interface. Based on our assumptions of the mechanism of the extraordinary ductility of tungsten foil we present three syntheses strategies and make recommendations for the synthesis of high temperature tungsten laminates.

Genetical, cytological and physiological studies on the induced mutants with special regard to effective methods for obtaining useful mutants in perennial woody plants

International Nuclear Information System (INIS)

Kukimura, H.; Ikeda, F.; Fujita, H.; Maeta, T.; Nakajima, K.; Katagiri, K.; Nakahira, K.; Somegou, M.

1975-01-01

The study was aimed at elucidating the biological aspects of artificially induced mutations in perennial tree crops and at promoting the utilization of such mutations in a practical breeding programme. A number of mutants obtained particularly in Cryptomeria and mulberry (Morus spp.) by means of gamma radiation were examined for their practical usefulness. Doses from 7.5 to 15.0 kR were used. In mulbery, some mutant strains showed increased shoot growth, and one mutant strain showed a remarkable increase also in rooting ability. Entire leaf mutants were investigated for their breeding behaviour. None of the mutant strains showed acquired disease resistance. Changes in the number of isozyme bands and different staining intensity was observed in all the mutant strains compared to the original strains

The functional importance of disease-associated mutation

Directory of Open Access Journals (Sweden)

Klein Teri E

2002-09-01

Full Text Available Abstract Background For many years, scientists believed that point mutations in genes are the genetic switches for somatic and inherited diseases such as cystic fibrosis, phenylketonuria and cancer. Some of these mutations likely alter a protein's function in a manner that is deleterious, and they should occur in functionally important regions of the protein products of genes. Here we show that disease-associated mutations occur in regions of genes that are conserved, and can identify likely disease-causing mutations. Results To show this, we have determined conservation patterns for 6185 non-synonymous and heritable disease-associated mutations in 231 genes. We define a parameter, the conservation ratio, as the ratio of average negative entropy of analyzable positions with reported mutations to that of every analyzable position in the gene sequence. We found that 84.0% of the 231 genes have conservation ratios less than one. 139 genes had eleven or more analyzable mutations and 88.0% of those had conservation ratios less than one. Conclusions These results indicate that phylogenetic information is a powerful tool for the study of disease-associated mutations. Our alignments and analysis has been made available as part of the database at http://cancer.stanford.edu/mut-paper/. Within this dataset, each position is annotated with the analysis, so the most likely disease-causing mutations can be identified.

Molecular and biochemical analyses of spontaneous and X-ray-induced mutants in human lymphoblastoid cells

Energy Technology Data Exchange (ETDEWEB)

Liber, H L; Call, K M; Little, J B

1987-05-01

The authors have isolated a series of 14 spontaneously arising and 28 X-ray-induced mutants at the hypoxanthine-guanine phosphoribosyltransferase (hgprt) locus in human lymphoblastoid cells. Among the spontaneous mutants, 5/14 (36%) had detectable alterations in their restriction fragment pattern after hybridization with a human cDNA probe for hgprt. Of the 10 remaining mutants, 4 had partial HGPRT enzyme activity, which suggested that they contained point mutations. Among the 28 mutants induced by 150 rad of X-rays, 15 (54%) had deletions of part or all of the hgprt gene. Of the remaining 13 (18% overall) 5 had partial HGPRT enzyme activity, which suggested that they contained point mutations. These data imply that in this human cell system, X-rays induce both point mutants which have residual enzyme activity as well as mutations involving relatively large deletions of DNA. 48 reference, 1 figure, 4 tables.

Feeding practices and potential risk factors for laminitis in dairy cows in Thailand

OpenAIRE

Pilachai, R.

2013-01-01

Laminitis is considered an important health problem facing the Thai dairy industry. Although the etiology of laminitis is multifactorial, nutrition is considered an important risk factor. Rumen acidosis, lipopolysaccharides (LPS) and histamine may play a role in the development of laminitis in dairy cattle. However, the relevancy of these risk factors in relation to the occurrence of laminitis under practical feeding conditions in Thailand is not clear. In Thailand, dairy rations are generall...

The role of shape memory alloy on impact response of glass/epoxy laminates under low temperature

International Nuclear Information System (INIS)

Kang, K. W.; Kim, H. J.

2007-01-01

The paper aims to evaluate the impact response of glass/epoxy laminates with embedded shape memory alloy (SMA) subject to low velocity impact at various temperatures. For the goal, the impact tests were performed by using an instrumented impact-testing machine at three temperatures: 293K, 263K and 233K for the baseline (laminates without SMA wires) and SMA laminates (laminates with embedded SMA wires). And the resultant damages were inspected through the scanning acoustic microscope (SAM). Also, based on the impact force history and the damage configuration, the impact resistance parameters were employed to evaluate damage resistance of laminates with embedded SMA wires. As a result, it was observed that the damage resistance of glass/epoxy laminates is influenced by embedded SMA wires and embedding SMA wires into laminates does not compromise the structure any differently to laminates without wires. In fact, it has been shown that under lower temperature, the SMA laminates have a little superior damage resistance compared with the baseline laminates

A Novel Electro-Thermal Laminated Ceramic with Carbon-Based Layer

Directory of Open Access Journals (Sweden)

Yi Ji

2017-06-01

Full Text Available A novel electro-thermal laminated ceramic composed of ceramic tile, carbon-based layer, dielectric layer, and foaming ceramic layer was designed and prepared by tape casting. The surface temperature achieved at an applied voltage of 10 V by the laminated ceramics was 40.3 °C when the thickness of carbon-based suspension was 1.0 mm and the adhesive strength between ceramic tile and carbon-based layer was 1.02 ± 0.06 MPa. In addition, the thermal aging results at 100 °C up to 192 h confirmed the high thermal stability and reliability of the electro-thermal laminated ceramics. The development of this laminated ceramic with excellent electro-thermal properties and safety provides a new individual heating device which is highly expected to be widely applied in the field of indoor heat supply.

Optimum design of laminated composite under axial compressive load

Indian Academy of Sciences (India)

In the present study optimal design of composite laminates, with and without rectangular cut-out, is carried out for maximizing the buckling load. Optimization study is carried out for obtaining the maximum buckling load with design variables as ply thickness, cut-out size and orientation of cut-out with respect to laminate.

Fabrication and Characterization of Graded Anodes for Anode-Supported Solid Oxide Fuel Cells by Tape Casting and Lamination

DEFF Research Database (Denmark)

Beltran-Lopez, J.F.; Laguna-Bercero, M.A.; Gurauskis, Jonas

2014-01-01

Graded anodes for anode-supported solid oxide fuel cells (SOFCs) are fabricated by tape casting and subsequent cold lamination of plates using different compositions. Rheological parameters are adjusted to obtain stable suspensions for tape casting. The conditions for the tape casting and laminat......Graded anodes for anode-supported solid oxide fuel cells (SOFCs) are fabricated by tape casting and subsequent cold lamination of plates using different compositions. Rheological parameters are adjusted to obtain stable suspensions for tape casting. The conditions for the tape casting...... and lamination will be described. Flexural strength of the reduced cermets measured using three-point bending configuration is 468±37MPa. The graded anode supports are characterized by scanning electron microscope observations, mercury porosimetry intrusion, and resistivity measurements, showing an adequate...... of tapes at room temperature without using plasticizers. This is made by the combination of two different binders with varying Tg (glass transition temperature) which resulted in plastic deformation at room temperature. Those results indicate that the proposed process is a cost-effective method...

Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment. (I). Nonalcoholic fatty liver disease and its association with cardiovascular disease.

Science.gov (United States)

Brea, Ángel; Pintó, Xavier; Ascaso, Juan F; Blasco, Mariano; Díaz, Ángel; González-Santos, Pedro; Hernández Mijares, Antonio; Mantilla, Teresa; Millán, Jesús; Pedro-Botet, Juan

Non-alcoholic fatty liver disease (NAFLD) comprises a series of histologically lesions similar to those induced by alcohol consumption in people with very little or no liver damage. The importance of NAFLD is its high prevalence in the Western world and, from the point of view of the liver, in its gradual progression from steatosis to steatohepatitis, cirrhosis, and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with acceleration of arteriosclerosis and events related to it, being the main cause of its morbidity and mortality. This review, updated to January 2016, consists of two parts, with the first part analysing the association of NAFLD with cardiovascular disease. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Rescue of glaucoma-causing mutant myocilin thermal stability by chemical chaperones

Science.gov (United States)

Burns, J. Nicole; Orwig, Susan D.; Harris, Julia L.; Watkins, J. Derrick; Vollrath, Douglas; Lieberman, Raquel L.

2010-01-01

Mutations in myocilin cause an inherited form of open angle glaucoma, a prevalent neurodegenerative disorder associated with increased intraocular pressure. Myocilin forms part of the trabecular meshwork extracellular matrix presumed to regulate intraocular pressure. Missense mutations, clustered in the olfactomedin (OLF) domain of myocilin, render the protein prone to aggregation in the endoplasmic reticulum of trabecular meshwork cells, causing cell dysfunction and death. Cellular studies have demonstrated temperature-sensitive secretion of myocilin mutants, but difficulties in expression and purification have precluded biophysical characterization of wild-type (wt) myocilin and disease-causing mutants in vitro. We have overcome these limitations by purifying wt and select glaucoma-causing mutant (D380A, I477N, I477S, K423E) forms of the OLF domain (228–504) fused to maltose binding protein (MBP) from E. coli. Monomeric fusion proteins can be isolated in solution. To determine the relative stability of wt and mutant OLF domains, we developed a fluorescence thermal stability assay without removal of MBP, and provide the first direct evidence that mutated OLF is folded but less thermally stable than wt. We tested the ability of seven chemical chaperones to stabilize mutant myocilin. Only sarcosine and trimethylamine N-oxide were capable of shifting the melting temperature of all mutants tested to near that of wt OLF. Our work lays the foundation for the identification of tailored small molecules capable of stabilizing mutant myocilin and promoting secretion to the extracellular matrix, to better control intraocular pressure and ultimately delay the onset of myocilin glaucoma. PMID:20334347

Establishment of Homozygote Mutant Human Embryonic Stem Cells by Parthenogenesis.

Science.gov (United States)

Epsztejn-Litman, Silvina; Cohen-Hadad, Yaara; Aharoni, Shira; Altarescu, Gheona; Renbaum, Paul; Levy-Lahad, Ephrat; Schonberger, Oshrat; Eldar-Geva, Talia; Zeligson, Sharon; Eiges, Rachel

2015-01-01

We report on the derivation of a diploid 46(XX) human embryonic stem cell (HESC) line that is homozygous for the common deletion associated with Spinal muscular atrophy type 1 (SMA) from a pathenogenetic embryo. By characterizing the methylation status of three different imprinted loci (MEST, SNRPN and H19), monitoring the expression of two parentally imprinted genes (SNRPN and H19) and carrying out genome-wide SNP analysis, we provide evidence that this cell line was established from the activation of a mutant oocyte by diploidization of the entire genome. Therefore, our SMA parthenogenetic HESC (pHESC) line provides a proof-of-principle for the establishment of diseased HESC lines without the need for gene manipulation. As mutant oocytes are easily obtained and readily available during preimplantation genetic diagnosis (PGD) cycles, this approach should provide a powerful tool for disease modelling and is especially advantageous since it can be used to induce large or complex mutations in HESCs, including gross DNA alterations and chromosomal rearrangements, which are otherwise hard to achieve.

Establishment of Homozygote Mutant Human Embryonic Stem Cells by Parthenogenesis.

Directory of Open Access Journals (Sweden)

Silvina Epsztejn-Litman

Full Text Available We report on the derivation of a diploid 46(XX human embryonic stem cell (HESC line that is homozygous for the common deletion associated with Spinal muscular atrophy type 1 (SMA from a pathenogenetic embryo. By characterizing the methylation status of three different imprinted loci (MEST, SNRPN and H19, monitoring the expression of two parentally imprinted genes (SNRPN and H19 and carrying out genome-wide SNP analysis, we provide evidence that this cell line was established from the activation of a mutant oocyte by diploidization of the entire genome. Therefore, our SMA parthenogenetic HESC (pHESC line provides a proof-of-principle for the establishment of diseased HESC lines without the need for gene manipulation. As mutant oocytes are easily obtained and readily available during preimplantation genetic diagnosis (PGD cycles, this approach should provide a powerful tool for disease modelling and is especially advantageous since it can be used to induce large or complex mutations in HESCs, including gross DNA alterations and chromosomal rearrangements, which are otherwise hard to achieve.

Optimization of Laminated Composite Structures

DEFF Research Database (Denmark)

Henrichsen, Søren Randrup

of the contributions of the PhD project are included in the second part of the thesis. Paper A presents a framework for free material optimization where commercially available finite element analysis software is used as analysis tool. Robust buckling optimization of laminated composite structures by including...... allows for a higher degree of tailoring of the resulting material. To enable better utilization of the composite materials, optimum design procedures can be used to assist the engineer. This PhD thesis is focused on developing numerical methods for optimization of laminated composite structures...... nonlinear analysis of structures, buckling and post-buckling analysis of structures, and formulations for optimization of structures considering stiffness, buckling, and post-buckling criteria. Lastly, descriptions, main findings, and conclusions of the papers are presented. The papers forming the basis...

Formaldehyde and TVOC emission behavior of laminate flooring by structure of laminate flooring and heating condition.

Science.gov (United States)

An, Jae-Yoon; Kim, Sumin; Kim, Hyun-Joong

2011-03-15

Formaldehyde was measured with a desiccator, a 20 L chamber and the FLEC method. The formaldehyde emission rate from laminate was the highest at 32 °C using the desiccator, which then decreased with time. The formaldehyde emission using the 20 L small chamber and FLEC showed a similar tendency. There was a strong correlation between the formaldehyde and total volatile organic compounds (TVOCs) with both types of floorings using the two different methods. The formaldehyde emission rate and TVOC results were higher when tested using the FLEC method than with the 20 L small chamber method. The emission rate was affected by the joint edge length in laminate flooring. Toluene, ethylbenzene and xylene were the main VOCs emitted from laminate flooring, and there were more unidentified VOCs emitted than identified VOCs. The samples heated with a floor heating system emitted more formaldehyde than those heated using an air circulation system due to the temperature difference between the bottom panel and flooring. The TVOC emission level of the samples was higher when an air circulation system was used than when a floor heating system was used due to the high ventilation rate. Copyright © 2010 Elsevier B.V. All rights reserved.

Overexpression of mutant ataxin-3 in mouse cerebellum induces ataxia and cerebellar neuropathology.

Science.gov (United States)

Nóbrega, Clévio; Nascimento-Ferreira, Isabel; Onofre, Isabel; Albuquerque, David; Conceição, Mariana; Déglon, Nicole; de Almeida, Luís Pereira

2013-08-01

Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is a fatal, dominant neurodegenerative disorder caused by the polyglutamine-expanded protein ataxin-3. Clinical manifestations include cerebellar ataxia and pyramidal signs culminating in severe neuronal degeneration. Currently, there is no therapy able to modify disease progression. In the present study, we aimed at investigating one of the most severely affected brain regions in the disorder--the cerebellum--and the behavioral defects associated with the neuropathology in this region. For this purpose, we injected lentiviral vectors encoding full-length human mutant ataxin-3 in the mouse cerebellum of 3-week-old C57/BL6 mice. We show that circumscribed expression of human mutant ataxin-3 in the cerebellum mediates within a short time frame--6 weeks, the development of a behavioral phenotype including reduced motor coordination, wide-based ataxic gait, and hyperactivity. Furthermore, the expression of mutant ataxin-3 resulted in the accumulation of intranuclear inclusions, neuropathological abnormalities, and neuronal death. These data show that lentiviral-based expression of mutant ataxin-3 in the mouse cerebellum induces localized neuropathology, which is sufficient to generate a behavioral ataxic phenotype. Moreover, this approach provides a physiologically relevant, cost-effective and time-effective animal model to gain further insights into the pathogenesis of MJD and for the evaluation of experimental therapeutics of MJD.

Poliovirus Mutants Resistant to Neutralization with Soluble Cell Receptors

Science.gov (United States)

Kaplan, Gerardo; Peters, David; Racaniello, Vincent R.

1990-12-01

Poliovirus mutants resistant to neutralization with soluble cellular receptor were isolated. Replication of soluble receptor-resistant (srr) mutants was blocked by a monoclonal antibody directed against the HeLa cell receptor for poliovirus, indicating that the mutants use this receptor to enter cells. The srr mutants showed reduced binding to HeLa cells and cell membranes. However, the reduced binding phenotype did not have a major impact on viral replication, as judged by plaque size and one-step growth curves. These results suggest that the use of soluble receptors as antiviral agents could lead to the selection of neutralization-resistant mutants that are able to bind cell surface receptors, replicate, and cause disease.

Feeding practices and potential risk factors for laminitis in dairy cows in Thailand

NARCIS (Netherlands)

Pilachai, R.

2013-01-01

Laminitis is considered an important health problem facing the Thai dairy industry. Although the etiology of laminitis is multifactorial, nutrition is considered an important risk factor. Rumen acidosis, lipopolysaccharides (LPS) and histamine may play a role in the development of laminitis in dairy

Eddy-current effect on resonant magnetoelectric coupling in magnetostrictive-piezoelectric laminated composites

Science.gov (United States)

Liu, Guoxi; Zhang, Chunli; Chen, Weiqiu; Dong, Shuxiang

2013-07-01

An analytical model of resonant magnetoelectric (ME) coupling in magnetostrictive (MS)-piezoelectric (PE) laminated composites in consideration of eddy-current effect in MS layer using equivalent circuit method is presented. Numerical calculations show that: (1) the eddy-current has a strong effect on ME coupling in MS-PE laminated composites at resonant frequency; and (2) the resonant ME coupling is then significantly dependent on the sizes of ME laminated composites, which were neglected in most previous theoretical analyses. The achieved results provide a theoretical guidance for the practice engineering design, manufacture, and application of ME laminated composites and devices.

Bonding techniques for flexural strengthening of R.C. beams using CFRP laminates

Directory of Open Access Journals (Sweden)

Alaa Morsy

2013-09-01

Full Text Available This paper presents an experimental study of an alternative method of attaching FRP laminates to reinforced concrete beams by the way of fasting steel rivets through the FRP laminate and concrete substrate. Five full scale R.C. beams were casted and strengthened in flexural using FRP laminate bonded with conventional epoxy and compared with other beams strengthened with FRP laminate and bonded with fastener “steel rivets” of 50 mm length and 10 mm diameter. Based on experimental evidence the beam strengthened with conventional bonding methods failed due to de-bonding with about 13% increase over the un-strengthened beam. On the other hand, the beams strengthened with FRP laminate and bonded by four steel fastener rivets only failed by de-bonding also but at higher flexural capacity with increase 19% over the un-strengthened beam.

Structural dataset for the PPARγ V290M mutant

Directory of Open Access Journals (Sweden)

Ana C. Puhl

2016-06-01

Full Text Available Loss-of-function mutation V290M in the ligand-binding domain of the peroxisome proliferator activated receptor γ (PPARγ is associated with a ligand resistance syndrome (PLRS, characterized by partial lipodystrophy and severe insulin resistance. In this data article we discuss an X-ray diffraction dataset that yielded the structure of PPARγ LBD V290M mutant refined at 2.3 Å resolution, that allowed building of 3D model of the receptor mutant with high confidence and revealed continuous well-defined electron density for the partial agonist diclofenac bound to hydrophobic pocket of the PPARγ. These structural data provide significant insights into molecular basis of PLRS caused by V290M mutation and are correlated with the receptor disability of rosiglitazone binding and increased affinity for corepressors. Furthermore, our structural evidence helps to explain clinical observations which point out to a failure to restore receptor function by the treatment with a full agonist of PPARγ, rosiglitazone.

78 FR 23591 - Certain Prepregs, Laminates, and Finished Circuit Boards

Science.gov (United States)

2013-04-19

... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-659 (Enforcement)] Certain Prepregs... United States after importation of certain prepregs, laminates, and finished circuit boards that infringe... prepregs and laminates that are the subject of the investigation or that otherwise infringe, induce, and/or...

Laminated lumber may be more profitable than sawn lumber

Science.gov (United States)

P. Koch

1976-01-01

By laminating 1/4-in. rotary-cut veneer into structural lumber, manufacturers can expand lumber output by at least 30% without increasing volume logged. The idea merits intensive study. Manufacturing plus raw material costs should total about $142/Mbf; sales price for desirable widths and lengths of the strong laminated product should approach or exceed $200/Mbf.

Binder-free highly conductive graphene laminate for low cost printed radio frequency applications

Energy Technology Data Exchange (ETDEWEB)

Huang, Xianjun; Leng, Ting; Zhang, Xiao; Hu, Zhirun, E-mail: Z.Hu@manchester.ac.uk [School of Electrical and Electronic Engineering, University of Manchester, Manchester (United Kingdom); Chen, Jia Cing; Chang, Kuo Hsin [BGT Materials Limited, Photon Science Institute, University of Manchester, Manchester M13 9PL (United Kingdom); Geim, Andre K. [Manchester Centre for Mesoscience and Nanotechnology, University of Manchester, Manchester (United Kingdom); Novoselov, Kostya S. [School of Physics and Astronomy, University of Manchester, Manchester (United Kingdom)

2015-05-18

In this paper, we demonstrate realization of printable radio frequency identification (RFID) antenna by low temperature processing of graphene ink. The required ultra-low resistance is achieved by rolling compression of binder-free graphene laminate. With compression, the conductivity of graphene laminate is increased by more than 50 times compared to that of as-deposited one. Graphene laminate with conductivity of 4.3 × 10{sup 4 }S/m and sheet resistance of 3.8 Ω/sq (with thickness of 6 μm) is presented. Moreover, the formation of graphene laminate from graphene ink reported here is simple and can be carried out in low temperature (100 °C), significantly reducing the fabrication costs. A dipole antenna based on the highly conductive graphene laminate is further patterned and printed on a normal paper to investigate its RF properties. The performance of the graphene laminate antenna is experimentally measured. The measurement results reveal that graphene laminate antenna can provide practically acceptable return loss, gain, bandwidth, and radiation patterns, making it ideal for low cost printed RF applications, such as RFID tags and wearable wireless sensor networks.

Binder-free highly conductive graphene laminate for low cost printed radio frequency applications

International Nuclear Information System (INIS)

Huang, Xianjun; Leng, Ting; Zhang, Xiao; Hu, Zhirun; Chen, Jia Cing; Chang, Kuo Hsin; Geim, Andre K.; Novoselov, Kostya S.

2015-01-01

In this paper, we demonstrate realization of printable radio frequency identification (RFID) antenna by low temperature processing of graphene ink. The required ultra-low resistance is achieved by rolling compression of binder-free graphene laminate. With compression, the conductivity of graphene laminate is increased by more than 50 times compared to that of as-deposited one. Graphene laminate with conductivity of 4.3 × 10 4  S/m and sheet resistance of 3.8 Ω/sq (with thickness of 6 μm) is presented. Moreover, the formation of graphene laminate from graphene ink reported here is simple and can be carried out in low temperature (100 °C), significantly reducing the fabrication costs. A dipole antenna based on the highly conductive graphene laminate is further patterned and printed on a normal paper to investigate its RF properties. The performance of the graphene laminate antenna is experimentally measured. The measurement results reveal that graphene laminate antenna can provide practically acceptable return loss, gain, bandwidth, and radiation patterns, making it ideal for low cost printed RF applications, such as RFID tags and wearable wireless sensor networks

Process monitoring of glass reinforced polypropylene laminates using fiber Bragg gratings

KAUST Repository

Mulle, Matthieu; Wafai, Husam; Yudhanto, Arief; Lubineau, Gilles; Yaldiz, R.; Schijve, W.; Verghese, N.

2015-01-01

Hot-press molding of glass-fiber-reinforced polypropylene (GFPP) laminates was monitored using longitudinally and transversely embedded fiber Bragg gratings (FBGs) at different locations in unidirectional laminates. The optical sensors proved

Stochastic-Strength-Based Damage Simulation of Ceramic Matrix Composite Laminates

Science.gov (United States)

Nemeth, Noel N.; Mital, Subodh K.; Murthy, Pappu L. N.; Bednarcyk, Brett A.; Pineda, Evan J.; Bhatt, Ramakrishna T.; Arnold, Steven M.

2016-01-01

The Finite Element Analysis-Micromechanics Analysis Code/Ceramics Analysis and Reliability Evaluation of Structures (FEAMAC/CARES) program was used to characterize and predict the progressive damage response of silicon-carbide-fiber-reinforced reaction-bonded silicon nitride matrix (SiC/RBSN) composite laminate tensile specimens. Studied were unidirectional laminates [0] (sub 8), [10] (sub 8), [45] (sub 8), and [90] (sub 8); cross-ply laminates [0 (sub 2) divided by 90 (sub 2),]s; angled-ply laminates [plus 45 (sub 2) divided by -45 (sub 2), ]s; doubled-edge-notched [0] (sub 8), laminates; and central-hole laminates. Results correlated well with the experimental data. This work was performed as a validation and benchmarking exercise of the FEAMAC/CARES program. FEAMAC/CARES simulates stochastic-based discrete-event progressive damage of ceramic matrix composite and polymer matrix composite material structures. It couples three software programs: (1) the Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC), (2) the Ceramics Analysis and Reliability Evaluation of Structures Life Prediction Program (CARES/Life), and (3) the Abaqus finite element analysis program. MAC/GMC contributes multiscale modeling capabilities and micromechanics relations to determine stresses and deformations at the microscale of the composite material repeating-unit-cell (RUC). CARES/Life contributes statistical multiaxial failure criteria that can be applied to the individual brittle-material constituents of the RUC, and Abaqus is used to model the overall composite structure. For each FEAMAC/CARES simulation trial, the stochastic nature of brittle material strength results in random, discrete damage events that incrementally progress until ultimate structural failure.

Laminitis in a mature elk hind (Cervus elaphus)

DEFF Research Database (Denmark)

Gray, Heather E.; Card, Claire; Baptiste, Keith E.

2001-01-01

Laminitis should be considered as a differential diagnosis in elk presenting with shifting leg lameness, reluctance to move, recumbency and hoof wall ridging. Eliminating the underlying cause and corrective trimming lead to a good prognosis for recovery.......Laminitis should be considered as a differential diagnosis in elk presenting with shifting leg lameness, reluctance to move, recumbency and hoof wall ridging. Eliminating the underlying cause and corrective trimming lead to a good prognosis for recovery....

Retortable Laminate/Polymeric Food Tubes for Specialized Feeding

Science.gov (United States)

2012-06-01

Report STP #3010 Results and Accomplishments (June 2010 – June 2012) Report No: FTR 303 CDRL Sequence: A003 June 2012 CORANET CONTRACT #: SP4701-08-D...June 2010 - June 2012 Retortable Laminate/Polymeric Food Tubes for Specialized Feeding - STP # 3010 SP4701-08-D-0004 MANTECH (0708011S) CORANET A003...on commercial off-the-shelf materials and not military unique. A market survey of commercially available laminated tubes revealed that they are all

Protein expression profiling of the drosophila fragile X mutant brain reveals up-regulation of monoamine synthesis.

Science.gov (United States)

Zhang, Yong Q; Friedman, David B; Wang, Zhe; Woodruff, Elvin; Pan, Luyuan; O'donnell, Janis; Broadie, Kendal

2005-03-01

Fragile X syndrome is the most common form of inherited mental retardation, associated with both cognitive and behavioral anomalies. The disease is caused by silencing of the fragile X mental retardation 1 (fmr1) gene, which encodes the mRNA-binding, translational regulator FMRP. Previously we established a disease model through mutation of Drosophila fmr1 (dfmr1) and showed that loss of dFMRP causes defects in neuronal structure, function, and behavioral output similar to the human disease state. To uncover molecular targets of dFMRP in the brain, we use here a proteomic approach involving two-dimensional difference gel electrophoresis analyses followed by mass spectrometry identification of proteins with significantly altered expression in dfmr1 null mutants. We then focus on two misregulated enzymes, phenylalanine hydroxylase (Henna) and GTP cyclohydrolase (Punch), both of which mediate in concert the synthetic pathways of two key monoamine neuromodulators, dopamine and serotonin. Brain enzymatic assays show a nearly 2-fold elevation of Punch activity in dfmr1 null mutants. Consistently brain neurochemical assays show that both dopamine and serotonin are significantly increased in dfmr1 null mutants. At a cellular level, dfmr1 null mutant neurons display a highly significant elevation of the dense core vesicles that package these monoamine neuromodulators for secretion. Taken together, these data indicate that dFMRP normally down-regulates the monoamine pathway, which is consequently up-regulated in the mutant condition. Elevated brain levels of dopamine and serotonin provide a plausible mechanistic explanation for aspects of cognitive and behavioral deficits in human patients.

Abnormal nuclear morphology is independent of longevity in a zmpste24-deficient fish model of Hutchinson-Gilford progeria syndrome (HGPS).

Science.gov (United States)

Tonoyama, Yasuhiro; Shinya, Minori; Toyoda, Atsushi; Kitano, Takeshi; Oga, Atsunori; Nishimaki, Toshiyuki; Katsumura, Takafumi; Oota, Hiroki; Wan, Miles T; Yip, Bill W P; Helen, Mok O L; Chisada, Shinichi; Deguchi, Tomonori; Au, Doris W T; Naruse, Kiyoshi; Kamei, Yasuhiro; Taniguchi, Yoshihito

2018-07-01

Lamin is an intermediate protein underlying the nuclear envelope and it plays a key role in maintaining the integrity of the nucleus. A defect in the processing of its precursor by a metalloprotease, ZMPSTE24, results in the accumulation of farnesylated prelamin in the nucleus and causes various diseases, including Hutchinson-Gilford progeria syndrome (HGPS). However, the role of lamin processing is unclear in fish species. Here, we generated zmpste24-deficient medaka and evaluated their phenotype. Unlike humans and mice, homozygous mutants did not show growth defects or lifespan shortening, despite lamin precursor accumulation. Gonadosomatic indices, blood glucose levels, and regenerative capacity of fins were similar in 1-year-old mutants and their wild-type (WT) siblings. Histological examination showed that the muscles, subcutaneous fat tissues, and gonads were normal in the mutants at the age of 1 year. However, the mutants showed hypersensitivity to X-ray irradiation, although p53target genes, p21 and mdm2, were induced 6 h after irradiation. Immunostaining of primary cultured cells from caudal fins and visualization of nuclei using H2B-GFP fusion proteins revealed an abnormal nuclear shape in the mutants both in vitro and in vivo. The telomere lengths were significantly shorter in the mutants compared to WT. Taken together, these results suggest that zmpste24-deficient medaka phenocopied HGPS only partially and that abnormal nuclear morphology and lifespan shortening are two independent events in vertebrates. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Numerical Material Model for Composite Laminates in High-Velocity Impact Simulation

Directory of Open Access Journals (Sweden)

Tao Liu

Full Text Available Abstract A numerical material model for composite laminate, was developed and integrated into the nonlinear dynamic explicit finite element programs as a material user subroutine. This model coupling nonlinear state of equation (EOS, was a macro-mechanics model, which was used to simulate the major mechanical behaviors of composite laminate under high-velocity impact conditions. The basic theoretical framework of the developed material model was introduced. An inverse flyer plate simulation was conducted, which demonstrated the advantage of the developed model in characterizing the nonlinear shock response. The developed model and its implementation were validated through a classic ballistic impact issue, i.e. projectile impacting on Kevlar29/Phenolic laminate. The failure modes and ballistic limit velocity were analyzed, and a good agreement was achieved when comparing with the analytical and experimental results. The computational capacity of this model, for Kevlar/Epoxy laminates with different architectures, i.e. plain-woven and cross-plied laminates, was further evaluated and the residual velocity curves and damage cone were accurately predicted.

Static and dynamic through thickness lamina properties of thick laminates

NARCIS (Netherlands)

Lahuerta, F.; Nijssen, R.P.L.; Van der Meer, F.P.; Sluys, L.J.

2015-01-01

Thick laminates are increasingly present in large composites structures such as wind turbine blades. Different factors are suspected to be involved in the decreased static and dynamic performance of thick laminates. These include the effect of self-heating, the scaling effect, and the manufacturing

Connexin mutants and cataracts

Directory of Open Access Journals (Sweden)

Eric C Beyer

2013-04-01

Full Text Available The lens is a multicellular, but avascular tissue that must stay transparent to allow normal transmission of light and focusing of it on the retina. Damage to lens cells and/or proteins can cause cataracts, opacities that disrupt these processes. The normal survival of the lens is facilitated by an extensive network of gap junctions formed predominantly of connexin46 and connexin50. Mutations of the genes that encode these connexins (GJA3 and GJA8 have been identified and linked to inheritance of cataracts in human families and mouse lines. In vitro expression studies of several of these mutants have shown that they exhibit abnormalities that may lead to disease. Many of the mutants reduce or modify intercellular communication due to channel alterations (including loss of function or altered gating or due to impaired cellular trafficking which reduces the number of gap junction channels within the plasma membrane. However, the abnormalities detected in studies of other mutants suggest that they cause cataracts through other mechanisms including gain of hemichannel function (leading to cell injury and death and formation of cytoplasmic accumulations (that may act as light scattering particles. These observations and the anticipated results of ongoing studies should elucidate the mechanisms of cataract development due to mutations of lens connexins and abnormalities of other lens proteins. They may also contribute to our understanding of the mechanisms of disease due to connexin mutations in other tissues.

Signal transduction by normal isoforms and W mutant variants of the Kit receptor tyrosine kinase.

Science.gov (United States)

Reith, A D; Ellis, C; Lyman, S D; Anderson, D M; Williams, D E; Bernstein, A; Pawson, T

1991-09-01

Germline mutations at the Dominant White Spotting (W) and Steel (Sl) loci have provided conclusive genetic evidence that c-kit mediated signal transduction pathways are essential for normal mouse development. We have analysed the interactions of normal and mutant W/c-kit gene products with cytoplasmic signalling proteins, using transient c-kit expression assays in COS cells. In addition to the previously identified c-kit gene product (Kit+), a second normal Kit isoform (KitA+) containing an in-frame insertion, Gly-Asn-Asn-Lys, within the extracellular domain, was detected in murine mast cell cultures and mid-gestation placenta. Both Kit+ and KitA+ isoforms showed increased autophosphorylation and enhanced association with phosphatidylinositol (PI) 3' kinase and PLC gamma 1, when stimulated with recombinant soluble Steel factor. No association or increase in phosphorylation of GAP and two GAP-associated proteins, p62 and p190, was observed. The two isoforms had distinct activities in the absence of exogenous soluble Steel factor; Kit+, but not KitA+, showed constitutive tyrosine phosphorylation that was accompanied by a low constitutive level of association with PI-3' kinase and PLC gamma 1. Introduction of the point substitutions associated with W37 (Glu582----Lys) or W41 (Val831----Met) mutant alleles into c-kit expression constructs abolished (W37) or reduced (W41) the Steel factor-induced association of the Kit receptor with signalling proteins in a manner proportional to the overall severity of the corresponding W mutant phenotype. These data suggest a diversity of normal Kit signalling pathways and indicate that W mutant phenotypes result from primary defects in the Kit receptor that affect its interaction with cytoplasmic signalling proteins.

Intergenic disease-associated regions are abundant in novel transcripts.

Science.gov (United States)

Bartonicek, N; Clark, M B; Quek, X C; Torpy, J R; Pritchard, A L; Maag, J L V; Gloss, B S; Crawford, J; Taft, R J; Hayward, N K; Montgomery, G W; Mattick, J S; Mercer, T R; Dinger, M E

2017-12-28

Genotyping of large populations through genome-wide association studies (GWAS) has successfully identified many genomic variants associated with traits or disease risk. Unexpectedly, a large proportion of GWAS single nucleotide polymorphisms (SNPs) and associated haplotype blocks are in intronic and intergenic regions, hindering their functional evaluation. While some of these risk-susceptibility regions encompass cis-regulatory sites, their transcriptional potential has never been systematically explored. To detect rare tissue-specific expression, we employed the transcript-enrichment method CaptureSeq on 21 human tissues to identify 1775 multi-exonic transcripts from 561 intronic and intergenic haploblocks associated with 392 traits and diseases, covering 73.9 Mb (2.2%) of the human genome. We show that a large proportion (85%) of disease-associated haploblocks express novel multi-exonic non-coding transcripts that are tissue-specific and enriched for GWAS SNPs as well as epigenetic markers of active transcription and enhancer activity. Similarly, we captured transcriptomes from 13 melanomas, targeting nine melanoma-associated haploblocks, and characterized 31 novel melanoma-specific transcripts that include fusion proteins, novel exons and non-coding RNAs, one-third of which showed allelically imbalanced expression. This resource of previously unreported transcripts in disease-associated regions ( http://gwas-captureseq.dingerlab.org ) should provide an important starting point for the translational community in search of novel biomarkers, disease mechanisms, and drug targets.

Hygrothermal Effect on Mechanical and Fatigue Properties of laminated Lower Limb Socket and Bacteria Growth

Directory of Open Access Journals (Sweden)

Fadhel Abbas Abdullah

2016-12-01

Full Text Available In this work, hygrothermal effect on the mechanical and fatigue properties of prosthetic socket lamination and its effect on the bacteria growth were studied. Two laminations composite materials were used in manufacturing prosthetic socket by using vacuum device. The reinforced materials of these laminations were perlon and carbon nanopowder (CNP while the matrix material was polyurethane resin. Tests performed in this work were the moisture absorption properties test to calculate percent moisture content according to ASTM 5229, tensile and fatigue tests with and without the hygrothermal effect to find the mechanical and fatigue properties, and the bacteria growth test under the hygrothermal effect to calculate the number of bacteria on the laminations. The results showed that the lamination (10 perlon+1 wt % CNP has mechanical properties than lamination (10 perlon with and without hygrothermal effect. The mechanical and fatigue properties for the two laminations were decreasing with increasing temperature and moisture.. Adding carbon nanopowder to the lamination (10 perlon increased ultimate stress, modulus of elastic, and endurance limit by (1.36, 2.35, and2.72 time respectively. Finally, the results showed that the Staphylococcus aureus growth increases with increasing temperature and moisture on the two laminations used in manufacturing prosthetic socket, and adding carbon nanopowder also increased the Staphylococcus aureus growth on the lamination.

Significance of Coronavirus Mutants in Feces and Diseased Tissues of Cats Suffering from Feline Infectious Peritonitis

Directory of Open Access Journals (Sweden)

Niels C. Pedersen

2009-08-01

Full Text Available The internal FECV→FIPV mutation theory and three of its correlates were tested in four sibs/half-sib kittens, a healthy contact cat, and in four unrelated cats that died of FIP at geographically disparate regions. Coronavirus from feces and extraintestinal FIP lesions from the same cat were always >99% related in accessory and structural gene sequences. SNPs and deletions causing a truncation of the 3c gene product were found in almost all isolates from the diseased tissues of the eight cats suffering from FIP, whereas most, but not all fecal isolates from these same cats had intact 3c genes. Other accessory and structural genes appeared normal in both fecal and lesional viruses. Deliterious mutations in the 3c gene were unique to each cat, indicating that they did not originate in one cat and were subsequently passed horizontally to the others. Compartmentalization of the parental and mutant forms was not absolute; virus of lesional type was sometimes found in feces of affected cats and virus identical to fecal type was occasionally identified in diseased tissues. Although 3c gene mutants in this study were not horizontally transmitted, the parental fecal virus was readily transmitted by contact from a cat that died of FIP to its housemate. There was a high rate of mutability in all structural and accessory genes both within and between cats, leading to minor genetic variants. More than one variant could be identified in both diseased tissues and feces of the same cat. Laboratory cats inoculated with a mixture of two closely related variants from the same FIP cat developed disease from one or the other variant, but not both. Significant genetic drift existed between isolates from geographically distinct regions of the Western US.

Significance of coronavirus mutants in feces and diseased tissues of cats suffering from feline infectious peritonitis.

Science.gov (United States)

Pedersen, Niels C; Liu, Hongwei; Dodd, Kimberly A; Pesavento, Patricia A

2009-09-01

The internal FECV→FIPV mutation theory and three of its correlates were tested in four sibs/half-sib kittens, a healthy contact cat, and in four unrelated cats that died of FIP at geographically disparate regions. Coronavirus from feces and extraintestinal FIP lesions from the same cat were always >99% related in accessory and structural gene sequences. SNPs and deletions causing a truncation of the 3c gene product were found in almost all isolates from the diseased tissues of the eight cats suffering from FIP, whereas most, but not all fecal isolates from these same cats had intact 3c genes. Other accessory and structural genes appeared normal in both fecal and lesional viruses. Deliterious mutations in the 3c gene were unique to each cat, indicating that they did not originate in one cat and were subsequently passed horizontally to the others. Compartmentalization of the parental and mutant forms was not absolute; virus of lesional type was sometimes found in feces of affected cats and virus identical to fecal type was occasionally identified in diseased tissues. Although 3c gene mutants in this study were not horizontally transmitted, the parental fecal virus was readily transmitted by contact from a cat that died of FIP to its housemate. There was a high rate of mutability in all structural and accessory genes both within and between cats, leading to minor genetic variants. More than one variant could be identified in both diseased tissues and feces of the same cat. Laboratory cats inoculated with a mixture of two closely related variants from the same FIP cat developed disease from one or the other variant, but not both. Significant genetic drift existed between isolates from geographically distinct regions of the Western US.

Fatigue crack growth in fiber-metal laminates

Science.gov (United States)

Ma, YuE; Xia, ZhongChun; Xiong, XiaoFeng

2014-01-01

Fiber-metal laminates (FMLs) consist of three layers of aluminum alloy 2024-T3 and two layers of glass/epoxy prepreg, and it (it means FMLs) is laminated by Al alloy and fiber alternatively. Fatigue crack growth rates in notched fiber-metal laminates under constant amplitude fatigue loading were studied experimentally and numerically and were compared with them in monolithic 2024-T3 Al alloy plates. It is shown that the fatigue life of FMLs is about 17 times longer than monolithic 2024-T3 Al alloy plate; and crack growth rates in FMLs panels remain constant mostly even when the crack is long, unlike in the monolithic 2024-T3 Al alloy plates. The formula to calculate bridge stress profiles of FMLs was derived based on the fracture theory. A program by Matlab was developed to calculate the distribution of bridge stress in FMLs, and then fatigue growth lives were obtained. Finite element models of FMLs were built and meshed finely to analyze the stress distributions. Both results were compared with the experimental results. They agree well with each other.

The First Scube3 Mutant Mouse Line with Pleiotropic Phenotypic Alterations.

Science.gov (United States)

Fuchs, Helmut; Sabrautzki, Sibylle; Przemeck, Gerhard K H; Leuchtenberger, Stefanie; Lorenz-Depiereux, Bettina; Becker, Lore; Rathkolb, Birgit; Horsch, Marion; Garrett, Lillian; Östereicher, Manuela A; Hans, Wolfgang; Abe, Koichiro; Sagawa, Nobuho; Rozman, Jan; Vargas-Panesso, Ingrid L; Sandholzer, Michael; Lisse, Thomas S; Adler, Thure; Aguilar-Pimentel, Juan Antonio; Calzada-Wack, Julia; Ehrhard, Nicole; Elvert, Ralf; Gau, Christine; Hölter, Sabine M; Micklich, Katja; Moreth, Kristin; Prehn, Cornelia; Puk, Oliver; Racz, Ildiko; Stoeger, Claudia; Vernaleken, Alexandra; Michel, Dian; Diener, Susanne; Wieland, Thomas; Adamski, Jerzy; Bekeredjian, Raffi; Busch, Dirk H; Favor, John; Graw, Jochen; Klingenspor, Martin; Lengger, Christoph; Maier, Holger; Neff, Frauke; Ollert, Markus; Stoeger, Tobias; Yildirim, Ali Önder; Strom, Tim M; Zimmer, Andreas; Wolf, Eckhard; Wurst, Wolfgang; Klopstock, Thomas; Beckers, Johannes; Gailus-Durner, Valerie; Hrabé de Angelis, Martin

2016-12-07

The vertebrate Scube (Signal peptide, CUB, and EGF-like domain-containing protein) family consists of three independent members, Scube1-3, which encode secreted cell surface-associated membrane glycoproteins. Limited information about the general function of this gene family is available, and their roles during adulthood. Here, we present the first Scube3 mutant mouse line (Scube3 N294K/N294K ), which clearly shows phenotypic alterations by carrying a missense mutation in exon 8, and thus contributes to our understanding of SCUBE3 functions. We performed a detailed phenotypic characterization in the German Mouse Clinic (GMC). Scube3 N294K/N294K mutants showed morphological abnormalities of the skeleton, alterations of parameters relevant for bone metabolism, changes in renal function, and hearing impairments. These findings correlate with characteristics of the rare metabolic bone disorder Paget disease of bone (PDB), associated with the chromosomal region of human SCUBE3 In addition, alterations in energy metabolism, behavior, and neurological functions were detected in Scube3 N294K/N294K mice. The Scube3 N294K/N294K mutant mouse line may serve as a new model for further studying the effect of impaired SCUBE3 gene function. Copyright © 2016 Fuchs et al.

The First Scube3 Mutant Mouse Line with Pleiotropic Phenotypic Alterations

Directory of Open Access Journals (Sweden)

Helmut Fuchs

2016-12-01

Full Text Available The vertebrate Scube (Signal peptide, CUB, and EGF-like domain-containing protein family consists of three independent members, Scube1–3, which encode secreted cell surface-associated membrane glycoproteins. Limited information about the general function of this gene family is available, and their roles during adulthood. Here, we present the first Scube3 mutant mouse line (Scube3N294K/N294K, which clearly shows phenotypic alterations by carrying a missense mutation in exon 8, and thus contributes to our understanding of SCUBE3 functions. We performed a detailed phenotypic characterization in the German Mouse Clinic (GMC. Scube3N294K/N294K mutants showed morphological abnormalities of the skeleton, alterations of parameters relevant for bone metabolism, changes in renal function, and hearing impairments. These findings correlate with characteristics of the rare metabolic bone disorder Paget disease of bone (PDB, associated with the chromosomal region of human SCUBE3. In addition, alterations in energy metabolism, behavior, and neurological functions were detected in Scube3N294K/N294K mice. The Scube3N294K/N294K mutant mouse line may serve as a new model for further studying the effect of impaired SCUBE3 gene function.

Self-heating forecasting for thick laminates testing coupons in fatigue

NARCIS (Netherlands)

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

2012-01-01

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. Due to the poor thermal conductivity properties of composites and the material self-heating that

Characterization of the Xylella fastidiosa PD1311 gene mutant and its suppression of Pierce's disease on grapevines.

Science.gov (United States)

Hao, Lingyun; Johnson, Kameka; Cursino, Luciana; Mowery, Patricia; Burr, Thomas J

2017-06-01

Xylella fastidiosa causes Pierce's disease (PD) on grapevines, leading to significant economic losses in grape and wine production. To further our understanding of X. fastidiosa virulence on grapevines, we examined the PD1311 gene, which encodes a putative acyl-coenzyme A (acyl-CoA) synthetase, and is highly conserved across Xylella species. It was determined that PD1311 is required for virulence, as the deletion mutant, ΔPD1311, was unable to cause disease on grapevines. The ΔPD1311 strain was impaired in behaviours known to be associated with PD development, including motility, aggregation and biofilm formation. ΔPD1311 also expressed enhanced sensitivity to H 2 O 2 and polymyxin B, and showed reduced survival in grapevine sap, when compared with wild-type X. fastidiosa Temecula 1 (TM1). Following inoculation, ΔPD1311 could not be detected in grape shoots, which may be related to its altered growth and sensitivity phenotypes. Inoculation with ΔPD1311 2 weeks prior to TM1 prevented the development of PD in a significant fraction of vines and eliminated detectable levels of TM1. In contrast, vines inoculated simultaneously with TM1 and ΔPD1311 developed disease at the same level as TM1 alone. In these vines, TM1 populations were distributed similarly to populations in TM1-only inoculated plants. These findings suggest that, through an indirect mechanism, pretreatment of vines with ΔPD1311 suppresses pathogen population and disease. © 2016 BSPP AND JOHN WILEY & SONS LTD.

New Directions in Gaucher Disease.

Science.gov (United States)

Horowitz, Mia; Elstein, Deborah; Zimran, Ari; Goker-Alpan, Ozlem

2016-11-01

In Gaucher disease (GD), mutant lysosomal acid β-glucocerebrosidase fails to properly hydrolyze its substrate, glucosylceramide, which accumulates in the lysosomes. Due to its phenotypic heterogeneity, GD has been classified into type 1, non-neuronopathic, and types 2 and 3, the neuronopathic forms, based on the primary involvement of the central nervous system. Neuroinflammation and necroptotic death may appear in the neuronopathic forms of GD, whereas type 1 GD patients may develop Parkinson disease (PD), a prototype of protein misfolding disorders of the nervous system. PD is significantly more prevalent among GD carriers and patients than among the non-GD populations. It is apparent that the amount of mutant enzyme present in lysosomes depends on the amount of mutant enzyme recognized as correctly folded in the endoplasmic reticulum (ER) for physiologically correct transport through the Golgi apparatus to the lysosome. Mutant enzyme recognized as misfolded is retained in the ER, inducing the Unfolded Protein Response. In the current review, we present three discrete areas of interest: molecular and cellular mechanisms underlying the association between GD and PD; the clinical and genetic associations between GD and PD; and treatment options for GD. We also discuss the relevance of induced pleuripotent stem cells to the above associations. © 2016 WILEY PERIODICALS, INC.

Mutant genes in pea breeding

International Nuclear Information System (INIS)

Swiecicki, W.K.

1990-01-01

Full text: Mutations of genes Dpo (dehiscing pods) and A (anthocyanin synthesis) played a role in pea domestication. A number of other genes were important in cultivar development for 3 types of usage (dry seeds, green vegetable types, fodder), e.g. fn, fna, le, p, v, fas and af. New genes (induced and spontaneous), are important for present ideotypes and are registered by the Pisum Genetics Association (PGA). Comparison of a pea variety ideotype with the variation available in gene banks shows that breeders need 'new' features. In mutation induction experiments, genotype, mutagen and method of treatment (e.g. combined or fractionated doses) are varied for broadening the mutation spectrum and selecting more genes of agronomic value. New genes are genetically analysed. In Poland, some mutant varieties with the gene afila were registered, controlling lodging by a shorter stem and a higher number of internodes. Really non-lodging pea varieties could strongly increase seed yield. But the probability of detecting a major gene for lodging resistance is low. Therefore, mutant genes with smaller influence on plant architecture are sought, to combine their effect by crossing. Promising seem to be the genes rogue, reductus and arthritic as well as a number of mutant genes not yet genetically identified. The gene det for terminal inflorescence - similarly to Vicia faba - changes plant development. Utilisation of assimilates and ripening should be better. Improvement of harvest index should give higher seed yield. A number of genes controlling disease resistance are well known (eg. Fw, Fnw, En, mo and sbm). Important in mass screening of resistance are closely linked gene markers. Pea gene banks collect respective lines, but mutants induced in highly productive cultivars would be better. Inducing gene markers sometimes seems to be easier than transfer by crossing. Mutation induction in pea breeding is probably more important because a high number of monogenic features are

Analysis of Mycobacterium avium subsp. paratuberculosis mutant libraries reveals loci-dependent transcription biases and strategies to novel mutant discovery

Science.gov (United States)

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiologic agent of Johne’s disease in ruminants and it has been implicated as a cause of Crohn’s disease in humans. The generation of comprehensive random mutant banks by transposon mutagenesis is a fundamental wide genomic technology utilized...

Dowelled structural connections in laminated bamboo and timber

OpenAIRE

Reynolds, Thomas Peter; Sharma, Bhavna; Harries, Kent; Ramage, Michael Hector

2015-01-01

Structural sections of laminated bamboo can be connected using methods common in timber engineering, however the different material properties of timber and laminated bamboo suggest that the behaviour of connections in the two materials would not be the same. This study investigates the dowelled connection, in which a connector is passed through a hole in the material, and load is resisted by shear in the connector and embedment into the surrounding material. Steel dowels were used in a conne...

Laminated dosimetric card

International Nuclear Information System (INIS)

Cox, F.M.; Chamberlain, J.D.; Shrader, E.F.; Shoffner, B.M.; Szalanczy, A.

1975-01-01

A laminated card with one or more apertures, each adapted to peripherally seal an encapsulated dosimeter, is formed by bonding a foraminous, code-adaptable, rigid sheet of low-Z material with a codedly transparent sheet of low-Z material in light-transmitting registry with particular code-holes of the rigid sheet. The laminated card may be coded to identify the person carrying it, and/or the location or circumstances related to its exposure to radiation. This card is particularly adapted for use in an instrument capable of evaluating a multiplicity of cards, substantially continuously. The coded identification from the card may be displayed by an appropriate machine, and if desired an evaluation may be recorded because of a ''parity checking'' system incorporated in each card, which permits ''auto-correction.'' Alternatively, where means for effecting the correction automatically are available, the operation of the machine may be interrupted to permit visual examination of a rejected card. The card of this invention is also coded for identifying the type of card with respect to its specific function, and whether or not a card is correctly positioned at any predetermined location during its sequential progress through the instrument in which it is evaluated. Dosimeters are evaluated and the card identified in one pass through the instrument. (auth)

Lamin B Receptor: Interplay between Structure, Function and Localization

Directory of Open Access Journals (Sweden)

Eleni Nikolakaki

2017-08-01

Full Text Available Lamin B receptor (LBR is an integral protein of the inner nuclear membrane, containing a hydrophilic N-terminal end protruding into the nucleoplasm, eight hydrophobic segments that span the membrane and a short, nucleoplasmic C-terminal tail. Two seemingly unrelated functions have been attributed to LBR. Its N-terminal domain tethers heterochromatin to the nuclear periphery, thus contributing to the shape of interphase nuclear architecture, while its transmembrane domains exhibit sterol reductase activity. Mutations within the transmembrane segments result in defects in cholesterol synthesis and are associated with diseases such as the Pelger–Huët anomaly and Greenberg skeletal dysplasia, whereas no such harmful mutations related to the anchoring properties of LBR have been reported so far. Recent evidence suggests a dynamic regulation of LBR expression levels, structural organization, localization and function, in response to various signals. The molecular mechanisms underlying this dynamic behavior have not yet been fully unraveled. Here, we provide an overview of the current knowledge of the interplay between the structure, function and localization of LBR, and hint at the interconnection of the two distinct functions of LBR.

Lamin A/C-dependent interaction with 53BP1 promotes cellular responses to DNA damage

DEFF Research Database (Denmark)

Gibbs-Seymour, Ian; Markiewicz, Ewa; Bekker-Jensen, Simon

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...

Induction and characterization of Arabidopsis mutants by Ion beam

International Nuclear Information System (INIS)

Yoon, Y. H.; Choi, J. D.; Park, J. Y.; Lee, J. R.; Sohn, H. S.

2008-03-01

This study was conducted to search the proper conditions and times for irradiating proton beam to seeds generally used for induction of mutant. Arabidopsis as model plants has good characters that is a short generation time, producing a lot of seeds, sequenced genome, developed maker. This points were the best materials for plant breeding for this study. The data of inducing mutants of Arabidopsis is used to be applicate to crops have more longer generation that is the final goals of this study. The goals of this project were to inducing and characterizing arabidopsis mutants by the proton ion beam and γ-ray. As well as, the purpose of this study was securing more than 10 lines of arabidopsis mutants in this project and also to know the changed DNA structure of the mutants using the basic data for applying to the more study

Induction and characterization of Arabidopsis mutants by Ion beam

Energy Technology Data Exchange (ETDEWEB)

Yoon, Y. H.; Choi, J. D.; Park, J. Y.; Lee, J. R.; Sohn, H. S. [Gyeongbuk Institute for Bio Industry, Andong (Korea, Republic of)

2008-03-15

This study was conducted to search the proper conditions and times for irradiating proton beam to seeds generally used for induction of mutant. Arabidopsis as model plants has good characters that is a short generation time, producing a lot of seeds, sequenced genome, developed maker. This points were the best materials for plant breeding for this study. The data of inducing mutants of Arabidopsis is used to be applicate to crops have more longer generation that is the final goals of this study. The goals of this project were to inducing and characterizing arabidopsis mutants by the proton ion beam and {gamma}-ray. As well as, the purpose of this study was securing more than 10 lines of arabidopsis mutants in this project and also to know the changed DNA structure of the mutants using the basic data for applying to the more study

Tungsten foil laminate for structural divertor applications – Joining of tungsten foils

Energy Technology Data Exchange (ETDEWEB)

Reiser, Jens, E-mail: jens.reiser@kit.edu [Karlsruhe Institute of Technology (KIT), Institute for Applied Materials (IAM-AWP) (Germany); Rieth, Michael; Möslang, Anton; Dafferner, Bernhard; Hoffmann, Jan [Karlsruhe Institute of Technology (KIT), Institute for Applied Materials (IAM-AWP) (Germany); Mrotzek, Tobias; Hoffmann, Andreas [PLANSEE SE, Reutte (Austria); Armstrong, D.E.J.; Yi, Xiaoou [University of Oxford, Department of Materials (United Kingdom)

2013-05-15

This paper is the fourth in our series on tungsten laminates. The aim of this paper is to discuss laminate synthesis, meaning the joining of tungsten foils. It is obvious that the properties of the tungsten laminate strongly depend on the combination of (i) interlayer and (ii) joining technology, as this combination defines (i) the condition of the tungsten foil after joining (as-received or recrystallised) as well as (ii) the characteristics of the interface between the tungsten foil and the interlayer (wettability or diffusion leading to a solid solution or the formation of intermetallics). From the example of tungsten laminates joined by brazing with (i) an eutectic silver copper brazing filler, (ii) copper, (iii) titanium, and (iv) zirconium, the microstructure will be discussed, with special focus on the interface. Based on our assumptions of the mechanism of the extraordinary ductility of tungsten foil we present three syntheses strategies and make recommendations for the synthesis of high temperature tungsten laminates.

Enhancement of Gas Barrier Properties of CFRP Laminates Fabricated Using Thin-Ply Prepregs

Science.gov (United States)

横関, 智弘; 高木, 智宏; 吉村, 彰記; Ogasawara, Toshio; 荻原, 慎二

Composite laminates manufactured using thin-ply prepregs are expected to have superior resistance properties against microcracking compared to those using standard prepregs. In this study, comparative investigations are presented on the microcrack accumulation and gas leakage characteristics of CFRP laminates fabricated using standard and thin-ply prepregs, consisting of high-performance carbon fiber and toughened epoxy, as a fundamental research on the cryogenic composite tanks for future space vehicles. It was shown that laminates using thin-ply prepregs exhibited much higher strain at microcrack initiation compared to those using standard prepregs at room and cryogenic temperatures. In addition, helium gas leak tests using CFRP laminated tubular specimens subjected to quasi-static tension loadings were performed. It was demonstrated that CFRP laminates using thin-ply prepregs have higher gas barrier properties than those using standard prepregs.

Hearing loss associated with enlarged vestibular aqueduct and zero or one mutant allele of SLC26A4.

Science.gov (United States)

Rose, Jane; Muskett, Julie A; King, Kelly A; Zalewski, Christopher K; Chattaraj, Parna; Butman, John A; Kenna, Margaret A; Chien, Wade W; Brewer, Carmen C; Griffith, Andrew J

2017-07-01

To characterize the severity and natural history of hearing loss, and the prevalence of having a cochlear implant in a maturing cohort of individuals with enlarged vestibular aqueduct (EVA) and zero or one mutant allele of SLC26A4. Prospective cohort study of subjects ascertained between 1998 and 2015 at the National Institutes of Health Clinical Center. Study subjects were 127 individuals (median age, 8 years; range, 0-59 years) with EVA in at least one ear. Ears with EVA and zero or one mutant allele of SLC26A4 had mean 0.5/1/2/4-kHz pure-tone averages of 62.6 and 52.9 dB HL, respectively, in contrast to EVA ears with two mutant alleles of SLC26A4 (88.1 dB HL; P zero, one, and two mutant alleles, respectively (P = .00833). This association was not independent (P = .534) but reflected underlying correlations with age at time of first audiogram (P = .003) or severity of hearing loss (P = .000). Ears with EVA and zero or one mutant allele of SLC26A4 have less severe hearing loss, no difference in prevalence of fluctuation, and a lower prevalence of cochlear implantation in comparison to ears with two mutant alleles of SLC26A4. NA Laryngoscope, 127:E238-E243, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Quantitative threefold allele-specific PCR (QuanTAS-PCR) for highly sensitive JAK2 V617F mutant allele detection

International Nuclear Information System (INIS)

Zapparoli, Giada V; Jorissen, Robert N; Hewitt, Chelsee A; McBean, Michelle; Westerman, David A; Dobrovic, Alexander

2013-01-01

The JAK2 V617F mutation is the most frequent somatic change in myeloproliferative neoplasms, making it an important tumour-specific marker for diagnostic purposes and for the detection of minimal residual disease. Sensitive quantitative assays are required for both applications, particularly for the monitoring of minimal residual disease, which requires not only high sensitivity but also very high specificity. We developed a highly sensitive probe-free quantitative mutant-allele detection method, Quantitative Threefold Allele-Specific PCR (QuanTAS-PCR), that is performed in a closed-tube system, thus eliminating the manipulation of PCR products. QuantTAS-PCR uses a threefold approach to ensure allele-specific amplification of the mutant sequence: (i) a mutant allele-specific primer, (ii) a 3′dideoxy blocker to suppress false-positive amplification from the wild-type template and (iii) a PCR specificity enhancer, also to suppress false-positive amplification from the wild-type template. Mutant alleles were quantified relative to exon 9 of JAK2. We showed that the addition of the 3′dideoxy blocker suppressed but did not eliminate false-positive amplification from the wild-type template. However, the addition of the PCR specificity enhancer near eliminated false-positive amplification from the wild-type allele. Further discrimination between true and false positives was enabled by using the quantification cycle (Cq) value of a single mutant template as a cut-off point, thus enabling robust distinction between true and false positives. As 10,000 JAK2 templates were used per replicate, the assay had a sensitivity of 1/10 -4 per replicate. Greater sensitivity could be reached by increasing the number of replicates analysed. Variation in replicates when low mutant-allele templates were present necessitated the use of a statistics-based approach to estimate the load of mutant JAK2 copies. QuanTAS-PCR showed comparable quantitative results when validated against a

Tay-Sachs disease mutations in HEXA target the α chain of hexosaminidase A to endoplasmic reticulum-associated degradation.

Science.gov (United States)

Dersh, Devin; Iwamoto, Yuichiro; Argon, Yair

2016-12-01

Loss of function of the enzyme β-hexosaminidase A (HexA) causes the lysosomal storage disorder Tay-Sachs disease (TSD). It has been proposed that mutations in the α chain of HexA can impair folding, enzyme assembly, and/or trafficking, yet there is surprisingly little known about the mechanisms of these potential routes of pathogenesis. We therefore investigated the biosynthesis and trafficking of TSD-associated HexA α mutants, seeking to identify relevant cellular quality control mechanisms. The α mutants E482K and G269S are defective in enzymatic activity, unprocessed by lysosomal proteases, and exhibit altered folding pathways compared with wild-type α. E482K is more severely misfolded than G269S, as observed by its aggregation and inability to associate with the HexA β chain. Importantly, both mutants are retrotranslocated from the endoplasmic reticulum (ER) to the cytosol and are degraded by the proteasome, indicating that they are cleared via ER-associated degradation (ERAD). Leveraging these discoveries, we observed that manipulating the cellular folding environment or ERAD pathways can alter the kinetics of mutant α degradation. Additionally, growth of patient fibroblasts at a permissive temperature or with chemical chaperones increases cellular Hex activity by improving mutant α folding. Therefore modulation of the ER quality control systems may be a potential therapeutic route for improving some forms of TSD. © 2016 Dersh et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

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

International Nuclear Information System (INIS)

Muchir, Antoine; Massart, Catherine; Engelen, Baziel G. van; Lammens, Martin; Bonne, Gisele; Worman, Howard J.

2006-01-01

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-1α 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

Vibrations of laminated composite thick shells of revolution having meridionally varying curvature

International Nuclear Information System (INIS)

Suzuki, Katsuyoshi; Shikanai, Genji; Baba, Iwato

1998-01-01

An exact solution is presented for solving free vibrations of laminated composite thick shells of revolution having meridionally varying curvature. Based on the thick lamination theory considering the 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 shells. Frequencies and mode shapes of shells of revolution having elliptical and parabolical meridians are presented for both ends clamped, and the effects of shear deformation and rotary inertia are discussed by comparing the results from the present theory with those from the thin lamination theory. (author)

Performance of stress-laminated timber highway bridges in cold climates

Science.gov (United States)

James P. Wacker

2009-01-01

This paper summarizes recent laboratory and field data studies on thermal performance of stress-laminated timber highway bridges. Concerns about the reliability of stress-laminated deck bridges when exposed to sub-freezing temperatures triggered several investigations. Two laboratory studies were conducted to study the effects of wood species, preservative, moisture...

Attenuation of the goose parvovirus strain B. Laboratory and field trials of the attenuated mutant for vaccination against Derzsy's disease.

Science.gov (United States)

Kisary, J; Derzsy, D; Meszaros, J

1978-07-01

Serial transfer of the goose parvovirus strain B, causal agent of Derzsy's gosling disease, in cultured goose-embryo fibroblast (GEF) resulted in a mutant (designated as Bav) apathogenic for both goose embryos and susceptible goslings. Goose embryos inoculated with the 38th or higher passages of strain B survived the infection, although the virus replicated in their organs. Susceptible goslings survived challenge with the Bav strain without showing symptoms, and developed normally. Only 4.2% of gosling progeny of parents vaccinated twice with strain Bav died after challenge with the virulent strain B goose parvovirus compared with 95% of gosling progeny of unvaccinated parents. Progeny of vaccinated and unvaccinated geese were placed on a farm on which Derzsy's disease was present. During the first month of life mortality was 7.7% in the progeny of vaccinated geese compared with 59.8% in the progeny of the unvaccinated geese. At 8 weeks of age the mean weight of the vaccinated goslings was 20% greater than for the unvaccinated goslings. These results indicate that the attenuated apathogenic Bav mutant is suitable for the immunisation of layers to protect their progeny by passive immunisation against Derzsy's disease.

Preparation of Chitin-PLA laminated composite for implantable application

Directory of Open Access Journals (Sweden)

Romana Nasrin

2017-12-01

Full Text Available The present study explores the possibilities of using locally available inexpensive waste prawn shell derived chitin reinforced and bioabsorbable polylactic acid (PLA laminated composites to develop new materials with excellent mechanical and thermal properties for implantable application such as in bone or dental implant. Chitin at different concentration (1–20% of PLA reinforced PLA films (CTP were fabricated by solvent casting process and laminated chitin-PLA composites (LCTP were prepared by laminating PLA film (obtained by hot press method with CTP also by hot press method at 160 °C. The effect of variation of chitin concentration on the resulting laminated composite's behavior was investigated. The detailed physico-mechanical, surface morphology and thermal were assessed with different characterization technique such as FT-IR, XRD, SEM and TGA. The FTIR spectra showed the characteristic peaks for chitin and PLA in the composites. SEM images showed an excellent dispersion of chitin in the films and composites. Thermogravimetric analysis (TGA showed that the complete degradation of chitin, PLA film, 5% chitin reinforced PLA film (CTP2 and LCTP are 98%, 95%, 87% and 98% respectively at temperature of 500 °C. The tensile strength of the LCTP was found 25.09 MPa which is significantly higher than pure PLA film (18.55 MPa and CTP2 film (8.83 MPa. After lamination of pure PLA and CTP2 film, the composite (LCTP yielded 0.265–1.061% water absorption from 30 min to 24 h immerse in water that is much lower than PLA and CTP. The increased mechanical properties of the laminated films with the increase of chitin content indicated good dispersion of chitin into PLA and strong interfacial actions between the polymer and chitin. The improvement of mechanical properties and the results of antimicrobial and cytotoxicity of the composites also evaluated and revealed the composite would be a suitable candidate for implant application in biomedical

Preparation of Chitin-PLA laminated composite for implantable application.

Science.gov (United States)

Nasrin, Romana; Biswas, Shanta; Rashid, Taslim Ur; Afrin, Sanjida; Jahan, Rumana Akhter; Haque, Papia; Rahman, Mohammed Mizanur

2017-12-01

The present study explores the possibilities of using locally available inexpensive waste prawn shell derived chitin reinforced and bioabsorbable polylactic acid (PLA) laminated composites to develop new materials with excellent mechanical and thermal properties for implantable application such as in bone or dental implant. Chitin at different concentration (1-20% of PLA) reinforced PLA films (CTP) were fabricated by solvent casting process and laminated chitin-PLA composites (LCTP) were prepared by laminating PLA film (obtained by hot press method) with CTP also by hot press method at 160 °C. The effect of variation of chitin concentration on the resulting laminated composite's behavior was investigated. The detailed physico-mechanical, surface morphology and thermal were assessed with different characterization technique such as FT-IR, XRD, SEM and TGA. The FTIR spectra showed the characteristic peaks for chitin and PLA in the composites. SEM images showed an excellent dispersion of chitin in the films and composites. Thermogravimetric analysis (TGA) showed that the complete degradation of chitin, PLA film, 5% chitin reinforced PLA film (CTP2) and LCTP are 98%, 95%, 87% and 98% respectively at temperature of 500 °C. The tensile strength of the LCTP was found 25.09 MPa which is significantly higher than pure PLA film (18.55 MPa) and CTP2 film (8.83 MPa). After lamination of pure PLA and CTP2 film, the composite (LCTP) yielded 0.265-1.061% water absorption from 30 min to 24 h immerse in water that is much lower than PLA and CTP. The increased mechanical properties of the laminated films with the increase of chitin content indicated good dispersion of chitin into PLA and strong interfacial actions between the polymer and chitin. The improvement of mechanical properties and the results of antimicrobial and cytotoxicity of the composites also evaluated and revealed the composite would be a suitable candidate for implant application in biomedical sector.

Relationships between structural fat properties with sensory, physical and textural attributes of yeast-leavened laminated salty baked product.

Science.gov (United States)

de la Horra, Ana E; Barrera, Gabriela N; Steffolani, Eugenia M; Ribotta, Pablo D; León, Alberto E

2017-08-01

The aim of this study was to establish relationships between structural fat properties and sensory, physical and textural attributes of yeast-leavened laminated salty products. Refined bovine fat (MG1) and shortening (MG2), with a solid fat content (SFC) higher than 20% at temperature range of 15-35 °C were more viscous and less sensitive to temperature changes. The micrographs of dough|fat|dough sections corresponding to samples with MG1 and MG2 revealed a lower penetration of the fat sheet in the dough section due to the more entangled fat structures that did not allow a great flow throughout the dough layer. Consequently, the structure of laminated dough pieces made the systems highly resistant to deformation. The laminated dough pieces elaborated with these fats showed the highest increments in their height and maintained symmetry. Products with fat with least SFC and higher destructuration rate produced smoother laminated structures due to the presence of pores. While products with MG1 and MG2 showed tortuous images and complex structures, associated to layers and extended pores. MG1 and MG2 products were preferred (flavor and appearance) over those with MG3. The highest ranking samples in the acceptability analysis were symmetric, presented very flaky crusts and had a high level of lamination.

Polycystic kidney disease in the medaka (Oryzias latipes pc mutant caused by a mutation in the Gli-Similar3 (glis3 gene.

Directory of Open Access Journals (Sweden)

Hisashi Hashimoto

Full Text Available Polycystic kidney disease (PKD is a common hereditary disease in humans. Recent studies have shown an increasing number of ciliary genes that are involved in the pathogenesis of PKD. In this study, the Gli-similar3 (glis3 gene was identified as the causal gene of the medaka pc mutant, a model of PKD. In the pc mutant, a transposon was found to be inserted into the fourth intron of the pc/glis3 gene, causing aberrant splicing of the pc/glis3 mRNA and thus a putatively truncated protein with a defective zinc finger domain. pc/glis3 mRNA is expressed in the epithelial cells of the renal tubules and ducts of the pronephros and mesonephros, and also in the pancreas. Antisense oligonucleotide-mediated knockdown of pc/glis3 resulted in cyst formation in the pronephric tubules of medaka fry. Although three other glis family members, glis1a, glis1b and glis2, were found in the medaka genome, none were expressed in the embryonic or larval kidney. In the pc mutant, the urine flow rate in the pronephros was significantly reduced, which was considered to be a direct cause of renal cyst formation. The cilia on the surface of the renal tubular epithelium were significantly shorter in the pc mutant than in wild-type, suggesting that shortened cilia resulted in a decrease in driving force and, in turn, a reduction in urine flow rate. Most importantly, EGFP-tagged pc/glis3 protein localized in primary cilia as well as in the nucleus when expressed in mouse renal epithelial cells, indicating a strong connection between pc/glis3 and ciliary function. Unlike human patients with GLIS3 mutations, the medaka pc mutant shows none of the symptoms of a pancreatic phenotype, such as impaired insulin expression and/or diabetes, suggesting that the pc mutant may be suitable for use as a kidney-specific model for human GLIS3 patients.

Effect of feeding glucose, fructose, and inulin on blood glucose and insulin concentrations in normal ponies and those predisposed to laminitis.

Science.gov (United States)

Borer, K E; Bailey, S R; Menzies-Gow, N J; Harris, P A; Elliott, J

2012-09-01

Identification of ponies (Equus caballus) at increased risk of pasture-associated laminitis would aid in the prevention of the disease. Insulin resistance has been associated with laminitis and could be used to identify susceptible individuals. Insulin resistance may be diagnosed by feeding supplementary water-soluble carbohydrate (WSC) and measuring blood glucose and insulin concentrations. The aim of this study was to assess the glycemic and insulinemic responses of 7 normal (NP) and 5 previously laminitic (PLP), mixed breed, native UK ponies fed glucose, fructose, and inulin [1 g/(kg·d) for 3 d] or no supplementary WSC (control) in spring and fall after a 7-d adaptation to a pasture or hay diet. Blood samples were taken for 12 h after feeding on each day, and baseline and peak concentrations and area under the curve (AUC) for glucose and insulin were recorded. Linear mixed models were used for statistical analysis. Differences between PLP and NP groups were most marked after glucose feeding with differences in peak glucose (P = 0.02) and peak insulin (P = 0.016) concentrations. Season and diet adaptation also affected results. Peak concentrations of glucose and insulin occurred 2 to 4 h after WSC feeding. Peak insulin concentration was greater and more variable in fall, particularly in PLP adapted to fall pasture. Baseline glucose and insulin concentrations varied between individuals and with season and diet adaptation but were not greater in PLP than NP. Insulin AUC was greater in PLP than NP after feeding both glucose and fructose (P = 0.017), but there were no differences between PLP and NP in glucose AUC. Glycemic and insulinemic changes were less (P ≤ 0.05) after feeding fructose than glucose, although differences between PLP and NP were still evident. Minimal changes in glucose and insulin concentrations occurred after inulin feeding. Measurement of peak insulin 2 h after feeding of a single dose of glucose (1 g/kg) may be a simple and practical way to

Tunable characteristics of bending resonance frequency in magnetoelectric laminated composites

Institute of Scientific and Technical Information of China (English)

Chen Lei; Li Ping; Wen Yu-Mei; Zhu Yong

2013-01-01

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 △E 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 0Oe (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.

Failure modes of laminate structures

Energy Technology Data Exchange (ETDEWEB)

Gordon, L.B.; Druce, R.L.; Wilson, M.J.

1987-06-01

Laminate structures composed of alternating thin layers of conductor and dielectric material are commonly used in energy storage and transmission components. The failure of the dielectric layers in regions of high field stress, with applied 60 Hz ac, dc and impulse voltages, was studied. Several geometries were compared, including staggered and flush edges. Electrical trees developed between the laminated dielectric layers. The visual characteristics and growth rates of the electrical trees under ac, dc and impulse stresses were different. Partial discharge detection and analysis was used to measure the inception voltage and discharge activity at the conductor edge voids, to observe tree formation and growth, and to predict impending failure due to dielectric erosion. Electric field distributions were modeled and partial discharge inception levels were estimated from known void geometries. The staggered edge geometry appears to enhance the electric field stress at the recessed electrode.

Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene / allele-specific silencing of mutant huntingtin

DEFF Research Database (Denmark)

Carroll, Jeffrey B; Warby, Simon C; Southwell, Amber L

2011-01-01

Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG-expansion in the huntingtin gene (HTT) that results in a toxic gain of function in the mutant huntingtin protein (mHTT). Reducing the expression of mHTT is therefore an attractive therapy for HD. However, wild...

Numerical evaluation of delamination in CFRP laminates by stereo X-ray pictures

International Nuclear Information System (INIS)

Kunoo, Kazuo; Uda, Nobuhide; Ono, Kousei; Onohara, Kaoru; Takahashi, Toshiaki; Tanaka, Hisahiro.

1989-01-01

This paper presents a method for quantifying damage in composite laminates by stereo X-ray pictures. A three dimensional image of delamination, which is one of the characteristic types of damage in composite laminates can be reconstructed with this method. A digital image processing technique is used to analyze X-ray pictures. Experimental results of reconstructing delaminations in carbon/epoxy cross-ply laminates show that this method is accurate enough for practical usage. (author)

GPNMB ameliorates mutant TDP-43-induced motor neuron cell death.

Science.gov (United States)

Nagahara, Yuki; Shimazawa, Masamitsu; Ohuchi, Kazuki; Ito, Junko; Takahashi, Hitoshi; Tsuruma, Kazuhiro; Kakita, Akiyoshi; Hara, Hideaki

2017-08-01

Glycoprotein nonmetastatic melanoma protein B (GPNMB) aggregates are observed in the spinal cord of amyotrophic lateral sclerosis (ALS) patients, but the detailed localization is still unclear. Mutations of transactive response DNA binding protein 43kDa (TDP-43) are associated with neurodegenerative diseases including ALS. In this study, we evaluated the localization of GPNMB aggregates in the spinal cord of ALS patients and the effect of GPNMB against mutant TDP-43 induced motor neuron cell death. GPNMB aggregates were not localized in the glial fibrillary acidic protein (GFAP)-positive astrocyte and ionized calcium binding adaptor molecule-1 (Iba1)-positive microglia. GPNMB aggregates were localized in the microtubule-associated protein 2 (MAP-2)-positive neuron and neurofilament H non-phosphorylated (SMI-32)-positive neuron, and these were co-localized with TDP-43 aggregates in the spinal cord of ALS patients. Mock or TDP-43 (WT, M337V, and A315T) plasmids were transfected into mouse motor neuron cells (NSC34). The expression level of GPNMB was increased by transfection of mutant TDP-43 plasmids. Recombinant GPNMB ameliorated motor neuron cell death induced by transfection of mutant TDP-43 plasmids and serum-free stress. Furthermore, the expression of phosphorylated ERK1/2 and phosphorylated Akt were decreased by this stress, and these expressions were increased by recombinant GPNMB. These results indicate that GPNMB has protective effects against mutant TDP-43 stress via activating the ERK1/2 and Akt pathways, and GPNMB may be a therapeutic target for TDP-43 proteinopathy in familial and sporadic ALS. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Increased intracellular proteolysis reduces disease severity in an ER stress–associated dwarfism

OpenAIRE

Mullan, Lorna; Mularczyk, Ewa; Kung, Louise; Forouhan, Mitra; Wragg, Jordan; Goodacre, Royston; Bateman, John F.; Swanton, Eileithyia; Briggs, Michael; Boot-Handford, Raymond

2017-01-01

The short-limbed dwarfism metaphyseal chondrodysplasia type Schmid (MCDS) is linked to mutations in type X collagen, which increase ER stress by inducing misfolding of the mutant protein and subsequently disrupting hypertrophic chondrocyte differentiation. Here, we show that carbamazepine (CBZ), an autophagy-stimulating drug that is clinically approved for the treatment of seizures and bipolar disease, reduced the ER stress induced by 4 different MCDS-causing mutant forms of collagen X in hum...

Hypomyelinating leukodystrophy-associated missense mutation in HSPD1 blunts mitochondrial dynamics

Energy Technology Data Exchange (ETDEWEB)

Miyamoto, Yuki [Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535 (Japan); Eguchi, Takahiro [The Institute of Medical Science, The University of Tokyo, Minato, Tokyo 108-8639 (Japan); Kawahara, Kazuko [Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535 (Japan); Hasegawa, Nanami [Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535 (Japan); Faculty of Pharmacy, Keio University, Minato, Tokyo 105-8512 (Japan); Nakamura, Kazuaki [Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535 (Japan); Funakoshi-Tago, Megumi [Faculty of Pharmacy, Keio University, Minato, Tokyo 105-8512 (Japan); Tanoue, Akito [Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535 (Japan); Tamura, Hiroomi [Faculty of Pharmacy, Keio University, Minato, Tokyo 105-8512 (Japan); Yamauchi, Junji, E-mail: yamauchi-j@ncchd.go.jp [Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535 (Japan); Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo, Tokyo 113-8510 (Japan)

2015-07-03

Myelin-forming glial cells undergo dynamic morphological changes in order to produce mature myelin sheaths with multiple layers. In the central nervous system (CNS), oligodendrocytes differentiate to insulate neuronal axons with myelin sheaths. Myelin sheaths play a key role in homeostasis of the nervous system, but their related disorders lead not only to dismyelination and repeated demyelination but also to severe neuropathies. Hereditary hypomyelinating leukodystrophies (HLDs) are a group of such diseases affecting oligodendrocytes and are often caused by missense mutations of the respective responsible genes. Despite increasing identification of gene mutations through advanced nucleotide sequencing technology, studies on the relationships between gene mutations and their effects on cellular and subcellular aberrance have not followed at the same rapid pace. In this study, we report that an HLD4-associated (Asp-29-to-Gly) mutant of mitochondrial heat shock 60-kDa protein 1 (HSPD1) causes short-length morphologies and increases the numbers of mitochondria due to their aberrant fission and fusion cycles. In experiments using a fluorescent dye probe, this mutation decreases the mitochondrial membrane potential. Also, mitochondria accumulate in perinuclear regions. HLD4-associated HSPD1 mutant blunts mitochondrial dynamics, probably resulting in oligodendrocyte malfunction. This study constitutes a first finding concerning the relationship between disease-associated HSPD1 mutation and mitochondrial dynamics, which may be similar to the relationship between another disease-associated HSPD1 mutation (MitCHAP-60 disease) and aberrant mitochondrial dynamics. - Highlights: • The HLD4 mutant of HSPD1 decreases mitochondrial fission frequency. • The HLD4 mutant decreases mitochondrial fusion frequency. • Mitochondria harboring the HLD4 mutant exhibit slow motility. • The HLD4 mutant of HSPD1 decreases mitochondrial membrane potential. • HLD4-related diseases may

Hypomyelinating leukodystrophy-associated missense mutation in HSPD1 blunts mitochondrial dynamics

International Nuclear Information System (INIS)

Miyamoto, Yuki; Eguchi, Takahiro; Kawahara, Kazuko; Hasegawa, Nanami; Nakamura, Kazuaki; Funakoshi-Tago, Megumi; Tanoue, Akito; Tamura, Hiroomi; Yamauchi, Junji

2015-01-01

Myelin-forming glial cells undergo dynamic morphological changes in order to produce mature myelin sheaths with multiple layers. In the central nervous system (CNS), oligodendrocytes differentiate to insulate neuronal axons with myelin sheaths. Myelin sheaths play a key role in homeostasis of the nervous system, but their related disorders lead not only to dismyelination and repeated demyelination but also to severe neuropathies. Hereditary hypomyelinating leukodystrophies (HLDs) are a group of such diseases affecting oligodendrocytes and are often caused by missense mutations of the respective responsible genes. Despite increasing identification of gene mutations through advanced nucleotide sequencing technology, studies on the relationships between gene mutations and their effects on cellular and subcellular aberrance have not followed at the same rapid pace. In this study, we report that an HLD4-associated (Asp-29-to-Gly) mutant of mitochondrial heat shock 60-kDa protein 1 (HSPD1) causes short-length morphologies and increases the numbers of mitochondria due to their aberrant fission and fusion cycles. In experiments using a fluorescent dye probe, this mutation decreases the mitochondrial membrane potential. Also, mitochondria accumulate in perinuclear regions. HLD4-associated HSPD1 mutant blunts mitochondrial dynamics, probably resulting in oligodendrocyte malfunction. This study constitutes a first finding concerning the relationship between disease-associated HSPD1 mutation and mitochondrial dynamics, which may be similar to the relationship between another disease-associated HSPD1 mutation (MitCHAP-60 disease) and aberrant mitochondrial dynamics. - Highlights: • The HLD4 mutant of HSPD1 decreases mitochondrial fission frequency. • The HLD4 mutant decreases mitochondrial fusion frequency. • Mitochondria harboring the HLD4 mutant exhibit slow motility. • The HLD4 mutant of HSPD1 decreases mitochondrial membrane potential. • HLD4-related diseases may

Vascular Dysfunction in Horses with Endocrinopathic Laminitis.

Directory of Open Access Journals (Sweden)

Ruth A Morgan

Full Text Available Endocrinopathic laminitis (EL is a vascular condition of the equine hoof resulting in severe lameness with both welfare and economic implications. EL occurs in association with equine metabolic syndrome and equine Cushing's disease. Vascular dysfunction, most commonly due to endothelial dysfunction, is associated with cardiovascular risk in people with metabolic syndrome and Cushing's syndrome. We tested the hypothesis that horses with EL have vascular, specifically endothelial, dysfunction. Healthy horses (n = 6 and horses with EL (n = 6 destined for euthanasia were recruited. We studied vessels from the hooves (laminar artery, laminar vein and the facial skin (facial skin arteries by small vessel wire myography. The response to vasoconstrictors phenylephrine (10-9-10-5M and 5-hydroxytryptamine (5HT; 10-9-10-5M and the vasodilator acetylcholine (10-9-10-5M was determined. In comparison with healthy controls, acetylcholine-induced relaxation was dramatically reduced in all intact vessels from horses with EL (% relaxation of healthy laminar arteries 323.5 ± 94.1% v EL 90.8 ± 4.4%, P = 0.01, laminar veins 129.4 ± 14.8% v EL 71.2 ± 4.1%, P = 0.005 and facial skin arteries 182.0 ± 40.7% v EL 91.4 ± 4.5%, P = 0.01. In addition, contractile responses to phenylephrine and 5HT were increased in intact laminar veins from horses with EL compared with healthy horses; these differences were endothelium-independent. Sensitivity to phenylephrine was reduced in intact laminar arteries (P = 0.006 and veins (P = 0.009 from horses with EL. Horses with EL exhibit significant vascular dysfunction in laminar vessels and in facial skin arteries. The systemic nature of the abnormalities suggest this dysfunction is associated with the underlying endocrinopathy and not local changes to the hoof.

Transgenic mice expressing mutant Pinin exhibit muscular dystrophy, nebulin deficiency and elevated expression of slow-type muscle fiber genes

International Nuclear Information System (INIS)

Wu, Hsu-Pin; Hsu, Shu-Yuan; Wu, Wen-Ai; Hu, Ji-Wei; Ouyang, Pin

2014-01-01

Highlights: •Pnn CCD domain functions as a dominant negative mutant regulating Pnn expression and function. •Pnn CCD mutant Tg mice have a muscle wasting phenotype during development and show dystrophic histological features. •Pnn mutant muscles are susceptible to slow fiber type gene transition and NEB reduction. •The Tg mouse generated by overexpression of the Pnn CCD domain displays many characteristics resembling NEB +/− mice. -- Abstract: Pinin (Pnn) is a nuclear speckle-associated SR-like protein. The N-terminal region of the Pnn protein sequence is highly conserved from mammals to insects, but the C-terminal RS domain-containing region is absent in lower species. The N-terminal coiled-coil domain (CCD) is, therefore, of interest not only from a functional point of view, but also from an evolutionarily standpoint. To explore the biological role of the Pnn CCD in a physiological context, we generated transgenic mice overexpressing Pnn mutant in skeletal muscle. We found that overexpression of the CCD reduces endogenous Pnn expression in cultured cell lines as well as in transgenic skeletal muscle fibers. Pnn mutant mice exhibited reduced body mass and impaired muscle function during development. Mutant skeletal muscles show dystrophic histological features with muscle fibers heavily loaded with centrally located myonuclei. Expression profiling and pathway analysis identified over-representation of genes in gene categories associated with muscle contraction, specifically those related to slow type fiber. In addition nebulin (NEB) expression level is repressed in Pnn mutant skeletal muscle. We conclude that Pnn downregulation in skeletal muscle causes a muscular dystrophic phenotype associated with NEB deficiency and the CCD domain is incapable of replacing full length Pnn in terms of functional capacity

Transgenic mice expressing mutant Pinin exhibit muscular dystrophy, nebulin deficiency and elevated expression of slow-type muscle fiber genes

Energy Technology Data Exchange (ETDEWEB)

Wu, Hsu-Pin; Hsu, Shu-Yuan [Department of Anatomy, Chang Gung University Medical College, Taiwan (China); Wu, Wen-Ai; Hu, Ji-Wei [Transgenic Mouse Core Laboratory, Chang Gung University, Taiwan (China); Ouyang, Pin, E-mail: ouyang@mail.cgu.edu.tw [Department of Anatomy, Chang Gung University Medical College, Taiwan (China); Transgenic Mouse Core Laboratory, Chang Gung University, Taiwan (China); Molecular Medicine Research Center, Chang Gung University, Taiwan (China)

2014-01-03

Highlights: •Pnn CCD domain functions as a dominant negative mutant regulating Pnn expression and function. •Pnn CCD mutant Tg mice have a muscle wasting phenotype during development and show dystrophic histological features. •Pnn mutant muscles are susceptible to slow fiber type gene transition and NEB reduction. •The Tg mouse generated by overexpression of the Pnn CCD domain displays many characteristics resembling NEB{sup +/−} mice. -- Abstract: Pinin (Pnn) is a nuclear speckle-associated SR-like protein. The N-terminal region of the Pnn protein sequence is highly conserved from mammals to insects, but the C-terminal RS domain-containing region is absent in lower species. The N-terminal coiled-coil domain (CCD) is, therefore, of interest not only from a functional point of view, but also from an evolutionarily standpoint. To explore the biological role of the Pnn CCD in a physiological context, we generated transgenic mice overexpressing Pnn mutant in skeletal muscle. We found that overexpression of the CCD reduces endogenous Pnn expression in cultured cell lines as well as in transgenic skeletal muscle fibers. Pnn mutant mice exhibited reduced body mass and impaired muscle function during development. Mutant skeletal muscles show dystrophic histological features with muscle fibers heavily loaded with centrally located myonuclei. Expression profiling and pathway analysis identified over-representation of genes in gene categories associated with muscle contraction, specifically those related to slow type fiber. In addition nebulin (NEB) expression level is repressed in Pnn mutant skeletal muscle. We conclude that Pnn downregulation in skeletal muscle causes a muscular dystrophic phenotype associated with NEB deficiency and the CCD domain is incapable of replacing full length Pnn in terms of functional capacity.

Enhanced laminated composite phase change material for energy storage

Energy Technology Data Exchange (ETDEWEB)

Darkwa, J.; Zhou, T. [Centre for Sustainable Energy Technologies (CSET), The University of Nottingham Ningbo, 199 Taikang East Road, Ningbo 315100 (China)

2011-02-15

This paper summarises studies undertaken towards the development of a laminated composite aluminium/hexadecane phase change material (PCM) drywall based on previous analytical work. The study also covered the selection and testing of various types of adhesive materials and identified Polyvinyl acetate (PVA) material as a suitable bonding material. For the purpose of comparison pure hexadecane and composite aluminium/hexadecane samples were developed and tested. The test results revealed faster thermal response by the aluminium/hexadecane sample regarding the rate of heat flux and also achieved about 10% and 15% heat transfer enhancements during the charging and discharging periods respectively. Its measured effective thermal conductivity also increased remarkably to 1.25 W/mK as compared with 0.15 W/mK for pure hexadecane. However there was about 5% less total cumulative thermal energy discharged at the end of the test which indicates that its effective thermal capacity was reduced by the presence of the aluminium particles. The study has shown that some of the scientific and technical barriers associated with the development of laminated composite PCM drywall systems can be overcome but further investigations of effects of adhesive materials are needed. (author)

Field performance of timber bridges. 9, Big Erick`s stress-laminated deck bridge

Science.gov (United States)

J. A. Kainz; J. P. Wacker; M. Nelson

The Big Erickas bridge was constructed during September 1992 in Baraga County, Michigan. The bridge is 72 ft long, 16 ft wide, and consists of three simple spans: two stress-laminated deck approach spans and a stress-laminated box center span. The bridge is unique in that it is one of the first known stress-laminated timber bridge applications to use Eastern Hemlock...

Laser displacement sensor to monitor the layup process of composite laminate production

Science.gov (United States)

Miesen, Nick; Groves, Roger M.; Sinke, Jos; Benedictus, Rinze

2013-04-01

Several types of flaw can occur during the layup process of prepreg composite laminates. Quality control after the production process checks the end product by testing the specimens for flaws which are included during the layup process or curing process, however by then these flaws are already irreversibly embedded in the laminate. This paper demonstrates the use of a laser displacement sensor technique applied during the layup process of prepreg laminates for in-situ flaw detection, for typical flaws that can occur during the composite production process. An incorrect number of layers and fibre wrinkling are dominant flaws during the process of layup. These and other dominant flaws have been modeled to determine the requirements for an in-situ monitoring during the layup process of prepreg laminates.

Complex phenotype linked to a mutation in exon 11 of the lamin A/C gene: Hypertrophic cardiomyopathy, atrioventricular block, severe dyslipidemia and diabetes.

Science.gov (United States)

Francisco, Ana Rita G; Santos Gonçalves, Inês; Veiga, Fátima; Mendes Pedro, Mónica; Pinto, Fausto J; Brito, Dulce

2017-09-01

The lamin A/C (LMNA) gene encodes lamins A and C, which have an important role in nuclear cohesion and chromatin organization. Mutations in this gene usually lead to the so-called laminopathies, the primary cardiac manifestations of which are dilated cardiomyopathy and intracardiac conduction defects. Some mutations, associated with lipodystrophy but not cardiomyopathy, have been linked to metabolic abnormalities such as diabetes and severe dyslipidemia. Herein we describe a new phenotype associated with a mutation in exon 11 of the LMNA gene: hypertrophic cardiomyopathy, atrioventricular block, severe dyslipidemia and diabetes. A 64-year-old woman with hypertrophic cardiomyopathy and a point mutation in exon 11 of the LMNA gene (c.1718C>T, Ser573Leu) presented with severe symptomatic ventricular hypertrophy and left ventricular outflow tract obstruction. She underwent septal alcohol ablation, followed by Morrow myectomy. The patient was also diagnosed with severe dyslipidemia, diabetes and obesity, and fulfilled diagnostic criteria for metabolic syndrome. No other characteristics of LMNA mutation-related phenotypes were identified. The development of type III atrioventricular block with no apparent cause, and mildly depressed systolic function, prompted referral for cardiac resynchronization therapy. In conclusion, the association between LMNA mutations and different phenotypes is complex and not fully understood, and can present with a broad spectrum of severity. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Tolerance for salinity and morphoagronomic characterization of rice mutants obtained by radioinduction

International Nuclear Information System (INIS)

Gonzalez, L.M.; Ramirez Fernandez, R.; Perez Talavera, S.

1997-01-01

Tolerance for salinity, agroindustrial efficiency, and resistance to diseases were appraised in a group of rice mutants obtained by means of mutation radioinduction, starting from the J-112 variety. Results show significant differences in the analyzed characteristics of radio mutants, and differences between those radio mutans and the donating variety. Radio mutants RM-12, RM-41, and RM-42, besides standing out for their high tolerance for salinity, boasted the highest agroindustrial efficiency and a good behaviour against the main plagues and diseases, which makes of them likely candidates for new varieties in the production from areas affected by salinity

[Mutant alleles associated to chloroquine and sulfadoxine-pyrimethanime resistance in Plasmodium falciparum of the Ecuador-Peru and Ecuador-Colombia borders].

Science.gov (United States)

Arróspide, Nancy; Hijar-Guerra, Gisely; de Mora, Doménica; Diaz-Cortéz, César Eduardo; Veloz-Perez, Raúl; Gutierrez, Sonia; Cabezas-Sánchez, César

2014-04-01

The frequency of mutations in pfCRT and DHFR/DHPS genes of Plasmodium falciparum associated with resistance to chloroquine and sulfadoxine-pyrimethamine was evaluated in 83 strains from the districts of Esmeralda and Machala, located on the borders of Ecuador-Peru and Ecuador-Colombia in 2002. Polymerase chain reaction (PCR), conventional and its variants, was used. Mutations in the pfCRT gene were found in more than 90% of the samples from Esmeralda and Machala. For the DHFR gene, 90% of the strains were mutant samples from Esmeralda, 3 were double mutations and 1 was a triple mutation. In Machala, 25% were simple mutant forms and 75% mixed mutant forms (wild forms/mutant). In conclusion, resistance to chloroquine has been fixed in strains carrying K76T pfCRT mutation, whereas genetic imprinting for resistance to pyrimethamine is evolving, particularly in the district of Esmeralda.

Probabilistic Modelling of Fatigue Life of Composite Laminates Using Bayesian Inference

DEFF Research Database (Denmark)

Dimitrov, Nikolay Krasimirov; Kiureghian, Armen Der

2014-01-01

A probabilistic model for estimating the fatigue life of laminated composite plates subjected to constant-amplitude or variable-amplitude loading is developed. The model is based on lamina-level input data, making it possible to predict fatigue properties for a wide range of laminate configuratio...

Haplotype association analysis of human disease traits using genotype data of unrelated individuals

DEFF Research Database (Denmark)

Tan, Qihua; Christiansen, Lene; Christensen, Kaare

2005-01-01

unphased multi-locus genotype data, ranging from the early approach by the simple gene-counting method to the recent work using the generalized linear model. However, these methods are either confined to case – control design or unable to yield unbiased point and interval estimates of haplotype effects....... Based on the popular logistic regression model, we present a new approach for haplotype association analysis of human disease traits. Using haplotype-based parameterization, our model infers the effects of specific haplotypes (point estimation) and constructs confidence interval for the risks...... on the well-known logistic regression model is a useful tool for haplotype association analysis of human disease traits....

On Poisson's ratio for metal matrix composite laminates. [aluminum boron composites

Science.gov (United States)

Herakovich, C. T.; Shuart, M. J.

1978-01-01

The definition of Poisson's ratio for nonlinear behavior of metal matrix composite laminates is discussed and experimental results for tensile and compressive loading of five different boron-aluminum laminates are presented. It is shown that there may be considerable difference in the value of Poisson's ratio as defined by a total strain or an incremental strain definition. It is argued that the incremental definition is more appropriate for nonlinear material behavior. Results from a (0) laminate indicate that the incremental definition provides a precursor to failure which is not evident if the total strain definition is used.

Breeding for blast-disease-resistant and high-yield Thai jasmine rice (Oryza sativa L. cv. KDML 105) mutants using low-energy ion beams

International Nuclear Information System (INIS)

Mahadtanapuk, S.; Teraarusiri, W.; Phanchaisri, B.; Yu, L.D.; Anuntalabhochai, S.

2013-01-01

Highlights: •N-ion beam bombarded Thai jasmine rice seeds to induce mutation. •Mutants with blast-disease resistance and high yield were screened. •Gene involved in the blast-disease resistance was analyzed. •The gene responsible for the resistance was linked to Spotted leaf protein 11. -- Abstract: Low-energy ion beam was applied on mutation induction for plant breeding of blast-disease-resistant Thai jasmine rice (Oryza sativa L. cv. KDML 105). Seeds of the wild-type rice were bombarded in vacuum by nitrogen ion beam at energy of 60–80 keV to a beam fluence range of 2 × 10 16 –2 × 10 17 ions/cm 2 . The ion-bombarded rice seeds were grown in soil for 2 weeks as transplanted rice in plastic pots at 1 seedling/pot. The seedlings were then screened for blast resistance by Pyricularia grisea inoculation with 10 6 spores/ml concentrations. The blast-resistant rice mutant was planted up to F6 generation with the consistent phenotypic variation. The high percentage of the blast-disease-resistant rice was analyzed with DNA fingerprint. The HAT-RAPD (high annealing temperature-random amplified polymorphic DNA) marker revealed the modified polymorphism fragment presenting in the mutant compared with wild type (KDML 105). The cDNA fingerprints were investigated and the polymorphism fragment was subcloned into pGEM-T easy vector and then sequenced. The sequence of this fragment was compared with those already contained in the database, and the fragment was found to be related to the Spotted leaf protein 11 (Spl11)

Environmental Effects on Flutter Characteristics of Laminated Composite Rectangular and Skew Panels

Directory of Open Access Journals (Sweden)

T.V.R. Chowdary

1996-01-01

Full Text Available A finite element method is presented for predicting the flutter response of laminated composite panels subjected to moisture concentration and temperature. The analysis accounts for material properties at elevated temperature and moisture concentration. The analysis is based on the first-order approximation to the linear piston theory and laminated plate theory that includes shear deformation. Both rectangular and skew panels are considered. Stability boundaries at moisture concentrations and temperatures for various lamination schemes and boundary conditions are discussed.

Alzheimer’s Disease Mutant Mice Exhibit Reduced Brain Tissue Stiffness Compared to Wild-type Mice in both Normoxia and following Intermittent Hypoxia Mimicking Sleep Apnea

Directory of Open Access Journals (Sweden)

Maria José Menal

2018-01-01

Full Text Available BackgroundEvidence from patients and animal models suggests that obstructive sleep apnea (OSA may increase the risk of Alzheimer’s disease (AD and that AD is associated with reduced brain tissue stiffness.AimTo investigate whether intermittent hypoxia (IH alters brain cortex tissue stiffness in AD mutant mice exposed to IH mimicking OSA.MethodsSix-eight month old (B6C3-Tg(APPswe,PSEN1dE985Dbo/J AD mutant mice and wild-type (WT littermates were subjected to IH (21% O2 40 s to 5% O2 20 s; 6 h/day or normoxia for 8 weeks. After euthanasia, the stiffness (E of 200-μm brain cortex slices was measured by atomic force microscopy.ResultsTwo-way ANOVA indicated significant cortical softening and weight increase in AD mice compared to WT littermates, but no significant effects of IH on cortical stiffness and weight were detected. In addition, reduced myelin was apparent in AD (vs. WT, but no significant differences emerged in the cortex extracellular matrix components laminin and glycosaminoglycans when comparing baseline AD and WT mice.ConclusionAD mutant mice exhibit reduced brain tissue stiffness following both normoxia and IH mimicking sleep apnea, and such differences are commensurate with increased edema and demyelination in AD.

Arabidopsis thaliana cdd1 mutant uncouples the constitutive activation of salicylic acid signalling from growth defects.

Science.gov (United States)

Swain, Swadhin; Roy, Shweta; Shah, Jyoti; Van Wees, Saskia; Pieterse, Corné M; Nandi, Ashis K

2011-12-01

Arabidopsis genotypes with a hyperactive salicylic acid-mediated signalling pathway exhibit enhanced disease resistance, which is often coupled with growth and developmental defects, such as dwarfing and spontaneous necrotic lesions on the leaves, resulting in reduced biomass yield. In this article, we report a novel recessive mutant of Arabidopsis, cdd1 (constitutive defence without defect in growth and development1), that exhibits enhanced disease resistance associated with constitutive salicylic acid signalling, but without any observable pleiotropic phenotype. Both NPR1 (NON-EXPRESSOR OF PATHOGENESIS-RELATED GENES1)-dependent and NPR1-independent salicylic acid-regulated defence pathways are hyperactivated in cdd1 mutant plants, conferring enhanced resistance against bacterial pathogens. However, a functional NPR1 allele is required for the cdd1-conferred heightened resistance against the oomycete pathogen Hyaloperonospora arabidopsidis. Salicylic acid accumulates at elevated levels in cdd1 and cdd1 npr1 mutant plants and is necessary for cdd1-mediated PR1 expression and disease resistance phenotypes. In addition, we provide data which indicate that the cdd1 mutation negatively regulates the npr1 mutation-induced hyperactivation of ethylene/jasmonic acid signalling. © 2011 The Authors. Molecular Plant Pathology © 2011 BSPP and Blackwell Publishing Ltd.

Delamination behaviour in differently copper laminated REBCO coated conductor tapes under transverse loading

Energy Technology Data Exchange (ETDEWEB)

Gorospe, Alking [Department of Mechanical Design Engineering, Andong National University, 1375 Kyungdong-Ro, Andong 760-749 (Korea, Republic of); Department of Engineering, Aurora State College of Technology, Baler Aurora 3200 (Philippines); Nisay, Arman [Department of Mechanical Design Engineering, Andong National University, 1375 Kyungdong-Ro, Andong 760-749 (Korea, Republic of); Shin, Hyung-Seop, E-mail: hsshin@andong.ac.kr [Department of Mechanical Design Engineering, Andong National University, 1375 Kyungdong-Ro, Andong 760-749 (Korea, Republic of)

2014-09-15

Highlights: • I{sub c} degradation behavior under transverse tension loading in different CC tape structure. • Weibull distribution analysis applied on delamination mechanism of CC tape. • Delamination mechanism on CC tapes depending on copper lamination type. • SEM and WDS mapping analysis of delamination sites under transverse loading. - Abstract: Laminated HTS coated conductor (CC) tapes having a unique multi-layer structure made them vulnerable when exposed to transverse loading. Electromechanical transport properties of these CC tapes can be affected by excessive transverse stresses. Due to the coefficient of thermal expansion (CTE) mismatch and incompatibility among constituent materials used in coil applications, delamination among layers occurs and causes critical current, I{sub c} degradation in the CC tapes. In this study, the delamination behaviors in copper (Cu) solder-laminated CC tapes by soldering and surround Cu-stabilized ones by electroplating under transverse tension loading were investigated. Similarly to the surround Cu-stabilized CC tapes in our previous reports, the Cu solder-laminated CC tapes also showed an abrupt and gradual I{sub c} degradation behavior. However, the Cu solder-laminated CC tapes showed different delamination morphologies as compared to the surround Cu-stabilized CC tapes; the superconducting side and the substrate side of the Cu solder laminated CC tapes were totally separated by delamination. On the other hand, the brass laminate did not show any significant effect on the delamination strength when it is added upon the surround Cu-stabilized CC tapes.

Laminated piezoelectric transformer

Science.gov (United States)

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.

Design, fabrication, testing and delivery of a feasibility model laminated ferrite memory

Science.gov (United States)

Heckler, H. C.

1973-01-01

The effect of using multiword addressing with laminated ferrite arrays was made. Both a reduction in the number of components, and a reduction in power consumption was obtained for memory capacities between one million bits and one million words. An investigation into the effect of variations in the processing steps resulted in a number of process modifications that improved the quality of the arrays. A feasibility model laminated ferrite memory system was constructed by modifying a commercial plated wire memory system to operate with laminated ferrite arrays. To provide flexibility for the testing of the laminated ferrite memory, an exerciser has been constructed to automatically control the loading and recirculation of arbitrary size checkerboard patterns of one's and zero's and to display the patterns of stored information on a CRT screen.

Increased BRAF Heterodimerization Is the Common Pathogenic Mechanism for Noonan Syndrome-Associated RAF1 Mutants

Science.gov (United States)

Wu, Xue; Yin, Jiani; Simpson, Jeremy; Kim, Kyoung-Han; Gu, Shengqing; Hong, Jenny H.; Bayliss, Peter; Backx, Peter H.

2012-01-01

Noonan syndrome (NS) is a relatively common autosomal dominant disorder characterized by congenital heart defects, short stature, and facial dysmorphia. NS is caused by germ line mutations in several components of the RAS–RAF–MEK–extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway, including both kinase-activating and kinase-impaired alleles of RAF1 (∼3 to 5%), which encodes a serine-threonine kinase for MEK1/2. To investigate how kinase-impaired RAF1 mutants cause NS, we generated knock-in mice expressing Raf1D486N. Raf1D486N/+ (here D486N/+) female mice exhibited a mild growth defect. Male and female D486N/D486N mice developed concentric cardiac hypertrophy and incompletely penetrant, but severe, growth defects. Remarkably, Mek/Erk activation was enhanced in Raf1D486N-expressing cells compared with controls. RAF1D486N, as well as other kinase-impaired RAF1 mutants, showed increased heterodimerization with BRAF, which was necessary and sufficient to promote increased MEK/ERK activation. Furthermore, kinase-activating RAF1 mutants also required heterodimerization to enhance MEK/ERK activation. Our results suggest that an increased heterodimerization ability is the common pathogenic mechanism for NS-associated RAF1 mutations. PMID:22826437

Laminate mechanics for balanced woven fabrics

NARCIS (Netherlands)

Akkerman, Remko

2006-01-01

Laminate mechanics equations are presented for composites with balanced woven fabric reinforcements. It is shown that mimicking these textile composites with equivalent transversely isotropic (‘unidirectional’) layers requires disputable manipulations. Various micromechanics predictions of textile

Accumulation of distinct prelamin A variants in human diploid fibroblasts differentially affects cell homeostasis

International Nuclear Information System (INIS)

Candelario, Jose; Borrego, Stacey; Reddy, Sita; Comai, Lucio

2011-01-01

Lamin A is a component of the nuclear lamina that plays a major role in the structural organization and function of the nucleus. Lamin A is synthesized as a prelamin A precursor which undergoes four sequential post-translational modifications to generate mature lamin A. Significantly, a large number of point mutations in the LMNA gene cause a range of distinct human disorders collectively known as laminopathies. The mechanisms by which mutations in lamin A affect cell function and cause disease are unclear. Interestingly, recent studies have suggested that alterations in the normal lamin A pathway can contribute to cellular dysfunction. Specifically, we and others have shown, at the cellular level, that in the absence of mutations or altered splicing events, increased expression of wild-type prelamin A results in a growth defective phenotype that resembles that of cells expressing the mutant form of lamin A, termed progerin, associated with Hutchinson-Gilford Progeria syndrome (HGPS). Remarkably, the phenotypes of cells expressing elevated levels of wild-type prelamin A can be reversed by either treatment with farnesyltransferase inhibitors or overexpression of ZMPSTE24, a critical prelamin A processing enzyme, suggesting that minor increases in the steady-state levels of one or more prelamin A intermediates is sufficient to induce cellular toxicity. Here, to investigate the molecular basis of the lamin A pathway toxicity, we characterized the phenotypic changes occurring in cells expressing distinct prelamin A variants mimicking specific prelamin A processing intermediates. This analysis demonstrates that distinct prelamin A variants differentially affect cell growth, nuclear membrane morphology, nuclear distribution of lamin A and the fundamental process of transcription. Expression of prelamin A variants that are constitutively farnesylated induced the formation of lamin A aggregates and dramatic changes in nuclear membrane morphology, which led to reduced

A Mycobacterium leprae Hsp65 mutant as a candidate for mitigating lupus aggravation in mice.

Directory of Open Access Journals (Sweden)

Eliana B Marengo

Full Text Available Hsp60 is an abundant and highly conserved family of intracellular molecules. Increased levels of this family of proteins have been observed in the extracellular compartment in chronic inflammation. Administration of M. leprae Hsp65 [WT] in [NZBxNZW]F(1 mice accelerates the Systemic Lupus Erythematosus [SLE] progression whereas the point mutated K(409A Hsp65 protein delays the disease. Here, the biological effects of M. leprae Hsp65 Leader pep and K(409A pep synthetic peptides, which cover residues 352-371, are presented. Peptides had immunomodulatory effects similar to that observed with their respective proteins on survival and the combined administration of K(409A+Leader pep or K(409A pep+WT showed that the mutant forms were able to inhibit the deleterious effect of WT on mortality, indicating the neutralizing potential of the mutant molecules in SLE progression. Molecular modeling showed that replacing Lysine by Alanine affects the electrostatic potential of the 352-371 region. The number of interactions observed for WT is much higher than for Hsp65 K(409A and mouse Hsp60. The immunomodulatory effects of the point-mutated protein and peptide occurred regardless of the catalytic activity. These findings may be related to the lack of effect on survival when F(1 mice were inoculated with Hsp60 or K(409A pep. Our findings indicate the use of point-mutated Hsp65 molecules, such as the K(409A protein and its corresponding peptide, that may minimize or delay the onset of SLE, representing a new approach to the treatment of autoimmune diseases.

Association between environmental exposure to pesticides and neurodegenerative diseases

Energy Technology Data Exchange (ETDEWEB)

Parron, Tesifon [University of Almeria, Department of Neurosciences and Health Sciences, Almeria (Spain); Andalusian Council of Health at Almeria province, Almeria (Spain); Requena, Mar [Andalusian Council of Health at Almeria province, Almeria (Spain); Hernandez, Antonio F., E-mail: ajerez@ugr.es [University of Granada School of Medicine, Granada (Spain); Alarcon, Raquel [Andalusian Council of Health at Almeria province, Almeria (Spain)

2011-11-15

Preliminary studies have shown associations between chronic pesticide exposure in occupational settings and neurological disorders. However, data on the effects of long-term non-occupational exposures are too sparse to allow any conclusions. This study examines the influence of environmental pesticide exposure on a number of neuropsychiatric conditions and discusses their underlying pathologic mechanisms. An ecological study was conducted using averaged prevalence rates of Alzheimer's disease, Parkinson's disease, multiple sclerosis, cerebral degeneration, polyneuropathies, affective psychosis and suicide attempts in selected Andalusian health districts categorized into areas of high and low environmental pesticide exposure based on the number of hectares devoted to intensive agriculture and pesticide sales per capita. A total of 17,429 cases were collected from computerized hospital records (minimum dataset) between 1998 and 2005. Prevalence rates and the risk of having Alzheimer's disease, Parkinson's disease, multiple sclerosis and suicide were significantly higher in districts with greater pesticide use as compared to those with lower pesticide use. The multivariate analyses showed that the population living in areas with high pesticide use had an increased risk for Alzheimer's disease and suicide attempts and that males living in these areas had increased risks for polyneuropathies, affective disorders and suicide attempts. In conclusion, this study supports and extends previous findings and provides an indication that environmental exposure to pesticides may affect the human health by increasing the incidence of certain neurological disorders at the level of the general population. -- Highlights: Black-Right-Pointing-Pointer Environmental exposure to pesticides and neurodegenerative-psychiatric disorders. Black-Right-Pointing-Pointer Increased risk for Alzheimer's disease and suicide attempts in high exposure areas. Black-Right-Pointing

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

Directory of Open Access Journals (Sweden)

Chad R Sethman

Full Text Available 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.

Detection of layup errors in prepreg laminates using shear ultrasonic waves

Science.gov (United States)

Hsu, David K.; Fischer, Brent A.

1996-11-01

The highly anisotropic elastic properties of the plies in a composite laminate manufactured from unidirectional prepregs interact strongly with the polarization direction of shear ultrasonic waves propagating through its thickness. The received signals in a 'crossed polarizer' transmission configuration are particularly sensitive to ply orientation and layup sequence in a laminate. Such measurements can therefore serve as an NDE tool for detecting layup errors. For example, it was shown experimentally recently that the sensitivity for detecting the presence of misoriented plies is better than one ply out of a 48-ply laminate of graphite epoxy. A physical model based on the decomposition and recombination of the shear polarization vector has been constructed and used in the interpretation and prediction of test results. Since errors should be detected early in the manufacturing process, this work also addresses the inspection of 'green' composite laminates using electromagnetic acoustic transducers (EMAT). Preliminary results for ply error detection obtained with EMAT probes are described.

Aggregation of Trp > Glu point mutants of human gamma-D crystallin provides a model for hereditary or UV-induced cataract.

Science.gov (United States)

Serebryany, Eugene; Takata, Takumi; Erickson, Erika; Schafheimer, Nathaniel; Wang, Yongting; King, Jonathan A

2016-06-01

Numerous mutations and covalent modifications of the highly abundant, long-lived crystallins of the eye lens cause their aggregation leading to progressive opacification of the lens, cataract. The nature and biochemical mechanisms of the aggregation process are poorly understood, as neither amyloid nor native-state polymers are commonly found in opaque lenses. The βγ-crystallin fold contains four highly conserved buried tryptophans, which can be oxidized to more hydrophilic products, such as kynurenine, upon UV-B irradiation. We mimicked this class of oxidative damage using Trp→Glu point mutants of human γD-crystallin. Such substitutions may represent a model of UV-induced photodamage-introduction of a charged group into the hydrophobic core generating "denaturation from within." The effects of Trp→Glu substitutions were highly position dependent. While each was destabilizing, only the two located in the bottom of the double Greek key fold-W42E and W130E-yielded robust aggregation of partially unfolded intermediates at 37°C and pH 7. The αB-crystallin chaperone suppressed aggregation of W130E, but not W42E, indicating distinct aggregation pathways from damage in the N-terminal vs C-terminal domain. The W130E aggregates had loosely fibrillar morphology, yet were nonamyloid, noncovalent, showed little surface hydrophobicity, and formed at least 20°C below the melting temperature of the native β-sheets. These features are most consistent with domain-swapped polymerization. Aggregation of partially destabilized crystallins under physiological conditions, as occurs in this class of point mutants, could provide a simple in vitro model system for drug discovery and optimization. © 2016 The Protein Society.

Cytoembryologic study of gamma-ray induced sterile Pisum sativum L. mutants

International Nuclear Information System (INIS)

Molkhova, E.; Vasileva, M.

1977-01-01

Three new pea mutant forms are described - 1878, Crampled petal Waxless type, and Lathyrus type - which were induced by different gamma-ray ( 60 Co) doses and rates. The flowers of the 1878 and Crampled petal Waxless type mutants were very much deformed, while those of the Lathyrus type had smaller flowers with normal morphology. The three mutant forms were entirely sterile and were propagated by segregation in the progeny of heterozygous sister plants. PMC meiosis and the development of the male gametophyte of the Lathyrus type mutant had a normal course, while in the mutant forms Crampled petal Waxless type and 1878 slight disturbances were observed, but the pollen of all three mutants was not functional. The development of the female gametophyte of the three mutants stops at an early phase and only in the Lathyrus type mutant in single cases embryosacks were formed with differentiated sex apparatus and early stages of embryo and endosperm development were scored, but they also soon degenerate. It is pointed out that sterility of the three pea mutant forms studied depends on factors, which stop at different stages the normal development of the generative organs, of the female gametophyte and of embryogenesis. (author)

PROCESS AND APPARATUS FOR SEPARATING INDIVIDUAL PANES FROM A LAMINATED GLASS SHEET

OpenAIRE

Kübler, R.; Rist, T.; Hoetger, B.

2011-01-01

The invention relates to a process for separating at least one individual pane of predefined size and edge form from a laminated glass sheet, which has at least two laminated glass sheet panes which are arranged one above another in adjacent form and between which there is arranged a plastic film, which permanently bonds the laminated glass sheet panes to one another, wherein - a laser track channel which at least weakens the plastic structure of the plastic film is laid into the plastic film...

Mutants induced in winter rye (Secale cereale L.): Short straw-mutant No. 2714 and late-senescence mutant

Energy Technology Data Exchange (ETDEWEB)

Muszynski, S; Darlewska, M [Department of Plant Breeding and Seed Science, Warsaw Agricultural University, Warsaw (Poland)

1990-01-01

Full text: Mutants were induced by treating dormant seeds with ionizing radiation (fast neutrons) or chemicals (N-nitroso-N-ethyl urea or sodium azide). Among several mutants obtained, of special value is the short-straw mutant No. 2714 and a late senescent mutant. (author)

Deletion map of CYC1 mutants and its correspondence to mutationally altered iso-1-cytochromes c of yeast

International Nuclear Information System (INIS)

Sherman, F.; Jackson, M.; Liebman, S.W.; Schweingruber, A.M.; Stewart, J.W.

1975-01-01

Mutants arising spontaneously from sporulated cultures of certain strains of yeast, Saccharomyces cerevisiae, contained deletions of the CYC1 gene which controls the primary structure of iso-1-cytochrome c. At least 60 different kinds of deletions were uncovered among the 104 deletions examined and these ranged in length from those encompassing only two adjacent point mutants to those encompassing at least the entire CYC1 gene. X-ray-induced recombination rates of crosses involving these deletions and cyc1 point mutants resulted in the assignment of 211 point mutants to 47 mutational sites and made it possible to unambiguously order 40 of these 47 sites. Except for one mutant, cyc1-15, there was a strict colinear relationship between the deletion map and the positions of 13 sites that were previously determined by amino acid alterations in iso-1-cytochromes c from intragenic revertants

Reaction of some soybean mutant lines to natural rust fungus caused by (phakopsora pachyrhizi syd)

International Nuclear Information System (INIS)

Ratma, R.

1988-01-01

Reaction of some soybean mutant lines to natural rust fungus caused by (phakopsora pachyhizi syd). Eleven soybean mutant lines of orba variety derived from gamma fungus disease in the wet season 1985/86 at the experimental station of Citayam, Bogor. Based on IWGSR rating system, soybean mutant lines No 18/PsJ was moderately resistant to rust fungus disease. The other mutant lines, 14/PsJ, 15/PsJ, 20/PsJ, 102/PsJ, 106/PsJ, 111/PsJ, 118/PsJ, 119/PsJ and 220/PsJ were susceptible. (author). 4 figs.; 8 refs

77 FR 61025 - Certain Prepregs, Laminates, and Finished Circuit Boards: Notice of Institution of Formal...

Science.gov (United States)

2012-10-05

... INTERNATIONAL TRADE COMMISSION [Inv. No. 337-TA-659] Certain Prepregs, Laminates, and Finished..., and the sale within the United States after importation of certain prepregs, laminates, and finished... for sale, and selling for importation into the United States prepregs and laminates that are the...

Influence of porosity on the interlaminar shear strength of fibre-metal laminates

NARCIS (Netherlands)

Lopes, C.S.; Remmers, J.J.C.; Gürdal, Z.

2008-01-01

Structures manufactured in fibre-metal laminates (e.g. Glare) have been designedconsidering ideal mechanical properties determined by the Classical Lamination Theory. Thismeans that among other assumptions, perfect bonding conditions between layers are assumed.However, more than often, perfect

Whole-Genome Sequencing of Sordaria macrospora Mutants Identifies Developmental Genes.

Science.gov (United States)

Nowrousian, Minou; Teichert, Ines; Masloff, Sandra; Kück, Ulrich

2012-02-01

The study of mutants to elucidate gene functions has a long and successful history; however, to discover causative mutations in mutants that were generated by random mutagenesis often takes years of laboratory work and requires previously generated genetic and/or physical markers, or resources like DNA libraries for complementation. Here, we present an alternative method to identify defective genes in developmental mutants of the filamentous fungus Sordaria macrospora through Illumina/Solexa whole-genome sequencing. We sequenced pooled DNA from progeny of crosses of three mutants and the wild type and were able to pinpoint the causative mutations in the mutant strains through bioinformatics analysis. One mutant is a spore color mutant, and the mutated gene encodes a melanin biosynthesis enzyme. The causative mutation is a G to A change in the first base of an intron, leading to a splice defect. The second mutant carries an allelic mutation in the pro41 gene encoding a protein essential for sexual development. In the mutant, we detected a complex pattern of deletion/rearrangements at the pro41 locus. In the third mutant, a point mutation in the stop codon of a transcription factor-encoding gene leads to the production of immature fruiting bodies. For all mutants, transformation with a wild type-copy of the affected gene restored the wild-type phenotype. Our data demonstrate that whole-genome sequencing of mutant strains is a rapid method to identify developmental genes in an organism that can be genetically crossed and where a reference genome sequence is available, even without prior mapping information.

Fire-Resistant Hydrogel-Fabric Laminates: A Simple Concept That May Save Lives.

Science.gov (United States)

Illeperuma, Widusha R K; Rothemund, Philipp; Suo, Zhigang; Vlassak, Joost J

2016-01-27

There is a large demand for fabrics that can survive high-temperature fires for an extended period of time, and protect the skin from burn injuries. Even though fire-resistant polymer fabrics are commercially available, many of these fabrics are expensive, decompose rapidly, and/or become very hot when exposed to high temperatures. We have developed a new class of fire-retarding materials by laminating a hydrogel and a fabric. The hydrogel contains around 90% water, which has a large heat capacity and enthalpy of vaporization. When the laminate is exposed to fire, a large amount of energy is absorbed as water heats up and evaporates. The temperature of the hydrogel cannot exceed 100 °C until it is fully dehydrated. The fabric has a low thermal conductivity and maintains the temperature gradient between the hydrogel and the skin. The laminates are fabricated using a recently developed tough hydrogel to ensure integrity of the laminate during processing and use. A thermal model predicts the performance of the laminates and shows that they have excellent heat resistance in good agreement with experiments, making them viable candidates in life saving applications such as fire-resistant blankets or apparel.

Control of free-edge interlaminar stresses in composite laminates using piezoelectric actuators

International Nuclear Information System (INIS)

Huang, Bin; Soo Kim, Heung

2014-01-01

The control of free-edge interlaminar stresses in laminated composite structures using a stress function-based approach is proposed. The assumed stress fields satisfy pointwise traction and free boundary conditions at surfaces. Governing equations are derived using the principle of complementary virtual work. A general eigenvalue solution procedure was adopted to obtain accurate stress states of the laminated composite structure. The results obtained from the proposed method were compared with those obtained by three-dimensional finite element analyses. It was found that interlaminar stresses generated by mechanical loadings could be significantly reduced by applying proper electric fields to piezoelectric actuators, which were surface bonded or embedded in composite laminates. Locations of piezoelectric actuators also influenced the distributions of interlaminar stresses. The results provided that piezoelectric actuators have potential in the application to actively control interlaminar stresses in composite laminates. (paper)

Werner complex deficiency in cells disrupts the Nuclear Pore Complex and the distribution of lamin B1.

Science.gov (United States)

Li, Zhi; Zhu, Yizhou; Zhai, Yujia; R Castroagudin, Michelle; Bao, Yifei; White, Tommy E; Glavy, Joseph S

2013-12-01

From the surrounding shell to the inner machinery, nuclear proteins provide the functional plasticity of the nucleus. This study highlights the nuclear association of Pore membrane (POM) protein NDC1 and Werner protein (WRN), a RecQ helicase responsible for the DNA instability progeria disorder, Werner Syndrome. In our previous publication, we connected the DNA damage sensor Werner's Helicase Interacting Protein (WHIP), a binding partner of WRN, to the NPC. Here, we confirm the association of the WRN/WHIP complex and NDC1. In established WRN/WHIP knockout cell lines, we further demonstrate the interdependence of WRN/WHIP and Nucleoporins (Nups). These changes do not completely abrogate the barrier of the Nuclear Envelope (NE) but do affect the distribution of FG Nups and the RAN gradient, which are necessary for nuclear transport. Evidence from WRN/WHIP knockout cell lines demonstrates changes in the processing and nucleolar localization of lamin B1. The appearance of "RAN holes" void of RAN corresponds to regions within the nucleolus filled with condensed pools of lamin B1. From WRN/WHIP knockout cell line extracts, we found three forms of lamin B1 that correspond to mature holoprotein and two potential post-translationally modified forms of the protein. Upon treatment with topoisomerase inhibitors lamin B1 cleavage occurs only in WRN/WHIP knockout cells. Our data suggest the link of the NDC1 and WRN as one facet of the network between the nuclear periphery and genome stability. Loss of WRN complex leads to multiple alterations at the NPC and the nucleolus. © 2013. Published by Elsevier B.V. All rights reserved.

Prevalence of precore-defective mutant of hepatitis B virus in HBV carriers.

Science.gov (United States)

Niitsuma, H; Ishii, M; Saito, Y; Miura, M; Kobayashi, K; Ohori, H; Toyota, T

1995-08-01

Two hundred and seventy-three serum specimens from hepatitis B virus (HBV) carriers were examined for the presence of a characteristic one point mutation at nucleotide (nt) 1896 from the EcoRI site of the HBV genome in the precore region (the preC mutant) using restriction fragment length polymorphism (RFLP) analysis. This assay approach could detect preC mutants or wild-type sequences when either form constituted more than 10% of the total sample. Overall, 65.5% (76/116) of HBeAg-positive carriers had only the preC wild-type. All HBeAg-positive asymptomatic carriers (n = 14) had only the preC wild-type. In patients with chronic hepatitis B and in anti-HBe-positive asymptomatic carriers, increased prevalence of the preC mutant was associated with the development of anti-HBe antibodies and normalization of the serum alanine aminotransferase concentration. Furthermore, 27 (29.0%) of 93 HBeAg-negative carriers had unexpectedly preC wild-type sequences only. Direct sequencing of the HBV precore region of HBV specimens from 24 patients revealed no mutation at nt 1896, supporting the specificity of the RFLP analysis. These results suggest that RFLP analysis was accurate for the detection of the preC mutation and that the absence of serum HBeAg cannot be explained solely by the dominance of the preC mutant.

Fatigue damage mechanism and strength of woven laminates

International Nuclear Information System (INIS)

Xiao, J.; Bathias, C.

1993-01-01

The apparent secant stiffness changes with the cyclic number for both unnotched and notched woven laminated specimens (two orthotropic and one quasi-isotropic) during tensile fatigue test at a fixed ratio of maximum fatigue load to UTS were observed. The observable damage initiation and evolution as a function of the cyclic number were directly measured at the notched specimen surface with a video-camera system. The fatigue strengths of the unnotched and notched specimens were determined. The results show that the normalized apparent secant stiffness change curves as a function of cyclic numbers can be divided into three stages. For the first and the second stages in notched specimens and for total life of unnotched specimens, the damage has not been evidently observed and certainly verified with the traditional experimental methods such as radiography and microscopy although many acoustic emission signals can be obtained. The last stage for the notched specimens (N/Nf>0.4, the secant stiffness decreases fast) corresponds to the initiation and evolution of the observable damages. The fatigue strength of these woven composite laminates is dominated by the third stage during which the observable damage develops along the specimen ligament until fracture. During the third stage, a critical dimension at the specimen ligament and a life threshold can be found beyond which a final catastrophic fracture will immediately occur. The quasi-isotropic laminate is of a fatigue strength lower than the two orthotropic laminates of which the fatigue strengths are approaching to each other. The fatigue life is also influenced by the stacking sequences. (orig.)

Sensitive detection of point mutation by electrochemiluminescence and DNA ligase-based assay

Science.gov (United States)

Zhou, Huijuan; Wu, Baoyan

2008-12-01

The technology of single-base mutation detection plays an increasingly important role in diagnosis and prognosis of genetic-based diseases. Here we reported a new method for the analysis of point mutations in genomic DNA through the integration of allele-specific oligonucleotide ligation assay (OLA) with magnetic beads-based electrochemiluminescence (ECL) detection scheme. In this assay the tris(bipyridine) ruthenium (TBR) labeled probe and the biotinylated probe are designed to perfectly complementary to the mutant target, thus a ligation can be generated between those two probes by Taq DNA Ligase in the presence of mutant target. If there is an allele mismatch, the ligation does not take place. The ligation products are then captured onto streptavidin-coated paramagnetic beads, and detected by measuring the ECL signal of the TBR label. Results showed that the new method held a low detection limit down to 10 fmol and was successfully applied in the identification of point mutations from ASTC-α-1, PANC-1 and normal cell lines in codon 273 of TP53 oncogene. In summary, this method provides a sensitive, cost-effective and easy operation approach for point mutation detection.

Risk prediction of ventricular arrhythmias and myocardial function in Lamin A/C mutation positive subjects

DEFF Research Database (Denmark)

Hasselberg, Nina E; Edvardsen, Thor; Petri, Helle

2014-01-01

Mutations in the Lamin A/C gene may cause atrioventricular block, supraventricular arrhythmias, ventricular arrhythmias (VA), and dilated cardiomyopathy. We aimed to explore the predictors and the mechanisms of VA in Lamin A/C mutation-positive subjects.METHODS AND RESULTS: We included 41 Lamin A/C...

Analysis of noncoplanar pressurized laminations in X2 steel pipes by non-linear finite element

Energy Technology Data Exchange (ETDEWEB)

Morales, Alfredo [Instituto Tecnologico de Puebla (Mexico). Dept. de Posgrado; Gonzalez, Jorge L.; Hallen, Jose M. [Instituto Politecnico Nacional (Mexico). Escuela Superior de Ingenieria Quimica e Industrias Extractivas (ESIQIE). Dept. de Ingenieria Metalurgica

2005-07-01

Hydrogen induced cracking is of great interest in the mechanical integrity assessment of sour gas pipelines. Multiple stepwise cracks with internal pressure called laminations are often observed in pipelines and their interaction and coalescence may significantly affect the residual strength of the pipes. In this work, the interacting fields of non coplanar pressurized laminations in the wall of a pipe under pressure are analyzed by non-lineal finite element, considering an isotropic hardening law and the real tensile properties of the X52 steel. The results are presented as the evolution of the stress fields in the interlaminar region as a function of the pressure inside the laminations. It is found that for two approaching stepwise laminations the critical pressure follows a hyperbolic type law, thus the effect of the lamination length is principal for greater lengths and for shorter lengths the effect is minimum. The critical pressure is defined as pressure inside the lamination that causes plastification of the interlaminar region. (author)

A pro-cathepsin L mutant is a luminal substrate for endoplasmic-reticulum-associated degradation in C. elegans.

Directory of Open Access Journals (Sweden)

Mark T Miedel

Full Text Available Endoplasmic-reticulum associated degradation (ERAD is a major cellular misfolded protein disposal pathway that is well conserved from yeast to mammals. In yeast, a mutant of carboxypeptidase Y (CPY* was found to be a luminal ER substrate and has served as a useful marker to help identify modifiers of the ERAD pathway. Due to its ease of genetic manipulation and the ability to conduct a genome wide screen for modifiers of molecular pathways, C. elegans has become one of the preferred metazoans for studying cell biological processes, such as ERAD. However, a marker of ERAD activity comparable to CPY* has not been developed for this model system. We describe a mutant of pro-cathepsin L fused to YFP that no longer targets to the lysosome, but is efficiently eliminated by the ERAD pathway. Using this mutant pro-cathepsin L, we found that components of the mammalian ERAD system that participate in the degradation of ER luminal substrates were conserved in C. elegans. This transgenic line will facilitate high-throughput genetic or pharmacological screens for ERAD modifiers using widefield epifluorescence microscopy.

Static and dynamic strain energy release rates in toughened thermosetting composite laminates

Science.gov (United States)

Cairns, Douglas S.

1992-01-01

In this work, the static and dynamic fracture properties of several thermosetting resin based composite laminates are presented. Two classes of materials are explored. These are homogeneous, thermosetting resins and toughened, multi-phase, thermosetting resin systems. Multi-phase resin materials have shown enhancement over homogenous materials with respect to damage resistance. The development of new dynamic tests are presented for composite laminates based on Width Tapered Double Cantilevered Beam (WTDCB) for Mode 1 fracture and the End Notched Flexure (ENF) specimen. The WTDCB sample was loaded via a low inertia, pneumatic cylinder to produce rapid cross-head displacements. A high rate, piezo-electric load cell and an accelerometer were mounted on the specimen. A digital oscilloscope was used for data acquisition. Typical static and dynamic load versus displacement plots are presented. The ENF specimen was impacted in three point bending with an instrumented impact tower. Fracture initiation and propagation energies under static and dynamic conditions were determined analytically and experimentally. The test results for Mode 1 fracture are relatively insensitive to strain rate effects for the laminates tested in this study. The test results from Mode 2 fracture indicate that the toughened systems provide superior fracture initiation and higher resistance to propagation under dynamic conditions. While the static fracture properties of the homogeneous systems may be relatively high, the apparent Mode 2 dynamic critical strain energy release rate drops significantly. The results indicate that static Mode 2 fracture testing is inadequate for determining the fracture performance of composite structures subjected to conditions such as low velocity impact. A good correlation between the basic Mode 2 dynamic fracture properties and the performance is a combined material/structural Compression After Impact (CAI) test is found. These results underscore the importance of

An Investigation on Tensile Properties of Glass Fiber/Aluminium Laminates

Directory of Open Access Journals (Sweden)

M. Sadighi

2009-12-01

Full Text Available The idea of combining low weight and good mechanical properties has led to efforts to develop a new light fiber/metal laminate (FML in the last decade. FMLs are hybrid composites consisting of alternating thin layers of metal sheets and fiber-reinforced epoxy prepregs. In this study, the effect of fiber orientation on tensile properties of this material is investigated both analytically and experimentally. An analytical constitutive model based on classical lamination theory by using Kirchhoff-Love assumption, which incorporates the elastic-plastic behavior of the aluminium alloy was applied. Test results show that fiber sheet, with zero angle in laminates, improve the tensile strength. The composite layers with different fiber orientation change specimens' mode of fracture. Good agreement is obtained between the model predictions and experimental results.

Breeding for blast-disease-resistant and high-yield Thai jasmine rice (Oryza sativa L. cv. KDML 105) mutants using low-energy ion beams

Energy Technology Data Exchange (ETDEWEB)

Mahadtanapuk, S. [School of Agriculture and Natural Resources, University of Phayao, Phayao 56000 (Thailand); Teraarusiri, W. [Central Laboratory, University of Phayao, Phayao 56000 (Thailand); Phanchaisri, B. [Science and Technology Research Institute, Chiang Mai University, Chiang Mai 50200 (Thailand); Yu, L.D., E-mail: yuld@frnf.science.cmu.ac.th [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand); Anuntalabhochai, S., E-mail: burinka@hotmail.com [Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand)

2013-07-15

Highlights: •N-ion beam bombarded Thai jasmine rice seeds to induce mutation. •Mutants with blast-disease resistance and high yield were screened. •Gene involved in the blast-disease resistance was analyzed. •The gene responsible for the resistance was linked to Spotted leaf protein 11. -- Abstract: Low-energy ion beam was applied on mutation induction for plant breeding of blast-disease-resistant Thai jasmine rice (Oryza sativa L. cv. KDML 105). Seeds of the wild-type rice were bombarded in vacuum by nitrogen ion beam at energy of 60–80 keV to a beam fluence range of 2 × 10{sup 16}–2 × 10{sup 17} ions/cm{sup 2}. The ion-bombarded rice seeds were grown in soil for 2 weeks as transplanted rice in plastic pots at 1 seedling/pot. The seedlings were then screened for blast resistance by Pyricularia grisea inoculation with 10{sup 6} spores/ml concentrations. The blast-resistant rice mutant was planted up to F6 generation with the consistent phenotypic variation. The high percentage of the blast-disease-resistant rice was analyzed with DNA fingerprint. The HAT-RAPD (high annealing temperature-random amplified polymorphic DNA) marker revealed the modified polymorphism fragment presenting in the mutant compared with wild type (KDML 105). The cDNA fingerprints were investigated and the polymorphism fragment was subcloned into pGEM-T easy vector and then sequenced. The sequence of this fragment was compared with those already contained in the database, and the fragment was found to be related to the Spotted leaf protein 11 (Spl11)

Zic deficiency in the cortical marginal zone and meninges results in cortical lamination defects resembling those in type II lissencephaly.

Science.gov (United States)

Inoue, Takashi; Ogawa, Masaharu; Mikoshiba, Katsuhiko; Aruga, Jun

2008-04-30

The formation of the highly organized cortical structure depends on the production and correct placement of the appropriate number and types of neurons. The Zic family of zinc-finger transcription factors plays essential roles in regulating the proliferation and differentiation of neuronal progenitors in the medial forebrain and the cerebellum. Examination of the expression of Zic genes demonstrated that Zic1, Zic2, and Zic3 were expressed by the progenitor cells in the septum and cortical hem, the sites of generation of the Cajal-Retzius (CR) cells. Immunohistochemical studies have revealed that Zic proteins were abundantly expressed in the meningeal cells and that the majority of the CR cells distributed in the medial and dorsal cortex also expressed Zic proteins in the mid-late embryonic and postnatal cortical marginal zones. During embryonic cortical development, Zic1/Zic3 double-mutant and hypomorphic Zic2 mutant mice showed a reduction in the number of CR cells in the rostral cortex, whereas the cell number remained unaffected in the caudal cortex. These mutants also showed mislocalization of the CR cells and cortical lamination defects, resembling the changes noted in type II (cobblestone) lissencephaly, throughout the brain. In the Zic1/3 mutant, reduced proliferation of the meningeal cells was observed before the thinner and disrupted organization of the pial basement membrane (BM) with reduced expression of the BM components and the meningeal cell-derived secretory factor. These defects correlated with the changes in the end feet morphology of the radial glial cells. These findings indicate that the Zic genes play critical roles in cortical development through regulating the proliferation of meningeal cells and the pial BM assembly.

Nuclear Structures Surrounding Internal Lamin Invaginations

Czech Academy of Sciences Publication Activity Database

Legartová, Soňa; Stixová, Lenka; Laur, O.; Kozubek, Stanislav; Sehnalová, Petra; Bártová, Eva

2014-01-01

Roč. 115, č. 3 (2014), s. 476-487 ISSN 0730-2312 R&D Projects: GA MŠk(CZ) LD11020 Institutional support: RVO:68081707 Keywords : LAMINS * NUCLEAR PORES * CHROMATIN Subject RIV: BO - Biophysics Impact factor: 3.263, year: 2014

Fatigue Analysis of Notched Laminates: A Time-Efficient Macro-Mechanical Approach

Science.gov (United States)

Naghipour, P.; Pineda, E. J.; Bednarcyk, B. A.; Arnold, S. M.; Waas, A. M.

2016-01-01

A coupled transversely isotropic deformation and damage fatigue model is implemented within the finite element method and was utilized along with a static progressive damage model to predict the fatigue life, stiffness degradation as a function of number of cycles, and post-fatigue tension and compression response of notched, multidirectional laminates. Initially, the material parameters for the fatigue model were obtained utilizing micromechanics simulations and the provided [0], [90] and [plus or minus 45] experimental composite laminate S-N (stress-cycle) data. Within the fatigue damage model, the transverse and shear properties of the plies were degraded with an isotropic scalar damage variable. The damage in the longitudinal (fiber) ply direction was suppressed, and only the strength of the fiber was degraded as a function of fatigue cycles. A maximum strain criterion was used to capture the failure in each element, and once this criterion was satisfied, the longitudinal stiffness of the element was decreased by a factor of 10 (sup 4). The resulting, degraded properties were then used to calculate the new stress state. This procedure was repeated until final failure of the composite laminate was achieved or a specified number of cycles reached. For post-fatigue tension and compression behavior, four internal state variables were used to control the damage and failure. The predictive capability of the above-mentioned approach was assessed by performing blind predictions of the notched multidirectional IM7/977-3 composite laminates response under fatigue and post-fatigue tensile and compressive loading, followed by a recalibration phase. Although three different multidirectional laminates were analyzed in the course of this study, only detailed results (i.e., stiffness degradation and post-fatigue stress-train curves as well as damage evolution states for a single laminate ([30/60/90/minus 30/minus 60] (sub 2s)) are discussed in detail here.

Roll-to-roll compatible organic thin film transistor manufacturing technique by printing, lamination, and laser ablation

International Nuclear Information System (INIS)

Hassinen, Tomi; Ruotsalainen, Teemu; Laakso, Petri; Penttilä, Raimo; Sandberg, Henrik G.O.

2014-01-01

We present roll-to-roll printing compatible techniques for manufacturing organic thin film transistors using two separately processed foils that are laminated together. The introduction of heat-assisted lamination opens up possibilities for material and processing combinations. The lamination of two separately processed substrates together will allow usage of pre-patterned electrodes on both substrates and materials with non-compatible solvents. Also, the surface microstructure is formed differently when laminating dry films together compared to film formation from liquid phase. Demonstrator transistors, inverters and ring oscillators were produced using lamination techniques. Finally, a roll-to-roll compatible lamination concept is proposed where also the source and drain electrodes are patterned by laser ablation. The demonstrator transistors have shown very good lifetime in air, which is contributed partly to the good material combination and partly to the enhanced interface formation in heat-assisted lamination process. - Highlights: • A roll-to-roll compatible lamination technique for printed electronics is proposed. • Laser ablation allows highly defined metal top and bottom electrodes. • Method opens up processing possibilities for incompatible materials and solvents. • Shearing forces may enhance molecular orientation and packing. • An air stable polymer transistor is demonstrated with a lifetime of years

Vibration and Energy Dissipation of Nanocomposite Laminates for Below Ballistic Impact Loading

Directory of Open Access Journals (Sweden)

G. Balaganesan

Full Text Available Abstract Composite laminates are made of glass woven roving mats of 610gsm, epoxy resin and nano clay which are subjected to projectile impact. Nano clay dispersion is varied from 1% to 5%. Impact tests are conducted in a gas gun setup with a spherical nose cylindrical projectile of diameter 9.5 mm of mass 7.6 g. The energy absorbed by the laminates when subjected to impact loading is studied, the velocity range is below ballistic limit. The effect of nano clay on energy absorption in vibration, delamination and matrix crack is studied for different weight % of nano clay and for different thickness values of the laminates. The natural frequencies and damping factors are obtained for the laminates during impact and the effect of nano clay is studied. The results show considerable improvement in energy absorption due to the presence of nano clay

Laminated electrospun nHA/PHB-composite scaffolds mimicking bone extracellular matrix for bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Chen, Zhuoyue [Lab of Tissue Engineering, Faculty of Life Science, Northwest University, 229 TaiBai North Road, Xi' an, Shaanxi Province 710069 (China); Provincial Key Laboratory of Biotechnology of Shaanxi, Northwest University, 229 TaiBai North Road, Xi' an, Shaanxi Province 710069 (China); Song, Yue [Lab of Tissue Engineering, Faculty of Life Science, Northwest University, 229 TaiBai North Road, Xi' an, Shaanxi Province 710069 (China); Zhang, Jing [Lab of Tissue Engineering, Faculty of Life Science, Northwest University, 229 TaiBai North Road, Xi' an, Shaanxi Province 710069 (China); Provincial Key Laboratory of Biotechnology of Shaanxi, Northwest University, 229 TaiBai North Road, Xi' an, Shaanxi Province 710069 (China); Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Ministry of Education, Northwest University, 229 TaiBai North Road, Xi' an, Shaanxi Province, 710069 (China); Liu, Wei [Lab of Tissue Engineering, Faculty of Life Science, Northwest University, 229 TaiBai North Road, Xi' an, Shaanxi Province 710069 (China); Cui, Jihong, E-mail: cjh@nwu.edu.cn [Lab of Tissue Engineering, Faculty of Life Science, Northwest University, 229 TaiBai North Road, Xi' an, Shaanxi Province 710069 (China); Provincial Key Laboratory of Biotechnology of Shaanxi, Northwest University, 229 TaiBai North Road, Xi' an, Shaanxi Province 710069 (China); Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Ministry of Education, Northwest University, 229 TaiBai North Road, Xi' an, Shaanxi Province, 710069 (China); and others

2017-03-01

Electrospinning is an effective means to generate nano- to micro-scale polymer fibers resembling native extracellular matrix for tissue engineering. However, a major problem of electrospun materials is that limited pore size and porosity may prevent adequate cellular infiltration and tissue ingrowth. In this study, we first prepared thin layers of hydroxyapatite nanoparticle (nHA)/poly-hydroxybutyrate (PHB) via electrospinning. We then laminated the nHA/PHB thin layers to obtain a scaffold for cell seeding and bone tissue engineering. The results demonstrated that the laminated scaffold possessed optimized cell-loading capacity. Bone marrow mesenchymal stem cells (MSCs) exhibited better adherence, proliferation and osteogenic phenotypes on nHA/PHB scaffolds than on PHB scaffolds. Thereafter, we seeded MSCs onto nHA/PHB scaffolds to fabricate bone grafts. Histological observation showed osteoid tissue formation throughout the scaffold, with most of the scaffold absorbed in the specimens 2 months after implantation, and blood vessels ingrowth into the graft could be observed in the graft. We concluded that electrospun and laminated nanoscaled biocomposite scaffolds hold great therapeutic potential for bone regeneration. - Highlights: • We laminated the nHA/PHB layers to obtain a scaffold for bone tissue engineering. • The laminated scaffold performed optimized cell-loading capacity. • MSCs exhibited osteogenic phenotypes on the laminated scaffold. • Osteoid tissue formed throughout the laminated scaffold after 2 months in vivo. The laminated bio-composite scaffolds can be applied to bone regeneration.

Laminated electrospun nHA/PHB-composite scaffolds mimicking bone extracellular matrix for bone tissue engineering

International Nuclear Information System (INIS)

Chen, Zhuoyue; Song, Yue; Zhang, Jing; Liu, Wei; Cui, Jihong

2017-01-01

Electrospinning is an effective means to generate nano- to micro-scale polymer fibers resembling native extracellular matrix for tissue engineering. However, a major problem of electrospun materials is that limited pore size and porosity may prevent adequate cellular infiltration and tissue ingrowth. In this study, we first prepared thin layers of hydroxyapatite nanoparticle (nHA)/poly-hydroxybutyrate (PHB) via electrospinning. We then laminated the nHA/PHB thin layers to obtain a scaffold for cell seeding and bone tissue engineering. The results demonstrated that the laminated scaffold possessed optimized cell-loading capacity. Bone marrow mesenchymal stem cells (MSCs) exhibited better adherence, proliferation and osteogenic phenotypes on nHA/PHB scaffolds than on PHB scaffolds. Thereafter, we seeded MSCs onto nHA/PHB scaffolds to fabricate bone grafts. Histological observation showed osteoid tissue formation throughout the scaffold, with most of the scaffold absorbed in the specimens 2 months after implantation, and blood vessels ingrowth into the graft could be observed in the graft. We concluded that electrospun and laminated nanoscaled biocomposite scaffolds hold great therapeutic potential for bone regeneration. - Highlights: • We laminated the nHA/PHB layers to obtain a scaffold for bone tissue engineering. • The laminated scaffold performed optimized cell-loading capacity. • MSCs exhibited osteogenic phenotypes on the laminated scaffold. • Osteoid tissue formed throughout the laminated scaffold after 2 months in vivo. The laminated bio-composite scaffolds can be applied to bone regeneration.

Estimation of physical properties of laminated composites via the method of inverse vibration problem

Energy Technology Data Exchange (ETDEWEB)

Balci, Murat [Dept. of Mechanical Engineering, Bayburt University, Bayburt (Turkmenistan); Gundogdu, Omer [Dept. of Mechanical Engineering, Ataturk University, Erzurum (Turkmenistan)

2017-01-15

In this study, estimation of some physical properties of a laminated composite plate was conducted via the inverse vibration problem. Laminated composite plate was modelled and simulated to obtain vibration responses for different length-to-thickness ratio in ANSYS. Furthermore, a numerical finite element model was developed for the laminated composite utilizing the Kirchhoff plate theory and programmed in MATLAB for simulations. Optimizing the difference between these two vibration responses, inverse vibration problem was solved to obtain some of the physical properties of the laminated composite using genetic algorithms. The estimated parameters are compared with the theoretical results, and a very good correspondence was observed.

Estimation of physical properties of laminated composites via the method of inverse vibration problem

International Nuclear Information System (INIS)

Balci, Murat; Gundogdu, Omer

2017-01-01

In this study, estimation of some physical properties of a laminated composite plate was conducted via the inverse vibration problem. Laminated composite plate was modelled and simulated to obtain vibration responses for different length-to-thickness ratio in ANSYS. Furthermore, a numerical finite element model was developed for the laminated composite utilizing the Kirchhoff plate theory and programmed in MATLAB for simulations. Optimizing the difference between these two vibration responses, inverse vibration problem was solved to obtain some of the physical properties of the laminated composite using genetic algorithms. The estimated parameters are compared with the theoretical results, and a very good correspondence was observed

Mutants of Cercospora kikuchii altered in cercosporin synthesis and pathogenicity

International Nuclear Information System (INIS)

Upchurch, R.G.; Walker, D.C.; Rollins, J.A.; Ehrenshaft, M.; Daub, M.E.

1991-01-01

The authors have obtained spontaneous and UV-induced stable mutants, altered in the synthesis of cercosporin, of the fungal soybean pathogen Cercospora kikuchii. The mutants were isolated on the basis of colony color on minimal medium. The UV-induced mutants accumulated, at most, 2% of wild-type cercosporin levels on all media tested. In contrast, cercosporin accumulation by the spontaneous mutants was strongly medium regulated, occurring only on potato dextrose medium but at concentrations comparable to those produced by the wild-type strain. UV-induced mutants unable to synthesize cercosporin on any medium were unable to incite lesions when inoculated onto the soybean host. Cercosporin was reproducibly isolated from all inoculated leaves showing lesions. Although cercosporin involvement in disease has been indirectly suggested by many previous studies, this is the first report in which mutants blocked in cercosporin synthesis have been used to demonstrate that cercosporin is a crucial pathogenicity factor for this fungal genus