3D Guided Wave Motion Analysis on Laminated Composites

Science.gov (United States)

Tian, Zhenhua; Leckey, Cara; Yu, Lingyu

2013-01-01

Ultrasonic guided waves have proved useful for structural health monitoring (SHM) and nondestructive evaluation (NDE) due to their ability to propagate long distances with less energy loss compared to bulk waves and due to their sensitivity to small defects in the structure. Analysis of actively transmitted ultrasonic signals has long been used to detect and assess damage. However, there remain many challenging tasks for guided wave based SHM due to the complexity involved with propagating guided waves, especially in the case of composite materials. The multimodal nature of the ultrasonic guided waves complicates the related damage analysis. This paper presents results from parallel 3D elastodynamic finite integration technique (EFIT) simulations used to acquire 3D wave motion in the subject laminated carbon fiber reinforced polymer composites. The acquired 3D wave motion is then analyzed by frequency-wavenumber analysis to study the wave propagation and interaction in the composite laminate. The frequency-wavenumber analysis enables the study of individual modes and visualization of mode conversion. Delamination damage has been incorporated into the EFIT model to generate "damaged" data. The potential for damage detection in laminated composites is discussed in the end.

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.

Laminated multilayer sheet structure and its utilization

International Nuclear Information System (INIS)

Chiba, K.; Itoh, K.; Mitani, Y.; Sobajima, S.; Yonemura, U.

1980-01-01

A laminated multilayer sheet structure is described comprising (A) an opaque flexible sheet layer, and (B) a flexible layer laminated on the surface of layer (A) and composed of a transparent thermic ray reflecting layer (B 1 ) bonded to a transparent synthetic resin layer (B 2 ), said layer (B 1 ) being a transparent thermic ray reflecting layer composed of (I) a layer of a metal having a thickness of about 50 to about 600 A, said metal being selected from the group consisting of gold, silver, copper, aluminum and a mixture of alloy of at least two of said metals, and (II) a high refractive substance layer having a thickness of about 50 to about 600 A, of an oxide of titanium derived from a layer of an organic titanium compound of the formula Ti 1 O/sub m/R/sub n/, where R is alkyl of 1-20 carbon atoms, l=1-30, m=4+3(1-1), and n=4+2(1-1), and containing the organic residual moiety of the organic titanium compound, the amount of said organic residual moiety being 0.1 to 30% by weight based on the weight of the high refractive substance layer; or said layer (B 1 ) being a transparent semiconductive layer having a thickness of about 500 to about 5,000 a and being composed of a compound selected from the group consisting of indium oxide, tin oxide, cadmium oxide, antimony oxide, copper iodide, and a mixture of at least two of said compounds. A method is described for heat-insulating a room, which comprises applying to the surface of a floor, wall, ceiling or partition in the room a laminated multilayer sheet structure comprising (A) an opaque flexible sheet layer, and (B) a flexible layer laminated on the surface of layer (A) and composed of a transparent thermic ray reflecting layer (B 1 ) bonded to a transparent synthetic resin layer

Vitamin C induces specific demethylation of H3K9me2 in mouse embryonic stem cells via Kdm3a/b.

Science.gov (United States)

Ebata, Kevin T; Mesh, Kathryn; Liu, Shichong; Bilenky, Misha; Fekete, Alexander; Acker, Michael G; Hirst, Martin; Garcia, Benjamin A; Ramalho-Santos, Miguel

2017-01-01

Histone methylation patterns regulate gene expression and are highly dynamic during development. The erasure of histone methylation is carried out by histone demethylase enzymes. We had previously shown that vitamin C enhances the activity of Tet enzymes in embryonic stem (ES) cells, leading to DNA demethylation and activation of germline genes. We report here that vitamin C induces a remarkably specific demethylation of histone H3 lysine 9 dimethylation (H3K9me2) in naïve ES cells. Vitamin C treatment reduces global levels of H3K9me2, but not other histone methylation marks analyzed, as measured by western blot, immunofluorescence and mass spectrometry. Vitamin C leads to widespread loss of H3K9me2 at large chromosomal domains as well as gene promoters and repeat elements. Vitamin C-induced loss of H3K9me2 occurs rapidly within 24 h and is reversible. Importantly, we found that the histone demethylases Kdm3a and Kdm3b are required for vitamin C-induced demethylation of H3K9me2. Moreover, we show that vitamin C-induced Kdm3a/b-mediated H3K9me2 demethylation and Tet-mediated DNA demethylation are independent processes at specific loci. Lastly, we document Kdm3a/b are partially required for the upregulation of germline genes by vitamin C. These results reveal a specific role for vitamin C in histone demethylation in ES cells and document that DNA methylation and H3K9me2 cooperate to silence germline genes in pluripotent cells.

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...

Molecular analysis on germline mutation caused by low-dose irradiation

International Nuclear Information System (INIS)

Uchiyama, R.; Fujikawa, K.; Nishimura, M.; Adzuma, H.; Shimada, Y.; Yamauchi, M.

2003-01-01

Full text: Genetic heterogeneity and a low frequency of germline mutation at single-copy gene loci have limited the direct measurement of germline mutation in human populations. Two conflicting results have been reported for the effect of ionizing radiation on germline mutation in human populations. A study conducted on the first-generation progeny of the survivors of the atomic bombs at Hiroshima and Nagasaki found no significant increase in germline mutations. On the other hand, a significant increase in germline mutation was reported among the human population in the Belarus area after the Chernobyl accident in 1986. We investigated the germline mutation at the molecular level using experimental mouse strains with different genetic backgrounds to assess the risk of ionizing radiation on human populations. The C3H male parents were exposed to X ray (0, 0.3, 1, and 3Gy) and mated with unexposed C57BL females after two weeks interval, so as to detect the germline mutation occurred at the spermatid stage. Genomic DNA samples were prepared from the both parents and F1s, and the genomic DNA sequences were compared between parents and offspring at the specific genomic gene loci, such as adenine phosphoribosyl transferase (aprt) gene and cytidine triphosphate synthetase (ctps) gene, using the automated DNA sequencer. Also hypervariable Pc-1 (Ms6-hm) minisatellite repeat locus was analyzed by using Southern blot hybridization technique. Our preliminary results indicated that the changes of the restriction DNA fragment length in offspring did not reflect the occurrence of the mutation, such as point mutation, insertion, and deletion, in the genomic gene loci including the intervening sequence (intron)

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.

Cell surface fucosylation does not affect development of colon tumors in mice with germline Smad3 mutation

Science.gov (United States)

Domino, Steven E.; Karnak, David M.; Hurd, Elizabeth A.

2006-01-01

Background/Aims: Neoplasia-related alterations in cell surface α(1,2)fucosylated glycans have been reported in multiple tumors including colon, pancreas, endometrium, cervix, bladder, lung, and choriocarcinoma. Spontaneous colorectal tumors from mice with a germline null mutation of transforming growth factor-β signaling gene Smad3 (Madh3) were tested for α(1,2)fucosylated glycan expression. Methods: Ulex Europaeus Agglutinin-I lectin staining, fucosyltransferase gene northern blot analysis, and a cross of mutant mice with Fut2 and Smad3 germline mutations were performed. Results: Spontaneous colorectal tumors from Smad3 (-/-) homozygous null mice were found to express α(1,2)fucosylated glycans in an abnormal pattern compared to adjacent nonneoplastic colon. Northern blot analysis of α(1,2)fucosyltransferase genes Fut1 and Fut2 revealed that Fut2, but not Fut1, steady-state mRNA levels were significantly increased in tumors relative to adjacent normal colonic mucosa. Mutant mice with a Fut2-inactivating germline mutation were crossed with Smad3 targeted mice. In Smad3 (-/-)/Fut2 (-/-) double knock-out mice, UEA-I lectin staining was eliminated from colon and colon tumors, however, the number and size of tumors present by 24 weeks of age did not vary regardless of the Fut2 genotype. Conclusions: In this model of colorectal cancer, cell surface α(1,2)fucosylation does not affect development of colon tumors. PMID:17264540

Germline V repertoires: Origin, maintenance, diversification.

Science.gov (United States)

Steele, E J; Lindley, R A

2018-06-01

In our view, Melvin Cohn (Scand J Immunol. 2018;87:e12640) has set out the logical guidelines towards a resolution of the very real enigma of the selectability of vertebrate germline Ig V repertoires under the current evolutionary paradigm…" A somatically derived repertoire scrambles this (germline VL + VH) substrate so that its specificities are lost, making it un-selectable in the germline. Consequently, evolution faced an incompatibility." It is argued here in Reply that a reverse transcriptase-based soma-to-germline process (S->G) targeting germline V segment arrays goes some considerable way to resolving fundamental contradictions on the origin, maintenance and then real-time adaptive diversification of these limited sets of V segments encoded within various V repertoire arrays. © 2018 The Foundation for the Scandinavian Journal of Immunology.

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.

Smart damping of laminated fuzzy fiber reinforced composite shells using 1–3 piezoelectric composites

International Nuclear Information System (INIS)

Kundalwal, S I; Suresh Kumar, R; Ray, M C

2013-01-01

This paper deals with the investigation of active constrained layer damping (ACLD) of smart laminated continuous fuzzy fiber reinforced composite (FFRC) shells. The distinct constructional feature of a novel FFRC is that the uniformly spaced short carbon nanotubes (CNTs) are radially grown on the circumferential surfaces of the continuous carbon fiber reinforcements. The constraining layer of the ACLD treatment is considered to be made of vertically/obliquely reinforced 1–3 piezoelectric composite materials. A finite element (FE) model is developed for the laminated FFRC shells integrated with the two patches of the ACLD treatment to investigate the damping characteristics of the laminated FFRC shells. The effect of variation of the orientation angle of the piezoelectric fibers on the damping characteristics of the laminated FFRC shells has been studied when the piezoelectric fibers are coplanar with either of the two mutually orthogonal vertical planes of the piezoelectric composite layer. It is revealed that radial growth of CNTs on the circumferential surfaces of the carbon fibers enhances the attenuation of the amplitude of vibrations and the natural frequencies of the laminated FFRC shells over those of laminated base composite shells without CNTs. (paper)

Direct observation of a-b twin laminate in monoclinic five-layered martensite of Ni-Mn-Ga magnetic shape memory single crystal

Czech Academy of Sciences Publication Activity Database

Heczko, Oleg; Klimša, Ladislav; Kopeček, Jaromír

2017-01-01

Roč. 131, Apr (2017), s. 76-79 ISSN 1359-6462 R&D Projects: GA MŠk LO1409; GA MŠk LM2015088; GA ČR GA15-00262S Grant - others:FUNBIO(XE) CZ.2.16/3.1.00/21568 Institutional support: RVO:68378271 Keywords : a-b twin laminate * magnetic shape memory alloys * martensitic trans formation * twinning Subject RIV: BM - Solid Matter Physics ; Magnetism OBOR OECD: Condensed matter physics (including formerly solid state physics, supercond.) Impact factor: 3.747, year: 2016

Note: Resonance magnetoelectric interactions in laminate of FeCuNbSiB and multilayer piezoelectric stack for magnetic sensor

Science.gov (United States)

Li, Jianqiang; Lu, Caijiang; Xu, Changbao; Zhong, Ming

2015-09-01

This paper develops a simple miniature magnetoelectric (ME) laminate FeCuNbSiB/PZT-stack made up of magnetostrictive Fe73.5Cu1Nb3Si13.5B9 (FeCuNbSiB) foils and piezoelectric Pb(Zr, Ti)O3 (PZT) multilayer stack vibrator. Resonant ME interactions of FeCuNbSiB/PZT-stack with different layers of FeCuNbSiB foil (L) are investigated in detail. The experimental results show that the ME voltage coefficient reaches maximum value of 141.5 (V/cm Oe) for FeCuNbSiB/PZT-stack with L = 6. The AC-magnetic sensitivities can reach 524.29 mV/Oe and 1.8 mV/Oe under resonance 91.6 kHz and off-resonance 1 kHz, respectively. The FeCuNbSiB/PZT-stack can distinguish small dc-magnetic field of ˜9 nT. The results indicate that the proposed ME composites are very promising for the cheap room-temperature magnetic field sensing technology.

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)

The oogenic germline starvation response in C. elegans.

Directory of Open Access Journals (Sweden)

Hannah S Seidel

Full Text Available Many animals alter their reproductive strategies in response to environmental stress. Here we have investigated how L4 hermaphrodites of Caenorhabditis elegans respond to starvation. To induce starvation, we removed food at 2 h intervals from very early- to very late-stage L4 animals. The starved L4s molted into adulthood, initiated oogenesis, and began producing embryos; however, all three processes were severely delayed, and embryo viability was reduced. Most animals died via 'bagging,' because egg-laying was inhibited, and embryos hatched in utero, consuming their parent hermaphrodites from within. Some animals, however, avoided bagging and survived long term. Long-term survival did not rely on embryonic arrest but instead upon the failure of some animals to produce viable progeny during starvation. Regardless of the bagging fate, starved animals showed two major changes in germline morphology: All oogenic germlines were dramatically reduced in size, and these germlines formed only a single oocyte at a time, separated from the remainder of the germline by a tight constriction. Both changes in germline morphology were reversible: Upon re-feeding, the shrunken germlines regenerated, and multiple oocytes formed concurrently. The capacity for germline regeneration upon re-feeding was not limited to the small subset of animals that normally survive starvation: When bagging was prevented ectopically by par-2 RNAi, virtually all germlines still regenerated. In addition, germline shrinkage strongly correlated with oogenesis, suggesting that during starvation, germline shrinkage may provide material for oocyte production. Finally, germline shrinkage and regeneration did not depend upon crowding. Our study confirms previous findings that starvation uncouples germ cell proliferation from germline stem cell maintenance. Our study also suggests that when nutrients are limited, hermaphrodites scavenge material from their germlines to reproduce. We discuss

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

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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.

Vasa promotes Drosophila germline stem cell differentiation by activating mei-P26 translation by directly interacting with a (U)-rich motif in its 3' UTR.

Science.gov (United States)

Liu, Niankun; Han, Hong; Lasko, Paul

2009-12-01

Vasa (Vas) is a DEAD-box RNA-binding protein required in Drosophila at several steps of oogenesis and for primordial germ cell (PGC) specification. Vas associates with eukaryotic initiation factor 5B (eIF5B), and this interaction has been implicated in translational activation of gurken mRNA in the oocyte. Vas is expressed in all ovarian germline cells, and aspects of the vas-null phenotype suggest a function in regulating the balance between germline stem cells (GSCs) and their fate-restricted descendants. We used a biochemical approach to recover Vas-associated mRNAs and obtained mei-P26, whose product represses microRNA activity and promotes GSC differentiation. We found that vas and mei-P26 mutants interact, and that mei-P26 translation is substantially reduced in vas mutant cells. In vitro, Vas protein bound specifically to a (U)-rich motif in the mei-P26 3' untranslated region (UTR), and Vas-dependent regulation of GFP-mei-P26 transgenes in vivo was dependent on the same (U)-rich 3' UTR domain. The ability of Vas to activate mei-P26 expression in vivo was abrogated by a mutation that greatly reduces its interaction with eIF5B. Taken together, our data support the conclusion that Vas promotes germ cell differentiation by directly activating mei-P26 translation in early-stage committed cells.

Germline recombination in a novel Cre transgenic line, Prl3b1-Cre mouse.

Science.gov (United States)

Al-Soudy, Al-Sayed; Nakanishi, Tsuyoshi; Mizuno, Seiya; Hasegawa, Yoshikazu; Shawki, Hossam H; Katoh, Megumi C; Basha, Walaa A; Ibrahim, Abdelaziz E; El-Shemy, Hany A; Iseki, Hiroyoshi; Yoshiki, Atsushi; Hiromori, Youhei; Nagase, Hisamitsu; Takahashi, Satoru; Oishi, Hisashi; Sugiyama, Fumihiro

2016-07-01

Spermatogenesis is a complex and highly regulated process by which spermatogonial stem cells differentiate into spermatozoa. To better understand the molecular mechanisms of the process, the Cre/loxP system has been widely utilized for conditional gene knockout in mice. In this study, we generated a transgenic mouse line that expresses Cre recombinase under the control of the 2.5 kbp of the Prolactin family 3, subfamily b, member 1 (Prl3b1) gene promoter (Prl3b1-cre). Prl3b1 was initially reported to code for placental lactogen 2 (PL-2) protein in placenta along with increased expression toward the end of pregnancy. PL-2 was found to be expressed in germ cells in the testis, especially in spermatocytes. To analyze the specificity and efficiency of Cre recombinase activity in Prl3b1-cre mice, the mice were mated with reporter R26GRR mice, which express GFP ubiquitously before and tdsRed exclusively after Cre recombination. The systemic examination of Prl3b1-cre;R26GRR mice revealed that tdsRed-positive cells were detected only in the testis and epididymis. Fluorescence imaging of Prl3b1-cre;R26GRR testes suggested that Cre-mediated recombination took place in the germ cells with approximately 74% efficiency determined by in vitro fertilization. In conclusion, our results suggest that the Prl3b1-cre mice line provides a unique resource to understand testicular germ-cell development. genesis 54:389-397, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Genetic loss of SH2B3 in acute lymphoblastic leukemia.

Science.gov (United States)

Perez-Garcia, Arianne; Ambesi-Impiombato, Alberto; Hadler, Michael; Rigo, Isaura; LeDuc, Charles A; Kelly, Kara; Jalas, Chaim; Paietta, Elisabeth; Racevskis, Janis; Rowe, Jacob M; Tallman, Martin S; Paganin, Maddalena; Basso, Giuseppe; Tong, Wei; Chung, Wendy K; Ferrando, Adolfo A

2013-10-03

The SH2B adaptor protein 3 (SH2B3) gene encodes a negative regulator of cytokine signaling with a critical role in the homeostasis of hematopoietic stem cells and lymphoid progenitors. Here, we report the identification of germline homozygous SH2B3 mutations in 2 siblings affected with developmental delay and autoimmunity, one in whom B-precursor acute lymphoblastic leukemia (ALL) developed. Mechanistically, loss of SH2B3 increases Janus kinase-signal transducer and activator of transcription signaling, promotes lymphoid cell proliferation, and accelerates leukemia development in a mouse model of NOTCH1-induced ALL. Moreover, extended mutation analysis showed homozygous somatic mutations in SH2B3 in 2 of 167 ALLs analyzed. Overall, these results demonstrate a Knudson tumor suppressor role for SH2B3 in the pathogenesis of ALL and highlight a possible link between genetic predisposition factors in the pathogenesis of autoimmunity and leukemogenesis.

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.

Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA.

Science.gov (United States)

Schrader, Kasmintan A; Cheng, Donavan T; Joseph, Vijai; Prasad, Meera; Walsh, Michael; Zehir, Ahmet; Ni, Ai; Thomas, Tinu; Benayed, Ryma; Ashraf, Asad; Lincoln, Annie; Arcila, Maria; Stadler, Zsofia; Solit, David; Hyman, David M; Hyman, David; Zhang, Liying; Klimstra, David; Ladanyi, Marc; Offit, Kenneth; Berger, Michael; Robson, Mark

2016-01-01

Tumor genetic sequencing identifies potentially targetable genetic alterations with therapeutic implications. Analysis has concentrated on detecting tumor-specific variants, but recognition of germline variants may prove valuable as well. To estimate the burden of germline variants identified through routine clinical tumor sequencing. Patients with advanced cancer diagnoses eligible for studies of targeted agents at Memorial Sloan Kettering Cancer Center are offered tumor-normal sequencing with MSK-IMPACT, a 341-gene panel. We surveyed the germline variants seen in 187 overlapping genes with Mendelian disease associations in 1566 patients who had undergone tumor profiling between March and October 2014. The number of presumed pathogenic germline variants (PPGVs) and variants of uncertain significance per person in 187 genes associated with single-gene disorders and the proportions of individuals with PPGVs in clinically relevant gene subsets, in genes consistent with known tumor phenotypes, and in genes with evidence of second somatic hits in their tumors. The mean age of the 1566 patients was 58 years, and 54% were women. Presumed pathogenic germline variants in known Mendelian disease-associated genes were identified in 246 of 1566 patients (15.7%; 95% CI, 14.0%-17.6%), including 198 individuals with mutations in genes associated with cancer susceptibility. Germline findings in cancer susceptibility genes were concordant with the individual's cancer type in only 81 of 198 cases (40.9%; 95% CI, 34.3%-47.9%). In individuals with PPGVs retained in the tumor, somatic alteration of the other allele was seen in 39 of 182 cases (21.4%; 95% CI, 16.1%-28.0%), of which 13 cases did not show a known correlation of the germline mutation and a known syndrome. Mutations in non-cancer-related Mendelian disease genes were seen in 55 of 1566 cases (3.5%; 95% CI, 27.1%-45.4%). Almost every individual had more than 1 variant of uncertain significance (1565 of 1566 patients; 99

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.

Germline variant FGFR4  p.G388R exposes a membrane-proximal STAT3 binding site.

Science.gov (United States)

Ulaganathan, Vijay K; Sperl, Bianca; Rapp, Ulf R; Ullrich, Axel

2015-12-24

Variant rs351855-G/A is a commonly occurring single-nucleotide polymorphism of coding regions in exon 9 of the fibroblast growth factor receptor FGFR4 (CD334) gene (c.1162G>A). It results in an amino-acid change at codon 388 from glycine to arginine (p.Gly388Arg) in the transmembrane domain of the receptor. Despite compelling genetic evidence for the association of this common variant with cancers of the bone, breast, colon, prostate, skin, lung, head and neck, as well as soft-tissue sarcomas and non-Hodgkin lymphoma, the underlying biological mechanism has remained elusive. Here we show that substitution of the conserved glycine 388 residue to a charged arginine residue alters the transmembrane spanning segment and exposes a membrane-proximal cytoplasmic signal transducer and activator of transcription 3 (STAT3) binding site Y(390)-(P)XXQ(393). We demonstrate that such membrane-proximal STAT3 binding motifs in the germline of type I membrane receptors enhance STAT3 tyrosine phosphorylation by recruiting STAT3 proteins to the inner cell membrane. Remarkably, such germline variants frequently co-localize with somatic mutations in the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Using Fgfr4 single nucleotide polymorphism knock-in mice and transgenic mouse models for breast and lung cancers, we validate the enhanced STAT3 signalling induced by the FGFR4 Arg388-variant in vivo. Thus, our findings elucidate the molecular mechanism behind the genetic association of rs351855 with accelerated cancer progression and suggest that germline variants of cell-surface molecules that recruit STAT3 to the inner cell membrane are a significant risk for cancer prognosis and disease progression.

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.

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.)

Discordant gene expression signatures and related phenotypic differences in lamin A- and A/C-related Hutchinson-Gilford progeria syndrome (HGPS.

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Martina Plasilova

Full Text Available Hutchinson-Gilford progeria syndrome (HGPS is a genetic disorder displaying features reminiscent of premature senescence caused by germline mutations in the LMNA gene encoding lamin A and C, essential components of the nuclear lamina. By studying a family with homozygous LMNA mutation (K542N, we showed that HGPS can also be caused by mutations affecting both isoforms, lamin A and C. Here, we aimed to elucidate the molecular mechanisms underlying the pathogenesis in both, lamin A- (sporadic and lamin A and C-related (hereditary HGPS. For this, we performed detailed molecular studies on primary fibroblasts of hetero- and homozygous LMNA K542N mutation carriers, accompanied with clinical examinations related to the molecular findings. By assessing global gene expression we found substantial overlap in altered transcription profiles (13.7%; 90/657 in sporadic and hereditary HGPS, with 83.3% (75/90 concordant and 16.7% (15/90 discordant transcriptional changes. Among the concordant ones we observed down-regulation of TWIST2, whose inactivation in mice and humans leads to loss of subcutaneous fat and dermal appendages, and loss of expression in dermal fibroblasts and periadnexial cells from a LMNA(K542N/K542N patient further confirming its pivotal role in skin development. Among the discordant transcriptional profiles we identified two key mediators of vascular calcification and bone metabolism, ENPP1 and OPG, which offer a molecular explanation for the major phenotypic differences in vascular and bone disease in sporadic and hereditary HGPS. Finally, this study correlates reduced TWIST2 and OPG expression with increased osteocalcin levels, thereby linking altered bone remodeling to energy homeostasis in hereditary HGPS.

Existence region of phases of laminated perovskite-like structre of A/sub 2/B/sub 2/O/sub 7/ composition

Energy Technology Data Exchange (ETDEWEB)

Sych, A M; Titov, Yu A [Kievskij Gosudarstvennyj Univ. (Ukrainian SSR)

1982-06-01

Generalizing the known data for ferroelectrics of A/sub 2/B/sub 2/O/sub 7/ type (LnTi/sub 2/O/sub 7/, in particular) geometrical conditions of existence of laminated perovskite-like structure are determined: 0.603 A < anti Rsub(Bsup(6)) <= 0.665 A, anti Rsub(Asup(12))/Rsub(Bsup(6)) > 2.045. The geometrical conditions presented are necessary but not sufficient. A supposition is made that phases GaLnTiNbO/sub 7/ (Ln = Pr - Eu) and CaLnTiTaO/sub 7/ (Ln = La - Eu) with laminated perovskite-like structure can be prepared under high pressures.

Self-vibration cancellation of a novel bi-directional magnetized NdFeB/magnetostrictive/piezoelectric laminate.

Science.gov (United States)

Leung, Chung Ming; Wang, Feifei; Wang, Ya

2016-06-01

A novel magnetoelectric (ME) laminated composite structure is proposed in this work, aiming to provide a good self-vibration cancellation performance under the magnetic field detection environment. The proposed structure consists of two Terfenol-D magnetostrictive alloy plates which are revised and length-magnetized by two NdFeB magnets bonded on the top surface of a thickness-polarized Pb(Zr, Ti)O3 (PZT) ceramic plate with separate electrodes. Experiments have shown that great vibration suppression up to 44 dB under harmonic disturbance was observed. The ME coefficient of the proposed structure also reaches up to ∼29 mV/Oe at non-resonance frequency and 758 mV/Oe at resonance frequency of 79 kHz which is ∼2 times larger than the traditional L-T Terfenol-D/PZT bilayer configuration of the same scale. Such performance improvement is achieved based on the bi-directional magnetic field bias (HBias) of two NdFeB magnets in magnetostrictive layer, internal in-series electrical wire connection in piezoelectric layer. The proposed design has great potential to be used for industrial applications associated with heavy environmental vibration noise.

Self-vibration cancellation of a novel bi-directional magnetized NdFeB/magnetostrictive/piezoelectric laminate

Science.gov (United States)

Leung, Chung Ming; Wang, Feifei; Wang, Ya

2016-06-01

A novel magnetoelectric (ME) laminated composite structure is proposed in this work, aiming to provide a good self-vibration cancellation performance under the magnetic field detection environment. The proposed structure consists of two Terfenol-D magnetostrictive alloy plates which are revised and length-magnetized by two NdFeB magnets bonded on the top surface of a thickness-polarized Pb(Zr, Ti)O3 (PZT) ceramic plate with separate electrodes. Experiments have shown that great vibration suppression up to 44 dB under harmonic disturbance was observed. The ME coefficient of the proposed structure also reaches up to ˜29 mV/Oe at non-resonance frequency and 758 mV/Oe at resonance frequency of 79 kHz which is ˜2 times larger than the traditional L-T Terfenol-D/PZT bilayer configuration of the same scale. Such performance improvement is achieved based on the bi-directional magnetic field bias (HBias) of two NdFeB magnets in magnetostrictive layer, internal in-series electrical wire connection in piezoelectric layer. The proposed design has great potential to be used for industrial applications associated with heavy environmental vibration noise.

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

International Nuclear Information System (INIS)

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

2008-01-01

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

Sound Insulation Property Study on Nylon 66 Scrim Reinforced PVF Laminated Membranes and their Composite Sound Proof Structure

Science.gov (United States)

Chen, Lihe; Chen, Zhaofeng; Zhang, Xinyang; Wang, Weiwei

2018-01-01

In this paper, we investigated the sound insulation property of nylon 66 scrim reinforced PVF laminated membranes and their corresponding composite structures with glass fiber felt and carbon fiber board. Sound transmission loss (STL) was measured by standing wave tube method. The results show that, with the decrease of nylon 66 gridlines spacing, STL of nylon 66 scrim reinforced PVF laminated membranes was improved. The sound insulation performance of laminated membranes with gridlines spacing of 3mm is the best, whose STL was up to 10dB at 6.3 kHz. Besides, STL was improved effectively as air layers were embedded into the composite sound proof construction consist of laminated membrane, glass fiber felt and carbon fiber board.

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.

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.

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

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

Germline Variants of Prostate Cancer in Japanese Families.

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Takahide Hayano

Full Text Available Prostate cancer (PC is the second most common cancer in men. Family history is the major risk factor for PC. Only two susceptibility genes were identified in PC, BRCA2 and HOXB13. A comprehensive search of germline variants for patients with PC has not been reported in Japanese families. In this study, we conducted exome sequencing followed by Sanger sequencing to explore responsible germline variants in 140 Japanese patients with PC from 66 families. In addition to known susceptibility genes, BRCA2 and HOXB13, we identified TRRAP variants in a mutually exclusive manner in seven large PC families (three or four patients per family. We also found shared variants of BRCA2, HOXB13, and TRRAP from 59 additional small PC families (two patients per family. We identified two deleterious HOXB13 variants (F127C and G132E. Further exploration of the shared variants in rest of the families revealed deleterious variants of the so-called cancer genes (ATP1A1, BRIP1, FANCA, FGFR3, FLT3, HOXD11, MUTYH, PDGFRA, SMARCA4, and TCF3. The germline variant profile provides a new insight to clarify the genetic etiology and heterogeneity of PC among Japanese men.

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.

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.

Repression of germline RNAi pathways in somatic cells by retinoblastoma pathway chromatin complexes.

Directory of Open Access Journals (Sweden)

Xiaoyun Wu

Full Text Available The retinoblastoma (Rb tumor suppressor acts with a number of chromatin cofactors in a wide range of species to suppress cell proliferation. The Caenorhabditis elegans retinoblastoma gene and many of these cofactors, called synMuv B genes, were identified in genetic screens for cell lineage defects caused by growth factor misexpression. Mutations in many synMuv B genes, including lin-35/Rb, also cause somatic misexpression of the germline RNA processing P granules and enhanced RNAi. We show here that multiple small RNA components, including a set of germline-specific Argonaute genes, are misexpressed in the soma of many synMuv B mutant animals, revealing one node for enhanced RNAi. Distinct classes of synMuv B mutants differ in the subcellular architecture of their misexpressed P granules, their profile of misexpressed small RNA and P granule genes, as well as their enhancement of RNAi and the related silencing of transgenes. These differences define three classes of synMuv B genes, representing three chromatin complexes: a LIN-35/Rb-containing DRM core complex, a SUMO-recruited Mec complex, and a synMuv B heterochromatin complex, suggesting that intersecting chromatin pathways regulate the repression of small RNA and P granule genes in the soma and the potency of RNAi. Consistent with this, the DRM complex and the synMuv B heterochromatin complex were genetically additive and displayed distinct antagonistic interactions with the MES-4 histone methyltransferase and the MRG-1 chromodomain protein, two germline chromatin regulators required for the synMuv phenotype and the somatic misexpression of P granule components. Thus intersecting synMuv B chromatin pathways conspire with synMuv B suppressor chromatin factors to regulate the expression of small RNA pathway genes, which enables heightened RNAi response. Regulation of small RNA pathway genes by human retinoblastoma may also underlie its role as a tumor suppressor gene.

Lessons for Inductive Germline Determination

Science.gov (United States)

Seervai, Riyad N.H.; Wessel, Gary M.

2015-01-01

SUMMARY Formation of the germline in an embryo marks a fresh round of reproductive potential, yet the developmental stage and location within the embryo where the primordial germ cells (PGCs) form differs wildly among species. In most animals, the germline is formed either by an inherited mechanism, in which maternal provisions within the oocyte drive localized germ-cell fate once acquired in the embryo, or an inductive mechanism that involves signaling between cells that directs germ-cell fate. The inherited mechanism has been widely studied in model organisms such as Drosophila melanogaster, Caenorhabditis elegans, Xenopus laevis, and Danio rerio. Given the rapid generation time and the effective adaptation for laboratory research of these organisms, it is not coincidental that research on these organisms has led the field in elucidating mechanisms for germline specification. The inductive mechanism, however, is less well understood and is studied primarily in the mouse (Mus musculus). In this review, we compare and contrast these two fundamental mechanisms for germline determination, beginning with the key molecular determinants that play a role in the formation of germ cells across all animal taxa. We next explore the current understanding of the inductive mechanism of germ-cell determination in mice, and evaluate the hypotheses for selective pressures on these contrasting mechanisms. We then discuss the hypothesis that the transition between these determination mechanisms, which has happened many times in phylogeny, is more of a continuum than a binary change. Finally, we propose an analogy between germline determination and sex determination in vertebrates—two of the milestones of reproduction and development—in which animals use contrasting strategies to activate similar pathways. PMID:23450642

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

Science.gov (United States)

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.

Laminated exfoliated graphite composite-metal compositions for fuel cell flow field plate or bipolar plate applications

Science.gov (United States)

Zhamu, Aruna; Shi, Jinjun; Guo, Jiusheng; Jang, Bor Z

2014-05-20

An electrically conductive laminate composition for fuel cell flow field plate or bipolar plate applications. The laminate composition comprises at least a thin metal sheet having two opposed exterior surfaces and a first exfoliated graphite composite sheet bonded to the first of the two exterior surfaces of the metal sheet wherein the exfoliated graphite composite sheet comprises: (a) expanded or exfoliated graphite and (b) a binder or matrix material to bond the expanded graphite for forming a cohered sheet, wherein the binder or matrix material is between 3% and 60% by weight based on the total weight of the first exfoliated graphite composite sheet. Preferably, the first exfoliated graphite composite sheet further comprises particles of non-expandable graphite or carbon in the amount of between 3% and 60% by weight based on the total weight of the non-expandable particles and the expanded graphite. Further preferably, the laminate comprises a second exfoliated graphite composite sheet bonded to the second surface of the metal sheet to form a three-layer laminate. Surface flow channels and other desired geometric features can be built onto the exterior surfaces of the laminate to form a flow field plate or bipolar plate. The resulting laminate has an exceptionally high thickness-direction conductivity and excellent resistance to gas permeation.

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

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.

C. elegans FOG-3/Tob can either promote or inhibit germline proliferation, depending on gene dosage and genetic context.

Science.gov (United States)

Snow, J J; Lee, M-H; Verheyden, J; Kroll-Conner, P L; Kimble, J

2013-05-23

Vertebrate Tob/BTG proteins inhibit cell proliferation when overexpressed in tissue-culture cells, and they can function as tumor suppressors in mice. The single Caenorhabditis elegans Tob/BTG ortholog, FOG-3, by contrast, was identified from its loss-of-function phenotype as a regulator of sperm fate specification. Here we report that FOG-3 also regulates proliferation in the germline tissue. We first demonstrate that FOG-3 is a positive regulator of germline proliferation. Thus, fog-3 null mutants possess fewer germ cells than normal, a modest but reproducible decrease observed for each of two distinct fog-3 null alleles. A similar decrease also occurred in fog-3/+ heterozygotes, again for both fog-3 alleles, revealing a haplo-insufficient effect on proliferation. Therefore, FOG-3 normally promotes proliferation, and two copies of the fog-3 gene are required for this function. We next overexpressed FOG-3 by removal of FBF, the collective term for FBF-1 and FBF-2, two nearly identical PUF RNA-binding proteins. We find that overexpressed FOG-3 blocks proliferation in fbf-1 fbf-2 mutants; whereas germ cells stop dividing and instead differentiate in fbf-1 fbf-2 double mutants, they continue to proliferate in fog-3; fbf-1 fbf-2 triple mutants. Therefore, like its vertebrate Tob/BTG cousins, overexpressed FOG-3 is 'antiproliferative'. Indeed, some fog-3; fbf-1 fbf-2 mutants possess small tumors, suggesting that FOG-3 can act as a tumor suppressor. Finally, we show that FOG-3 and FBF work together to promote tumor formation in animals carrying oncogenic Notch mutations. A similar effect was not observed when germline tumors were induced by manipulation of other regulators; therefore, this FOG-3 tumor-promoting effect is context dependent. We conclude that FOG-3 can either promote or inhibit proliferation in a manner that is sensitive to both genetic context and gene dosage. The discovery of these FOG-3 effects on proliferation has implications for our understanding of

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

America. The second task dealt with a study of current lamination processes in the various laminate industries, and development of concepts for integrating RF lamination into new or existing processes. The third task explored the use of a non-destructive technique for analyzing laminate adhesion with the University of Illinois at Urbana-Champaign. The fourth task focused on developing concepts for curved glass lamination using RF lamination. The fifth and sixth tasks together comprised an analysis of laminate product markets, ranking for applicability and commercialization potential, and the development of commercialization strategies for those products. In addition, throughout the project as new experimental data and conventional process data were obtained, the benefits analysis of RF lamination was refined. The goals of the project described above were achieved, positioning RF lamination for the next stage growth envisioned in the original Industrial Grand Challenge proposal. Working with Pilkington North America, lamination of flat autoglass with PVB was achieved, meeting all 16 stringent industry tests. In particular, PVB laminates made with RF lamination passed environmental tests including the high temperature, 120°C bake test, without significant formation of bubbles (defects). The adhesion of PVB to glass was measured using the pummel method. Adhesion values ranging from 1 to 7 out of 10 were obtained. The significant process parameters affecting the environmental and adhesion performance were identified through a designed experiment. Pre-lamination process variables including PVB storage humidity and the de-airing process (vacuum or nip rolling) were significant, as well as the level of pressure applied to the laminate during the RF process. Analysis of manufacturing with RF lamination equipment, based on the processes developed indicated that 3 RF presses could replace a typical auto-industry autoclave to achieve equal or greater throughput with possibly less

Energy Saving Glass Lamination via Selective Radio Frequency Heating

Energy Technology Data Exchange (ETDEWEB)

Allan, Shawn M.

2012-02-27

America. The second task dealt with a study of current lamination processes in the various laminate industries, and development of concepts for integrating RF lamination into new or existing processes. The third task explored the use of a non-destructive technique for analyzing laminate adhesion with the University of Illinois at Urbana-Champaign. The fourth task focused on developing concepts for curved glass lamination using RF lamination. The fifth and sixth tasks together comprised an analysis of laminate product markets, ranking for applicability and commercialization potential, and the development of commercialization strategies for those products. In addition, throughout the project as new experimental data and conventional process data were obtained, the benefits analysis of RF lamination was refined. The goals of the project described above were achieved, positioning RF lamination for the next stage growth envisioned in the original Industrial Grand Challenge proposal. Working with Pilkington North America, lamination of flat autoglass with PVB was achieved, meeting all 16 stringent industry tests. In particular, PVB laminates made with RF lamination passed environmental tests including the high temperature, 120 C bake test, without significant formation of bubbles (defects). The adhesion of PVB to glass was measured using the pummel method. Adhesion values ranging from 1 to 7 out of 10 were obtained. The significant process parameters affecting the environmental and adhesion performance were identified through a designed experiment. Pre-lamination process variables including PVB storage humidity and the de-airing process (vacuum or nip rolling) were significant, as well as the level of pressure applied to the laminate during the RF process. Analysis of manufacturing with RF lamination equipment, based on the processes developed indicated that 3 RF presses could replace a typical auto-industry autoclave to achieve equal or greater throughput with possibly less

Methods in Molecular Biology: Germline Stem Cells | Center for Cancer Research

Science.gov (United States)

The protocols in Germline Stem Cells are intended to present selected genetic, molecular, and cellular techniques used in germline stem cell research. The book is divided into two parts. Part I covers germline stem cell identification and regulation in model organisms. Part II covers current techniques used in in vitro culture and applications of germline stem cells.

Subset of Kappa and Lambda Germline Sequences Result in Light Chains with a Higher Molecular Mass Phenotype.

Science.gov (United States)

Barnidge, David R; Lundström, Susanna L; Zhang, Bo; Dasari, Surendra; Murray, David L; Zubarev, Roman A

2015-12-04

In our previous work, we showed that electrospray ionization of intact polyclonal kappa and lambda light chains isolated from normal serum generates two distinct, Gaussian-shaped, molecular mass distributions representing the light-chain repertoire. During the analysis of a large (>100) patient sample set, we noticed a low-intensity molecular mass distribution with a mean of approximately 24 250 Da, roughly 800 Da higher than the mean of the typical kappa molecular-mass distribution mean of 23 450 Da. We also observed distinct clones in this region that did not appear to contain any typical post-translational modifications that would account for such a large mass shift. To determine the origin of the high molecular mass clones, we performed de novo bottom-up mass spectrometry on a purified IgM monoclonal light chain that had a calculated molecular mass of 24 275.03 Da. The entire sequence of the monoclonal light chain was determined using multienzyme digestion and de novo sequence-alignment software and was found to belong to the germline allele IGKV2-30. The alignment of kappa germline sequences revealed ten IGKV2 and one IGKV4 sequences that contained additional amino acids in their CDR1 region, creating the high-molecular-mass phenotype. We also performed an alignment of lambda germline sequences, which showed additional amino acids in the CDR2 region, and the FR3 region of functional germline sequences that result in a high-molecular-mass phenotype. The work presented here illustrates the ability of mass spectrometry to provide information on the diversity of light-chain molecular mass phenotypes in circulation, which reflects the germline sequences selected by the immunoglobulin-secreting B-cell population.

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.

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.

Low temperature measurement of thermal and mechanical properties of phenolic laminate, the pultruded polyester fiberglass and A and B epoxy putty

International Nuclear Information System (INIS)

Wang, S.T.; Kim, S.H.; Kim, N.S.; Cheng, R.S.; Hoffman, J.; Gonczy, J.

1979-01-01

Low temperature measurements were made and are reported of thermal and mechanical properties of phenolic laminate, pultruded polyester fiberglass, and A and B epoxy putty. To determine the modulus, compressive and tensile stress and strain, an Instron machine, a Tinus-Olsen testing machine, a Wheatstone bridge and strain gages were used

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

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.

NuMA and nuclear lamins are cleaved during viral infection - inhibition of caspase activity prevents cleavage and rescues HeLa cells from measles virus-induced but not from rhinovirus 1B-induced cell death

International Nuclear Information System (INIS)

Taimen, Pekka; Berghaell, Heidi; Vainionpaeae, Raija; Kallajoki, Markku

2004-01-01

Nuclear matrix is a structural framework of important nuclear processes. We studied the effect of two different types of viral infections on nuclear matrix. HeLa cells were infected with human rhinovirus 1B (HRV 1B) or measles virus (MV), and Nuclear Mitotic Apparatus protein (NuMA) and lamins A/C and B were used as markers for internal nuclear matrix and peripheral nuclear lamina, respectively. We show that NuMA, lamins, and poly(ADP-ribose) polymerase-1 are cleaved during viral infection in a virus family-specific manner suggesting that these viruses activate different sets of proteases. Morphologically, NuMA was excluded from the condensed chromatin, lamins showed a folded distribution, and both proteins finally remained around the nuclear fragments. A general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-FMK) prevented the nuclear disintegration and the cleavage of the proteins studied. Interestingly, z-VAD-FMK rescued MV-infected but not HRV 1B-infected cells from cell death. These results show for the first time that NuMA and lamins are specific target proteins during virus-induced programmed cell death

40 CFR 63.5820 - What are my options for meeting the standards for continuous lamination/casting operations?

Science.gov (United States)

2010-07-01

... standards for continuous lamination/casting operations? 63.5820 Section 63.5820 Protection of Environment... meeting the standards for continuous lamination/casting operations? You must use one or more of the... continuous lamination line and each continuous casting line complies with the applicable standard. (b...

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.

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.

Germline Hypermethylation of MLH1 and EPCAM Deletions Are a Frequent Cause of Lynch Syndrome

NARCIS (Netherlands)

Niessen, Renee C.; Hofstra, Robert M. W.; Westers, Helga; Ligtenberg, Marjolijn J. L.; Kooi, Krista; Jager, Paul O. J.; de Groote, Marloes L.; Dijkhuizen, Trijnie; Olderode-Berends, Maran J. W.; Hollema, Harry; Kleibeuker, Jan H.; Sijmons, Rolf H.

It was shown that Lynch syndrome can be caused by germline hypermethylation of the MLH1 and MSH2 promoters. Furthermore, it has been demonstrated very recently that germline deletions of the 3' region of EPCAM cause transcriptional read-through which results in silencing of MSH2 by hypermethylation.

Germline hypermethylation of MLH1 and EPCAM deletions are a frequent cause of Lynch syndrome.

NARCIS (Netherlands)

Niessen, R.C.; Hofstra, R.M.; Westers, H.; Ligtenberg, M.J.L.; Kooi, K.; Jager, P.O.; Groote, M.L. de; Dijkhuizen, T.; Olderode-Berends, M.J.; Hollema, H.; Kleibeuker, J.H.; Sijmons, R.H.

2009-01-01

It was shown that Lynch syndrome can be caused by germline hypermethylation of the MLH1 and MSH2 promoters. Furthermore, it has been demonstrated very recently that germline deletions of the 3' region of EPCAM cause transcriptional read-through which results in silencing of MSH2 by hypermethylation.

Minisatellite germline mutation rate in the Techa River population

Energy Technology Data Exchange (ETDEWEB)

Dubrova, Yuri E. [Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH (United Kingdom)]. E-mail: yed2@le.ac.uk; Ploshchanskaya, Olga G. [Urals Research Centre for Radiation Medicine, Medgorodok, Chelyabinsk 454076 (Russian Federation); Department of Radiobiology, Chelyabinsk State University, Chelyabinsk 454021 (Russian Federation); Kozionova, Olga S. [Urals Research Centre for Radiation Medicine, Medgorodok, Chelyabinsk 454076 (Russian Federation); Department of Radiobiology, Chelyabinsk State University, Chelyabinsk 454021 (Russian Federation); Akleyev, Alexander V. [Urals Research Centre for Radiation Medicine, Medgorodok, Chelyabinsk 454076 (Russian Federation); Department of Radiobiology, Chelyabinsk State University, Chelyabinsk 454021 (Russian Federation)

2006-12-01

Germline mutation at eight minisatellite loci has been studied among the irradiated families from the Techa River population and non-exposed families from the rural area of the Chelyabinsk and Kurgan Oblasts. The groups were matched by ethnicity, parental age, occupation and smoking habit. A statistically significant 1.7-fold increase in mutation rate was found in the germline of irradiated fathers, whereas maternal germline mutation rate in the exposed families was not elevated. Most of the minisatellite loci showed an elevated paternal mutation rate in the exposed group, indicating a generalised increase in minisatellite germline mutation rate in the Techa River population. These data suggest that the elevated minisatellite mutation rate can be attributed to radioactive exposure. The spectra of paternal mutation seen in the unexposed and exposed families were indistinguishable.

Minisatellite germline mutation rate in the Techa River population

International Nuclear Information System (INIS)

Dubrova, Yuri E.; Ploshchanskaya, Olga G.; Kozionova, Olga S.; Akleyev, Alexander V.

2006-01-01

Germline mutation at eight minisatellite loci has been studied among the irradiated families from the Techa River population and non-exposed families from the rural area of the Chelyabinsk and Kurgan Oblasts. The groups were matched by ethnicity, parental age, occupation and smoking habit. A statistically significant 1.7-fold increase in mutation rate was found in the germline of irradiated fathers, whereas maternal germline mutation rate in the exposed families was not elevated. Most of the minisatellite loci showed an elevated paternal mutation rate in the exposed group, indicating a generalised increase in minisatellite germline mutation rate in the Techa River population. These data suggest that the elevated minisatellite mutation rate can be attributed to radioactive exposure. The spectra of paternal mutation seen in the unexposed and exposed families were indistinguishable

A double B1-mode 4-layer laminated piezoelectric linear motor.

Science.gov (United States)

Li, Xiaotian; Chen, Zhijiang; Dong, Shuxiang

2012-12-01

We report a miniature piezoelectric ultrasonic linear motor that is made of four Pb(Zr,Ti)O(3) (PZT) piezoelectric ceramic layers for low-voltage work. The 4-layer piezoelectric laminate works in two orthogonal first-bending modes for producing elliptical oscillations, which are then used to drive a contacting slider into continuous linear motion. Experimental results show that the miniature linear motor (size: 4 × 4 × 12 mm, weight: 1.7 g) can generate a large driving force of 0.48 N and a linear motion speed of up to 160 mm/s, using a 40 V(pp)/mm voltage drive at its resonance frequency of 64.5 kHz. The maximum efficiency of the linear motor is 30%.

"Subclinical" laminitis in dairy cattle.

Science.gov (United States)

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.

Fracture toughness of Ti-Al3Ti-Al-Al3Ti laminate composites under static and cyclic loading conditions

Science.gov (United States)

Patselov, A. M.; Gladkovskii, S. V.; Lavrikov, R. D.; Kamantsev, I. S.

2015-10-01

The static and cyclic fracture toughnesses of a Ti-Al3Ti-Al-Al3Ti laminate composite material containing at most 15 vol % intermetallic compound are studied. Composite specimens are prepared by terminating reaction sintering of titanium and aluminum foils under pressure. The fracture of the titanium layers is quasi-cleavage during cyclic crack growth and is ductile during subsequent static loading.

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...

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.

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

Contribution to the ATLAS B-field 3D model

International Nuclear Information System (INIS)

Vorozhtsov, S.B.; Titkova, I.V.; Nessi, M.

1996-01-01

The results from the simplified Tile-Cal B-field models calculations are presented. The effects of glue gaps, end plates, front plates, laminated iron layer near girder, 2 mm iron layers between tiles have been estimated. An interpretation of the existing field measurements of the TileCal segments is fulfilled. Some proposals for the general ATLAS B-field map calculation are given. 12 refs., 10 figs

Germline contamination and leakage in whole genome somatic single nucleotide variant detection.

Science.gov (United States)

Sendorek, Dorota H; Caloian, Cristian; Ellrott, Kyle; Bare, J Christopher; Yamaguchi, Takafumi N; Ewing, Adam D; Houlahan, Kathleen E; Norman, Thea C; Margolin, Adam A; Stuart, Joshua M; Boutros, Paul C

2018-01-31

The clinical sequencing of cancer genomes to personalize therapy is becoming routine across the world. However, concerns over patient re-identification from these data lead to questions about how tightly access should be controlled. It is not thought to be possible to re-identify patients from somatic variant data. However, somatic variant detection pipelines can mistakenly identify germline variants as somatic ones, a process called "germline leakage". The rate of germline leakage across different somatic variant detection pipelines is not well-understood, and it is uncertain whether or not somatic variant calls should be considered re-identifiable. To fill this gap, we quantified germline leakage across 259 sets of whole-genome somatic single nucleotide variant (SNVs) predictions made by 21 teams as part of the ICGC-TCGA DREAM Somatic Mutation Calling Challenge. The median somatic SNV prediction set contained 4325 somatic SNVs and leaked one germline polymorphism. The level of germline leakage was inversely correlated with somatic SNV prediction accuracy and positively correlated with the amount of infiltrating normal cells. The specific germline variants leaked differed by tumour and algorithm. To aid in quantitation and correction of leakage, we created a tool, called GermlineFilter, for use in public-facing somatic SNV databases. The potential for patient re-identification from leaked germline variants in somatic SNV predictions has led to divergent open data access policies, based on different assessments of the risks. Indeed, a single, well-publicized re-identification event could reshape public perceptions of the values of genomic data sharing. We find that modern somatic SNV prediction pipelines have low germline-leakage rates, which can be further reduced, especially for cloud-sharing, using pre-filtering software.

Nuclear envelope alterations in fibroblasts from LGMD1B patients carrying nonsense Y259X heterozygous or homozygous mutation in lamin A/C gene.

NARCIS (Netherlands)

Muchir, A.; Engelen, B.G.M. van; Lammens, M.M.Y.; Mislow, J.M.; McNally, E.; Schwartz, K.; Bonne, G.

2003-01-01

Mutations in the LMNA gene encoding nuclear lamins A and C are responsible for seven inherited disorders affecting specific tissues. We have analyzed skin fibroblasts from a patient with type 1B limb-girdle muscular dystrophy and from her deceased newborn grandchild carrying, respectively, a

Field performance of timber bridges. 15, Pueblo County, Colorado, stress-laminated deck bridge

Science.gov (United States)

L. E. Hislop

The Pueblo County 204B bridge was constructed in March 1990 in Pueblo, Colorado, as a demonstration bridge under the USDA Forest Service Timber Bridge Initiative. The stress-laminated deck superstructure is approximately 10 m long, 9 m wide, and 406 mm deep, with a skew of 10 degrees. Performance monitoring was conducted for 3 years, beginning at...

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.

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.

Long-term culture of chicken primordial germ cells isolated from embryonic blood and production of germline chimaeric chickens.

Science.gov (United States)

Naito, Mitsuru; Harumi, Takashi; Kuwana, Takashi

2015-02-01

Production of germline chimaeric chickens by the transfer of cultured primordial germ cells (PGC) is a useful system for germline manipulation. A novel culture system was developed for chicken PGC isolated from embryonic blood. The isolated PGC were cultured on feeder cells derived from chicken embryonic fibroblast. The cultured PGC formed colonies and they proliferated about 300-times during the first 30 days. The cultured PGC retained the ability to migrate to recipient gonads and were also chicken VASA homologue (CVH)-positive. Female PGC were present in the mixed-sex PGC populations cultured for more than 90 days and gave rise to viable offspring efficiently via germline chimaeric chickens. Male cultured PGC were transferred to recipient embryos and produced putative chimaeric chickens. The DNA derived from the cultured PGC was detected in the sperm samples of male putative chimaeric chickens, but no donor derived offspring were obtained. Donor-derived offspring were also obtained from germline chimaeric chickens by the transfer of frozen-thawed cultured PGC. The culture method for PGC developed in the present study is useful for manipulation of the germline in chickens, such as preservation of genetic resources and gene transfer. Copyright © 2014 Elsevier B.V. All rights reserved.

DESIGN ALTERNATIVES ON THE LAMINATES

Directory of Open Access Journals (Sweden)

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.

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

Identification of germline transcriptional regulatory elements in Aedes aegypti

Science.gov (United States)

Akbari, Omar S.; Papathanos, Philippos A.; Sandler, Jeremy E.; Kennedy, Katie; Hay, Bruce A.

2014-02-01

The mosquito Aedes aegypti is the principal vector for the yellow fever and dengue viruses, and is also responsible for recent outbreaks of the alphavirus chikungunya. Vector control strategies utilizing engineered gene drive systems are being developed as a means of replacing wild, pathogen transmitting mosquitoes with individuals refractory to disease transmission, or bringing about population suppression. Several of these systems, including Medea, UDMEL, and site-specific nucleases, which can be used to drive genes into populations or bring about population suppression, utilize transcriptional regulatory elements that drive germline-specific expression. Here we report the identification of multiple regulatory elements able to drive gene expression specifically in the female germline, or in the male and female germline, in the mosquito Aedes aegypti. These elements can also be used as tools with which to probe the roles of specific genes in germline function and in the early embryo, through overexpression or RNA interference.

Asymmetric distribution of pl10 and bruno2, new members of a conserved core of early germline determinants in cephalochordates

Directory of Open Access Journals (Sweden)

Simon eDailey

2016-01-01

Full Text Available Molecular fingerprinting of conserved germline and somatic ¨stemness¨ markers in different taxa have been key in defining the mechanism of germline specification (preformation or epigenesis, as well as expression domains of somatic progenitors. The distribution of molecular markers for primordial germ cells (PGCs, including vasa, nanos and piwil1, as well as Vasa antibody staining, support a determinative mechanism of germline specification in the cephalochordate Branchiostoma lanceolatum, similarly to other amphioxus species. pl10 and bruno2, but not bruno4/6, are also expressed in a pattern consistent with these other germline genes, adding to our repertoire of PGC markers in lancelets. Expression of nanos, vasa and the remaining markers (musashi, pufA, pufB, pumilio and piwil2 may define populations of putative somatic progenitors in the tailbud, the amphioxus posterior growth zone, or zones of proliferative activity. Finally, we also identify a novel expression domain for musashi, a classic neural stem cell marker, during notochord development in amphioxus. These results are discussed in the context of germline determination in other taxa, stem cell regulation and regenerative capacity in adult amphioxus.

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.

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)

Glucocorticoids and laminitis in the horse.

Science.gov (United States)

Johnson, Philip J; Slight, Simon H; Ganjam, Venkataseshu K; Kreeger, John M

2002-08-01

The administration of exogenously administered GCs and syndromes associated with GC excess are both attended by increased risk for the development of laminitis in adult horses. However, there exists substantial controversy as to whether excess GCs cause laminitis de novo. If true, the pathogenesis of laminitis arising from the effects of GC excess is probably different from that associated with diseases of the gastrointestinal tract and endotoxemia. Although a satisfactory explanation for the development of laminitis as a consequence of GC action is currently lacking, numerous possible and plausible theoretical mechanisms do exist. Veterinarians must exert caution with respect to the use of GCs in adult horses. The extent to which individual horses are predisposed to laminitis as a result of GC effect cannot be predicted based on current information. However, the administration of systemic GCs to horses that have been previously affected by laminitis should be used only with extreme caution, and should be accompanied by careful monitoring for further signs of laminitis. The risk of laminitis appears to be greater during treatment using some GCs (especially dexamethasone and triamcinalone) compared with others (prednisone and prednisolone). Whenever possible, to reduce the risk of laminitis, GCs should be administered locally. For example, the risk of GC-associated laminitis is evidently considerably reduced in horses affected with chronic obstructive pulmonary disease (COPD) if GC treatment is administered via inhalation. We have hypothesized that structural changes in the equine hoof that resemble laminitis may arise as a consequence of excess GC effect. Although these changes are not painful per se, and are not associated with inflammation, they could likely predispose affected horses to the development of bona fide laminitis for other reasons. Moreover, the gross morphological appearance of the chronically GC-affected hoof resembles that of a chronically

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...

Analysis of functional germline variants in APOBEC3 and driver genes on breast cancer risk in Moroccan study population

International Nuclear Information System (INIS)

Marouf, Chaymaa; Göhler, Stella; Filho, Miguel Inacio Da Silva; Hajji, Omar; Hemminki, Kari; Nadifi, Sellama; Försti, Asta

2016-01-01

Breast cancer (BC) is the most prevalent cancer in women and a major public health problem in Morocco. Several Moroccan studies have focused on studying this disease, but more are needed, especially at the genetic and molecular levels. Therefore, we investigated the potential association of several functional germline variants in the genes commonly mutated in sporadic breast cancer. In this case–control study, we examined 36 single nucleotide polymorphisms (SNPs) in 13 genes (APOBEC3A, APOBEC3B, ARID1B, ATR, MAP3K1, MLL2, MLL3, NCOR1, RUNX1, SF3B1, SMAD4, TBX3, TTN), which were located in the core promoter, 5’-and 3’UTR or which were nonsynonymous SNPs to assess their potential association with inherited predisposition to breast cancer development. Additionally, we identified a ~29.5-kb deletion polymorphism between APOBEC3A and APOBEC3B and explored possible associations with BC. A total of 226 Moroccan breast cancer cases and 200 matched healthy controls were included in this study. The analysis showed that12 SNPs in 8 driver genes, 4 SNPs in APOBEC3B gene and 1 SNP in APOBEC3A gene were associated with BC risk and/or clinical outcome at P ≤ 0.05 level. RUNX1-rs8130963 (odds ratio (OR) = 2.25; 95 % CI 1.42-3.56; P = 0.0005; dominant model), TBX3-rs8853 (OR = 2.04; 95 % CI 1.38-3.01; P = 0.0003; dominant model), TBX3-rs1061651 (OR = 2.14; 95 % CI1.43-3.18; P = 0.0002; dominant model), TTN-rs12465459 (OR = 2.02; 95 % confidence interval 1.33-3.07; P = 0.0009; dominant model), were the most significantly associated SNPs with BC risk. A strong association with clinical outcome were detected for the genes SMAD4 -rs3819122 with tumor size (OR = 0.45; 95 % CI 0.25-0.82; P = 0.009) and TTN-rs2244492 with estrogen receptor (OR = 0.45; 95 % CI 0.25-0.82; P = 0.009). Our results suggest that genetic variations in driver and APOBEC3 genes were associated with the risk of BC and may have impact on clinical outcome. However, the reported association between the

Antibody Heavy Chain Variable Domains of Different Germline Gene Origins Diversify through Different Paths

Directory of Open Access Journals (Sweden)

Ufuk Kirik

2017-11-01

Full Text Available B cells produce antibodies, key effector molecules in health and disease. They mature their properties, including their affinity for antigen, through hypermutation events; processes that involve, e.g., base substitution, codon insertion and deletion, often in association with an isotype switch. Investigations of antibody evolution define modes whereby particular antibody responses are able to form, and such studies provide insight important for instance for development of efficient vaccines. Antibody evolution is also used in vitro for the design of antibodies with improved properties. To better understand the basic concepts of antibody evolution, we analyzed the mutational paths, both in terms of amino acid substitution and insertions and deletions, taken by antibodies of the IgG isotype. The analysis focused on the evolution of the heavy chain variable domain of sets of antibodies, each with an origin in 1 of 11 different germline genes representing six human heavy chain germline gene subgroups. Investigated genes were isolated from cells of human bone marrow, a major site of antibody production, and characterized by next-generation sequencing and an in-house bioinformatics pipeline. Apart from substitutions within the complementarity determining regions, multiple framework residues including those in protein cores were targets of extensive diversification. Diversity, both in terms of substitutions, and insertions and deletions, in antibodies is focused to different positions in the sequence in a germline gene-unique manner. Altogether, our findings create a framework for understanding patterns of evolution of antibodies from defined germline genes.

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.

Predisposing factors of laminitis in cattle.

Science.gov (United States)

Vermunt, J J; Greenough, P R

1994-01-01

Laminitis is regarded as a major predisposing factor in lameness caused by claw disorders. Despite intensive study, both by experiment and by clinical observation, knowledge of the precise aetiology and pathogenesis of bovine laminitis is still incomplete. It is often hypothesized that changes in the micro-circulation of the corum (dermis) of the bovine claw contribute significantly to the development of laminitis; arteriovenous anastomoses (AVAs) playing a crucial role. Many factors have been implicated as contributing causes of laminitis in cattle; the disease has a multifactorial aetiology. The cause of laminitis should be considered as a combination of predisposing factors leading to vascular (AVAs in particular) reactivity and inhibition of normal horn synthesis. Nutrition, disease, management and behaviour appear to be closely involved in the pathogenesis of bovine laminitis. The major factors predisposing to laminitis in cattle, as reported or suggested in the literature, are reviewed, including systemic disease, nutrition (barley grain, protein, carbohydrate and fibre), management (housing, bedding and exercise), calving, season, age, growth, genetics, conformation and behaviour.

Laminitis and the equine metabolic syndrome.

Science.gov (United States)

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.

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 ...

Lamin A reassembly at the end of mitosis is regulated by its SUMO-interacting motif

Energy Technology Data Exchange (ETDEWEB)

Moriuchi, Takanobu; Kuroda, Masaki; Kusumoto, Fumiya; Osumi, Takashi; Hirose, Fumiko, E-mail: fhirose@sci.u-hyogo.ac.jp

2016-03-01

Modification of proteins with small ubiquitin-related modifier (SUMO; SUMOylation) is involved in the regulation of various biological processes. Recent studies have demonstrated that noncovalent associations between SUMOylated proteins and co-operative proteins containing SUMO-interacting motifs (SIMs) are important for the spatiotemporal organization of many protein complexes. In this study, we demonstrate that interactions between lamin A, a major component of the nuclear lamina, and SUMO isoforms are dependent on one of the four SIMs (SIM3) resided in lamin A polypeptide in vitro. Live cell imaging and immunofluorescence staining showed that SIM3 is required for accumulation of lamin A on the chromosomes during telophase, and subsequent evaluation of a panel of deletion mutants determined that a 156-amino acid region spanning the carboxyl-terminal Ig-fold domain of lamin A is sufficient for this accumulation. Notably, mutation of SIM3 abrogated the dephosphorylation of mitosis-specific phosphorylation at Ser-22 of lamin A, which normally occurs during telophase, and the subsequent nuclear lamina reorganization. Furthermore, expression of a conjugation-defective SUMO2 mutant, which was previously shown to inhibit endogenous SUMOylation in a dominant-negative manner, also impaired the accumulation of wild type lamin A on telophase chromosomes. These findings suggest that interactions between SIM3 of lamin A and a putative SUMO2-modified protein plays an important role in the reorganization of the nuclear lamina at the end of mitosis. - Highlights: • Lamin A interacts with SUMO2 via a SUMO-interacting motif (SIM) in the Ig domain. • SIM3 of lamin A is responsible for chromosomal accumulation during telophase. • A 156-aa region spanning the Ig domain is sufficient for chromosomal accumulation. • Accumulation of lamin A is required for timely dephosphorylation on chromosomes. • A putative SUMO2-modified protein may mediate chromosomal accumulation of lamin

Lamin A reassembly at the end of mitosis is regulated by its SUMO-interacting motif

International Nuclear Information System (INIS)

Moriuchi, Takanobu; Kuroda, Masaki; Kusumoto, Fumiya; Osumi, Takashi; Hirose, Fumiko

2016-01-01

Modification of proteins with small ubiquitin-related modifier (SUMO; SUMOylation) is involved in the regulation of various biological processes. Recent studies have demonstrated that noncovalent associations between SUMOylated proteins and co-operative proteins containing SUMO-interacting motifs (SIMs) are important for the spatiotemporal organization of many protein complexes. In this study, we demonstrate that interactions between lamin A, a major component of the nuclear lamina, and SUMO isoforms are dependent on one of the four SIMs (SIM3) resided in lamin A polypeptide in vitro. Live cell imaging and immunofluorescence staining showed that SIM3 is required for accumulation of lamin A on the chromosomes during telophase, and subsequent evaluation of a panel of deletion mutants determined that a 156-amino acid region spanning the carboxyl-terminal Ig-fold domain of lamin A is sufficient for this accumulation. Notably, mutation of SIM3 abrogated the dephosphorylation of mitosis-specific phosphorylation at Ser-22 of lamin A, which normally occurs during telophase, and the subsequent nuclear lamina reorganization. Furthermore, expression of a conjugation-defective SUMO2 mutant, which was previously shown to inhibit endogenous SUMOylation in a dominant-negative manner, also impaired the accumulation of wild type lamin A on telophase chromosomes. These findings suggest that interactions between SIM3 of lamin A and a putative SUMO2-modified protein plays an important role in the reorganization of the nuclear lamina at the end of mitosis. - Highlights: • Lamin A interacts with SUMO2 via a SUMO-interacting motif (SIM) in the Ig domain. • SIM3 of lamin A is responsible for chromosomal accumulation during telophase. • A 156-aa region spanning the Ig domain is sufficient for chromosomal accumulation. • Accumulation of lamin A is required for timely dephosphorylation on chromosomes. • A putative SUMO2-modified protein may mediate chromosomal accumulation of lamin

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.

OGT (O-GlcNAc Transferase) Selectively Modifies Multiple Residues Unique to Lamin A.

Science.gov (United States)

Simon, Dan N; Wriston, Amanda; Fan, Qiong; Shabanowitz, Jeffrey; Florwick, Alyssa; Dharmaraj, Tejas; Peterson, Sherket B; Gruenbaum, Yosef; Carlson, Cathrine R; Grønning-Wang, Line M; Hunt, Donald F; Wilson, Katherine L

2018-05-17

The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity. Mutations in LMNA cause over 12 diseases ('laminopathies'). Lamins A and C are identical for their first 566 residues. However, they form separate filaments in vivo, with apparently distinct roles. We report that lamin A is β- O -linked N -acetylglucosamine- (O -GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver. In vitro assays with purified O -GlcNAc transferase (OGT) enzyme showed robust O -GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails. Using mass spectrometry, we identified 11 O -GlcNAc sites in a 'sweet spot' unique to lamin A, with up to seven sugars per peptide. Most sites were unpredicted by current algorithms. Double-mutant (S612A/T643A) lamin A tails were still robustly O -GlcNAc-modified at seven sites. By contrast, O -GlcNAcylation was undetectable on tails bearing deletion Δ50, which causes Hutchinson⁻Gilford progeria syndrome, and greatly reduced by deletion Δ35. We conclude that residues deleted in progeria are required for substrate recognition and/or modification by OGT in vitro. Interestingly, deletion Δ35, which does not remove the majority of identified O -GlcNAc sites, does remove potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1. These biochemical results are significant because they identify a novel molecular pathway that may profoundly influence lamin A function. The hypothesis that lamin A is selectively regulated by OGT warrants future testing in vivo, along with two predictions: genetic variants may contribute to disease by perturbing OGT-dependent regulation, and nutrient or other stresses might cause OGT to misregulate wildtype lamin A.

Selfish genetic elements favor the evolution of a distinction between soma and germline.

Science.gov (United States)

Johnson, Louise J

2008-08-01

Many multicellular organisms have evolved a dedicated germline. This can benefit the whole organism, but its advantages to genetic parasites have not been explored. Here I model the evolutionary success of a selfish element, such as a transposable element or endosymbiont, which is capable of creating or strengthening a germline-soma distinction in a primitively multicellular host, and find that it will always benefit the element to do so. Genes causing germline sequestration can therefore spread in a population even if germline sequestration is maladaptive for the host organism. Costly selfish elements are expected to survive only in sexual populations, so sexual species may experience an additional push toward germline-soma distinction, and hence toward cell differentiation and multicellularity.

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

Amyloid domains in the cell nucleus controlled by nucleoskeletal protein lamin B1 reveal a new pathway of mercury neurotoxicity

Science.gov (United States)

Arnhold, Florian; Gührs, Karl-Heinz

2015-01-01

Mercury (Hg) is a bioaccumulating trace metal that globally circulates the atmosphere and waters in its elemental, inorganic and organic chemical forms. While Hg represents a notorious neurotoxicant, the underlying cellular pathways are insufficiently understood. We identify amyloid protein aggregation in the cell nucleus as a novel pathway of Hg-bio-interactions. By mass spectrometry of purified protein aggregates, a subset of spliceosomal components and nucleoskeletal protein lamin B1 were detected as constituent parts of an Hg-induced nuclear aggregome network. The aggregome network was located by confocal imaging of amyloid-specific antibodies and dyes to amyloid cores within splicing-speckles that additionally recruit components of the ubiquitin-proteasome system. Hg significantly enhances global proteasomal activity in the nucleus, suggesting that formation of amyloid speckles plays a role in maintenance of protein homeostasis. RNAi knock down showed that lamin B1 for its part regulates amyloid speckle formation and thus likewise participates in nuclear protein homeostasis. As the Hg-induced cascade of interactions between the nucleoskeleton and protein homeostasis reduces neuronal signalling, amyloid fibrillation in the cell nucleus is introduced as a feature of Hg-neurotoxicity that opens new avenues of future research. Similar to protein aggregation events in the cytoplasm that are controlled by the cytoskeleton, amyloid fibrillation of nuclear proteins may be driven by the nucleoskeleton. PMID:25699204

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.

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

Pediatric MDS: GATA screen the germline.

Science.gov (United States)

Stieglitz, Elliot; Loh, Mignon L

2016-03-17

In this issue of Blood, Wlodarski and colleagues demonstrate that as many as 72% of adolescents diagnosed with myelodysplastic syndrome (MDS) and monosomy 7 harbor germline mutations in GATA2. Although pediatric MDS is a very rare diagnosis, occurring in 0.8 to 4 cases per million, Wlodarski et al screened >600 cases of primary or secondary MDS in children and adolescents who were enrolled in the European Working Group on MDS consortium over a period of 15 years. The overall frequency of germline GATA2 mutations in children with primary MDS was 7%, and 15% in those presenting with advanced disease. Notably, mutations in GATA2 were absent in patients with therapy-related MDS or acquired aplastic anemia.

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

Group 3 medulloblastoma in a patient with a GYS2 germline mutation and glycogen storage disease 0a.

Science.gov (United States)

Holsten, Till; Tsiakas, Konstantinos; Kordes, Uwe; Bison, Brigitte; Pietsch, Torsten; Rutkowski, Stefan; Santer, René; Schüller, Ulrich

2018-03-01

Glycogen storage disease (GSD) 0a is a rare congenital metabolic disease with symptoms in infancy and childhood caused by biallelic GYS2 germline variants. A predisposition to cancer has not been described yet. We report here a boy with GSD 0a, who developed a malignant brain tumor at the age of 4.5 years. The tumor was classified as a group 3 medulloblastoma, and the patient died from cancer 27 months after initial tumor diagnosis. This case appears interesting as group 3 medulloblastoma is so far not known to arise in hereditary syndromes and the biology of sporadic group 3 medulloblastoma is largely unknown.

File list: His.Adl.50.AllAg.Germline_containing_young_adult [Chip-atlas[Archive

Lifescience Database Archive (English)

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Modal analysis of pre and post impacted nano composite laminates

Directory of Open Access Journals (Sweden)

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.

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File list: His.Adl.10.AllAg.Germline_containing_young_adult [Chip-atlas[Archive

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Full Text Available His.Adl.10.AllAg.Germline_containing_young_adult ce10 Histone Adult Germline containing young adult...archive.biosciencedbc.jp/kyushu-u/ce10/assembled/His.Adl.10.AllAg.Germline_containing_young_adult.bed ...

File list: His.Adl.20.AllAg.Germline_containing_young_adult [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Adl.20.AllAg.Germline_containing_young_adult ce10 Histone Adult Germline containing young adult...archive.biosciencedbc.jp/kyushu-u/ce10/assembled/His.Adl.20.AllAg.Germline_containing_young_adult.bed ...

File list: Oth.Adl.10.AllAg.Germline_containing_young_adult [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Adl.10.AllAg.Germline_containing_young_adult ce10 TFs and others Adult Germline containing young adult....jp/kyushu-u/ce10/assembled/Oth.Adl.10.AllAg.Germline_containing_young_adult.bed ...

File list: Oth.Adl.50.AllAg.Germline_containing_young_adult [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Adl.50.AllAg.Germline_containing_young_adult ce10 TFs and others Adult Germline containing young adult....jp/kyushu-u/ce10/assembled/Oth.Adl.50.AllAg.Germline_containing_young_adult.bed ...

File list: Unc.Adl.10.AllAg.Germline_containing_young_adult [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Adl.10.AllAg.Germline_containing_young_adult ce10 Unclassified Adult Germline containing young adult... http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Unc.Adl.10.AllAg.Germline_containing_young_adult.bed ...

File list: Unc.Adl.20.AllAg.Germline_containing_young_adult [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Adl.20.AllAg.Germline_containing_young_adult ce10 Unclassified Adult Germline containing young adult... http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Unc.Adl.20.AllAg.Germline_containing_young_adult.bed ...

File list: Unc.Adl.50.AllAg.Germline_containing_young_adult [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Adl.50.AllAg.Germline_containing_young_adult ce10 Unclassified Adult Germline containing young adult... http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Unc.Adl.50.AllAg.Germline_containing_young_adult.bed ...

File list: ALL.Adl.50.AllAg.Germline_containing_young_adult [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Adl.50.AllAg.Germline_containing_young_adult ce10 All antigens Adult Germline containing young adult...e.biosciencedbc.jp/kyushu-u/ce10/assembled/ALL.Adl.50.AllAg.Germline_containing_young_adult.bed ...

Microstructure evolution and shear strength of vacuum brazed joint for super-Ni/NiCr laminated composite with Ni–Cr–Si–B amorphous interlayer

International Nuclear Information System (INIS)

Wu, Na; Li, Yajiang; Ma, Qunshuang

2014-01-01

Highlights: • Divorced eutectic of γ-Ni and Ni 3 B formed in the brazed region. • The detailed isothermal solidification mechanism was proposed. • Borides formed at the interfaces at different temperatures were identified. • Effect of brazing temperatures on microstructure and shear strength was investigated. • Excellent joint with shear strength of 191 MPa was obtained at 1100 °C for 20 min. - Abstract: Vacuum brazing of super-Ni/NiCr laminated composite and Cr18–Ni8 steel was carried out with Ni–Cr–Si–B amorphous interlayer at different temperatures (1060–1150 °C). The effects of brazing temperature on the microstructure evolution and shear strength of the joints were investigated. Microstructure, chemical composition and microhardness of the joints were studied using field emission scanning electron microscope, energy dispersive spectroscopy, X-ray diffraction and microsclerometer. Shear strength of the joints were measured by the electromechanical universal testing machine. Diffusion of B was the controlling factor for microstructure evolution. The detailed isothermal solidification mechanism was proposed in this study. The fracture morphology of the joint made at 1100 °C exhibited plastic feature and the shear strength reached 191 MPa. Bulky Ni 3 B formed in super-Ni cover layer near the brazed region when performed at 1060–1100 °C while Ni–B eutectic formed instead at 1150 °C

File list: Pol.Adl.20.AllAg.Germline_containing_young_adult [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Adl.20.AllAg.Germline_containing_young_adult ce10 RNA polymerase Adult Germline containing young adult... http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Adl.20.AllAg.Germline_containing_young_adult.bed ...

File list: Pol.Adl.50.AllAg.Germline_containing_young_adult [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Adl.50.AllAg.Germline_containing_young_adult ce10 RNA polymerase Adult Germline containing young adult... http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Adl.50.AllAg.Germline_containing_young_adult.bed ...

File list: Pol.Adl.05.AllAg.Germline_containing_young_adult [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Adl.05.AllAg.Germline_containing_young_adult ce10 RNA polymerase Adult Germline containing young adult... http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/Pol.Adl.05.AllAg.Germline_containing_young_adult.bed ...

Germline TERT promoter mutations are rare in familial melanoma

DEFF Research Database (Denmark)

Harland, Mark; Petljak, Mia; Robles-Espinoza, Carla Daniela

2016-01-01

Germline CDKN2A mutations occur in 40 % of 3-or-more case melanoma families while mutations of CDK4, BAP1, and genes involved in telomere function (ACD, TERF2IP, POT1), have also been implicated in melanomagenesis. Mutation of the promoter of the telomerase reverse transcriptase (TERT) gene (c.-57...... T>G variant) has been reported in one family. We tested for the TERT promoter variant in 675 multicase families wild-type for the known high penetrance familial melanoma genes, 1863 UK population-based melanoma cases and 529 controls. Germline lymphocyte telomere length was estimated in carriers....... The c.-57 T>G TERT promoter variant was identified in one 7-case family with multiple primaries and early age of onset (earliest, 15 years) but not among population cases or controls. One family member had multiple primary melanomas, basal cell carcinomas and a bladder tumour. The blood leukocyte...

Birefringence Bragg Binary (3B) grating, quasi-Bragg grating and immersion gratings

Science.gov (United States)

Ebizuka, Noboru; Morita, Shin-ya; Yamagata, Yutaka; Sasaki, Minoru; Bianco, Andorea; Tanabe, Ayano; Hashimoto, Nobuyuki; Hirahara, Yasuhiro; Aoki, Wako

2014-07-01

A volume phase holographic (VPH) grating achieves high angular dispersion and very high diffraction efficiency for the first diffraction order and for S or P polarization. However the VPH grating could not achieve high diffraction efficiency for non-polarized light at a large diffraction angle because properties of diffraction efficiencies for S and P polarizations are different. Furthermore diffraction efficiency of the VPH grating extinguishes toward a higher diffraction order. A birefringence binary Bragg (3B) grating is a thick transmission grating with optically anisotropic material such as lithium niobate or liquid crystal. The 3B grating achieves diffraction efficiency up to 100% for non-polarized light by tuning of refractive indices for S and P polarizations, even in higher diffraction orders. We fabricated 3B grating with liquid crystal and evaluated the performance of the liquid crystal grating. A quasi-Bragg (QB) grating, which consists long rectangle mirrors aligned in parallel precisely such as a window shade, also achieves high diffraction efficiency toward higher orders. We fabricated QB grating by laminating of silica glass substrates and glued by pressure fusion of gold films. A quasi-Bragg immersion (QBI) grating has smooth mirror hypotenuse and reflector array inside the hypotenuse, instead of step-like grooves of a conventional immersion grating. An incident beam of the QBI grating reflects obliquely at a reflector, then reflects vertically at the mirror surface and reflects again at the same reflector. We are going to fabricate QBI gratings by laminating of mirror plates as similar to fabrication of the QB grating. We will also fabricate silicon and germanium immersion gratings with conventional step-like grooves by means of the latest diamond machining methods. We introduce characteristics and performance of these gratings.

Lamins, laminopathies and disease mechanisms

Indian Academy of Sciences (India)

2011-07-08

Jul 8, 2011 ... Lamins, laminopathies and disease mechanisms: Possible role for proteasomal degradation of ... Mutations in the human lamin genes lead to highly degenerative genetic diseases that affect a number of different ... June 2018.

Germline mutations in lysine specific demethylase 1 (LSD1/KDM1A) confer susceptibility to multiple myeloma.

Science.gov (United States)

Wei, Xiaomu; Calvo-Vidal, M Nieves; Chen, Siwei; Wu, Gang; Revuelta, Maria V; Sun, Jian; Zhang, Jinghui; Walsh, Michael F; Nichols, Kim E; Joseph, Vijai; Snyder, Carrie; Vachon, Celine M; McKay, James D; Wang, Shu-Ping; Jayabalan, David S; Jacobs, Lauren M; Becirovic, Dina; Waller, Rosalie G; Artomov, Mykyta; Viale, Agnes; Patel, Jayeshkumar; Phillip, Jude M; Chen-Kiang, Selina; Curtin, Karen; Salama, Mohamed; Atanackovic, Djordje; Niesvizky, Ruben; Landgren, Ola; Slager, Susan L; Godley, Lucy A; Churpek, Jane; Garber, Judy E; Anderson, Kenneth C; Daly, Mark J; Roeder, Robert G; Dumontet, Charles; Lynch, Henry T; Mullighan, Charles G; Camp, Nicola J; Offit, Kenneth; Klein, Robert J; Yu, Haiyuan; Cerchietti, Leandro; Lipkin, Steven M

2018-03-20

Given the frequent and largely incurable occurrence of multiple myeloma (MM), identification of germline genetic mutations that predispose cells to MM may provide insight into disease etiology and the developmental mechanisms of its cell of origin, the plasma cell. Here we identified familial and early-onset MM kindreds with truncating mutations in lysine-specific demethylase 1 (LSD1/KDM1A), an epigenetic transcriptional repressor that primarily demethylates histone H3 on lysine 4 and regulates hematopoietic stem cell self-renewal. Additionally, we found higher rates of germline truncating and predicted deleterious missense KDM1A mutations in MM patients unselected for family history compared to controls. Both monoclonal gammopathy of unknown significance (MGUS) and MM cells have significantly lower KDM1A transcript levels compared with normal plasma cells. Transcriptome analysis of MM cells from KDM1A mutation carriers shows enrichment of pathways and MYC target genes previously associated with myeloma pathogenesis. In mice, antigen challenge followed by pharmacological inhibition of KDM1A promoted plasma cell expansion, enhanced secondary immune response, elicited appearance of serum paraprotein, and mediated upregulation of MYC transcriptional targets. These changes are consistent with the development of MGUS. Collectively, our findings show KDM1A is the first autosomal dominant MM germline predisposition gene, providing new insights into its mechanistic roles as a tumor suppressor during post-germinal center B cell differentiation. Copyright ©2018, American Association for Cancer Research.

Probing the germline-dependence of epigenetic inheritance using artificial insemination in mice

Science.gov (United States)

Bohacek, Johannes; von Werdt, Sarah; Mansuy, Isabelle M.

2016-01-01

Abstract We developed a simple, noninvasive artificial insemination technique to study epigenetic germline inheritance in mice. This technique avoids interfering factors introduced by superovulation, surgery, in vitro culture or mating that can confound the transmission of acquired epigenetic information through the germline. Using a stress model, we demonstrate that our method is suited to test the causal involvement of the male germline in transmitting acquired information from father to offspring. PMID:29492284

Tet2 and Tet3 cooperate with B-lineage transcription factors to regulate DNA modification and chromatin accessibility.

Science.gov (United States)

Lio, Chan-Wang; Zhang, Jiayuan; González-Avalos, Edahí; Hogan, Patrick G; Chang, Xing; Rao, Anjana

2016-11-21

Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine, facilitating DNA demethylation and generating new epigenetic marks. Here we show that concomitant loss of Tet2 and Tet3 in mice at early B cell stage blocked the pro- to pre-B cell transition in the bone marrow, decreased Irf4 expression and impaired the germline transcription and rearrangement of the Igκ locus. Tet2/3-deficient pro-B cells showed increased CpG methylation at the Igκ 3' and distal enhancers that was mimicked by depletion of E2A or PU.1, as well as a global decrease in chromatin accessibility at enhancers. Importantly, re-expression of the Tet2 catalytic domain in Tet2/3-deficient B cells resulted in demethylation of the Igκ enhancers and restored their chromatin accessibility. Our data suggest that TET proteins and lineage-specific transcription factors cooperate to influence chromatin accessibility and Igκ enhancer function by modulating the modification status of DNA.

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.

Germline Mutations of Inhibins in Early-Onset Ovarian Epithelial Tumors

Science.gov (United States)

Tournier, Isabelle; Marlin, Régine; Walton, Kelly; Charbonnier, Françoise; Coutant, Sophie; Théry, Jean-Christophe; Charbonnier, Camille; Spurrell, Cailyn; Vezain, Myriam; Ippolito, Lorena; Bougeard, Gaëlle; Roman, Horace; Tinat, Julie; Sabourin, Jean-Christophe; Stoppa-Lyonnet, Dominique; Caron, Olivier; Bressac-de Paillerets, Brigitte; Vaur, Dominique; King, Mary-Claire; Harrison, Craig; Frebourg, Thierry

2014-01-01

To identify novel genetic bases of early-onset epithelial ovarian tumors, we used the trio exome sequencing strategy in a patient without familial history of cancer who presented metastatic serous ovarian adenocarcinomas at 21 years of age. We identified a single de novo mutation (c.1157A>G/p.Asn386Ser) within the INHBA gene encoding the βA-subunit of inhibins/activins, which play a key role in ovarian development. In vitro, this mutation alters the ratio of secreted activins and inhibins. In a second patient with early-onset serous borderline papillary cystadenoma, we identified an unreported germline mutation (c.179G>T/p.Arg60Leu) of the INHA gene encoding the α-subunit, the partner of the βA-subunit. This mutation also alters the secreted activin/inhibin ratio, by disrupting both inhibin A and inhibin B biosynthesis. In a cohort of 62 cases, we detected an additional unreported germline mutation of the INHBA gene (c.839G>A/p.Gly280Glu). Our results strongly suggest that inhibin mutations contribute to the genetic determinism of epithelial ovarian tumors. PMID:24302632

Wear Behavior of Cold Pressed and Sintered Al2O3/TiC/CaF2Al2O3/TiC Laminated Ceramic Composite

Institute of Scientific and Technical Information of China (English)

Xuefeng YANG; Jian CHENG; Peilong SONG; Shouren WANG; Liying YANG; Yanjun WANG; Ken MAO

2013-01-01

A novel laminated Al2O3/TiC/CaF2-Al2O3/TiC sandwich ceramic composite was fabricated through cold pressing and sintering to achieve better anti-wear performance,such as low friction coefficient and low wear rate.Al2O3/TiC/CaF2 and Al2O3/TiC composites were alternatively built layer-by-layer to obtain a sandwich structure.Solid lubricant CaF2 was added evenly into the Al2O3/TiC/CaF2 layer to reduce the friction and wear.Al2O3/TiC ceramic was also cold pressed and sintered for comparison.Friction analysis of the two ceramics was then conducted via a wear-and-tear machine.Worn surface and surface compositions were examined by scanning electron microscopy and energy dispersion spectrum,respectively.Results showed that the laminated Al2O3/TiC/CaF2-Al2O3/TiC sandwich ceramic composite has lower friction coefficient and lower wear rate than those of Al2O3/TiC ceramic alone because of the addition of CaF2 into the laminated Al2O3/TiC/CaF2-Al2O3/TiC sandwich ceramic composite.Under the friction load,the tiny CaF2 particles were scraped from the Al2O3/TiC/CaF2 layer and spread on friction pairs before falling off into micropits.This process formed a smooth,self-lubricating film,which led to better anti-wear properties.Adhesive wear is the main wear mechanism of Al2O3/TiC/CaF2 layer and abrasive wear is the main wear mechanism of Al2O3/TiC layer.

Masking ability of bi- and tri- laminate all-ceramic veneers on tooth-colored ceramic discs.

Science.gov (United States)

Farhan, Daniel; Sukumar, Smitha; von Stein-Lausnitz, Axel; Aarabi, Ghazal; Alawneh, Ahmad; Reissmann, Daniel R

2014-01-01

A predictable esthetic outcome is imperative when placing ceramic veneers. Discolored teeth pose a major challenge as sufficient material thickness is required to achieve a good esthetic result. There is limited evidence in the literature that compares the masking ability of multi-laminate veneers. The aim of this in-vitro study was to compare the masking ability of bi-laminate (BL) and tri-laminate (TL) all-ceramic veneers cemented on tooth-colored ceramic discs. A total of 40 veneers (shade A1, 10-mm diameter, 0.8-mm thick) were manufactured-20 BL veneers (0.4-mm pressable ceramic coping veneered with 0.4-mm thick enamel layer) and 20 TL veneers (0.4-mm coping veneered with 0.2-mm thick opaque interlayer and 0.2-mm thick enamel layer). A bonding apparatus was utilized to adhesively cement all veneers on the ceramic discs (shade A1), simulating teeth of light and dark color. The resulting groups (N = 10 each) were the reference groups (shade A1 ceramic base) BL-1 and TL-1 veneers, and the test groups (shade A4 ceramic base) BL-4 and TL-4 veneers. The color of the cemented veneers was measured using a spectrophotometer. The data were converted to CIE L*a*b* coordinates, and ΔE* were calculated to allow for statistical analysis. The color differences between the samples with the A1 and A4 ceramic bases were significantly lower when covered with TL veneers (mean ΔE*: 3.2 units) than with BL veneers (mean ΔE*: 4.0 units: p bi-laminate veneers. Patients with discolored/darker teeth may benefit from a more predictable esthetic result when teeth restored with tri-laminate rather than bi-laminate veneers. © 2014 Wiley Periodicals, Inc.

Pan-cancer analysis reveals technical artifacts in TCGA germline variant calls.

Science.gov (United States)

Buckley, Alexandra R; Standish, Kristopher A; Bhutani, Kunal; Ideker, Trey; Lasken, Roger S; Carter, Hannah; Harismendy, Olivier; Schork, Nicholas J

2017-06-12

Cancer research to date has largely focused on somatically acquired genetic aberrations. In contrast, the degree to which germline, or inherited, variation contributes to tumorigenesis remains unclear, possibly due to a lack of accessible germline variant data. Here we called germline variants on 9618 cases from The Cancer Genome Atlas (TCGA) database representing 31 cancer types. We identified batch effects affecting loss of function (LOF) variant calls that can be traced back to differences in the way the sequence data were generated both within and across cancer types. Overall, LOF indel calls were more sensitive to technical artifacts than LOF Single Nucleotide Variant (SNV) calls. In particular, whole genome amplification of DNA prior to sequencing led to an artificially increased burden of LOF indel calls, which confounded association analyses relating germline variants to tumor type despite stringent indel filtering strategies. The samples affected by these technical artifacts include all acute myeloid leukemia and practically all ovarian cancer samples. We demonstrate how technical artifacts induced by whole genome amplification of DNA can lead to false positive germline-tumor type associations and suggest TCGA whole genome amplified samples be used with caution. This study draws attention to the need to be sensitive to problems associated with a lack of uniformity in data generation in TCGA data.

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.

File list: InP.Adl.50.AllAg.Germline_containing_young_adult [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: ALL.Adl.20.AllAg.Germline_containing_young_adult [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: ALL.Adl.05.AllAg.Germline_containing_young_adult [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: ALL.Adl.10.AllAg.Germline_containing_young_adult [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Adl.10.AllAg.Germline_containing_young_adult ce10 All antigens Adult Germline containing young adult...4938,SRX466563,SRX495065,SRX495061,SRX494933,SRX495102,SRX494887 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/ALL.Adl.10.AllAg.Germline_containing_young_adult.bed ...

Converse magnetoelectric effect in laminated composite of Metglas and Pb(Zr,TiO3 with screen-printed interdigitated electrodes

Directory of Open Access Journals (Sweden)

Yuan Zhang

2014-06-01

Full Text Available In this study, we investigate the converse magnetoelectric (CME effect in a laminated composite consisting of Metglas ribbons and Pb(Zr,TiO3 (PZT plate with screen-printed interdigitated electrodes and operating in longitudinal magnetization and longitudinal polarization (L-L mode. Large CME coefficients of 0.134 G·cm/V at frequency of 1 kHz and 2.75 G·cm/V at resonance frequency of 43.5 kHz under a small bias magnetic field of 7 Oe are achieved. The large CME effect can be attributed to the L-L mode and low mechanical loss of the Metglas/PZT laminated composite.

3D calculations of the Superconducting Super Collider (SSC) 3 Tesla magnet

International Nuclear Information System (INIS)

Lari, R.J.

1984-01-01

A 20 TeV Superconducting Super Collider (SSC) proton accelerator is being proposed by the High Energy Physics Community. One proposal would consist of a ring of magnets 164 km in circumference with a field strength of 3 Tesla and would cost 2.7 billion dollars. The magnet consists of stacked steel laminations with superconducting coils. The desired field uniformity is obtained for all fields from 0.2 to 3 Tesla by using three (or more) different pole shapes. These three different laminations are stacked in the order 1-2-3-1-2-3-... creating a truly three dimensional geometry. A three laminated stack 1-2-3 with periodic boundary conditions at 1 and 3 was assigned about 5000 finite elements per lamination and solved using the computer program TOSCA. To check the TOSCA results, the field of each of the three different shaped laminations was calculated separately using periodic boundary conditions and compared to the two dimensional field calculations using TRIM. This was done for a constant permeability of 2000 and using the B-H table for fully annealed 1010 steel. The difference of the field calculations in the region of interest was always less than +-.2%

File list: NoD.Adl.05.AllAg.Germline_containing_young_adult [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Adl.05.AllAg.Germline_containing_young_adult ce10 No description Adult Germline containing young adult... http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/NoD.Adl.05.AllAg.Germline_containing_young_adult.bed ...

File list: NoD.Adl.10.AllAg.Germline_containing_young_adult [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Adl.10.AllAg.Germline_containing_young_adult ce10 No description Adult Germline containing young adult... http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/NoD.Adl.10.AllAg.Germline_containing_young_adult.bed ...

File list: NoD.Adl.20.AllAg.Germline_containing_young_adult [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Adl.20.AllAg.Germline_containing_young_adult ce10 No description Adult Germline containing young adult... http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/NoD.Adl.20.AllAg.Germline_containing_young_adult.bed ...

File list: NoD.Adl.50.AllAg.Germline_containing_young_adult [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Adl.50.AllAg.Germline_containing_young_adult ce10 No description Adult Germline containing young adult... http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/assembled/NoD.Adl.50.AllAg.Germline_containing_young_adult.bed ...

Negligible elongation of mucin glycans with Gal β1-3 units distinguishes the laminated layer of Echinococcus multilocularis from that of Echinococcus granulosus.

Science.gov (United States)

Del Puerto, Lucía; Rovetta, Romina; Navatta, Marco; Fontana, Carolina; Lin, Gerardo; Moyna, Guillermo; Dematteis, Sylvia; Brehm, Klaus; Koziol, Uriel; Ferreira, Fernando; Díaz, Alvaro

2016-05-01

The larval stages of the cestodes Echinococcus multilocularis and Echinococcus granulosus cause the important zoonoses known as larval echinococcoses. These larvae are protected by a unique, massive, mucin-based structure known as the laminated layer. The mucin glycans of the E. granulosus laminated layer are core 1- or core 2-based O-glycans in which the core Galpβ1-3 residue can initiate a chain comprising one to three additional Galpβ1-3 residues, a motif not known in mammalian carbohydrates. This chain can be capped with a Galpα1-4 residue, and can be ramified with GlcNAcpβ1-6 residues. These, as well as the GlcNAcpβ1-6 residue in core 2, can be decorated with the Galpα1-4Galpβ1-4 disaccharide. Here we extend our analysis to the laminated layer of E. multilocularis, showing that the non-decorated cores, together with Galpβ1-3(Galpα1-4Galpβ1-4GlcNAcpβ1-6)GalNAc, comprise over 96% of the glycans in molar terms. This simple laminated layer glycome is exhibited by E. multilocularis grown either in vitro or in vivo. Interestingly, all the differences with the complex laminated layer glycome found in E. granulosus may be explained in terms of strongly reduced activity in E. multilocularis of a putative glycosyltransferase catalysing the elongation with Galpβ1-3. Comparative inter-species analysis of available genomic and transcriptomic data suggested a candidate for this enzyme, amongst more than 20 putative (non-core 1) Gal/GlcNAc β1-3 transferases present in each species as a result of a taeniid-specific gene expansion. The candidate gene was experimentally verified to be transcribed at much higher levels in the larva of E. granulosus than that of E. multilocularis. Copyright © 2016 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Germline progenitors escape the widespread phenomenon of homolog pairing during Drosophila development.

Directory of Open Access Journals (Sweden)

Eric F Joyce

Full Text Available Homolog pairing, which plays a critical role in meiosis, poses a potential risk if it occurs in inappropriate tissues or between nonallelic sites, as it can lead to changes in gene expression, chromosome entanglements, and loss-of-heterozygosity due to mitotic recombination. This is particularly true in Drosophila, which supports organismal-wide pairing throughout development. Discovered over a century ago, such extensive pairing has led to the perception that germline pairing in the adult gonad is an extension of the pairing established during embryogenesis and, therefore, differs from the mechanism utilized in most species to initiate pairing specifically in the germline. Here, we show that, contrary to long-standing assumptions, Drosophila meiotic pairing in the gonad is not an extension of pairing established during embryogenesis. Instead, we find that homologous chromosomes are unpaired in primordial germ cells from the moment the germline can be distinguished from the soma in the embryo and remain unpaired even in the germline stem cells of the adult gonad. We further establish that pairing originates immediately after the stem cell stage. This pairing occurs well before the initiation of meiosis and, strikingly, continues through the several mitotic divisions preceding meiosis. These discoveries indicate that the spatial organization of the Drosophila genome differs between the germline and the soma from the earliest moments of development and thus argue that homolog pairing in the germline is an active process as versus a passive continuation of pairing established during embryogenesis.

Exploration of the Germline Genome of the Ciliate Chilodonella uncinata through Single-Cell Omics (Transcriptomics and Genomics

Directory of Open Access Journals (Sweden)

Xyrus X. Maurer-Alcalá

2018-01-01

Full Text Available Separate germline and somatic genomes are found in numerous lineages across the eukaryotic tree of life, often separated into distinct tissues (e.g., in plants, animals, and fungi or distinct nuclei sharing a common cytoplasm (e.g., in ciliates and some foraminifera. In ciliates, germline-limited (i.e., micronuclear-specific DNA is eliminated during the development of a new somatic (i.e., macronuclear genome in a process that is tightly linked to large-scale genome rearrangements, such as deletions and reordering of protein-coding sequences. Most studies of germline genome architecture in ciliates have focused on the model ciliates Oxytricha trifallax, Paramecium tetraurelia, and Tetrahymena thermophila, for which the complete germline genome sequences are known. Outside of these model taxa, only a few dozen germline loci have been characterized from a limited number of cultivable species, which is likely due to difficulties in obtaining sufficient quantities of “purified” germline DNA in these taxa. Combining single-cell transcriptomics and genomics, we have overcome these limitations and provide the first insights into the structure of the germline genome of the ciliate Chilodonella uncinata, a member of the understudied class Phyllopharyngea. Our analyses reveal the following: (i large gene families contain a disproportionate number of genes from scrambled germline loci; (ii germline-soma boundaries in the germline genome are demarcated by substantial shifts in GC content; (iii single-cell omics techniques provide large-scale quality germline genome data with limited effort, at least for ciliates with extensively fragmented somatic genomes. Our approach provides an efficient means to understand better the evolution of genome rearrangements between germline and soma in ciliates.

Histologic and inflammatory lamellar changes in horses with oligofructose-induced laminitis treated with a CXCR1/2 antagonist

OpenAIRE

Lima, Leonardo R. de; Mendes, Heloisa M.F.; Soriani, Frederico M.; Souza, Danielle G. de; Alves, Geraldo Eleno S.; Teixeira, Mauro M.; Faleiros, Rafael R.

2016-01-01

Abstract: With the hypothesis that blocking chemokine signaling can ameliorate acute laminitis, the aim was to evaluate the therapeutic effect of intravenous DF1681B, a selective antagonist for CXCR1 and CXCR2 (chemokine receptors), in an oligofructose equine laminitis model. To twelve mixed breed clinically healthy hoses with no previous history of hoof-related lameness was administered oligofructose (10g/kg given by nasogastric tube) and divided into two groups: treated (intravenous DF1681B...

Study on the dielectric properties of Al2O3/TiO2 sub-nanometric laminates: effect of the bottom electrode and the total thickness

Science.gov (United States)

Ben Elbahri, M.; Kahouli, A.; Mercey, B.; Lebedev, O.; Donner, W.; Lüders, U.

2018-02-01

Dielectrics based on amorphous sub-nanometric laminates of TiO2 and Al2O3 are subject to elevated dielectric losses and leakage currents, in large parts due to the extremely thin individual layer thickness chosen for the creation of the Maxwell-Wagner relaxation and therefore the high apparent dielectric constants. The optimization of performances of the laminate itself being strongly limited by this contradiction concerning its internal structure, we will show in this study that modifications of the dielectric stack of capacitors based on these sub-nanometric laminates can positively influence the dielectric losses and the leakage, as for example the nature of the electrodes, the introduction of thick insulating layers at the laminate/electrode interfaces and the modification of the total laminate thickness. The optimization of the dielectric stack leads to the demonstration of a capacitor with an apparent dielectric constant of 90, combined with low dielectric loss (tan δ) of 7 · 10-2 and with leakage currents smaller than 1  ×  10-6 A cm-2 at 10 MV m-1.

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...

The influences of contamination during lamination on the properties of composite materials

Energy Technology Data Exchange (ETDEWEB)

Hall Beng, G.M. (Univ. of Portsmouth, School of Systems Engineering, Portsmouth (United Kingdom)); Mason, S.E. (Univ. of Portsmouth, School of Systems Engineering, Portsmouth (United Kingdom))

1993-11-01

The quality of a fibrous composite laminate can be largely attributed to the laminating process. It is therefore important to control parameters which will ultimately affect the desired quality of the laminate. Although several composite manufacturing organisations have installed clean room facilities with the hope of controlling potential contaminants, which may be detrimental to the process, the unavoidable reductions in productivity, coupled with the initial capital and maintenance costs make it an expensive solution to an unquantified problem. This study investigates the influences of contamination on structural fibre reinforced composites. Initial testing has involved contaminating Carbon/Epoxy (Fiberite 7714B) prepregs on a gross level. Contaminants have been selected on a tactile level in order to be as closely representative of situations likely to be encountered in the laminating process. The research has concentrated on airborne particulates, including fibres, condensation and humidity. Modes of contamination have been proposed for each, and suitable test methods selected to verify the modes. Test methods include the sort beam shear test (interlaminar shear strength), double cantilever beam test (interlaminar fracture data) and tensile tests. Such high levels of contamination enables the identification of those contaminants that are most detrimental to final laminate quality. Strategic reduction in the contamination levels of those identified will enable the clean room operating level to be sought. (orig.).

The influences of contamination during lamination on the properties of composite materials

International Nuclear Information System (INIS)

Hall Beng, G.M.; Mason, S.E.

1993-01-01

The quality of a fibrous composite laminate can be largely attributed to the laminating process. It is therefore important to control parameters which will ultimately affect the desired quality of the laminate. Although several composite manufacturing organisations have installed clean room facilities with the hope of controlling potential contaminants, which may be detrimental to the process, the unavoidable reductions in productivity, coupled with the initial capital and maintenance costs make it an expensive solution to an unquantified problem. This study investigates the influences of contamination on structural fibre reinforced composites. Initial testing has involved contaminating Carbon/Epoxy (Fiberite 7714B) prepregs on a gross level. Contaminants have been selected on a tactile level in order to be as closely representative of situations likely to be encountered in the laminating process. The research has concentrated on airborne particulates, including fibres, condensation and humidity. Modes of contamination have been proposed for each, and suitable test methods selected to verify the modes. Test methods include the sort beam shear test (interlaminar shear strength), double cantilever beam test (interlaminar fracture data) and tensile tests. Such high levels of contamination enables the identification of those contaminants that are most detrimental to final laminate quality. Strategic reduction in the contamination levels of those identified will enable the clean room operating level to be sought. (orig.)

3D Printing, Ink Casting and Micromachined Lamination (3D PICLμM): A Makerspace Approach to the Fabrication of Biological Microdevices

OpenAIRE

Avra Kundu; Tariq Ausaf; Swaminathan Rajaraman

2018-01-01

We present a novel benchtop-based microfabrication technology: 3D printing, ink casting, micromachined lamination (3D PICLμM) for rapid prototyping of lab-on-a-chip (LOC) and biological devices. The technology uses cost-effective, makerspace-type microfabrication processes, all of which are ideally suited for low resource settings, and utilizing a combination of these processes, we have demonstrated the following devices: (i) 2D microelectrode array (MEA) targeted at in vitro neural and cardi...

Exome sequencing reveals frequent deleterious germline variants in cancer susceptibility genes in women with invasive breast cancer undergoing neoadjuvant chemotherapy.

Science.gov (United States)

Ellingson, Marissa S; Hart, Steven N; Kalari, Krishna R; Suman, Vera; Schahl, Kimberly A; Dockter, Travis J; Felten, Sara J; Sinnwell, Jason P; Thompson, Kevin J; Tang, Xiaojia; Vedell, Peter T; Barman, Poulami; Sicotte, Hugues; Eckel-Passow, Jeanette E; Northfelt, Donald W; Gray, Richard J; McLaughlin, Sarah A; Moreno-Aspitia, Alvaro; Ingle, James N; Moyer, Ann M; Visscher, Daniel W; Jones, Katie; Conners, Amy; McDonough, Michelle; Wieben, Eric D; Wang, Liewei; Weinshilboum, Richard; Boughey, Judy C; Goetz, Matthew P

2015-09-01

When sequencing blood and tumor samples to identify targetable somatic variants for cancer therapy, clinically relevant germline variants may be uncovered. We evaluated the prevalence of deleterious germline variants in cancer susceptibility genes in women with breast cancer referred for neoadjuvant chemotherapy and returned clinically actionable results to patients. Exome sequencing was performed on blood samples from women with invasive breast cancer referred for neoadjuvant chemotherapy. Germline variants within 142 hereditary cancer susceptibility genes were filtered and reviewed for pathogenicity. Return of results was offered to patients with deleterious variants in actionable genes if they were not aware of their result through clinical testing. 124 patients were enrolled (median age 51) with the following subtypes: triple negative (n = 43, 34.7%), HER2+ (n = 37, 29.8%), luminal B (n = 31, 25%), and luminal A (n = 13, 10.5%). Twenty-eight deleterious variants were identified in 26/124 (21.0%) patients in the following genes: ATM (n = 3), BLM (n = 1), BRCA1 (n = 4), BRCA2 (n = 8), CHEK2 (n = 2), FANCA (n = 1), FANCI (n = 1), FANCL (n = 1), FANCM (n = 1), FH (n = 1), MLH3 (n = 1), MUTYH (n = 2), PALB2 (n = 1), and WRN (n = 1). 121/124 (97.6%) patients consented to return of research results. Thirteen (10.5%) had actionable variants, including four that were returned to patients and led to changes in medical management. Deleterious variants in cancer susceptibility genes are highly prevalent in patients with invasive breast cancer referred for neoadjuvant chemotherapy undergoing exome sequencing. Detection of these variants impacts medical management.

Un-laminated Gafchromic EBT3 film for ultraviolet radiation monitoring

International Nuclear Information System (INIS)

Welch, David; Randers-Pehrson, Gerhard; Brenner, David J.; Spotnitz, Henry M.

2017-01-01

Measurement of ultraviolet (UV) radiation is important for human health, especially with the expanded usage of short wavelength UV for sterilization purposes. This work examines un-laminated Gafchromic EBT3 film for UV radiation monitoring. The authors exposed the film to select wavelengths in the UV spectrum, ranging from 207 to 328 nm, and measured the change in optical density. The response of the film is wavelength dependent, and of the wavelengths tested, the film was most sensitive to 254 nm light, with measurable values as low as 10 μJ/cm 2 . The film shows a dose-dependent response that extends over more than four orders of magnitude. The response of the film to short wavelength UV is comparable to the daily safe exposure limits for humans, thus making it valuable as a tool for passive UV radiation monitoring. (authors)

Connections: Superplasticity, Damascus Steels, Laminated Steels, and Carbon Dating

Science.gov (United States)

Wadsworth, Jeffrey

2016-12-01

In this paper, a description is given of the connections that evolved from the initial development of a family of superplastic plain carbon steels that came to be known as Ultra-High Carbon Steels (UHCS). It was observed that their very high carbon contents were similar, if not identical, to those of Damascus steels. There followed a series of attempts to rediscover how the famous patterns found on Damascus steels blades were formed. At the same time, in order to improve the toughness at room temperature of the newly-developed UHCS, laminated composites were made of alternating layers of UHCS and mild steel (and subsequently other steels and other metals). This led to a study of ancient laminated composites, the motives for their manufacture, and the plausibility of some of the claims relating to the number of layers in the final blades. One apparently ancient laminated composite, recovered in 1837 from the great pyramid of Giza which was constructed in about 2750 B.C., stimulated a carbon dating study of ancient steels. The modern interest in "Bladesmithing" has connections back to many of these ancient weapons.

Solid renal tumor severity in von Hippel Lindau disease is related to germline deletion length and location.

Science.gov (United States)

Maranchie, Jodi K; Afonso, Anoushka; Albert, Paul S; Kalyandrug, Sivaram; Phillips, John L; Zhou, Shubo; Peterson, James; Ghadimi, Bijan M; Hurley, Katheen; Riss, Joseph; Vasselli, James R; Ried, Thomas; Zbar, Berton; Choyke, Peter; Walther, McClellan M; Klausner, Richard D; Linehan, W Marston

2004-01-01

von Hippel Lindau disease (VHL) is an autosomal dominant familial cancer syndrome linked to alteration of the VHL tumor suppressor gene. Affected patients are predisposed to develop pheochromocytomas and cystic and solid tumors of the kidney, CNS, pancreas, retina, and epididymis. However, organ involvement varies considerably among families and has been shown to correlate with the underlying germline alteration. Clinically, we observed a paradoxically lower prevalence of renal cell carcinoma (RCC) in patients with complete germline deletion of VHL. To determine if a relationship existed between the type of VHL deletion and disease, we retrospectively evaluated 123 patients from 55 families with large germline VHL deletions, including 42 intragenic partial deletions and 13 complete VHL deletions, by history and radiographic imaging. Each individual and family was scored for cystic or solid involvement of CNS, pancreas, and kidney, and for pheochromocytoma. Germline deletions were mapped using a combination of fluorescent in situ hybridization (FISH) and quantitative Southern and Southern blot analysis. An age-adjusted comparison demonstrated a higher prevalence of RCC in patients with partial germline VHL deletions relative to complete deletions (48.9 vs. 22.6%, p=0.007). This striking phenotypic dichotomy was not seen for cystic renal lesions or for CNS (p=0.22), pancreas (p=0.72), or pheochromocytoma (p=0.34). Deletion mapping revealed that development of RCC had an even greater correlation with retention of HSPC300 (C3orf10), located within the 30-kb region of chromosome 3p, immediately telomeric to VHL (52.3 vs. 18.9%, p <0.001), suggesting the presence of a neighboring gene or genes critical to the development and maintenance of RCC. Careful correlation of genotypic data with objective phenotypic measures will provide further insight into the mechanisms of tumor formation. Copyright 2003 Wiley-Liss, Inc.

Detection of induced male germline mutation: Correlations and comparisons between traditional germline mutation assays, transgenic rodent assays and expanded simple tandem repeat instability assays

Energy Technology Data Exchange (ETDEWEB)

Singer, Timothy M. [Mutagenesis Section, Environmental and Occupational Toxicology Division, Safe Environments Programme, 0803A, Health Canada, Ottawa, Ont., K1A 0K9 (Canada); Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, Ont., K1S 5B6 (Canada); Lambert, Iain B. [Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, Ont., K1S 5B6 (Canada); Williams, Andrew [Biostatistics and Epidemiology Division, Safe Environments Programme, 6604B, Health Canada, Ottawa, Ont., K1A 0K9 (Canada); Douglas, George R. [Mutagenesis Section, Environmental and Occupational Toxicology Division, Safe Environments Programme, 0803A, Health Canada, Ottawa, Ont., K1A 0K9 (Canada); Yauk, Carole L. [Mutagenesis Section, Environmental and Occupational Toxicology Division, Safe Environments Programme, 0803A, Health Canada, Ottawa, Ont., K1A 0K9 (Canada)]. E-mail: carole_yauk@hc-sc.gc.ca

2006-06-25

Several rodent assays are capable of monitoring germline mutation. These include traditional assays, such as the dominant lethal (DL) assay, the morphological specific locus (SL) test and the heritable translocation (HT) assay, and two assays that have been developed more recently-the expanded simple tandem repeat (ESTR) and transgenic rodent (TGR) mutation assays. In this paper, we have compiled the limited amount of experimental data that are currently available to make conclusions regarding the comparative ability of the more recently developed assays to detect germline mutations induced by chemical and radiological agents. The data suggest that ESTR and TGR assays are generally comparable with SL in detecting germline mutagenicity induced by alkylating agents and radiation, though TGR offered less sensitivity than ESTR in some cases. The DL and HT assays detect clastogenic events and are most susceptible to mutations arising in post-spermatogonial cells, and they may not provide the best comparisons with TGR and ESTR instability. The measurement of induced ESTR instability represents a relatively sensitive method of identifying agents causing germline mutation in rodents, and may also be useful for bio-monitoring exposed individuals in the human population. Any future use of the TGR and ESTR germline mutation assays in a regulatory testing context will entail more robust and extensive characterization of assay performance. This will require substantially more data, including experiments measuring multiple endpoints, a greatly expanded database of chemical agents and a focus on characterizing stage-specific activity of mutagens in these assays, preferably by sampling epididymal sperm exposed at defined pre-meiotic, meiotic and post-meiotic stages of development.

Detection of induced male germline mutation: Correlations and comparisons between traditional germline mutation assays, transgenic rodent assays and expanded simple tandem repeat instability assays

International Nuclear Information System (INIS)

Singer, Timothy M.; Lambert, Iain B.; Williams, Andrew; Douglas, George R.; Yauk, Carole L.

2006-01-01

Several rodent assays are capable of monitoring germline mutation. These include traditional assays, such as the dominant lethal (DL) assay, the morphological specific locus (SL) test and the heritable translocation (HT) assay, and two assays that have been developed more recently-the expanded simple tandem repeat (ESTR) and transgenic rodent (TGR) mutation assays. In this paper, we have compiled the limited amount of experimental data that are currently available to make conclusions regarding the comparative ability of the more recently developed assays to detect germline mutations induced by chemical and radiological agents. The data suggest that ESTR and TGR assays are generally comparable with SL in detecting germline mutagenicity induced by alkylating agents and radiation, though TGR offered less sensitivity than ESTR in some cases. The DL and HT assays detect clastogenic events and are most susceptible to mutations arising in post-spermatogonial cells, and they may not provide the best comparisons with TGR and ESTR instability. The measurement of induced ESTR instability represents a relatively sensitive method of identifying agents causing germline mutation in rodents, and may also be useful for bio-monitoring exposed individuals in the human population. Any future use of the TGR and ESTR germline mutation assays in a regulatory testing context will entail more robust and extensive characterization of assay performance. This will require substantially more data, including experiments measuring multiple endpoints, a greatly expanded database of chemical agents and a focus on characterizing stage-specific activity of mutagens in these assays, preferably by sampling epididymal sperm exposed at defined pre-meiotic, meiotic and post-meiotic stages of development

Natural fabric sandwich laminate composites: development and ...

Indian Academy of Sciences (India)

3Department of Production Technology, MIT Campus, Anna University, Chennai 600044, India. MS received ... In this work, eco-friendly natural fabric sandwich laminate (NFSL) composites are formulated using ... and eco-friendly quality [22].

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.

Human Germline Genome Editing

OpenAIRE

Ormond, Kelly E.; Mortlock, Douglas P.; Scholes, Derek T.; Bombard, Yvonne; Brody, Lawrence C.; Faucett, W. Andrew; Garrison, Nanibaa’ A.; Hercher, Laura; Isasi, Rosario; Middleton, Anna; Musunuru, Kiran; Shriner, Daniel; Virani, Alice; Young, Caroline E.

2017-01-01

With CRISPR/Cas9 and other genome-editing technologies, successful somatic and germline genome editing are becoming feasible. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in March 2017. The workgroup included representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Gen...

C. elegans germline-deficient mutants respond to pathogen infection using shared and distinct mechanisms.

Directory of Open Access Journals (Sweden)

Michael TeKippe

2010-07-01

Full Text Available Reproduction extracts a cost in resources that organisms are then unable to utilize to deal with a multitude of environmental stressors. In the nematode C. elegans, development of the germline shortens the lifespan of the animal and increases its susceptibility to microbial pathogens. Prior studies have demonstrated germline-deficient nematodes to have increased resistance to gram negative bacteria. We show that germline-deficient strains display increased resistance across a broad range of pathogens including gram positive and gram negative bacteria, and the fungal pathogen Cryptococcus neoformans. Furthermore, we show that the FOXO transcription factor DAF-16, which regulates longevity and immunity in C. elegans, appears to be crucial for maintaining longevity in both wild-type and germline-deficient backgrounds. Our studies indicate that germline-deficient mutants glp-1 and glp-4 respond to pathogen infection using common and different mechanisms that involve the activation of DAF-16.

Effect of ATM heterozygosity on heritable DNA damage in mice following paternal F0 germline irradiation

International Nuclear Information System (INIS)

Baulch, Janet E.; Li, M.-W.; Raabe, Otto G.

2007-01-01

The ataxia telangiectasia mutated (ATM) gene product maintains genome integrity and initiates cellular DNA repair pathways following exposures to genotoxic agents. ATM also plays a significant role in meiotic recombination during spermatogenesis. Fertilization with sperm carrying damaged DNA could lead to adverse effects in offspring including developmental defects or increased cancer susceptibility. Currently, there is little information regarding the effect of ATM heterozygosity on germline DNA repair and heritable effects of paternal germline-ionizing irradiation. We used neutral pH comet assays to evaluate spermatozoa 45 days after acute whole-body irradiation of male mice (0.1 Gy, attenuated 137 Cs γ rays) to determine the effect of ATM heterozygosity on delayed DNA damage effects of Type A/B spermatogonial irradiation. Using the neutral pH sperm comet assay, significant irradiation-related differences were found in comet tail length, percent tail DNA and tail extent moment, but there were no observed differences in effect between wild-type and ATM +/- mice. However, evaluation of spermatozoa from third generation descendants of irradiated male mice for heritable chromatin effects revealed significant differences in DNA electrophoretic mobility in the F 3 descendants that were based upon the irradiated F 0 sire's genotype. In this study, radiation-induced chromatin alterations to Type A/B spermatogonia, detected in mature sperm 45 days post-irradiation, led to chromatin effects in mature sperm three generations later. The early cellular response to and repair of DNA damage is critical and appears to be affected by ATM zygosity. Our results indicate that there is potential for heritable genetic or epigenetic changes following Type A/B spermatogonial irradiation and that ATM heterozygosity increases this effect

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Lifescience Database Archive (English)

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Wnt6 maintains anterior escort cells as an integral component of the germline stem cell niche.

Science.gov (United States)

Wang, Xiaoxi; Page-McCaw, Andrea

2018-02-07

Stem cells reside in a niche, a local environment whose cellular and molecular complexity is still being elucidated. In Drosophila ovaries, germline stem cells depend on cap cells for self-renewing signals and physical attachment. Germline stem cells also contact the anterior escort cells, and here we report that anterior escort cells are absolutely required for germline stem cell maintenance. When escort cells die from impaired Wnt signaling or hid expression, the loss of anterior escort cells causes loss of germline stem cells. Anterior escort cells function as an integral niche component by promoting DE-cadherin anchorage and by transiently expressing the Dpp ligand to promote full-strength BMP signaling in germline stem cells. Anterior escort cells are maintained by Wnt6 ligands produced by cap cells; without Wnt6 signaling, anterior escort cells die leaving vacancies in the niche, leading to loss of germline stem cells. Our data identify anterior escort cells as constituents of the germline stem cell niche, maintained by a cap cell-produced Wnt6 survival signal. © 2018. Published by The Company of Biologists Ltd.

Use of Germline Polymorphisms in Predicting Concurrent Chemoradiotherapy Response in Esophageal Cancer

International Nuclear Information System (INIS)

Chen, Pei-Chun; Chen, Yen-Ching; Lai, Liang-Chuan; Tsai, Mong-Hsun; Chen, Shin-Kuang; Yang, Pei-Wen; Lee, Yung-Chie; Hsiao, Chuhsing K.; Lee, Jang-Ming; Chuang, Eric Y.

2012-01-01

Purpose: To identify germline polymorphisms to predict concurrent chemoradiation therapy (CCRT) response in esophageal cancer patients. Materials and Methods: A total of 139 esophageal cancer patients treated with CCRT (cisplatin-based chemotherapy combined with 40 Gy of irradiation) and subsequent esophagectomy were recruited at the National Taiwan University Hospital between 1997 and 2008. After excluding confounding factors (i.e., females and patients aged ≥70 years), 116 patients were enrolled to identify single nucleotide polymorphisms (SNPs) associated with specific CCRT responses. Genotyping arrays and mass spectrometry were used sequentially to determine germline polymorphisms from blood samples. These polymorphisms remain stable throughout disease progression, unlike somatic mutations from tumor tissues. Two-stage design and additive genetic models were adopted in this study. Results: From the 26 SNPs identified in the first stage, 2 SNPs were found to be significantly associated with CCRT response in the second stage. Single nucleotide polymorphism rs16863886, located between SGPP2 and FARSB on chromosome 2q36.1, was significantly associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.62–10.30) under additive models. Single nucleotide polymorphism rs4954256, located in ZRANB3 on chromosome 2q21.3, was associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.57–10.87). The predictive accuracy for CCRT response was 71.59% with these two SNPs combined. Conclusions: This is the first study to identify germline polymorphisms with a high accuracy for predicting CCRT response in the treatment of esophageal cancer.

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....

C. elegans DAF-16/FOXO interacts with TGF-ß/BMP signaling to induce germline tumor formation via mTORC1 activation.

Directory of Open Access Journals (Sweden)

Wenjing Qi

2017-05-01

Full Text Available Activation of the FOXO transcription factor DAF-16 by reduced insulin/IGF signaling (IIS is considered to be beneficial in C. elegans due to its ability to extend lifespan and to enhance stress resistance. In the germline, cell-autonomous DAF-16 activity prevents stem cell proliferation, thus acting tumor-suppressive. In contrast, hypodermal DAF-16 causes a tumorous germline phenotype characterized by hyperproliferation of the germline stem cells and rupture of the adjacent basement membrane. Here we show that cross-talk between DAF-16 and the transforming growth factor ß (TGFß/bone morphogenic protein (BMP signaling pathway causes germline hyperplasia and results in disruption of the basement membrane. In addition to activating MADM/NRBP/hpo-11 gene alone, DAF-16 also directly interacts with both R-SMAD proteins SMA-2 and SMA-3 in the nucleus to regulate the expression of mTORC1 pathway. Knocking-down of BMP genes or each of the four target genes in the hypodermis was sufficient to inhibit germline proliferation, indicating a cell-non-autonomously controlled regulation of stem cell proliferation by somatic tissues. We propose the existence of two antagonistic DAF-16/FOXO functions, a cell-proliferative somatic and an anti-proliferative germline activity. Whereas germline hyperplasia under reduced IIS is inhibited by DAF-16 cell-autonomously, activation of somatic DAF-16 in the presence of active IIS promotes germline proliferation and eventually induces tumor-like germline growth. In summary, our results suggest a novel pathway crosstalk of DAF-16 and TGF-ß/BMP that can modulate mTORC1 at the transcriptional level to cause stem-cell hyperproliferation. Such cell-type specific differences may help explaining why human FOXO activity is considered to be tumor-suppressive in most contexts, but may become oncogenic, e.g. in chronic and acute myeloid leukemia.

C. elegans DAF-16/FOXO interacts with TGF-ß/BMP signaling to induce germline tumor formation via mTORC1 activation.

Science.gov (United States)

Qi, Wenjing; Yan, Yijian; Pfeifer, Dietmar; Donner V Gromoff, Erika; Wang, Yimin; Maier, Wolfgang; Baumeister, Ralf

2017-05-01

Activation of the FOXO transcription factor DAF-16 by reduced insulin/IGF signaling (IIS) is considered to be beneficial in C. elegans due to its ability to extend lifespan and to enhance stress resistance. In the germline, cell-autonomous DAF-16 activity prevents stem cell proliferation, thus acting tumor-suppressive. In contrast, hypodermal DAF-16 causes a tumorous germline phenotype characterized by hyperproliferation of the germline stem cells and rupture of the adjacent basement membrane. Here we show that cross-talk between DAF-16 and the transforming growth factor ß (TGFß)/bone morphogenic protein (BMP) signaling pathway causes germline hyperplasia and results in disruption of the basement membrane. In addition to activating MADM/NRBP/hpo-11 gene alone, DAF-16 also directly interacts with both R-SMAD proteins SMA-2 and SMA-3 in the nucleus to regulate the expression of mTORC1 pathway. Knocking-down of BMP genes or each of the four target genes in the hypodermis was sufficient to inhibit germline proliferation, indicating a cell-non-autonomously controlled regulation of stem cell proliferation by somatic tissues. We propose the existence of two antagonistic DAF-16/FOXO functions, a cell-proliferative somatic and an anti-proliferative germline activity. Whereas germline hyperplasia under reduced IIS is inhibited by DAF-16 cell-autonomously, activation of somatic DAF-16 in the presence of active IIS promotes germline proliferation and eventually induces tumor-like germline growth. In summary, our results suggest a novel pathway crosstalk of DAF-16 and TGF-ß/BMP that can modulate mTORC1 at the transcriptional level to cause stem-cell hyperproliferation. Such cell-type specific differences may help explaining why human FOXO activity is considered to be tumor-suppressive in most contexts, but may become oncogenic, e.g. in chronic and acute myeloid leukemia.

Cell lineage analysis of the mammalian female germline.

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Yitzhak Reizel

Full Text Available Fundamental aspects of embryonic and post-natal development, including maintenance of the mammalian female germline, are largely unknown. Here we employ a retrospective, phylogenetic-based method for reconstructing cell lineage trees utilizing somatic mutations accumulated in microsatellites, to study female germline dynamics in mice. Reconstructed cell lineage trees can be used to estimate lineage relationships between different cell types, as well as cell depth (number of cell divisions since the zygote. We show that, in the reconstructed mouse cell lineage trees, oocytes form clusters that are separate from hematopoietic and mesenchymal stem cells, both in young and old mice, indicating that these populations belong to distinct lineages. Furthermore, while cumulus cells sampled from different ovarian follicles are distinctly clustered on the reconstructed trees, oocytes from the left and right ovaries are not, suggesting a mixing of their progenitor pools. We also observed an increase in oocyte depth with mouse age, which can be explained either by depth-guided selection of oocytes for ovulation or by post-natal renewal. Overall, our study sheds light on substantial novel aspects of female germline preservation and development.

Analysis of the low-frequency magnetoelectric performance in three-phase laminate composites with Fe-based nanocrystalline ribbon

International Nuclear Information System (INIS)

Chen, Lei; Li, Ping; Wen, Yumei; Zhu, Yong

2013-01-01

The theoretical analysis of magnetoelectric (ME) performance in three-phase Terfenol-D/PZT/FeCuNbSiB (MPF) laminate composite is presented in this paper. The ME couplings at low frequency for ideal and less than ideal interface couplings are studied, respectively, and our analysis predicts that (i) the ME voltage coefficient for ideal interface coupling increases with the increasing layers (n) of Fe-based nanocrystalline ribbon FeCuNbSiB (Fe 73.5 Cu 1 Nb 3 Si 13.5 B 9 ) while the sizes of PZT (Pb(Zr 1−x Ti x )O 3 ) and Terfenol-D (Tb 1−x Dy x Fe 2−y ) are kept constant, and then it tends to be a constant when the layers of FeCuNbSiB are >100; (ii) by introducing the interface coupling factor k and considering the degradation of d 33m,f with n, the ME voltage coefficient for a less than ideal interface condition is predicted. As the FeCuNbSiB layer increases, it first increases and reaches to a maximum value, and then slowly decreases. Various MPF laminates are fabricated and tested. It is found that the theoretical predictions for the consideration of actual boundary conditions at the interface are in agreement with the experimental observations. This study plays a guiding role for the design of MPF composite in real applications. (paper)

Evaluation of Behaviours of Laminated Glass

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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.

Behaviour of Mechanically Laminated CLT Members

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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.

The Landscape of Somatic Genetic Alterations in Breast Cancers From ATM Germline Mutation Carriers.

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Weigelt, Britta; Bi, Rui; Kumar, Rahul; Blecua, Pedro; Mandelker, Diana L; Geyer, Felipe C; Pareja, Fresia; James, Paul A; Couch, Fergus J; Eccles, Diana M; Blows, Fiona; Pharoah, Paul; Li, Anqi; Selenica, Pier; Lim, Raymond S; Jayakumaran, Gowtham; Waddell, Nic; Shen, Ronglai; Norton, Larry; Wen, Hannah Y; Powell, Simon N; Riaz, Nadeem; Robson, Mark E; Reis-Filho, Jorge S; Chenevix-Trench, Georgia

2018-02-28

Pathogenic germline variants in ataxia-telangiectasia mutated (ATM), a gene that plays a role in DNA damage response and cell cycle checkpoints, confer an increased breast cancer (BC) risk. Here, we investigated the phenotypic characteristics and landscape of somatic genetic alterations in 24 BCs from ATM germline mutation carriers by whole-exome and targeted sequencing. ATM-associated BCs were consistently hormone receptor positive and largely displayed minimal immune infiltrate. Although 79.2% of these tumors exhibited loss of heterozygosity of the ATM wild-type allele, none displayed high activity of mutational signature 3 associated with defective homologous recombination DNA (HRD) repair. No TP53 mutations were found in the ATM-associated BCs. Analysis of an independent data set confirmed that germline ATM variants and TP53 somatic mutations are mutually exclusive. Our findings indicate that ATM-associated BCs often harbor bi-allelic inactivation of ATM, are phenotypically distinct from BRCA1/2-associated BCs, lack HRD-related mutational signatures, and that TP53 and ATM genetic alterations are likely epistatic.

Al2O3 Passivation Effect in HfO2·Al2O3 Laminate Structures Grown on InP Substrates.

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Kang, Hang-Kyu; Kang, Yu-Seon; Kim, Dae-Kyoung; Baik, Min; Song, Jin-Dong; An, Youngseo; Kim, Hyoungsub; Cho, Mann-Ho

2017-05-24

The passivation effect of an Al 2 O 3 layer on the electrical properties was investigated in HfO 2 -Al 2 O 3 laminate structures grown on indium phosphide (InP) substrate by atomic-layer deposition. The chemical state obtained using high-resolution X-ray photoelectron spectroscopy showed that interfacial reactions were dependent on the presence of the Al 2 O 3 passivation layer and its sequence in the HfO 2 -Al 2 O 3 laminate structures. Because of the interfacial reaction, the Al 2 O 3 /HfO 2 /Al 2 O 3 structure showed the best electrical characteristics. The top Al 2 O 3 layer suppressed the interdiffusion of oxidizing species into the HfO 2 films, whereas the bottom Al 2 O 3 layer blocked the outdiffusion of In and P atoms. As a result, the formation of In-O bonds was more effectively suppressed in the Al 2 O 3 /HfO 2 /Al 2 O 3 /InP structure than that in the HfO 2 -on-InP system. Moreover, conductance data revealed that the Al 2 O 3 layer on InP reduces the midgap traps to 2.6 × 10 12 eV -1 cm -2 (compared to that of HfO 2 /InP, that is, 5.4 × 10 12 eV -1 cm -2 ). The suppression of gap states caused by the outdiffusion of In atoms significantly controls the degradation of capacitors caused by leakage current through the stacked oxide layers.

High sensitivity zero-biased magnetic field sensor based on multiphase laminate heterostructures with FeCuNbSiB nanocrystalline soft magnetic alloy

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Qiu, Jing; Wen, Yumei; Li, Ping; Chen, Hengjia

2016-05-01

In this paper, a high sensitivity zero-biased magnetic field sensor based on multiphase laminate heterostructures consisting of FeCuNbSiB/Terfenol-D (Tb1-xDyxFe2)/PZT (Pb(Zr1-x,Tix)O3)/Terfenol-D/PZT/Ternol-D/FeCuNbSiB (FMPMPMF) is presented, whose ME coupling characteristics and sensing performances have been investigated. Compared to traditional Terfenol-D/PZT/Terfenol-D (MPM) and Terfenol-D/PZT/Terfenol-D/PZT/Terfenol-D (MPMPM) sensors, the zero-biased ME coupling characteristics of FMPMPMF sensor were significantly improved, owing to a build-in magnetic field in FeCuNbSiB/Terfenol-D layers. The optimum zero-biased resonant ME voltage coefficient of 3.02 V/Oe is achieved, which is 1.65 times as great as that of MPMPM and 2.51 times of MPM sensors. The mean value of low-frequency ME field coefficient of FMPMPMF reaches 122.53 mV/cm Oe, which is 2.39 times as great as that of MPMPM and 1.79 times of MPM sensors. Meanwhile, the induced zero-biased ME voltage of FMPMPMF sensor shows an excellent linear relationship to ac magnetic field both at the low frequency (1 kHz) and the resonant frequency (106.6 kHz). Remarkably, it indicates that the proposed zero-biased magnetic field sensor give the prospect of being able to applied to the field of highly sensitive ac magnetic field sensing.

Self-heating forecasting for thick laminate specimens in fatigue

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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.

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

Male germline stem cells in non-human primates

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S. Sharma

2017-09-01

Full Text Available Over the past few decades, several studies have attempted to decipher the biology of mammalian germline stem cells (GSCs. These studies provide evidence that regulatory mechanisms for germ cell specification and migration are evolutionarily conserved across species. The characteristics and functions of primate GSCs are highly distinct from rodent species; therefore the findings from rodent models cannot be extrapolated to primates. Due to limited availability of human embryonic and testicular samples for research purposes, two non-human primate models (marmoset and macaque monkeys are extensively employed to understand human germline development and differentiation. This review provides a broader introduction to the in vivo and in vitro germline stem cell terminology from primordial to differentiating germ cells. Primordial germ cells (PGCs are the most immature germ cells colonizing the gonad prior to sex differentiation into testes or ovaries. PGC specification and migratory patterns among different primate species are compared in the review. It also reports the distinctions and similarities in expression patterns of pluripotency markers (OCT4A, NANOG, SALL4 and LIN28 during embryonic developmental stages, among marmosets, macaques and humans. This review presents a comparative summary with immunohistochemical and molecular evidence of germ cell marker expression patterns during postnatal developmental stages, among humans and non-human primates. Furthermore, it reports findings from the recent literature investigating the plasticity behavior of germ cells and stem cells in other organs of humans and monkeys. The use of non-human primate models would enable bridging the knowledge gap in primate GSC research and understanding the mechanisms involved in germline development. Reported similarities in regulatory mechanisms and germ cell expression profile in primates demonstrate the preclinical significance of monkey models for development of

Effect of BRCA germline mutations on breast cancer prognosis

Science.gov (United States)

Baretta, Zora; Mocellin, Simone; Goldin, Elena; Olopade, Olufunmilayo I.; Huo, Dezheng

2016-01-01

Abstract Background: The contribution of BRCA germline mutational status to breast cancer patients’ prognosis is unclear. We aimed to systematically review and perform meta-analysis of the available evidence of effects of BRCA germline mutations on multiple survival outcomes of breast cancer patients as a whole and in specific subgroups of interest, including those with triple negative breast cancer, those with Ashkenazi Jewish ancestry, and patients with stage I–III disease. Methods: Sixty studies met all inclusion criteria and were considered for this meta-analysis. These studies involved 105,220 breast cancer patients, whose 3588 (3.4%) were BRCA mutations carriers. The associations between BRCA genes mutational status and overall survival (OS), breast cancer-specific survival (BCSS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS) were evaluated using random-effect models. Results: BRCA1 mutation carriers have worse OS than BRCA-negative/sporadic cases (hazard ratio, HR 1.30, 95% CI: 1.11–1.52) and worse BCSS than sporadic/BRCA-negative cases among patients with stage I–III breast cancer (HR 1.45, 95% CI: 1.01–2.07). BRCA2 mutation carriers have worse BCSS than sporadic/BRCA-negative cases (HR 1.29, 95% CI: 1.03–1.62), although they have similar OS. Among triple negative breast cancer, BRCA1/2 mutations carriers had better OS than BRCA-negative counterpart (HR 0.49, 95% CI: 0.26–0.92). Among Ashkenazi Jewish women, BRCA1/2 mutations carriers presented higher risk of death from breast cancer (HR 1.44, 95% CI: 1.05–1.97) and of distant metastases (HR 1.82, 95% CI: 1.05–3.16) than sporadic/BRCA-negative patients. Conclusion: Our results support the evaluation of BRCA mutational status in patients with high risk of harboring BRCA germline mutations to better define the prognosis of breast cancer in these patients. PMID:27749552

Germline minisatellite mutations in workers occupationally exposed to radiation at the Sellafield nuclear facility

International Nuclear Information System (INIS)

Tawn, E Janet; Curwen, Gillian B; Rees, Gwen S; Jonas, Patricia

2015-01-01

Germline minisatellite mutation rates were investigated in male workers occupationally exposed to radiation at the Sellafield nuclear facility. DNA samples from 160 families with 255 offspring were analysed for mutations at eight hypervariable minisatellite loci (B6.7, CEB1, CEB15, CEB25, CEB36, MS1, MS31, MS32) by Southern hybridisation. No significant difference was observed between the paternal mutation rate of 5.0% (37 mutations in 736 alleles) for control fathers with a mean preconceptional testicular dose of 9 mSv and that of 5.8% (66 in 1137 alleles) for exposed fathers with a mean preconceptional testicular dose of 194 mSv. Subgrouping the exposed fathers into two dose groups with means of 111 mSv and 274 mSv revealed paternal mutation rates of 6.0% (32 mutations in 536 alleles) and 5.7% (34 mutations in 601 alleles), respectively, neither of which was significantly different in comparisons with the rate for the control fathers. Maternal mutation rates of 1.6% (12 mutations in 742 alleles) for the partners of control fathers and 1.7% (19 mutations in 1133 alleles) for partners of exposed fathers were not significantly different. This study provides evidence that paternal preconceptional occupational radiation exposure does not increase the germline minisatellite mutation rate and therefore refutes suggestions that such exposure could result in a destabilisation of the germline that can be passed on to future generations. (paper)

Temporal remodeling of the cell cycle accompanies differentiation in the Drosophila germline.

Science.gov (United States)

Hinnant, Taylor D; Alvarez, Arturo A; Ables, Elizabeth T

2017-09-01

Development of multicellular organisms relies upon the coordinated regulation of cellular differentiation and proliferation. Growing evidence suggests that some molecular regulatory pathways associated with the cell cycle machinery also dictate cell fate; however, it remains largely unclear how the cell cycle is remodeled in concert with cell differentiation. During Drosophila oogenesis, mature oocytes are created through a series of precisely controlled division and differentiation steps, originating from a single tissue-specific stem cell. Further, germline stem cells (GSCs) and their differentiating progeny remain in a predominantly linear arrangement as oogenesis proceeds. The ability to visualize the stepwise events of differentiation within the context of a single tissue make the Drosophila ovary an exceptional model for study of cell cycle remodeling. To describe how the cell cycle is remodeled in germ cells as they differentiate in situ, we used the Drosophila Fluorescence Ubiquitin-based Cell Cycle Indicator (Fly-FUCCI) system, in which degradable versions of GFP::E2f1 and RFP::CycB fluorescently label cells in each phase of the cell cycle. We found that the lengths of the G1, S, and G2 phases of the cell cycle change dramatically over the course of differentiation, and identified the 4/8-cell cyst as a key developmental transition state in which cells prepare for specialized cell cycles. Our data suggest that the transcriptional activator E2f1, which controls the transition from G1 to S phase, is a key regulator of mitotic divisions in the early germline. Our data support the model that E2f1 is necessary for proper GSC proliferation, self-renewal, and daughter cell development. In contrast, while E2f1 degradation by the Cullin 4 (Cul4)-containing ubiquitin E3 ligase (CRL4) is essential for developmental transitions in the early germline, our data do not support a role for E2f1 degradation as a mechanism to limit GSC proliferation or self-renewal. Taken

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.

The effects of physical aging at elevated temperatures on the viscoelastic creep on IM7/K3B

Science.gov (United States)

Gates, Thomas S.; Feldman, Mark

1994-01-01

Physical aging at elevated temperature of the advanced composite IM7/K3B was investigated through the use of creep compliance tests. Testing consisted of short term isothermal, creep/recovery with the creep segments performed at constant load. The matrix dominated transverse tensile and in-plane shear behavior were measured at temperatures ranging from 200 to 230 C. Through the use of time based shifting procedures, the aging shift factors, shift rates and momentary master curve parameters were found at each temperature. These material parameters were used as input to a predictive methodology, which was based upon effective time theory and linear viscoelasticity combined with classical lamination theory. Long term creep compliance test data was compared to predictions to verify the method. The model was then used to predict the long term creep behavior for several general laminates.

Germline PRKACA amplification leads to Cushing syndrome caused by 3 adrenocortical pathologic phenotypes.

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Carney, J Aidan; Lyssikatos, Charalampos; Lodish, Maya B; Stratakis, Constantine A

2015-01-01

We describe the pathology of 5 patients with germline PRKACA copy number gain and Cushing syndrome: 4 males and 1 female, aged 2 to 43 years, including a mother and son. Imaging showed normal or slightly enlarged adrenal glands in 4 patients and a unilateral mass in the fifth. Biochemically, the patients had corticotropin-independent hypercortisolism. Four underwent bilateral adrenalectomy; unilateral adrenalectomy was performed in the patient with the adrenal mass. Pathologically, 3 patients, including the 1 with the tumor (adenoma), had primary pigmented nodular adrenocortical disease with extranodular cortical atrophy and mild intracapsular and extracapsular extension of cortical cells. The other 2 patients had cortical hyperplasia and prominent capsular and extracapsular micronodular cortical hyperplasia. Immunoperoxidase staining revealed differences for synaptophysin, inhibin-A, and Ki-67 (nuclei) in the atrophic cortices (patients 1, 2, and 3) and hyperplastic cortices (patients 4 and 5) and for Ki-67 (nuclei) and vimentin in the extracortical nodules in the 2 groups of patients. β-Catenin stained the cell membrane, cytoplasm, and nuclei of the adenoma. The patients were well at follow-up (1-23 years); 24-hour urinary cortisol excretion was elevated in the patient who had unilateral adrenalectomy. Copyright © 2014 Elsevier Inc. All rights reserved.

Germline APC mutations in hepatoblastoma.

Science.gov (United States)

Yang, Adeline; Sisson, Rebecca; Gupta, Anita; Tiao, Greg; Geller, James I

2018-04-01

Conflicting reports on the frequency of germline adenomatous polyposis coli (APC) gene mutations in patients with hepatoblastoma (HB) have called into question the clinical value of APC mutation testing on apparently sporadic HB. An Institutional Review Board approved retrospective review of clinical data collected from patients with HB who received APC testing at our institution was conducted. All HB patients seen at Cincinnati Children's Hospital Medical Center were eligible for testing. Potential genotype/phenotype correlations were assessed. As of July 2015, 29 patients with HB had received constitutional APC testing. Four (14%) were found to have APC pathogenic truncations of the APC protein and in addition two (7%) had APC missense variants of unknown clinical significance. Two patients (7%) had family histories indicative of familial adenomatous polyposis (FAP). Response to chemotherapy tracked differently in APC pathogenic cases, with a slower imaging response despite an equivalent or slightly faster α-fetoprotein (AFP) response. The prevalence of pathogenic APC variants in apparently sporadic HB may be higher than previously detected. Differences in time to imaging response, despite similar AFP response, may impact surgical planning. All patients with HB warrant germline APC mutation testing for underlying FAP. © 2017 Wiley Periodicals, Inc.

Flow cytometry sorting of nuclei enables the first global characterization of Paramecium germline DNA and transposable elements.

Science.gov (United States)

Guérin, Frédéric; Arnaiz, Olivier; Boggetto, Nicole; Denby Wilkes, Cyril; Meyer, Eric; Sperling, Linda; Duharcourt, Sandra

2017-04-26

DNA elimination is developmentally programmed in a wide variety of eukaryotes, including unicellular ciliates, and leads to the generation of distinct germline and somatic genomes. The ciliate Paramecium tetraurelia harbors two types of nuclei with different functions and genome structures. The transcriptionally inactive micronucleus contains the complete germline genome, while the somatic macronucleus contains a reduced genome streamlined for gene expression. During development of the somatic macronucleus, the germline genome undergoes massive and reproducible DNA elimination events. Availability of both the somatic and germline genomes is essential to examine the genome changes that occur during programmed DNA elimination and ultimately decipher the mechanisms underlying the specific removal of germline-limited sequences. We developed a novel experimental approach that uses flow cell imaging and flow cytometry to sort subpopulations of nuclei to high purity. We sorted vegetative micronuclei and macronuclei during development of P. tetraurelia. We validated the method by flow cell imaging and by high throughput DNA sequencing. Our work establishes the proof of principle that developing somatic macronuclei can be sorted from a complex biological sample to high purity based on their size, shape and DNA content. This method enabled us to sequence, for the first time, the germline DNA from pure micronuclei and to identify novel transposable elements. Sequencing the germline DNA confirms that the Pgm domesticated transposase is required for the excision of all ~45,000 Internal Eliminated Sequences. Comparison of the germline DNA and unrearranged DNA obtained from PGM-silenced cells reveals that the latter does not provide a faithful representation of the germline genome. We developed a flow cytometry-based method to purify P. tetraurelia nuclei to high purity and provided quality control with flow cell imaging and high throughput DNA sequencing. We identified 61

Protection of germline gene expression by the C. elegans Argonaute CSR-1.

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Wedeles, Christopher J; Wu, Monica Z; Claycomb, Julie M

2013-12-23

In Caenorhabditis elegans, the Piwi-interacting small RNA (piRNA)-mediated germline surveillance system encodes more than 30,000 unique 21-nucleotide piRNAs, which silence a variety of foreign nucleic acids. What mechanisms allow endogenous germline-expressed transcripts to evade silencing by the piRNA pathway? One likely candidate in a protective mechanism is the Argonaute CSR-1, which interacts with 22G-small RNAs that are antisense to nearly all germline-expressed genes. Here, we use an in vivo RNA tethering assay to demonstrate that the recruitment of CSR-1 to a transcript licenses expression of the transcript, protecting it from piRNA-mediated silencing. Licensing occurs mainly at the level of transcription, as we observe changes in pre-mRNA levels consistent with transcriptional activation when CSR-1 is tethered. Furthermore, the recruitment of CSR-1 to a previously silenced locus transcriptionally activates its expression. Together, these results demonstrate a rare positive role for an endogenous Argonaute pathway in heritably licensing and protecting germline transcripts.

TGF-β superfamily signaling in testis formation and early male germline development.

Science.gov (United States)

Young, Julia C; Wakitani, Shoichi; Loveland, Kate L

2015-09-01

The TGF-β ligand superfamily contains at least 40 members, many of which are produced and act within the mammalian testis to facilitate formation of sperm. Their progressive expression at key stages and in specific cell types determines the fertility of adult males, influencing testis development and controlling germline differentiation. BMPs are essential for the interactive instructions between multiple cell types in the early embryo that drive initial specification of gamete precursors. In the nascent foetal testis, several ligands including Nodal, TGF-βs, Activins and BMPs, serve as key masculinizing switches by regulating male germline pluripotency, somatic and germline proliferation, and testicular vascularization and architecture. In postnatal life, local production of these factors determine adult testis size by regulating Sertoli cell multiplication and differentiation, in addition to specifying germline differentiation and multiplication. Because TGF-β superfamily signaling is integral to testis formation, it affects processes that underlie testicular pathologies, including testicular cancer, and its potential to contribute to subfertility is beginning to be understood. Copyright © 2015 Elsevier Ltd. All rights reserved.

Isolation and characterization of string-forming female germline stem cells from ovaries of neonatal mice.

Science.gov (United States)

Liu, Jing; Shang, Dantong; Xiao, Yao; Zhong, Pei; Cheng, Hanhua; Zhou, Rongjia

2017-09-29

Germline stem cells are essential in the generation of both male and female gametes. In mammals, the male testis produces sperm throughout the entire lifetime, facilitated by testicular germline stem cells. Oocyte renewal ceases in postnatal or adult life in mammalian females, suggesting that germline stem cells are absent from the mammalian ovary. However, studies in mice, rats, and humans have recently provided evidence for ovarian female germline stem cells (FGSCs). A better understanding of the role of FGSCs in ovaries could help improve fertility treatments. Here, we developed a rapid and efficient method for isolating FGSCs from ovaries of neonatal mice. Notably, our FGSC isolation method could efficiently isolate on average 15 cell "strings" per ovary from mice at 1-3 days postpartum. FGSCs isolated from neonatal mice displayed the string-forming cell configuration at mitosis ( i.e. a "stringing" FGSC (sFGSC) phenotype) and a disperse phenotype in postnatal mice. We also found that sFGSCs undergo vigorous mitosis especially at 1-3 days postpartum. After cell division, the sFGSC membranes tended to be connected to form sFGSCs. Moreover, F-actin filaments exhibited a cell-cortex distribution in sFGSCs, and E-cadherin converged in cell-cell connection regions, resulting in the string-forming morphology. Our new method provides a platform for isolating FGSCs from the neonatal ovary, and our findings indicate that FGCSs exhibit string-forming features in neonatal mice. The sFGSCs represent a valuable resource for analysis of ovary function and an in vitro model for future clinical use to address ovarian dysfunction. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Co-option of the piRNA pathway for germline-specific alternative splicing of C. elegans TOR.

Science.gov (United States)

Barberán-Soler, Sergio; Fontrodona, Laura; Ribó, Anna; Lamm, Ayelet T; Iannone, Camilla; Cerón, Julián; Lehner, Ben; Valcárcel, Juan

2014-09-25

Many eukaryotic genes contain embedded antisense transcripts and repetitive sequences of unknown function. We report that male germline-specific expression of an antisense transcript contained in an intron of C. elegans Target of Rapamycin (TOR, let-363) is associated with (1) accumulation of endo-small interfering RNAs (siRNAs) against an embedded Helitron transposon and (2) activation of an alternative 3' splice site of TOR. The germline-specific Argonaute proteins PRG-1 and CSR-1, which participate in self/nonself RNA recognition, antagonistically regulate the generation of these endo-siRNAs, TOR mRNA levels, and 3' splice-site selection. Supply of exogenous double-stranded RNA against the region of sense/antisense overlap reverses changes in TOR expression and splicing and suppresses the progressive multigenerational sterility phenotype of prg-1 mutants. We propose that recognition of a "nonself" intronic transposon by endo-siRNAs/the piRNA system provides physiological regulation of expression and alternative splicing of a host gene that, in turn, contributes to the maintenance of germline function across generations. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

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.

DAF-16 and TCER-1 Facilitate Adaptation to Germline Loss by Restoring Lipid Homeostasis and Repressing Reproductive Physiology in C. elegans

Science.gov (United States)

Amrit, Francis Raj Gandhi; Steenkiste, Elizabeth Marie; Ratnappan, Ramesh; Chen, Shaw-Wen; McClendon, T. Brooke; Kostka, Dennis; Yanowitz, Judith; Olsen, Carissa Perez; Ghazi, Arjumand

2016-01-01

Elimination of the proliferating germline extends lifespan in C. elegans. This phenomenon provides a unique platform to understand how complex metazoans retain metabolic homeostasis when challenged with major physiological perturbations. Here, we demonstrate that two conserved transcription regulators essential for the longevity of germline-less adults, DAF-16/FOXO3A and TCER-1/TCERG1, concurrently enhance the expression of multiple genes involved in lipid synthesis and breakdown, and that both gene classes promote longevity. Lipidomic analyses revealed that key lipogenic processes, including de novo fatty acid synthesis, triglyceride production, desaturation and elongation, are augmented upon germline removal. Our data suggest that lipid anabolic and catabolic pathways are coordinately augmented in response to germline loss, and this metabolic shift helps preserve lipid homeostasis. DAF-16 and TCER-1 also perform essential inhibitory functions in germline-ablated animals. TCER-1 inhibits the somatic gene-expression program that facilitates reproduction and represses anti-longevity genes, whereas DAF-16 impedes ribosome biogenesis. Additionally, we discovered that TCER-1 is critical for optimal fertility in normal adults, suggesting that the protein acts as a switch supporting reproductive fitness or longevity depending on the presence or absence of the germline. Collectively, our data offer insights into how organisms adapt to changes in reproductive status, by utilizing the activating and repressive functions of transcription factors and coordinating fat production and degradation. PMID:26862916

Suspension state increases reattachment of breast cancer cells by up-regulating lamin A/C.

Science.gov (United States)

Zhang, Xiaomei; Lv, Yonggang

2017-12-01

Extravasation is a rate-limiting step of tumor metastasis, for which adhesion to endothelium of circulating tumor cells (CTCs) is the prerequisite. The suspension state of CTCs undergoing detachment from primary tumor is a persistent biomechanical cue, which potentially regulates the biophysical characteristics and cellular behaviors of tumor cells. In this study, breast tumor cells MDA-MB-231 in suspension culture condition were used to investigate the effect of suspension state on reattachment of CTCs. Our study demonstrated that suspension state significantly increased the adhesion ability of breast tumor cells. In addition, suspension state markedly promoted the formation of stress fibers and focal adhesions and reduced the motility in reattached breast cancer cells. Moreover, lamin A/C was reversibly accumulated at posttranscriptional level under suspension state, improving the cell stiffness of reattached breast cancer cells. Disruption of actin cytoskeleton by cytochalasin D caused lamin A/C accumulation. Conversely, decreasing actomyosin contraction by ROCK inhibitor Y27632 reduced lamin A/C level. Knocking down lamin A/C weakened the suspension-induced increase of adhesion, and also abolished the suspension-induced decrease of motility and increase of stress fibers and focal adhesion in reattaching tumor cells, suggesting a crucial role of lamin A/C. In conclusion, it was demonstrated that suspension state promoted the reattachment of breast tumor cells by up-regulating lamin A/C via cytoskeleton disruption. These findings highlight the important role of suspension state for tumor cells in tumor metastasis. Copyright © 2017 Elsevier B.V. All rights reserved.

Direct current force sensing device based on compressive spring, permanent magnet, and coil-wound magnetostrictive/piezoelectric laminate.

Science.gov (United States)

Leung, Chung Ming; Or, Siu Wing; Ho, S L

2013-12-01

A force sensing device capable of sensing dc (or static) compressive forces is developed based on a NAS106N stainless steel compressive spring, a sintered NdFeB permanent magnet, and a coil-wound Tb(0.3)Dy(0.7)Fe(1.92)/Pb(Zr, Ti)O3 magnetostrictive∕piezoelectric laminate. The dc compressive force sensing in the device is evaluated theoretically and experimentally and is found to originate from a unique force-induced, position-dependent, current-driven dc magnetoelectric effect. The sensitivity of the device can be increased by increasing the spring constant of the compressive spring, the size of the permanent magnet, and/or the driving current for the coil-wound laminate. Devices of low-force (20 N) and high-force (200 N) types, showing high output voltages of 262 and 128 mV peak, respectively, are demonstrated at a low driving current of 100 mA peak by using different combinations of compressive spring and permanent magnet.

Expression of germline markers in three species of amphioxus supports a preformation mechanism of germ cell development in cephalochordates

Science.gov (United States)

2013-01-01

Background In a previous study, we showed that the cephalochordate amphioxus Branchiostoma floridae has localized maternal transcripts of conserved germ cell markers Vasa and Nanos in its early embryos. These results provided strong evidence to support a preformation mechanism for primordial germ cell (PGC) development in B. floridae. Results In this study, we further characterize the expression of B. floridae homologs of Piwi and Tudor, which play important roles in germline development in diverse metazoan animals. We show that maternal mRNA of one of the identified Piwi-like homologs, Bf-Piwil1, also colocalizes with Vasa in the vegetal germ plasm and has zygotic expression in both the putative PGCs and the tail bud, suggesting it may function in both germline and somatic stem cells. More interestingly, one Tudor family gene, Bf-Tdrd7, is only expressed maternally and colocalizes with Vasa in germ plasm, suggesting that it may function exclusively in germ cell specification. To evaluate the conservation of the preformation mechanism among amphioxus species, we further analyze Vasa, Nanos, Piwil1, and Tdrd7 expression in two Asian amphioxus species, B. belcheri and B. japonicum. Their maternal transcripts all localize in similar patterns to those seen in B. floridae. In addition, we labeled putative PGCs with Vasa antibody to trace their dynamic distribution in developing larvae. Conclusions We identify additional germ plasm components in amphioxus and demonstrate the molecular distinction between the putative germline stem cells and somatic stem cells. Moreover, our results suggest that preformation may be a conserved mechanism for PGC specification among Branchiostoma species. Our Vasa antibody staining results suggest that after the late neurula stage, amphioxus PGCs probably proliferate with the tail bud cells during posterior elongation and are deposited near the forming myomere boundaries. Subsequently, these PGCs would concentrate at the ventral tip of the

Screening for germline phosphatase and tensin homolog-mutations in suspected Cowden syndrome and Cowden syndrome-like families among uterine cancer patients

Science.gov (United States)

TZORTZATOS, GERASIMOS; ARAVIDIS, CHRISTOS; LINDBLOM, ANNIKA; MINTS, MIRIAM; THAM, EMMA

2015-01-01

Cowden syndrome (CS) is an autosomal dominant disorder characterized by multiple hamartomas in the breast, thyroid and endometrium, with a prevalence of 1 per 250,000. Females with CS have a 21–28% lifetime risk of developing uterine cancer. Germline mutations in the phosphatase and tensin homolog (PTEN) gene, a tumor suppressor gene, are responsible for 30–80% of CS cases. PTEN is a nine-exon gene, located on chromosome 10q23.3, which encodes the 403 amino acid PTEN protein. It negatively regulates the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway, affecting various cellular processes and signaling pathways. The present study examined whether PTEN mutations are present in CS-like families with uterine cancer (UC). UC patients underwent surgery at Karolinska University Hospital, Stockholm, Sweden (2008–2012). Pedigrees were analyzed and 54 unrelated CS-like families were identified. CS-like families were defined as having at least one occurrence of uterine cancer and one of breast cancer, as well as at least one additional Cowden-associated tumor (uterine, breast, thyroid, colon or kidney cancer) in the same individual or in first-degree relatives. Genomic DNA was amplified using polymerase chain reaction, and DNA sequencing analysis of all nine exons of the PTEN gene was conducted. No germline PTEN mutations or polymorphisms were identified. Germline PTEN mutations are rare in CS-like families with uterine cancer, therefore, genetic screening must be restricted to patients that meet the strict National Comprehensive Cancer Network criteria. Gynecologists must be aware of the CS criteria and identify potential cases of CS in females where uterine cancer is the sentinel cancer. PMID:25789042

Experimental Characterization and Cohesive Laws for Delamination of Off-Axis GFRP Laminates

DEFF Research Database (Denmark)

Lindgaard, Esben; Bak, Brian Lau Verndal

2015-01-01

This work experimentally characterizes mixed mode delamination in glass fibre reinforced polymer laminates taking into account the influence of the off-axis angle between the lamina orientation and the crack growth direction on the fracture properties. Thus, providing a cohesive law that enables...... analysis of 3D models in which mixed mode crack growth within laminates having anisotropic fracture properties takes place....

A germline FANCA alteration that is associated with increased sensitivity to DNA damaging agents.

Science.gov (United States)

Wilkes, David C; Sailer, Verena; Xue, Hui; Cheng, Hongwei; Collins, Colin C; Gleave, Martin; Wang, Yuzhuo; Demichelis, Francesca; Beltran, Himisha; Rubin, Mark A; Rickman, David S

2017-09-01

Defects in genes involved in DNA damage repair (DDR) pathway are emerging as novel biomarkers and targets for new prostate cancer drug therapies. A previous report revealed an association between an exceptional response to cisplatin treatment and a somatic loss of heterozygosity (LOH) of FANCA in a patient with metastatic prostate cancer who also harbored a germline FANCA variant (S1088F). Although germline FANCA mutations are the most frequent alterations in patients with Fanconi anemia, germline alterations are less common in prostate cancer. We hypothesized that the germline S1088F FANCA variant in combination with FANCA LOH was deleterious for FANCA function and contributed to the patient's exceptional response to cisplatin. We show that although it properly localizes to the nucleus, the S1088F FANCA mutant protein disrupts the FANC protein complex resulting in increased sensitivity to DNA damaging agents. Because molecular stratification is emerging as a strategy for treating men with metastatic, castrate-resistant prostate cancer harboring specific DDR gene defects, our findings suggest that more biomarker studies are needed to better define clinically relevant germline and somatic alterations. © 2017 Wilkes et al.; Published by Cold Spring Harbor Laboratory Press.

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...

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

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.

Germline fumarate hydratase mutations in patients with ovarian mucinous cystadenoma

DEFF Research Database (Denmark)

Ylisaukko-oja, Sanna K.; Cybulski, Cezary; Lehtonen, Rainer

2006-01-01

Germline mutations in the fumarate hydratase (FH) gene were recently shown to predispose to the dominantly inherited syndrome, hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC is characterized by benign leiomyomas of the skin and the uterus, renal cell carcinoma, and uterine...... leiomyosarcoma. The aim of this study was to identify new families with FH mutations, and to further examine the tumor spectrum associated with FH mutations. FH germline mutations were screened from 89 patients with RCC, skin leiomyomas or ovarian tumors. Subsequently, 13 ovarian and 48 bladder carcinomas were...

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.

Laminating solution-processed silver nanowire mesh electrodes onto solid-state dye-sensitized solar cells

KAUST Repository

Hardin, Brian E.

2011-06-01

Solution processed silver nanowire meshes (Ag NWs) were laminated on top of solid-state dye-sensitized solar cells (ss-DSCs) as a reflective counter electrode. Ag NWs were deposited in <1 min and were less reflective compared to evaporated Ag controls; however, AgNW ss-DSC devices consistently had higher fill factors (0.6 versus 0.69), resulting in comparable power conversion efficiencies (2.7%) compared to thermally evaporated Ag control (2.8%). Laminated Ag NW electrodes enable higher throughput manufacturing and near unity material usage, resulting in a cheaper alternative to thermally evaporated electrodes. © 2011 Elsevier B.V. All rights reserved.

Profiling of Biomarkers for the Exposure of Polycyclic Aromatic Hydrocarbons: Lamin-A/C Isoform 3, Poly[ADP-ribose] Polymerase 1, and Mitochondria Copy Number Are Identified as Universal Biomarkers

Directory of Open Access Journals (Sweden)

Hwan-Young Kim

2014-01-01

Full Text Available This study investigated the profiling of polycyclic aromatic hydrocarbon- (PAH- induced genotoxicity in cell lines and zebrafish. Each type of cells displayed different proportionality of apoptosis. Mitochondrial DNA (mtDNA copy number was dramatically elevated after 5-day treatment of fluoranthene and pyrene. The notable deregulated proteins for PAHs exposure were displayed as follows: lamin-A/C isoform 3 and annexin A1 for benzopyrene; lamin-A/C isoform 3 and DNA topoisomerase 2-alpha for pentacene; poly[ADP-ribose] polymerase 1 (PARP-1 for fluoranthene; and talin-1 and DNA topoisomerase 2-alpha for pyrene. Among them, lamin-A/C isoform 3 and PARP-1 were further confirmed using mRNA and protein expression study. Obvious morphological abnormalities including curved backbone and cardiomegaly in zebrafish were observed in the 54 hpf with more than 400 nM of benzopyrene. In conclusion, the change of mitochondrial genome (increased mtDNA copy number was closely associated with PAH exposure in cell lines and mesenchymal stem cells. Lamin-A/C isoform 3, talin-1, and annexin A1 were identified as universal biomarkers for PAHs exposure. Zebrafish, specifically at embryo stage, showed suitable in vivo model for monitoring PAHs exposure to hematopoietic tissue and other organs.

Cancer-germline antigen vaccines and epigenetic enhancers

DEFF Research Database (Denmark)

Gjerstorff, Morten Frier; Burns, Jorge; Ditzel, Henrik Jorn

2010-01-01

IMPORTANCE OF THE FIELD: Immunotherapy holds great potential for disseminated cancer, and cancer-germline (CG) antigens are among the most promising tumor targets. They are widely expressed in different cancer types and are essentially tumor-specific, since their expression in normal tissues is l...

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

Equivalent magnetic noise reduction at high frequency range due to polarized direction optimization in Terfenol-D/Pb(Mg{sub 1/3}Nb{sub 2/3})O{sub 3}-PbTiO{sub 3} magnetoelectric laminate sensors

Energy Technology Data Exchange (ETDEWEB)

Fang, Cong, E-mail: fangcong86@gmail.com [Key Laboratory of Inorganic Functional Material and Device, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 201800 (China); University of Chinese Academy of Sciences, Beijing, 100049 (China); Ma, Jiashuai; Yao, Meng [Key Laboratory of Inorganic Functional Material and Device, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 201800 (China); University of Chinese Academy of Sciences, Beijing, 100049 (China); Di, Wenning; Lin, Di; Xu, Haiqing; Wang, Wei [Key Laboratory of Inorganic Functional Material and Device, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 201800 (China); Luo, Haosu, E-mail: hsluo@mail.sic.ac.cn [Key Laboratory of Inorganic Functional Material and Device, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 201800 (China)

2017-02-01

In this paper, we investigate the responsivities and output voltage noise power spectral densities of magnetoelectric (ME) laminate sensors, consisting of length magnetized Terfenol-D alloys and transverse/width poled Pb(Mg{sub 1/3}Nb{sub 2/3})O{sub 3}-PbTiO{sub 3} (PMNT) crystals (i.e. L-T mode and L-W mode respectively), which are directly integrated with custom-build low noise charge amplifier circuits. Both the theoretical analyses and experimental results prove that the L-W mode sensor with the optimized polarized direction of the PMNT plate possesses lower magnetic detection limit at the interested high frequency range of 10 kHz≤f≤50 kHz. The equivalent magnetic noise (EMN) of the L-W mode sensor is 0.78 pT/Hz{sup 1/2} at 30 kHz, which is about 1.7 times lower than the 1.35 pT/Hz{sup 1/2} for conventional L-T mode sensor. Furthermore, an effective method of using operational amplifiers with low equivalent input noise voltage and employing ME laminate composites with high voltage coefficient to reduce the EMNs of the ME laminate sensors at high frequency range has been established. - Highlights: • We present fabrications and properties of the L-T and L-T mode ME composites. • The equivalent magnetic noise levels at high frequency are measured. • The equivalent magnetic noise of the L-W mode sensor is 0.78 pT/Hz{sup 1/2} at 30 kHz. • The dominated noise source can be confirmed from OPA at high frequency range.

CSR-1 and P granules suppress sperm-specific transcription in the C. elegans germline.

Science.gov (United States)

Campbell, Anne C; Updike, Dustin L

2015-05-15

Germ granules (P granules) in C. elegans are required for fertility and function to maintain germ cell identity and pluripotency. Sterility in the absence of P granules is often accompanied by the misexpression of soma-specific proteins and the initiation of somatic differentiation in germ cells. To investigate whether this is caused by the accumulation of somatic transcripts, we performed mRNA-seq on dissected germlines with and without P granules. Strikingly, we found that somatic transcripts do not increase in the young adult germline when P granules are impaired. Instead, we found that impairing P granules causes sperm-specific mRNAs to become highly overexpressed. This includes the accumulation of major sperm protein (MSP) transcripts in germ cells, a phenotype that is suppressed by feminization of the germline. A core component of P granules, the endo-siRNA-binding Argonaute protein CSR-1, has recently been ascribed with the ability to license transcripts for germline expression. However, impairing CSR-1 has very little effect on the accumulation of its mRNA targets. Instead, we found that CSR-1 functions with P granules to prevent MSP and sperm-specific mRNAs from being transcribed in the hermaphrodite germline. These findings suggest that P granules protect germline integrity through two different mechanisms, by (1) preventing the inappropriate expression of somatic proteins at the level of translational regulation, and by (2) functioning with CSR-1 to limit the domain of sperm-specific expression at the level of transcription. © 2015. Published by The Company of Biologists Ltd.

Influences of lamin A levels on induction of pluripotent stem cells

Directory of Open Access Journals (Sweden)

Bingfeng Zuo

2012-09-01

Lamin A is an inner nuclear membrane protein that maintains nuclear structure integrity, is involved in transcription, DNA damage response and genomic stability, and also links to cell differentiation, senescence, premature aging and associated diseases. Induced pluripotent stem (iPS cells have been successfully generated from various types of cells and used to model human diseases. It remains unclear whether levels of lamin A influence reprogramming of somatic cells to pluripotent states during iPS induction. Consistently, lamin A is expressed more in differentiated than in relatively undifferentiated somatic cells, and increases in expression levels with age. Somatic cells with various expression levels of lamin A differ in their dynamics and efficiency during iPS cell induction. Cells with higher levels of lamin A show slower reprogramming and decreased efficiency to iPS cells. Furthermore, depletion of lamin A by transient shRNA accelerates iPS cell induction from fibroblasts. Reduced levels of lamin A are associated with increased expression of pluripotent genes Oct4 and Nanog, and telomerase genes Tert and Terc. On the contrary, overexpression of lamin A retards somatic cell reprogramming to iPS-like colony formation. Our data suggest that levels of lamin A influence reprogramming of somatic cells to pluripotent stem cells and that artificial silencing of lamin A facilitates iPS cell induction. These findings may have implications in enhancing rejuvenation of senescent or older cells by iPS technology and manipulating lamin A levels.

Germline mutations in MAP3K6 are associated with familial gastric cancer.

Directory of Open Access Journals (Sweden)

Daniel Gaston

2014-10-01

Full Text Available Gastric cancer is among the leading causes of cancer-related deaths worldwide. While heritable forms of gastric cancer are relatively rare, identifying the genes responsible for such cases can inform diagnosis and treatment for both hereditary and sporadic cases of gastric cancer. Mutations in the E-cadherin gene, CDH1, account for 40% of the most common form of familial gastric cancer (FGC, hereditary diffuse gastric cancer (HDGC. The genes responsible for the remaining forms of FGC are currently unknown. Here we examined a large family from Maritime Canada with FGC without CDH1 mutations, and identified a germline coding variant (p.P946L in mitogen-activated protein kinase kinase kinase 6 (MAP3K6. Based on conservation, predicted pathogenicity and a known role of the gene in cancer predisposition, MAP3K6 was considered a strong candidate and was investigated further. Screening of an additional 115 unrelated individuals with non-CDH1 FGC identified the p.P946L MAP3K6 variant, as well as four additional coding variants in MAP3K6 (p.F849Sfs*142, p.P958T, p.D200Y and p.V207G. A somatic second-hit variant (p.H506Y was present in DNA obtained from one of the tumor specimens, and evidence of DNA hypermethylation within the MAP3K6 gene was observed in DNA from the tumor of another affected individual. These findings, together with previous evidence from mouse models that MAP3K6 acts as a tumor suppressor, and studies showing the presence of somatic mutations in MAP3K6 in non-hereditary gastric cancers and gastric cancer cell lines, point towards MAP3K6 variants as a predisposing factor for FGC.

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.

A comparative study on low-velocity impact response of fabric composite laminates

International Nuclear Information System (INIS)

Zhang, Diantang; Sun, Ying; Chen, Li; Pan, Ning

2013-01-01

Highlights: • We examine the low-velocity behavior of single-ply 3D orthogonal woven fabric composites. • Three-coordinate measuring device was used to acquire the 3D topographies. • Single-ply 3D orthogonal woven fabric composites show better impact performance. • Impact properties will increase if in-plane yarns and Z-yarns of single-ply 3D orthogonal woven fabric are optimized. - Abstract: Impact behaviors at low velocity of composite laminates reinforced with fabrics of different architectures are investigated. Unidirectional prepreg, 2D woven and 3D orthogonal fabrics, all formed of Ultrahigh Molecular Weight Polyethylene (UHMWPE) filaments, were selected as reinforcements to form composite laminates using hot pressing technology. Low velocity impact tests were conducted using a drop-weight impact equipment at the energy level of 35 J. A three-coordinate measuring device was employed to determine the volume of plastic deformation and surface dent diameter. The results show that the composite laminates of single-ply 3D orthogonal woven fabric exhibit better energy absorbed capacity and impact damage resistance as compared to those of unidirectional and 2D plain-woven fabric

3D Progressive Damage Modeling for Laminated Composite Based on Crack Band Theory and Continuum Damage Mechanics

Science.gov (United States)

Wang, John T.; Pineda, Evan J.; Ranatunga, Vipul; Smeltzer, Stanley S.

2015-01-01

A simple continuum damage mechanics (CDM) based 3D progressive damage analysis (PDA) tool for laminated composites was developed and implemented as a user defined material subroutine to link with a commercially available explicit finite element code. This PDA tool uses linear lamina properties from standard tests, predicts damage initiation with an easy-to-implement Hashin-Rotem failure criteria, and in the damage evolution phase, evaluates the degradation of material properties based on the crack band theory and traction-separation cohesive laws. It follows Matzenmiller et al.'s formulation to incorporate the degrading material properties into the damaged stiffness matrix. Since nonlinear shear and matrix stress-strain relations are not implemented, correction factors are used for slowing the reduction of the damaged shear stiffness terms to reflect the effect of these nonlinearities on the laminate strength predictions. This CDM based PDA tool is implemented as a user defined material (VUMAT) to link with the Abaqus/Explicit code. Strength predictions obtained, using this VUMAT, are correlated with test data for a set of notched specimens under tension and compression loads.

Linking the environment, DAF-7/TGFβ signaling and LAG-2/DSL ligand expression in the germline stem cell niche.

Science.gov (United States)

Pekar, Olga; Ow, Maria C; Hui, Kailyn Y; Noyes, Marcus B; Hall, Sarah E; Hubbard, E Jane Albert

2017-08-15

The developmental accumulation of proliferative germ cells in the C. elegans hermaphrodite is sensitive to the organismal environment. Previously, we found that the TGFβ signaling pathway links the environment and proliferative germ cell accumulation. Neuronal DAF-7/TGFβ causes a DAF-1/TGFβR signaling cascade in the gonadal distal tip cell (DTC), the germline stem cell niche, where it negatively regulates a DAF-3 SMAD and DAF-5 Sno-Ski. LAG-2, a founding DSL ligand family member, is produced in the DTC and activates the GLP-1/Notch receptor on adjacent germ cells to maintain germline stem cell fate. Here, we show that DAF-7/TGFβ signaling promotes expression of lag-2 in the DTC in a daf-3- dependent manner. Using ChIP and one-hybrid assays, we find evidence for direct interaction between DAF-3 and the lag-2 promoter. We further identify a 25 bp DAF-3 binding element required for the DTC lag-2 reporter response to the environment and to DAF-7/TGFβ signaling. Our results implicate DAF-3 repressor complex activity as a key molecular mechanism whereby the environment influences DSL ligand expression in the niche to modulate developmental expansion of the germline stem cell pool. © 2017. Published by The Company of Biologists Ltd.

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

Energy Technology Data Exchange (ETDEWEB)

Al-Saaidi, Rasha [Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus (Denmark); Rasmussen, Torsten B. [Department of Cardiology, Aarhus University Hospital, Aarhus (Denmark); Palmfeldt, Johan [Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus (Denmark); Nissen, Peter H. [Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus (Denmark); Beqqali, Abdelaziz [Heart Failure Research Center, Academic Medical Center, Amsterdam (Netherlands); Hansen, Jakob [Department of Forensic Medicine, Bioanalytical Unit, University of Aarhus (Denmark); Pinto, Yigal M. [Heart Failure Research Center, Academic Medical Center, Amsterdam (Netherlands); Boesen, Thomas [Department of Molecular Biology and Genetics, University of Aarhus (Denmark); Mogensen, Jens [Department of Cardiology, Odense University Hospital, Odense (Denmark); Bross, Peter, E-mail: peter.bross@ki.au.dk [Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus (Denmark)

2013-11-15

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

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.

Fitness loss and germline mutations in barn swallows breeding in Chernobyl

Energy Technology Data Exchange (ETDEWEB)

Ellegren, Hans; Lindgren, Gabriella; Primmer, C.R. [Swedish Univ. of Agricultural Sciences, Animal Breeding and Genetics Dept., Uppsala (Sweden); Moeller, A.P. [Universite Pierre et Marie Curie. Lab. d`Ecologie, Paris, 75 (France)

1997-10-09

The severe nuclear accident at Chernobyl in 1986 resulted in the worst reported accidental exposure of radioactive material to free-living organisms. Short-term effects on human populations inhabiting polluted areas include increased incidence of thyroid cancer, infant leukaemia, and congenital malformations in newborns. Two recent studies have reported, although with some controversy, that germline mutation rates were increased in humans and voles living close to Chernobyl, but little is known about the viability of the organisms affected. Here we report an increased frequency of partial albinism, a morphological aberration associated with a loss of fitness, among barn swallows, Hirundo rustica, breeding close to Chernobyl. Heretability estimates indicate that mutations causing albinism were at least partly of germline origin. Furthermore, evidence for an increased germline mutation rate was obtained from segregation analysis at two hypervariable microsatellite loci, indicating that mutation events in barn swallows from Chernobyl were two- to tenfold higher than in birds from control areas in Ukraine and Italy. (author).

Fitness loss and germline mutations in barn swallows breeding in Chernobyl

International Nuclear Information System (INIS)

Ellegren, Hans; Lindgren, Gabriella; Primmer, C.R.; Moeller, A.P.

1997-01-01

The severe nuclear accident at Chernobyl in 1986 resulted in the worst reported accidental exposure of radioactive material to free-living organisms. Short-term effects on human populations inhabiting polluted areas include increased incidence of thyroid cancer, infant leukaemia, and congenital malformations in newborns. Two recent studies have reported, although with some controversy, that germline mutation rates were increased in humans and voles living close to Chernobyl, but little is known about the viability of the organisms affected. Here we report an increased frequency of partial albinism, a morphological aberration associated with a loss of fitness, among barn swallows, Hirundo rustica, breeding close to Chernobyl. Heretability estimates indicate that mutations causing albinism were at least partly of germline origin. Furthermore, evidence for an increased germline mutation rate was obtained from segregation analysis at two hypervariable microsatellite loci, indicating that mutation events in barn swallows from Chernobyl were two- to tenfold higher than in birds from control areas in Ukraine and Italy. (author)

[Laminitis in cattle: a literature review].

Science.gov (United States)

Lischer, C; Ossent, P

1994-10-01

Worldwide afflictions of the claws belong to the economically important diseases in dairy cattle. The significance of laminitis has gained importance in the last years since the condition is regarded as the most important predisposing factor for the development of lesions such as sole ulcer, white line disease and heel horn erosion. Apart from the clinical stages (acute, subacute, chronic, chronic-recurrent) there is also a subclinical form of laminitis which does not cause lameness. It is characterized by soft yellowish sole and heel horn with haemorrhages in the sole and along the white line. Laminitis is a multifactorial event in which nutrition, genetic disposition and the perinatal period, combined with the associated diseases of high-yielding cows, have a particular significance. Currently, two principally different hypotheses on the pathogenesis are discussed. The generally accepted theory bases on a disturbance in the microcirculation of the corium. According to the other theory the circulatory disturbances are secondary to changes which occur in the horn producing cells of the stratum basale of the epidermis. The predisposing factors and the pathogenesis of laminitis are discussed in the light of possible therapeutic and prophylactic measures.

Germline and somatic mutations in the MTOR gene in focal cortical dysplasia and epilepsy

DEFF Research Database (Denmark)

Møller, Rikke S; Weckhuysen, Sarah; Chipaux, Mathilde

2016-01-01

OBJECTIVE: To assess the prevalence of somatic MTOR mutations in focal cortical dysplasia (FCD) and of germline MTOR mutations in a broad range of epilepsies. METHODS: We collected 20 blood-brain paired samples from patients with FCD and searched for somatic variants using deep-targeted gene panel...... sequencing. Germline mutations in MTOR were assessed in a French research cohort of 93 probands with focal epilepsies and in a diagnostic Danish cohort of 245 patients with a broad range of epilepsies. Data sharing among collaborators allowed us to ascertain additional germline variants in MTOR. RESULTS: We...... detected recurrent somatic variants (p.Ser2215Phe, p.Ser2215Tyr, and p.Leu1460Pro) in the MTOR gene in 37% of participants with FCD II and showed histologic evidence for activation of the mTORC1 signaling cascade in brain tissue. We further identified 5 novel de novo germline missense MTOR variants in 6...

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.

Shade evaluation of ceramic laminates according to different try-in materials.

Science.gov (United States)

Lopes, Lawrence Gonzaga; Vaz, Maysa Magalhaes; de Magalhaes, Ana Paula Rodrigues; Cardoso, Paula Carvalho; de Souza, Joao Batista; de Torres, Erica Miranda

2014-01-01

The porcelain laminate replaces the visible portion of enamel with a ceramic, which is attached to the dental surface. To enhance cosmetic results, a preliminary color matching procedure is performed prior to cementing the veneers. This procedure can be performed using water, water-soluble gel, or try-in paste. The different shades of cement and try-in pastes are intended to obtain better color and esthetics of the final restoration. This study sought to evaluate the shade of ceramic veneers produced by different try-in materials. Forty bovine teeth and 40 ceramic discs (0.6 mm thick) were prepared. The samples were divided into 4 groups (n = 10). For Group 1 samples, no material was used between the tooth and the ceramic, Group 2 interposed samples with water, Group 3 used a water-soluble gel, and Group 4 used try-in paste (value 0). The color was measured with a spectrophotometer, obtaining L*, a*, and b* values to calculate the color difference (ΔE*). The data were subjected to normality tests and 1-way ANOVA. No significant statistical differences were found among the groups, indicating that the different try-in materials had similar effects on the color of the ceramic laminates.

Design Investigation of a Laminated Waveguide Fed Multi-Band DRA for Military Applications

Science.gov (United States)

Kumar, Pramod; Dwari, Santanu; Singh, Shailendra; Agrawal, N. K.

2017-12-01

In this paper a laminated waveguide fed DR Antenna is investigated. It can use for moderate power military applications. Cylindrical DRA is excited by two closely spaced asymmetric longitudinal slots on the broad wall of the laminated cavity are responsible for producing three different frequency bands. Parametric study of slots has been done with the help of commercial software ANSOFT HFSS. All the bands have sharp rejection. The final model of the antenna is simulated, fabricated and experimentally measured. Measured results are in quite accordant with design results. SIW feeding structures have small losses, moderate power handling capacity, low costs, compact sizes and can be seamlessly integrated with planar circuits. At all the bands 9.76 GHz, 10.53 GHz and 11.8 GHz resonant frequency, the antenna shows 56 MHz, 160 MHz, and 250 MHz impedance bandwidth (for VSWR<2) with 6 dB,6.2 dB and 6.8 dB gain respectively. Simulated and measured results reveal outstanding performance with a cross-polar level of 29 dB lower than that of the co-polar level at 9.76 GHz, the cross-polar level of 32 dB lower than that of the co-polar level at 10.53, GHz, and similarly cross-polar level of 30 dB lower than that of the co-polar level at 11.8 GHz.

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...

Static and Dynamic Behavior of High Modulus Hybrid Boron/Glass/Aluminum Fiber Metal Laminates

Science.gov (United States)

Yeh, Po-Ching

2011-12-01

This dissertation presents the investigation of a newly developed hybrid fiber metal laminates (FMLs) which contains commingled boron fibers, glass fibers, and 2024-T3 aluminum sheets. Two types of hybrid boron/glass/aluminum FMLs are developed. The first, type I hybrid FMLs, contained a layer of boron fiber prepreg in between two layers of S2-glass fiber prepreg, sandwiched by two aluminum alloy 2024-T3 sheets. The second, type II hybrid FMLs, contained three layer of commingled hybrid boron/glass fiber prepreg layers, sandwiched by two aluminum alloy 2024-T3 sheets. The mechanical behavior and deformation characteristics including blunt notch strength, bearing strength and fatigue behavior of these two types of hybrid boron/glass/aluminum FMLs were investigated. Compared to traditional S2-glass fiber reinforced aluminum laminates (GLARE), the newly developed hybrid boron/glass/aluminum fiber metal laminates possess high modulus, high yielding stress, and good blunt notch properties. From the bearing test result, the hybrid boron/glass/aluminum fiber metal laminates showed outstanding bearing strength. The high fiber volume fraction of boron fibers in type II laminates lead to a higher bearing strength compared to both type I laminates and traditional GLARE. Both types of hybrid FMLs have improved fatigue crack initiation lives and excellent fatigue crack propagation resistance compared to traditional GLARE. The incorporation of the boron fibers improved the Young's modulus of the composite layer in FMLs, which in turn, improved the fatigue crack initiation life and crack propagation rates of the aluminum sheets. Moreover, a finite element model was established to predict and verify the properties of hybrid boron/glass/aluminum FMLs. The simulated results showed good agreement with the experimental results.

Studies in Cup Drawing Behavior of Polymer Laminated Sheet Metal

Science.gov (United States)

Elnagmi, M.; Jain, M.; Bruhis, M.; Nielsen, K.

2011-08-01

Axisymmetric deep drawing behavior of a polymer laminated sheet metal (PLSM) is investigated using an axisymmetric cup drawing test. PLSMs are of interest as a replacement for painted finishes for automotive applications as they have the potential to achieve good quality long lasting and aesthetically appealing surfaces on stamped parts. However, there is limited understanding of PLSMs in automotive deep drawing situations to produce complex 3-D parts. The tests are carried out using well-controlled, laboratory-based, dual-action, servo-hydraulic forming presses under blank-holder force and punch displacement control conditions. An optical strain mapping system is used to measure the surface strains (and to construct 3D strain maps) from the film side of the deformed samples for a range of forming conditions. Deep drawing characteristics such as punch load versus punch displacement traces, strain distribution along the cup profile, flange wrinkling and fracture characteristics are experimentally assessed for stainless steel-plastic film laminated sheet materials. Also the effect of lamination pressure on wrinkling and delamination is investigated for a decorative pressure sensitive adhesive film affixed to the stainless steel sheet.

Shape forming by thermal expansion mismatch and shape memory locking in polymer/elastomer laminates

Science.gov (United States)

Yuan, Chao; Ding, Zhen; Wang, T. J.; Dunn, Martin L.; Qi, H. Jerry

2017-10-01

This paper studies a novel method to fabricate three-dimensional (3D) structure from 2D thermo-responsive shape memory polymer (SMP)/elastomer bilayer laminate. In this method, the shape change is actuated by the thermal mismatch strain between the SMP and the elastomer layers upon heating. However, the glass transition behavior of the SMP locks the material into a new 3D shape that is stable even upon cooling. Therefore, the second shape becomes a new permanent shape of the laminate. A theoretical model that accounts for the temperature-dependent thermomechanical behavior of the SMP material and thermal mismatch strain between the two layers is developed to better understand the underlying physics. Model predictions and experiments show good agreement and indicate that the theoretical model can well predict the bending behavior of the bilayer laminate. The model is then used in the optimal design of geometrical configuration and material selection. The latter also illustrates the requirement of thermomechanical behaviors of the SMP to lock the shape. Based on the fundamental understandings, several self-folding structures are demonstrated by the bilayer laminate design.

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.

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.

Genotype and phenotype spectrum of NRAS germline variants

NARCIS (Netherlands)

Altmuller, F.; Lissewski, C.; Bertola, D.; Flex, E.; Stark, Z.; Spranger, S.; Baynam, G.; Buscarilli, M.; Dyack, S.; Gillis, J.; Yntema, H.G.; Pantaleoni, F.; Loon, R.L. van; MacKay, S.; Mina, K.; Schanze, I.; Tan, T.Y.; Walsh, M.; White, S.M.; Niewisch, M.R.; Garcia-Minaur, S.; Plaza, D.; Ahmadian, M.R.; Cave, H.; Tartaglia, M.; Zenker, M.

2017-01-01

RASopathies comprise a group of disorders clinically characterized by short stature, heart defects, facial dysmorphism, and varying degrees of intellectual disability and cancer predisposition. They are caused by germline variants in genes encoding key components or modulators of the highly

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

Directory of Open Access Journals (Sweden)

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

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

Human germline hedgehog pathway mutations predispose to fatty liver.

Science.gov (United States)

Guillen-Sacoto, Maria J; Martinez, Ariel F; Abe, Yu; Kruszka, Paul; Weiss, Karin; Everson, Joshua L; Bataller, Ramon; Kleiner, David E; Ward, Jerrold M; Sulik, Kathleen K; Lipinski, Robert J; Solomon, Benjamin D; Muenke, Maximilian

2017-10-01

Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease. Activation of hedgehog (Hh) signaling has been implicated in the progression of NAFLD and proposed as a therapeutic target; however, the effects of Hh signaling inhibition have not been studied in humans with germline mutations that affect this pathway. Patients with holoprosencephaly (HPE), a disorder associated with germline mutations disrupting Sonic hedgehog (SHH) signaling, were clinically evaluated for NAFLD. A combined mouse model of Hh signaling attenuation (Gli2 heterozygous null: Gli2 +/- ) and diet-induced NAFLD was used to examine aspects of NAFLD and hepatic gene expression profiles, including molecular markers of hepatic fibrosis and inflammation. Patients with HPE had a higher prevalence of liver steatosis compared to the general population, independent of obesity. Exposure of Gli2 +/- mice to fatty liver-inducing diets resulted in increased liver steatosis compared to wild-type mice. Similar to humans, this effect was independent of obesity in the mutant mice and was associated with decreased expression of pro-fibrotic and pro-inflammatory genes, and increased expression of PPARγ, a potent anti-fibrogenic and anti-inflammatory regulator. Interestingly, tumor suppressors p53 and p16INK4 were found to be downregulated in the Gli2 +/- mice exposed to a high-fat diet. Our results indicate that germline mutations disrupting Hh signaling promotes liver steatosis, independent of obesity, with reduced fibrosis. While Hh signaling inhibition has been associated with a better NAFLD prognosis, further studies are required to evaluate the long-term effects of mutations affecting this pathway. Lay summary: Non-alcoholic fatty liver disease (NAFLD) is characterized by excess fat deposition in the liver predominantly due to high calorie intake and a sedentary lifestyle. NAFLD progression is usually accompanied by activation of the Sonic hedgehog (SHH) pathway leading to fibrous

Germline-specific MATH-BTB substrate adaptor MAB1 regulates spindle length and nuclei identity in maize.

Science.gov (United States)

Juranič, Martina; Srilunchang, Kanok-orn; Krohn, Nádia Graciele; Leljak-Levanic, Dunja; Sprunck, Stefanie; Dresselhaus, Thomas

2012-12-01

Germline and early embryo development constitute ideal model systems to study the establishment of polarity, cell identity, and asymmetric cell divisions (ACDs) in plants. We describe here the function of the MATH-BTB domain protein MAB1 that is exclusively expressed in the germ lineages and the zygote of maize (Zea mays). mab1 (RNA interference [RNAi]) mutant plants display chromosome segregation defects and short spindles during meiosis that cause insufficient separation and migration of nuclei. After the meiosis-to-mitosis transition, two attached nuclei of similar identity are formed in mab1 (RNAi) mutants leading to an arrest of further germline development. Transient expression studies of MAB1 in tobacco (Nicotiana tabacum) Bright Yellow-2 cells revealed a cell cycle-dependent nuclear localization pattern but no direct colocalization with the spindle apparatus. MAB1 is able to form homodimers and interacts with the E3 ubiquitin ligase component Cullin 3a (CUL3a) in the cytoplasm, likely as a substrate-specific adapter protein. The microtubule-severing subunit p60 of katanin was identified as a candidate substrate for MAB1, suggesting that MAB1 resembles the animal key ACD regulator Maternal Effect Lethal 26 (MEL-26). In summary, our findings provide further evidence for the importance of posttranslational regulation for asymmetric divisions and germline progression in plants and identified an unstable key protein that seems to be involved in regulating the stability of a spindle apparatus regulator(s).

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...

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

Effect of heat treatment regime on structural lamination in ferritic-austenitic steels

International Nuclear Information System (INIS)

Sizov, R.A.; Zakharova, M.I.; Novikov, I.I.; Bannykh, O.A.

1983-01-01

The effect of preliminary thermal treatment on lamination and viscosity of EhP-53 and KO-3 steels after durable aging at the temperature of 350 is studied. It is shown that preliminary heat treatment considerably affects lamination processes in the result of aging of 0Kh18G8N2T steel. The lowest rate of lamination and higher impact strength after aging at 350 deg C for 4500 hours corresponds to the following heat treatment: 10 hour aging at 650 deg C with cooling in the air, then quenching in water from 950 deg C after aging for 30 min and the following tempering (650 deg C, 5 hours). Unlike the 0Kh18G8N2T steel, lamination parameters of steel 0Kh22N6T practically do not change after the application of heat treatment. Nevertherless, taking into account results of impact strength, it is advisable to have thermal treatment according to the regime: quenching in water at 950 deg C after aging for 30 min

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...

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.

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...

Global transcriptional repression in C. elegans germline precursors by regulated sequestration of TAF-4.

Science.gov (United States)

Guven-Ozkan, Tugba; Nishi, Yuichi; Robertson, Scott M; Lin, Rueyling

2008-10-03

In C. elegans, four asymmetric divisions, beginning with the zygote (P0), generate transcriptionally repressed germline blastomeres (P1-P4) and somatic sisters that become transcriptionally active. The protein PIE-1 represses transcription in the later germline blastomeres but not in the earlier germline blastomeres P0 and P1. We show here that OMA-1 and OMA-2, previously shown to regulate oocyte maturation, repress transcription in P0 and P1 by binding to and sequestering in the cytoplasm TAF-4, a component critical for assembly of TFIID and the pol II preinitiation complex. OMA-1/2 binding to TAF-4 is developmentally regulated, requiring phosphorylation by the DYRK kinase MBK-2, which is activated at meiosis II after fertilization. OMA-1/2 are normally degraded after the first mitosis, but ectopic expression of wild-type OMA-1 is sufficient to repress transcription in both somatic and later germline blastomeres. We propose that phosphorylation by MBK-2 serves as a developmental switch, converting OMA-1/2 from oocyte to embryo regulators.

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.

Biallelic germline and somatic mutations in malignant mesothelioma: multiple mutations in transcription regulators including mSWI/SNF genes.

Science.gov (United States)

Yoshikawa, Yoshie; Sato, Ayuko; Tsujimura, Tohru; Otsuki, Taiichiro; Fukuoka, Kazuya; Hasegawa, Seiki; Nakano, Takashi; Hashimoto-Tamaoki, Tomoko

2015-02-01

We detected low levels of acetylation for histone H3 tail lysines in malignant mesothelioma (MM) cell lines resistant to histone deacetylase inhibitors. To identify the possible genetic causes related to the low histone acetylation levels, whole-exome sequencing was conducted with MM cell lines established from eight patients. A mono-allelic variant of BRD1 was common to two MM cell lines with very low acetylation levels. We identified 318 homozygous protein-damaging variants/mutations (18-78 variants/mutations per patient); annotation analysis showed enrichment of the molecules associated with mammalian SWI/SNF (mSWI/SNF) chromatin remodeling complexes and co-activators that facilitate initiation of transcription. In seven of the patients, we detected a combination of variants in histone modifiers or transcription factors/co-factors, in addition to variants in mSWI/SNF. Direct sequencing showed that homozygous mutations in SMARCA4, PBRM1 and ARID2 were somatic. In one patient, homozygous germline variants were observed for SMARCC1 and SETD2 in chr3p22.1-3p14.2. These exhibited extended germline homozygosity and were in regions containing somatic mutations, leading to a loss of BAP1 and PBRM1 expression in MM cell line. Most protein-damaging variants were heterozygous in normal tissues. Heterozygous germline variants were often converted into hemizygous variants by mono-allelic deletion, and were rarely homozygous because of acquired uniparental disomy. Our findings imply that MM might develop through the somatic inactivation of mSWI/SNF complex subunits and/or histone modifiers, including BAP1, in subjects that have rare germline variants of these transcription regulators and/or transcription factors/co-factors, and in regions prone to mono-allelic deletion during oncogenesis. © 2014 UICC.

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

The role of germline promoters and I exons in cytokine-induced gene-specific class switch recombination.

Science.gov (United States)

Dunnick, Wesley A; Shi, Jian; Holden, Victoria; Fontaine, Clinton; Collins, John T

2011-01-01

Germline transcription precedes class switch recombination (CSR). The promoter regions and I exons of these germline transcripts include binding sites for activation- and cytokine-induced transcription factors, and the promoter regions/I exons are essential for CSR. Therefore, it is a strong hypothesis that the promoter/I exons regions are responsible for much of cytokine-regulated, gene-specific CSR. We tested this hypothesis by swapping the germline promoter and I exons for the murine γ1 and γ2a H chain genes in a transgene of the entire H chain C-region locus. We found that the promoter/I exon for γ1 germline transcripts can direct robust IL-4-induced recombination to the γ2a gene. In contrast, the promoter/I exon for the γ2a germline transcripts works poorly in the context of the γ1 H chain gene, resulting in expression of γ1 H chains that is level. Nevertheless, the small amount of recombination to the chimeric γ1 gene is induced by IFN-γ. These results suggest that cytokine regulation of CSR, but not the magnitude of CSR, is regulated by the promoter/I exons.

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.

Theoretical estimates of maximum fields in superconducting resonant radio frequency cavities: stability theory, disorder, and laminates

Science.gov (United States)

Liarte, Danilo B.; Posen, Sam; Transtrum, Mark K.; Catelani, Gianluigi; Liepe, Matthias; Sethna, James P.

2017-03-01

Theoretical limits to the performance of superconductors in high magnetic fields parallel to their surfaces are of key relevance to current and future accelerating cavities, especially those made of new higher-T c materials such as Nb3Sn, NbN, and MgB2. Indeed, beyond the so-called superheating field {H}{sh}, flux will spontaneously penetrate even a perfect superconducting surface and ruin the performance. We present intuitive arguments and simple estimates for {H}{sh}, and combine them with our previous rigorous calculations, which we summarize. We briefly discuss experimental measurements of the superheating field, comparing to our estimates. We explore the effects of materials anisotropy and the danger of disorder in nucleating vortex entry. Will we need to control surface orientation in the layered compound MgB2? Can we estimate theoretically whether dirt and defects make these new materials fundamentally more challenging to optimize than niobium? Finally, we discuss and analyze recent proposals to use thin superconducting layers or laminates to enhance the performance of superconducting cavities. Flux entering a laminate can lead to so-called pancake vortices; we consider the physics of the dislocation motion and potential re-annihilation or stabilization of these vortices after their entry.

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.

Germline competence of mouse ES and iPS cell lines: Chimera technologies and genetic background.

Science.gov (United States)

Carstea, Ana Claudia; Pirity, Melinda K; Dinnyes, Andras

2009-12-31

In mice, gene targeting by homologous recombination continues to play an essential role in the understanding of functional genomics. This strategy allows precise location of the site of transgene integration and is most commonly used to ablate gene expression ("knock-out"), or to introduce mutant or modified alleles at the locus of interest ("knock-in"). The efficacy of producing live, transgenic mice challenges our understanding of this complex process, and of the factors which influence germline competence of embryonic stem cell lines. Increasingly, evidence indicates that culture conditions and in vitro manipulation can affect the germline-competence of Embryonic Stem cell (ES cell) lines by accumulation of chromosome abnormalities and/or epigenetic alterations of the ES cell genome. The effectiveness of ES cell derivation is greatly strain-dependent and it may also influence the germline transmission capability. Recent technical improvements in the production of germline chimeras have been focused on means of generating ES cells lines with a higher germline potential. There are a number of options for generating chimeras from ES cells (ES chimera mice); however, each method has its advantages and disadvantages. Recent developments in induced pluripotent stem (iPS) cell technology have opened new avenues for generation of animals from genetically modified somatic cells by means of chimera technologies. The aim of this review is to give a brief account of how the factors mentioned above are influencing the germline transmission capacity and the developmental potential of mouse pluripotent stem cell lines. The most recent methods for generating specifically ES and iPS chimera mice, including the advantages and disadvantages of each method are also discussed.

Neurotransmitter Transporter-Like: a male germline-specific SLC6 transporter required for Drosophila spermiogenesis.

Directory of Open Access Journals (Sweden)

Nabanita Chatterjee

2011-01-01

Full Text Available The SLC6 class of membrane transporters, known primarily as neurotransmitter transporters, is increasingly appreciated for its roles in nutritional uptake of amino acids and other developmentally specific functions. A Drosophila SLC6 gene, Neurotransmitter transporter-like (Ntl, is expressed only in the male germline. Mobilization of a transposon inserted near the 3' end of the Ntl coding region yields male-sterile mutants defining a single complementation group. Germline transformation with Ntl cDNAs under control of male germline-specific control elements restores Ntl/Ntl homozygotes to normal fertility, indicating that Ntl is required only in the germ cells. In mutant males, sperm morphogenesis appears normal, with elongated, individualized and coiled spermiogenic cysts accumulating at the base of the testes. However, no sperm are transferred to the seminal vesicle. The level of polyglycylation of Ntl mutant sperm tubulin appears to be significantly lower than that of wild type controls. Glycine transporters are the most closely related SLC6 transporters to Ntl, suggesting that Ntl functions as a glycine transporter in developing sperm, where augmentation of the cytosolic pool of glycine may be required for the polyglycylation of the massive amounts of tubulin in the fly's giant sperm. The male-sterile phenotype of Ntl mutants may provide a powerful genetic system for studying the function of an SLC6 transporter family in a model organism.

Method and Apparatus for High-Permeability Magnetostrictive/Piezo-Fiber Laminates Having Colossal, Near-Ideal Magnetoelectricity

OpenAIRE

2007-01-01

An ME composite laminate of at least one (1-3) piezo-fiber layer coupled with high-permeability alloy magnetostrictive layers, optionally formed of FeBSiC or equivalent. The composite laminate alternates the (1-3) piezo-fiber and high-permeability alloy magnetostrictive layers in a stacked manner. Optionally, the magnetization direction of the high-permeability alloy magnetostrictive layers and polarization direction of the piezo-fiber layer are an (L-L) arrangement. Optionally, thin film pol...

Germline-specific H1 variants: the "sexy" linker histones.

Science.gov (United States)

Pérez-Montero, Salvador; Carbonell, Albert; Azorín, Fernando

2016-03-01

The eukaryotic genome is packed into chromatin, a nucleoprotein complex mainly formed by the interaction of DNA with the abundant basic histone proteins. The fundamental structural and functional subunit of chromatin is the nucleosome core particle, which is composed by 146 bp of DNA wrapped around an octameric protein complex formed by two copies of each core histone H2A, H2B, H3, and H4. In addition, although not an intrinsic component of the nucleosome core particle, linker histone H1 directly interacts with it in a monomeric form. Histone H1 binds nucleosomes near the exit/entry sites of linker DNA, determines nucleosome repeat length and stabilizes higher-order organization of nucleosomes into the ∼30 nm chromatin fiber. In comparison to core histones, histone H1 is less well conserved through evolution. Furthermore, histone H1 composition in metazoans is generally complex with most species containing multiple variants that play redundant as well as specific functions. In this regard, a characteristic feature is the presence of specific H1 variants that replace somatic H1s in the germline and during early embryogenesis. In this review, we summarize our current knowledge about their structural and functional properties.

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.

Hybridizing polypyrrole chains with laminated and two-dimensional Ti3C2Tx toward high-performance electromagnetic wave absorption

Science.gov (United States)

Tong, Yuan; He, Man; Zhou, Yuming; Zhong, Xi; Fan, Lidan; Huang, Tingyuan; Liao, Qiang; Wang, Yongjuan

2018-03-01

In this study, multilayer sandwich heterostructural Ti3C2Tx MXenes decorated with polypyrrole chains have been synthesized successfully via HF etching treatment and in-situ chemical oxidative polymerization approach. The hybrids were investigated as EM wave absorbers for the first time. It is found that the composites consisting of 25 wt% Ti3C2Tx/PPy hybrids in a paraffin matrix exhibit a minimum reflection loss of -49.2 dB (∼99.99% absorption) at the thickness of 3.2 mm and a maximum effective absorption bandwidth of 4.9 GHz (12.4-17.3 GHz) corresponding to an absorber thickness of 2.0 mm. Additionally, a broad effective absorption bandwidth of 13.7 GHz (4.3-18.0 GHz) can be reached up by adjusting the thickness from 1.5 to 5.0 mm. Furthermore, the highest effective absorption bandwidth of 5.7 GHz can be reached when the mass fraction is 15 wt%. The enhanced comprehensive electromagnetic wave absorption has close correlation with the well-designed heterogeneous multilayered microstructure, generated heterogeneous interfaces, conductive paths, surface functional groups, localized defects and synergistic effect between laminated Ti3C2Tx and conductive polypyrrole network, which significantly improve impedance matching and attenuation abilities. The superior absorbing performance together with strong absorption and broad bandwidth endows the Ti3C2Tx/PPy hybrids with the potential prospect to be advanced EM wave absorbers.

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...

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

Directory of Open Access Journals (Sweden)

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.

Modeling and Chaotic Dynamics of the Laminated Composite Piezoelectric Rectangular Plate

Directory of Open Access Journals (Sweden)

Minghui Yao

2014-01-01

Full Text Available This paper investigates the multipulse heteroclinic bifurcations and chaotic dynamics of a laminated composite piezoelectric rectangular plate by using an extended Melnikov method in the resonant case. According to the von Karman type equations, Reddy’s third-order shear deformation plate theory, and Hamilton’s principle, the equations of motion are derived for the laminated composite piezoelectric rectangular plate with combined parametric excitations and transverse excitation. The method of multiple scales and Galerkin’s approach are applied to the partial differential governing equation. Then, the four-dimensional averaged equation is obtained for the case of 1 : 3 internal resonance and primary parametric resonance. The extended Melnikov method is used to study the Shilnikov type multipulse heteroclinic bifurcations and chaotic dynamics of the laminated composite piezoelectric rectangular plate. The necessary conditions of the existence for the Shilnikov type multipulse chaotic dynamics are analytically obtained. From the investigation, the geometric structure of the multipulse orbits is described in the four-dimensional phase space. Numerical simulations show that the Shilnikov type multipulse chaotic motions can occur. To sum up, both theoretical and numerical studies suggest that chaos for the Smale horseshoe sense in motion exists for the laminated composite piezoelectric rectangular plate.

Germline-Specific MATH-BTB Substrate Adaptor MAB1 Regulates Spindle Length and Nuclei Identity in Maize[W

Science.gov (United States)

Juranić, Martina; Srilunchang, Kanok-orn; Krohn, Nádia Graciele; Leljak-Levanić, Dunja; Sprunck, Stefanie; Dresselhaus, Thomas

2012-01-01

Germline and early embryo development constitute ideal model systems to study the establishment of polarity, cell identity, and asymmetric cell divisions (ACDs) in plants. We describe here the function of the MATH-BTB domain protein MAB1 that is exclusively expressed in the germ lineages and the zygote of maize (Zea mays). mab1 (RNA interference [RNAi]) mutant plants display chromosome segregation defects and short spindles during meiosis that cause insufficient separation and migration of nuclei. After the meiosis-to-mitosis transition, two attached nuclei of similar identity are formed in mab1 (RNAi) mutants leading to an arrest of further germline development. Transient expression studies of MAB1 in tobacco (Nicotiana tabacum) Bright Yellow-2 cells revealed a cell cycle–dependent nuclear localization pattern but no direct colocalization with the spindle apparatus. MAB1 is able to form homodimers and interacts with the E3 ubiquitin ligase component Cullin 3a (CUL3a) in the cytoplasm, likely as a substrate-specific adapter protein. The microtubule-severing subunit p60 of katanin was identified as a candidate substrate for MAB1, suggesting that MAB1 resembles the animal key ACD regulator Maternal Effect Lethal 26 (MEL-26). In summary, our findings provide further evidence for the importance of posttranslational regulation for asymmetric divisions and germline progression in plants and identified an unstable key protein that seems to be involved in regulating the stability of a spindle apparatus regulator(s). PMID:23250449

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.

Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing.

Science.gov (United States)

Mandelker, Diana; Zhang, Liying; Kemel, Yelena; Stadler, Zsofia K; Joseph, Vijai; Zehir, Ahmet; Pradhan, Nisha; Arnold, Angela; Walsh, Michael F; Li, Yirong; Balakrishnan, Anoop R; Syed, Aijazuddin; Prasad, Meera; Nafa, Khedoudja; Carlo, Maria I; Cadoo, Karen A; Sheehan, Meg; Fleischut, Megan H; Salo-Mullen, Erin; Trottier, Magan; Lipkin, Steven M; Lincoln, Anne; Mukherjee, Semanti; Ravichandran, Vignesh; Cambria, Roy; Galle, Jesse; Abida, Wassim; Arcila, Marcia E; Benayed, Ryma; Shah, Ronak; Yu, Kenneth; Bajorin, Dean F; Coleman, Jonathan A; Leach, Steven D; Lowery, Maeve A; Garcia-Aguilar, Julio; Kantoff, Philip W; Sawyers, Charles L; Dickler, Maura N; Saltz, Leonard; Motzer, Robert J; O'Reilly, Eileen M; Scher, Howard I; Baselga, Jose; Klimstra, David S; Solit, David B; Hyman, David M; Berger, Michael F; Ladanyi, Marc; Robson, Mark E; Offit, Kenneth

2017-09-05

Guidelines for cancer genetic testing based on family history may miss clinically actionable genetic changes with established implications for cancer screening or prevention. To determine the proportion and potential clinical implications of inherited variants detected using simultaneous sequencing of the tumor and normal tissue ("tumor-normal sequencing") compared with genetic test results based on current guidelines. From January 2014 until May 2016 at Memorial Sloan Kettering Cancer Center, 10 336 patients consented to tumor DNA sequencing. Since May 2015, 1040 of these patients with advanced cancer were referred by their oncologists for germline analysis of 76 cancer predisposition genes. Patients with clinically actionable inherited mutations whose genetic test results would not have been predicted by published decision rules were identified. Follow-up for potential clinical implications of mutation detection was through May 2017. Tumor and germline sequencing compared with the predicted yield of targeted germline sequencing based on clinical guidelines. Proportion of clinically actionable germline mutations detected by universal tumor-normal sequencing that would not have been detected by guideline-directed testing. Of 1040 patients, the median age was 58 years (interquartile range, 50.5-66 years), 65.3% were male, and 81.3% had stage IV disease at the time of genomic analysis, with prostate, renal, pancreatic, breast, and colon cancer as the most common diagnoses. Of the 1040 patients, 182 (17.5%; 95% CI, 15.3%-19.9%) had clinically actionable mutations conferring cancer susceptibility, including 149 with moderate- to high-penetrance mutations; 101 patients tested (9.7%; 95% CI, 8.1%-11.7%) would not have had these mutations detected using clinical guidelines, including 65 with moderate- to high-penetrance mutations. Frequency of inherited mutations was related to case mix, stage, and founder mutations. Germline findings led to discussion or initiation of

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.)

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...

Integrated tumor and germline whole-exome sequencing identifies mutations in MAPK and PI3K pathway genes in an adolescent with rosette-forming glioneuronal tumor of the fourth ventricle

Science.gov (United States)

Lin, Frank Y.; Bergstrom, Katie; Person, Richard; Bavle, Abhishek; Ballester, Leomar Y.; Scollon, Sarah; Raesz-Martinez, Robin; Jea, Andrew; Birchansky, Sherri; Wheeler, David A.; Berg, Stacey L.; Chintagumpala, Murali M.; Adesina, Adekunle M.; Eng, Christine; Roy, Angshumoy; Plon, Sharon E.; Parsons, D. Williams

2016-01-01

The integration of genome-scale studies such as whole-exome sequencing (WES) into the clinical care of children with cancer has the potential to provide insight into the genetic basis of an individual's cancer with implications for clinical management. This report describes the results of clinical tumor and germline WES for a patient with a rare tumor diagnosis, rosette-forming glioneuronal tumor of the fourth ventricle (RGNT). Three pathogenic gene alterations with implications for clinical care were identified: somatic activating hotspot mutations in FGFR1 (p.N546K) and PIK3CA (p.H1047R) and a germline pathogenic variant in PTPN11 (p.N308S) diagnostic for Noonan syndrome. The molecular landscape of RGNT is not well-described, but these data are consistent with prior observations regarding the importance of the interconnected MAPK and PI3K/AKT/mTOR signaling pathways in this rare tumor. The co-occurrence of FGFR1, PIK3CA, and PTPN11 alterations provides further evidence for consideration of RGNT as a distinct molecular entity from pediatric low-grade gliomas and suggests potential therapeutic strategies for this patient in the event of tumor recurrence as novel agents targeting these pathways enter pediatric clinical trials. Although RGNT has not been definitively linked with cancer predisposition syndromes, two prior cases have been reported in patients with RASopathies (Noonan syndrome and neurofibromatosis type 1 [NF1]), providing an additional link between these tumors and the mitogen-activated protein kinase (MAPK) signaling pathway. In summary, this case provides an example of the potential for genome-scale sequencing technologies to provide insight into the biology of rare tumors and yield both tumor and germline results of potential relevance to patient care. PMID:27626068

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.

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.

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

Science.gov (United States)

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).

Correlation of FCGR3A and EGFR germline polymorphisms with the efficacy of cetuximab in KRAS wild-type metastatic colorectal cancer

NARCIS (Netherlands)

Pander, Jan; Gelderblom, Hans; Antonini, Ninja F.; Tol, Jolien; van Krieken, Johan H. J. M.; van der Straaten, Tahar; Punt, Cornelis J. A.; Guchelaar, Henk-Jan

2010-01-01

Next to KRAS mutation status, additional predictive markers are needed for the response to cetuximab in patients with metastatic colorectal cancer (mCRC). Previous studies indicated that germline polymorphisms in specific genes may predict efficacy and toxicity of cetuximab in mCRC patients.

Study of the Formability of Laminated Lightweight Metallic Materials

Directory of Open Access Journals (Sweden)

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.

Preleukemic and second-hit mutational events in an acute myeloid leukemia patient with a novel germline RUNX1 mutation.

Science.gov (United States)

Ng, Isaac Ks; Lee, Joanne; Ng, Christopher; Kosmo, Bustamin; Chiu, Lily; Seah, Elaine; Mok, Michelle Meng Huang; Tan, Karen; Osato, Motomi; Chng, Wee-Joo; Yan, Benedict; Tan, Lip Kun

2018-01-01

Germline mutations in the RUNX1 transcription factor give rise to a rare autosomal dominant genetic condition classified under the entity: Familial Platelet Disorders with predisposition to Acute Myeloid Leukaemia (FPD/AML). While several studies have identified a myriad of germline RUNX1 mutations implicated in this disorder, second-hit mutational events are necessary for patients with hereditary thrombocytopenia to develop full-blown AML. The molecular picture behind this process remains unclear. We describe a patient of Malay descent with an unreported 7-bp germline RUNX1 frameshift deletion, who developed second-hit mutations that could have brought about the leukaemic transformation from a pre-leukaemic state. These mutations were charted through the course of the treatment and stem cell transplant, showing a clear correlation between her clinical presentation and the mutations present. The patient was a 27-year-old Malay woman who presented with AML on the background of hereditary thrombocytopenia affecting her father and 3 brothers. Initial molecular testing revealed the same novel RUNX1 mutation in all 5 individuals. The patient received standard induction, consolidation chemotherapy, and a haploidentical stem cell transplant from her mother with normal RUNX1 profile. Comprehensive genomic analyses were performed at diagnosis, post-chemotherapy and post-transplant. A total of 8 mutations ( RUNX1 , GATA2 , DNMT3A , BCORL1 , BCOR , 2 PHF6 and CDKN2A ) were identified in the pre-induction sample, of which 5 remained ( RUNX1 , DNMT3A , BCORL1 , BCOR and 1 out of 2 PHF6 ) in the post-treatment sample and none were present post-transplant. In brief, the 3 mutations which were lost along with the leukemic cells at complete morphological remission were most likely acquired leukemic driver mutations that were responsible for the AML transformation from a pre-leukemic germline RUNX1 -mutated state. On the contrary, the 5 mutations that persisted post

Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer.

Science.gov (United States)

Li, Junyan; Jing, Ruilin; Wei, Hongyi; Wang, Minghao; Qi, Xiaowei; Liu, Haoxi; Liu, Jian; Ou, Jianghua; Jiang, Weihua; Tian, Fuguo; Sheng, Yuan; Li, Hengyu; Xu, Hong; Zhang, Ruishan; Guan, Aihua; Liu, Ke; Jiang, Hongchuan; Ren, Yu; He, Jianjun; Huang, Weiwei; Liao, Ning; Cai, Xiangjun; Ming, Jia; Ling, Rui; Xu, Yan; Hu, Chunyan; Zhang, Jianguo; Guo, Baoliang; Ouyang, Lizhi; Shuai, Ping; Liu, Zhenzhen; Zhong, Ling; Zeng, Zhen; Zhang, Ting; Xuan, Zhaoling; Tan, Xuanni; Liang, Junbin; Pan, Qinwen; Chen, Li; Zhang, Fan; Fan, Linjun; Zhang, Yi; Yang, Xinhua; Li, Jingbo; Chen, Chongjian; Jiang, Jun

2018-05-12

Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n=937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n=18), PALB2 (n=11), CHEK2 (n=6), ATM (n=6), and BARD1 (n=5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rates (1.9% and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes. This article is protected by copyright. All rights reserved. © 2018 UICC.

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...

Histologic and inflammatory lamellar changes in horses with oligofructose-induced laminitis treated with a CXCR1/2 antagonist

Directory of Open Access Journals (Sweden)

Leonardo R. de Lima

2016-01-01

Full Text Available Abstract: With the hypothesis that blocking chemokine signaling can ameliorate acute laminitis, the aim was to evaluate the therapeutic effect of intravenous DF1681B, a selective antagonist for CXCR1 and CXCR2 (chemokine receptors, in an oligofructose equine laminitis model. To twelve mixed breed clinically healthy hoses with no previous history of hoof-related lameness was administered oligofructose (10g/kg given by nasogastric tube and divided into two groups: treated (intravenous DF1681B at 30mg/kg 6, 12, 18, and 24h after oligofructose and non-treated groups. Laminar biopsies were performed before and 12, 36, and 72h after administering oligofructose. Samples were stained with periodic acid-Schiff (PAS and scored from 0 to 6 according to epidermal cell and basal membrane changes. The IL-1β, IL-6, and CXCL1 RNA expressions were determined by RT-PCR. Parametric and non-parametric tests were used to compare times within each group (P<0.05. The PAS grades and IL-1β and IL-6 RNA expression increased in the non-treated group, but remained constant in the treated horses. In conclusion, DF1681B therapy reduced laminar inflammation and epidermal deterioration in treated horses. CXCR1/2 blockage should be considered therapeutically for equine acute laminitis.

About LTCC materials in the substance system of CaO-La{sub 2}O{sub 3}-Al{sub 2}O{sub 3}-B{sub 2}O{sub 3}; Ueber LTCC-Werkstoffe aus dem Stoffsystem CaO-La{sub 2}O{sub 3}-Al{sub 2}O{sub 3}-B{sub 2}O{sub 3}

Energy Technology Data Exchange (ETDEWEB)

Gemeinert, Marion

2009-09-01

Glass ceramic composites made of glassy and crystalline powders offer numerous possibilities for modifying materials properties e.g. sintering behaviour, thermal expansion coefficient, mechanical behaviour, chemical durability, dielectric properties and surface quality for special use. Glass ceramic composite powders can be used for the production of ceramic green tapes which are processed by LTCC (Low Temperature Co-fired Ceramics)- technology to form ceramic multilayers for electronic packaging in microsystems. During free sintering of LTCC-multilayers a lateral shrinkage occurs which is connected with a comparatively high shrinkage tolerance. Different sintering technologies are used to avoid the lateral shrinkage. A new possibility to achieve a zero lateral shrinkage is given by use of a self-constrained laminate. Therefore a multilayer is produced of two different materials for inner and outer layers, showing different sintering temperatures ({delta}T>50 K). Object of this dissertation was the development of LTCC-materials, which can be used for inner layers of a self-constrained laminate to reduce the lateral shrinkage nearly to zero. Therefore LTCC-materials in the field of CaO-La{sub 2}O{sub 3}-Al{sub 2}O{sub 3}-B{sub 2}O{sub 3}, which can be sintered below 800 C, were investigated. Starting from the development of adapted glasses based on calcium lanthanium borate- and calcium lanthanium alumoborate glasses glass ceramic composites were produced by the addition of corundum powder. The composites crystallize during the sintering process almost completely. Lanthanum borate crystallizes from the glassy phase and calcium alumoborate and calcium alumoborate oxide respectively is formed by a chemical solid state reaction of the residual glassy phase, which is enriched by calcium borate, and the corundum. The proportional relation of the new crystalline phases determines the thermal and dielectric properties of the material. The most important formed new

Germ-line mutations of the p53 tumor suppressor gene in patients with high risk for cancer inactivate the p53 protein.

Science.gov (United States)

Frebourg, T; Kassel, J; Lam, K T; Gryka, M A; Barbier, N; Andersen, T I; Børresen, A L; Friend, S H

1992-07-15

Germ-line mutations in the p53 tumor suppressor gene have been observed in patients with Li-Fraumeni syndrome, brain tumors, second malignancies, and breast cancers. It is unclear whether all of these mutations have inactivated p53 and thereby provide an increased risk for cancer. Therefore, it is necessary to establish the biological significance of these germ-line mutations by the functional and structural analysis of the resulting mutant p53 proteins. We analyzed the ability of seven germ-line mutant proteins observed in patients with Li-Fraumeni syndrome, second primary neoplasms, or familial breast cancer to block the growth of malignant cells and compared the structural properties of the mutant proteins to that of the wild-type protein. Six of seven missense mutations disrupted the growth inhibitory properties and structure of the wild-type protein. One germ-line mutation retained the features of the wild-type p53. Genetic analysis of the breast cancer family in which this mutation was observed indicated that this germ-line mutation was not associated with the development of cancer. These results demonstrate that germ-line p53 mutations observed in patients with Li-Fraumeni syndrome and with second malignancies have inactivated the p53 tumor suppressor gene. The inability of the germ-line p53 mutants to block the growth of malignant cells can explain why patients with these germ-line mutations have an increased risk for cancer. The observation of a functionally silent germ-line mutation indicates that, before associating a germ-line tumor suppressor gene mutation with cancer risk, it is prudent to consider its functional significance.

Germ-line mutations of the p53 tumor suppressor gene in patients with high risk for cancer inactivate the p53 protein.

Science.gov (United States)

Frebourg, T; Kassel, J; Lam, K T; Gryka, M A; Barbier, N; Andersen, T I; Børresen, A L; Friend, S H

1992-01-01

Germ-line mutations in the p53 tumor suppressor gene have been observed in patients with Li-Fraumeni syndrome, brain tumors, second malignancies, and breast cancers. It is unclear whether all of these mutations have inactivated p53 and thereby provide an increased risk for cancer. Therefore, it is necessary to establish the biological significance of these germ-line mutations by the functional and structural analysis of the resulting mutant p53 proteins. We analyzed the ability of seven germ-line mutant proteins observed in patients with Li-Fraumeni syndrome, second primary neoplasms, or familial breast cancer to block the growth of malignant cells and compared the structural properties of the mutant proteins to that of the wild-type protein. Six of seven missense mutations disrupted the growth inhibitory properties and structure of the wild-type protein. One germ-line mutation retained the features of the wild-type p53. Genetic analysis of the breast cancer family in which this mutation was observed indicated that this germ-line mutation was not associated with the development of cancer. These results demonstrate that germ-line p53 mutations observed in patients with Li-Fraumeni syndrome and with second malignancies have inactivated the p53 tumor suppressor gene. The inability of the germ-line p53 mutants to block the growth of malignant cells can explain why patients with these germ-line mutations have an increased risk for cancer. The observation of a functionally silent germ-line mutation indicates that, before associating a germ-line tumor suppressor gene mutation with cancer risk, it is prudent to consider its functional significance. Images PMID:1631137

Proven germline mosaicism in a father of two children with CHARGE syndrome.

Science.gov (United States)

Pauli, S; Pieper, L; Häberle, J; Grzmil, P; Burfeind, P; Steckel, M; Lenz, U; Michelmann, H W

2009-05-01

CHARGE syndrome is an autosomal dominant malformation syndrome caused by mutations in the CHD7 gene. The majority of cases are sporadic and only few familial cases have been reported. In these families, mosaicism in one parent, as well as parent- to-child transmission of a CHD7 mutation, has been described. In some further cases, germline mosaicism has been suggested. Here, we report the first case in which germline mosaicism could be demonstrated in a father of two affected children with CHARGE syndrome. The truncating mutation c.7302dupA in exon 34 of the CHD7 gene was found in both affected children but was not detected in parental lymphocytes. However, in DNA extracted from the father's spermatozoa, the c.7302dupA mutation could be identified. Furthermore, mutation analysis of DNA isolated from 59 single spermatozoa revealed that the c.7302dupA mutation occurs in 16 spermatozoa, confirming germline mosaicism in the father of the affected children. This result has a high impact for genetic counselling of the family and for their recurrence risk in further pregnancies.

The signature of somatic hypermutation appears to be written into the germline IgV segment repertoire.

Science.gov (United States)

Blanden, R V; Rothenfluh, H S; Zylstra, P; Weiller, G F; Steele, E J

1998-04-01

We present here a unifying hypothesis for the molecular mechanism of somatic hypermutation and somatic gene conversion in IgV genes involving reverse transcription using RNA templates from the V-gene loci to produce cDNA which undergoes homologous recombination with chromosomal V(D)J DNA. Experimental evidence produced over the last 20 years is essentially consistent with this hypothesis. We also review evidence suggesting that somatically generated IgV sequences from B lymphocytes have been fed back to germline DNA over evolutionary time.

The Fanconi anemia DNA damage repair pathway in the spotlight for germline predisposition to colorectal cancer.

Science.gov (United States)

Esteban-Jurado, Clara; Franch-Expósito, Sebastià; Muñoz, Jenifer; Ocaña, Teresa; Carballal, Sabela; López-Cerón, Maria; Cuatrecasas, Miriam; Vila-Casadesús, Maria; Lozano, Juan José; Serra, Enric; Beltran, Sergi; Brea-Fernández, Alejandro; Ruiz-Ponte, Clara; Castells, Antoni; Bujanda, Luis; Garre, Pilar; Caldés, Trinidad; Cubiella, Joaquín; Balaguer, Francesc; Castellví-Bel, Sergi

2016-10-01

Colorectal cancer (CRC) is one of the most common neoplasms in the world. Fanconi anemia (FA) is a very rare genetic disease causing bone marrow failure, congenital growth abnormalities and cancer predisposition. The comprehensive FA DNA damage repair pathway requires the collaboration of 53 proteins and it is necessary to restore genome integrity by efficiently repairing damaged DNA. A link between FA genes in breast and ovarian cancer germline predisposition has been previously suggested. We selected 74 CRC patients from 40 unrelated Spanish families with strong CRC aggregation compatible with an autosomal dominant pattern of inheritance and without mutations in known hereditary CRC genes and performed germline DNA whole-exome sequencing with the aim of finding new candidate germline predisposition variants. After sequencing and data analysis, variant prioritization selected only those very rare alterations, producing a putative loss of function and located in genes with a role compatible with cancer. We detected an enrichment for variants in FA DNA damage repair pathway genes in our familial CRC cohort as 6 families carried heterozygous, rare, potentially pathogenic variants located in BRCA2/FANCD1, BRIP1/FANCJ, FANCC, FANCE and REV3L/POLZ. In conclusion, the FA DNA damage repair pathway may play an important role in the inherited predisposition to CRC.

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

The protein kinase MBK-1 contributes to lifespan extension in daf-2 mutant and germline-deficient Caenorhabditis elegans.

Science.gov (United States)

Mack, Hildegard I D; Zhang, Peichuan; Fonslow, Bryan R; Yates, John R

2017-05-25

In Caenorhabditis elegans , reduction of insulin/IGF-1 like signaling and loss of germline stem cells both increase lifespan by activating the conserved transcription factor DAF-16 (FOXO). While the mechanisms that regulate DAF-16 nuclear localization in response to insulin/IGF-1 like signaling are well characterized, the molecular pathways that act in parallel to regulate DAF-16 transcriptional activity, and the pathways that couple DAF-16 activity to germline status, are not fully understood at present. Here, we report that inactivation of MBK-1, the C. elegans ortholog of the human FOXO1-kinase DYRK1A substantially shortens the prolonged lifespan of daf-2 and glp-1 mutant animals while decreasing wild-type lifespan to a lesser extent. On the other hand, lifespan-reduction by mutation of the MBK-1-related kinase HPK-1 was not preferential for long-lived mutants. Interestingly, mbk-1 loss still allowed for DAF-16 nuclear accumulation but reduced expression of certain DAF-16 target genes in germline-less, but not in daf-2 mutant animals. These findings indicate that mbk-1 and daf-16 functionally interact in the germline- but not in the daf-2 pathway. Together, our data suggest mbk-1 as a novel regulator of C. elegans longevity upon both, germline ablation and DAF-2 inhibition, and provide evidence for mbk-1 regulating DAF-16 activity in germline-deficient animals.

Germline PMS2 mutation screened by mismatch repair protein immunohistochemistry of colorectal cancer in Japan.

Science.gov (United States)

Sugano, Kokichi; Nakajima, Takeshi; Sekine, Shigeki; Taniguchi, Hirokazu; Saito, Shinya; Takahashi, Masahiro; Ushiama, Mineko; Sakamoto, Hiromi; Yoshida, Teruhiko

2016-11-01

Germline PMS2 gene mutations were detected by RT-PCR/direct sequencing of total RNA extracted from puromycin-treated peripheral blood lymphocytes (PBL) and multiplex ligation-dependent probe amplification (MLPA) analyses of Japanese patients with colorectal cancer (CRC) fulfilling either the revised Bethesda Guidelines or being an age at disease onset of younger than 70 years, and screened by mismatch repair protein immunohistochemistry of formalin-fixed paraffin embedded sections. Of the 501 subjects examined, 7 (1.40%) showed the downregulated expression of the PMS2 protein alone and were referred to the genetic counseling clinic. Germline PMS2 mutations were detected in 6 (85.7%), including 3 nonsense and 1 frameshift mutations by RT-PCR/direct sequencing and 2 genomic deletions by MLPA. No mutations were identified in the other MMR genes (i.e. MSH2, MLH1 and MSH6). The prevalence of the downregulated expression of the PMS2 protein alone was 1.40% among the subjects examined and IHC results predicted the presence of PMS2 germline mutations. RT-PCR from puromycin-treated PBL and MLPA may be employed as the first screening step to detect PMS2 mutations without pseudogene interference, followed by the long-range PCR/nested PCR validation using genomic DNA. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Human germline gene editing: Recommendations of ESHG and ESHRE

NARCIS (Netherlands)

de Wert, Guido; Pennings, Guido; Clarke, Angus; Eichenlaub-Ritter, Ursula; van El, Carla G.; Forzano, Francesca; Goddijn, Mariëtte; Heindryckx, Björn; Howard, Heidi C.; Radojkovic, Dragica; Rial-Sebbag, Emmanuelle; Tarlatzis, Basil C.; Cornel, Martina C.

2018-01-01

Technological developments in gene editing raise high expectations for clinical applications, first of all for somatic gene editing but in theory also for germline gene editing (GLGE). GLGE is currently not allowed in many countries. This makes clinical applications in these countries impossible

Xeroderma Pigmentosum: Low Prevalence of Germline XPA Mutations in a Brazilian XP Population

Directory of Open Access Journals (Sweden)

Karina Miranda Santiago

2015-04-01

Full Text Available Xeroderma pigmentosum (XP is a rare autosomal recessive disorder characterized by DNA repair defects that cause photophobia, sunlight-induced cancers, and neurodegeneration. Prevalence of germline mutations in the nucleotide excision repair gene XPA vary significantly in different populations. No Brazilian patients have been reported to carry a germline mutation in this gene. In this study, the germline mutational status of XPA was determined in Brazilian patients exhibiting major clinical features of XP syndrome. The study was conducted on 27 unrelated patients from select Brazilian families. A biallelic inactivating transition mutation c.619C>T (p.Arg207Ter was identified in only one patient with a history of neurological impairment and mild skin abnormalities. These findings suggest that XP syndrome is rarely associated with inherited disease-causing XPA mutations in the Brazilian population. Additionally, this report demonstrates the effectiveness of genotype-phenotype correlation as a valuable tool to guide direct genetic screening.

Xeroderma pigmentosum: low prevalence of germline XPA mutations in a Brazilian XP population.

Science.gov (United States)

Santiago, Karina Miranda; França de Nóbrega, Amanda; Rocha, Rafael Malagoli; Rogatto, Silvia Regina; Achatz, Maria Isabel

2015-04-22

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by DNA repair defects that cause photophobia, sunlight-induced cancers, and neurodegeneration. Prevalence of germline mutations in the nucleotide excision repair gene XPA vary significantly in different populations. No Brazilian patients have been reported to carry a germline mutation in this gene. In this study, the germline mutational status of XPA was determined in Brazilian patients exhibiting major clinical features of XP syndrome. The study was conducted on 27 unrelated patients from select Brazilian families. A biallelic inactivating transition mutation c.619C>T (p.Arg207Ter) was identified in only one patient with a history of neurological impairment and mild skin abnormalities. These findings suggest that XP syndrome is rarely associated with inherited disease-causing XPA mutations in the Brazilian population. Additionally, this report demonstrates the effectiveness of genotype-phenotype correlation as a valuable tool to guide direct genetic screening.

EPHB2 germline variants in patients with colorectal cancer or hyperplastic polyposis

International Nuclear Information System (INIS)

Kokko, Antti; Tomlinson, Ian PM; Vahteristo, Pia; Aaltonen, Lauri A; Laiho, Päivi; Lehtonen, Rainer; Korja, Sanna; Carvajal-Carmona, Luis G; Järvinen, Heikki; Mecklin, Jukka-Pekka; Eng, Charis; Schleutker, Johanna

2006-01-01

Ephrin receptor B2 (EPHB2) has recently been proposed as a novel tumor suppressor gene in colorectal cancer (CRC). Inactivation of the gene has been shown to correlate with progression of colorectal tumorigenesis, and somatic mutations have been reported in both colorectal and prostate tumors. Here we have analyzed the EPHB2 gene for germline alterations in 101 individuals either with 1) CRC and a personal or family history of prostate cancer (PC), or 2) intestinal hyperplastic polyposis (HPP), a condition associated with malignant degeneration such as serrated adenoma and CRC. Four previously unknown missense alterations were observed, which may be associated with the disease phenotype. Two of the changes, I361V and R568W, were identified in Finnish CRC patients, but not in over 300 Finnish familial CRC or PC patients or more than 200 population-matched healthy controls. The third change, D861N, was observed in a UK HPP patient, but not in additional 40 UK HPP patients or in 200 UK healthy controls. The fourth change R80H, originally identified in a Finnish CRC patient, was also found in 1/106 familial CRC patients and in 9/281 healthy controls and is likely to be a neutral polymorphism. We detected novel germline EPHB2 alterations in patients with colorectal tumors. The results suggest a limited role for these EPHB2 variants in colon tumor predisposition. Further studies including functional analyses are needed to confirm this

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

Epigenetic modulation of cancer-germline antigen gene expression in tumorigenic human mesenchymal stem cells: implications for cancer therapy

DEFF Research Database (Denmark)

Gjerstorff, Morten; Burns, Jorge S; Nielsen, Ole

2009-01-01

Cancer-germline antigens are promising targets for cancer immunotherapy, but whether such therapies will also eliminate the primary tumor stem cell population remains undetermined. We previously showed that long-term cultures of telomerized adult human bone marrow mesenchymal stem cells can...... spontaneously evolve into tumor-initiating, mesenchymal stem cells (hMSC-TERT20), which have characteristics of clinical sarcoma cells. In this study, we used the hMSC-TERT20 tumor stem cell model to investigate the potential of cancer-germline antigens to serve as tumor stem cell targets. We found...... of cancer-germline antigens in hMSC-TERT20 cells, while their expression levels in primary human mesenchymal stem cells remained unaffected. The expression pattern of cancer-germline antigens in tumorigenic mesenchymal stem cells and sarcomas, plus their susceptibility to enhancement by epigenetic...

Stem cells are units of natural selection for tissue formation, for germline development, and in cancer development.

Science.gov (United States)

Weissman, Irving L

2015-07-21

It is obvious that natural selection operates at the level of individuals and collections of individuals. Nearly two decades ago we showed that in multi-individual colonies of protochordate colonial tunicates sharing a blood circulation, there exists an exchange of somatic stem cells and germline stem cells, resulting in somatic chimeras and stem cell competitions for gonadal niches. Stem cells are unlike other cells in the body in that they alone self-renew, so that they form clones that are perpetuated for the life of the organism. Stem cell competitions have allowed the emergence of competitive somatic and germline stem cell clones. Highly successful germline stem cells usually outcompete less successful competitors both in the gonads of the genotype partner from which they arise and in the gonads of the natural parabiotic partners. Therefore, natural selection also operates at the level of germline stem cell clones. In the colonial tunicate Botryllus schlosseri the formation of natural parabionts is prevented by a single-locus highly polymorphic histocompatibility gene called Botryllus histocompatibility factor. This limits germline stem cell predation to kin, as the locus has hundreds of alleles. We show that in mice germline stem cells compete for gonad niches, and in mice and humans, blood-forming stem cells also compete for bone marrow niches. We show that the clonal progression from blood-forming stem cells to acute leukemias by successive genetic and epigenetic events in blood stem cells also involves competition and selection between clones and propose that this is a general theme in cancer.

Prevalence of deleterious ATM germline mutations in gastric cancer patients.

Science.gov (United States)

Huang, Dong-Sheng; Tao, Hou-Quan; He, Xu-Jun; Long, Ming; Yu, Sheng; Xia, Ying-Jie; Wei, Zhang; Xiong, Zikai; Jones, Sian; He, Yiping; Yan, Hai; Wang, Xiaoyue

2015-12-01

Besides CDH1, few hereditary gastric cancer predisposition genes have been previously reported. In this study, we discovered two germline ATM mutations (p.Y1203fs and p.N1223S) in a Chinese family with a history of gastric cancer by screening 83 cancer susceptibility genes. Using a published exome sequencing dataset, we found deleterious germline mutations of ATM in 2.7% of 335 gastric cancer patients of different ethnic origins. The frequency of deleterious ATM mutations in gastric cancer patients is significantly higher than that in general population (p=0.0000435), suggesting an association of ATM mutations with gastric cancer predisposition. We also observed biallelic inactivation of ATM in tumors of two gastric cancer patients. Further evaluation of ATM mutations in hereditary gastric cancer will facilitate genetic testing and risk assessment.

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.

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 ...

Organometal halide perovskite light-emitting diodes with laminated carbon nanotube electrodes

Science.gov (United States)

Shan, Xin; Bade, Sri Ganesh R.; Geske, Thomas; Davis, Melissa; Smith, Rachel; Yu, Zhibin

2017-08-01

Organometal halide perovskite light-emitting diodes (LEDs) with laminated carbon nanotube (CNT) electrodes are reported. The LEDs have an indium tin oxide (ITO) bottom electrode, a screen printed methylammonium lead tribromide (MAPbBr3)/polymer composite thin film as the emissive layer, and laminated CNT as the top electrode. The devices can be turned on at 2.2 V, reaching a brightness of 4,960 cd m-2 and a current efficiency of 1.54 cd A-1 at 6.9 V. The greatly simplified fabrication process in this work can potentially lead to the scalable manufacturing of large size and low cost LED panels in the future.

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...

A protective effect of the laminated layer on Echinococcus granulosus survival dependent on upregulation of host arginase.

Science.gov (United States)

Amri, Manel; Touil-Boukoffa, Chafia

2015-09-01

The role of nitric oxide (NO) in host defense against Echinococcus granulosus larvae was previously reported. However, NO production by NOS2 (inducible NO synthase) is counteracted by the expression of Arginase. In the present study, our aim is to evaluate the involvement of the laminated layer (external layer of parasitic cyst) in Arginase induction and the protoscoleces (living and infective part of the cyst) survival. Our in vitro results indicate that this cystic compound increases the Arginase activity in macrophages. Moreover, C-type lectin receptors (CLRs) with specificity for mannan and the TGF-β are implicated in this effect as shown after adding Mannan and Anti-TGFβ. Interestingly, the laminated layer increases protoscoleces survival in macrophages-parasite co-cultures. Our results indicate that the laminated layer protects E. granulosus against the NOS2 protective response through Arginase pathway, a hallmark of M2 macrophages. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Global transcriptional repression in C. elegans germline precursors by regulated sequestration of TFIID component TAF-4

Science.gov (United States)

Guven-Ozkan, Tugba; Nishi, Yuichi; Robertson, Scott M.; Lin, Rueyling

2008-01-01

In C. elegans, four asymmetric divisions, beginning with the zygote (P0), generate transcriptionally repressed germline blastomeres (P1–P4) and somatic sisters that become transcriptionally active. The protein PIE-1 represses transcription in the later germline blastomeres, but not in the earlier germline blastomeres P0 and P1. We show here that OMA-1 and OMA-2, previously shown to regulate oocyte maturation, repress transcription in P0 and P1 by binding to and sequestering in the cytoplasm TAF-4, a component critical for assembly of TFIID and the pol II preinitiation complex. OMA-1/2 binding to TAF-4 is developmentally regulated, requiring phosphorylation by the DYRK kinase MBK-2, which is activated at meiosis II following fertilization. OMA-1/2 are normally degraded after the first mitosis, but ectopic expression of wildtype OMA-1 is sufficient to repress transcription in both somatic and later germline blastomeres. We propose that phosphorylation by MBK-2 serves as a developmental switch, converting OMA-1/2 from oocyte to embryo regulators. PMID:18854162

A germline FANCA alteration that is associated with increased sensitivity to DNA damaging agents.

OpenAIRE

Wilkes, David C; Sailer, Verena; Xue, Hui; Cheng, Hongwei; Collins, Colin C; Gleave, Martin; Wang, Yuzhuo; Demichelis, Francesca; Beltran, Himisha; Rubin, Mark Andrew; Rickman, David S

2017-01-01

Defects in genes involved in DNA damage repair (DDR) pathway are emerging as novel biomarkers and targets for new prostate cancer drug therapies. A previous report revealed an association between an exceptional response to cisplatin treatment and a somatic loss of heterozygosity (LOH) of FANCA in a patient with metastatic prostate cancer who also harbored a germline FANCA variant (S1088F). Although germline FANCA mutations are the most frequent alterations in patients with Fanconi anemia, ger...

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

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.

C. elegans AMPKs promote survival and arrest germline development during nutrient stress

Directory of Open Access Journals (Sweden)

Masamitsu Fukuyama

2012-08-01

Mechanisms controlling development, growth, and metabolism are coordinated in response to changes in environmental conditions, enhancing the likelihood of survival to reproductive maturity. Much remains to be learned about the molecular basis underlying environmental influences on these processes. C. elegans larvae enter a developmentally dormant state called L1 diapause when hatched into nutrient-poor conditions. The nematode pten homologue daf-18 is essential for maintenance of survival and germline stem cell quiescence during this period (Fukuyama et al., 2006; Sigmond et al., 2008, but the details of the signaling network(s in which it functions remain to be elucidated. Here, we report that animals lacking both aak-1 and aak-2, which encode the two catalytic α subunits of AMP-activated protein kinase (AMPK, show reduced viability and failure to maintain mitotic quiescence in germline stem cells during L1 diapause. Furthermore, failure to arrest germline proliferation has a long term consequence; aak double mutants that have experienced L1 diapause develop into sterile adults when returned to food, whereas their continuously fed siblings are fertile. Both aak and daf-18 appear to maintain germline quiescence by inhibiting activity of the common downstream target, TORC1 (TOR Complex 1. In contrast, rescue of the lethality phenotype indicates that aak-2 acts not only in the intestine, as does daf-18, but also in neurons, likely promoting survival by preventing energy deprivation during L1 diapause. These results not only provide evidence that AMPK contributes to survival during L1 diapause in a manner distinct from that by which it controls dauer diapause, but they also suggest that AMPK suppresses TORC1 activity to maintain stem cell quiescence.

Experimental and Numerical Investigation of Metal Type and Thickness Effects on the Impact Resistance of Fiber Metal Laminates

NARCIS (Netherlands)

Sadighi, M.; Pärnänen, T.; Alderliesten, R.C.; Sayeaftabi, M.; Benedictus, R.

2012-01-01

The impact response of fiber metal laminates (FMLs), has been investigated with experiments and numerical simulations, which is reported in this article. Low-velocity impacts were carried out to study the effects of metal type and thickness within FMLs. Glare5-3/2 laminates with two aluminum layer

Combining molecular and immunohistochemical analyses of key drivers in primary melanomas: interplay between germline and somatic variations.

Science.gov (United States)

Bruno, William; Martinuzzi, Claudia; Dalmasso, Bruna; Andreotti, Virginia; Pastorino, Lorenza; Cabiddu, Francesco; Gualco, Marina; Spagnolo, Francesco; Ballestrero, Alberto; Queirolo, Paola; Grillo, Federica; Mastracci, Luca; Ghiorzo, Paola

2018-01-19

Due to the high mutational somatic burden of Cutaneous Malignant Melanoma (CMM) a thorough profiling of the driver mutations and their interplay is necessary to explain the timing of tumorigenesis or for the identification of actionable genetic events. The aim of this study was to establish the mutation rate of some of the key drivers in melanoma tumorigenesis combining molecular analyses and/or immunohistochemistry in 93 primary CMMs from an Italian cohort also characterized for germline status, and to investigate an interplay between germline and somatic variants. BRAF mutations were present in 68% of cases, while CDKN2A germline mutations were found in 16 % and p16 loss in tissue was found in 63%. TERT promoter somatic mutations were detected in 38% of cases while the TERT -245T>C polymorphism was found in 51% of cases. NRAS mutations were found in 39% of BRAF negative or undetermined cases. NF1 was expressed in all cases analysed. MC1R variations were both considered as a dichotomous variable or scored. While a positive, although not significant association between CDKN2A germline mutations, but not MC1R variants, and BRAF somatic mutation was found, we did not observe other associations between germline and somatic events. A yet undescribed inverse correlation between TERT -245T>C polymorphism and the presence of BRAF mutation was found. It is possible to hypothesize that -245T>C polymorphism could be included in those genotypes which may influence the occurrence of BRAF mutations. Further studies are needed to investigate the role of -245T>C polymorphism as a germline predictor of BRAF somatic mutation status.

Screening for germline mutations of MLH1, MSH2, MSH6 and PMS2 genes in Slovenian colorectal cancer patients: implications for a population specific detection strategy of Lynch syndrome.

Science.gov (United States)

Berginc, Gasper; Bracko, Matej; Ravnik-Glavac, Metka; Glavac, Damjan

2009-01-01

Microsatellite instability (MSI) is present in more than 90% of colorectal cancers of patients with Lynch syndrome, and is therefore a feasible marker for the disease. Mutations in MLH1, MSH2, MSH6 and PMS2, which are one of the main causes of deficient mismatch repair and subsequent MSI, have been linked to the disease. In order to establish the role of each of the 4 genes in Slovenian Lynch syndrome patients, we performed MSI analysis on 593 unselected CRC patients and subsequently searched for the presence of point mutations, larger genomic rearrangements and MLH1 promoter hypermethylation in patients with MSI-high tumours. We detected 43 (7.3%) patients with MSI-H tumours, of which 7 patients (1.3%) harboured germline defects: 2 in MLH1, 4 in MSH2, 1 in PMS2 and none in MSH6. Twenty-nine germline sequence variations of unknown significance and 17 deleterious somatic mutations were found. MLH1 promoter methylation was detected in 56% of patients without detected germline defects and in 1 (14%) suspected Lynch syndrome. Due to the minor role of germline MSH6 mutations, we adapted the Lynch syndrome detection strategy for the Slovenian population of CRC patients, whereby germline alterations should be first sought in MLH1 and MSH2 followed by a search for larger genomic rearrangements in these two genes. When no germline mutations are found tumors should be further tested for the presence of germline defects in PMS2 and MSH6. The choice about which gene should be tested first can be guided more accurately by the immunohistochemical analysis. Our study demonstrates that the incidence of MMR mutations in a population should be known prior to the application of one of several suggested strategies for detection of Lynch syndrome.

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)

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.

Detection of mismatch repair gene germline mutation carrier among Chinese population with colorectal cancer

International Nuclear Information System (INIS)

Jin, Hei-Ying; Zhao, Ronghua; Liu, Xiufang; Li, Vicky Ka Ming; Ding, Yijiang; Yang, Bolin; Geng, Jianxiang; Lai, Rensheng; Ding, Shuqing; Ni, Min

2008-01-01

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome. The National Cancer Institute (NCI) has recommended the Revised Bethesda guidelines for screening HNPCC. There has been a great deal of research on the value of these tests in other countries. However, literature about the Chinese population is scarce. Our objective is to detect and study microsatellite instability (MSI) and mismatch repair (MMR) gene germline mutation carriers among a Chinese population with colorectal cancer. In 146 prospectively recruited consecutive patients with clinically proven colorectal cancer, MSI carriers were identified by analysis of tumor tissue using multiplex fluorescence polymerase chain reaction (PCR) using the NCI recommended panel and classified into microsatellite instability-low (MSI-L), microsatellite instability-high (MSI-H) and microsatellite stable (MSS) groups. Immunohistochemical staining for MSH2, MSH6 and MLH1 on tissue microarrays (TMAs) was performed, and methylation of the MLH1 promoter was analyzed by quantitative methylation specific PCR (MSP). Germline mutation analysis of blood samples was performed for MSH2, MSH6 and MLH1 genes. Thirty-four out of the 146 colorectal cancers (CRCs, 23.2%) were MSI, including 19 MSI-H CRCs and 15 MSI-L CRCS. Negative staining for MSH2 was found in 8 CRCs, negative staining for MSH6 was found in 6 CRCs. One MSI-H CRC was negative for both MSH6 and MSH2. Seventeen CRCs stained negatively for MLH1. MLH1 promoter methylation was determined in 34 MSI CRCs. Hypermethylation of the MLH1 promoter occurred in 14 (73.7%) out of 19 MSI-H CRCs and 5 (33.3%) out of 15 MSI-L CRCs. Among the 34 MSI carriers and one MSS CRC with MLH1 negative staining, 8 had a MMR gene germline mutation, which accounted for 23.5% of all MSI colorectal cancers and 5.5% of all the colorectal cancers. Five patients harbored MSH2 germline mutations, and three patients harbored MSH6 germline mutations. None of the patients had an MLH

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.

LESIONS ASSOCIATED WITH SUBCLINICAL LAMINITIS AND DIGITAL RADIOGRAPHIC EXAM IN HOLSTEIN COWS IN THE TRANSITIONAL PERIOD

Directory of Open Access Journals (Sweden)

Antonio Amaral Barbosa

2016-10-01

Full Text Available Subclinical laminitis has been responsible for economic losses in dairy industry; thus, its diagnostic    is very important to prevent negative responses to milk production industry. The aim of this study  was to identify lesions associated with subclinical laminitis during the transition period with presence or absence of radiographic signs linked to this disease in Holstein cows. The cows were evaluated during the transition period and categorized into two groups (with and without laminitis according to the lesions associated with this subclinical disease. The radiological dynamic was performed in two target points during the transition period (prepartum and postpartum, with the objective of determining capsular position possible alterations and third phalanx bone degeneration (F3. There was no effect of the presence of lesions associated with subclinical laminitis regarding the position of the third phalanx to the hoof wall (p>0.05. Significant radiographic angular differences (p0.05. Overall, this study did not show radiographic signs of phalangeal misalignment in the hoof of dairy cows with lesions associated with subclinical laminitis during the transition period . Keywords:  aseptic pododermatitis; bovines; complementary exams; hoof.

Induction of atherosclerosis in mice and hamsters without germline genetic engineering

DEFF Research Database (Denmark)

Bjørklund, Martin Mæng; Hollensen, Anne Kruse; Hagensen, Mette Kallestrup

2014-01-01

RATIONALE: Atherosclerosis can be achieved in animals by germline genetic engineering, leading to hypercholesterolemia, but such models are constrained to few species and strains, and they are difficult to combine with other powerful techniques involving genetic manipulation or variation. OBJECTIVE......: To develop a method for induction of atherosclerosis without germline genetic engineering. METHODS AND RESULTS: Recombinant adeno-associated viral vectors were engineered to encode gain-of-function proprotein convertase subtilisin/kexin type 9 mutants, and mice were given a single intravenous vector...... injection followed by high-fat diet feeding. Plasma proprotein convertase subtilisin/kexin type 9 and total cholesterol increased rapidly and were maintained at high levels, and after 12 weeks, mice had atherosclerotic lesions in the aorta. Histology of the aortic root showed progression of lesions...

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

Hermes (Rbpms is a Critical Component of RNP Complexes that Sequester Germline RNAs during Oogenesis

Directory of Open Access Journals (Sweden)

Tristan Aguero

2016-01-01

Full Text Available The germ cell lineage in Xenopus is specified by the inheritance of germ plasm that assembles within the mitochondrial cloud or Balbiani body in stage I oocytes. Specific RNAs, such as nanos1, localize to the germ plasm. nanos1 has the essential germline function of blocking somatic gene expression and thus preventing Primordial Germ Cell (PGC loss and sterility. Hermes/Rbpms protein and nanos RNA co-localize within germinal granules, diagnostic electron dense particles found within the germ plasm. Previous work indicates that nanos accumulates within the germ plasm through a diffusion/entrapment mechanism. Here we show that Hermes/Rbpms interacts with nanos through sequence specific RNA localization signals found in the nanos-3′UTR. Importantly, Hermes/Rbpms specifically binds nanos, but not Vg1 RNA in the nucleus of stage I oocytes. In vitro binding data show that Hermes/Rbpms requires additional factors that are present in stage I oocytes in order to bind nanos1. One such factor may be hnRNP I, identified in a yeast-2-hybrid screen as directly interacting with Hermes/Rbpms. We suggest that Hermes/Rbpms functions as part of a RNP complex in the nucleus that facilitates selection of germline RNAs for germ plasm localization. We propose that Hermes/Rbpms is required for nanos RNA to form within the germinal granules and in this way, participates in the germline specific translational repression and sequestration of nanos RNA.

Hermes (Rbpms) is a Critical Component of RNP Complexes that Sequester Germline RNAs during Oogenesis.

Science.gov (United States)

Aguero, Tristan; Zhou, Yi; Kloc, Malgorzata; Chang, Patrick; Houliston, Evelyn; King, Mary Lou

2016-03-01

The germ cell lineage in Xenopus is specified by the inheritance of germ plasm that assembles within the mitochondrial cloud or Balbiani body in stage I oocytes. Specific RNAs, such as nanos1 , localize to the germ plasm. nanos1 has the essential germline function of blocking somatic gene expression and thus preventing Primordial Germ Cell (PGC) loss and sterility. Hermes/Rbpms protein and nanos RNA co-localize within germinal granules, diagnostic electron dense particles found within the germ plasm. Previous work indicates that nanos accumulates within the germ plasm through a diffusion/entrapment mechanism. Here we show that Hermes/Rbpms interacts with nanos through sequence specific RNA localization signals found in the nanos -3'UTR. Importantly, Hermes/Rbpms specifically binds nanos , but not Vg1 RNA in the nucleus of stage I oocytes. In vitro binding data show that Hermes/Rbpms requires additional factors that are present in stage I oocytes in order to bind nanos1 . One such factor may be hnRNP I, identified in a yeast-2-hybrid screen as directly interacting with Hermes/Rbpms. We suggest that Hermes/Rbpms functions as part of a RNP complex in the nucleus that facilitates selection of germline RNAs for germ plasm localization. We propose that Hermes/Rbpms is required for nanos RNA to form within the germinal granules and in this way, participates in the germline specific translational repression and sequestration of nanos RNA .

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

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

International Nuclear Information System (INIS)

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

2008-01-01

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

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.

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...

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

Laminated electrospun nHA/PHB-composite scaffolds mimicking bone extracellular matrix for bone tissue engineering.

Science.gov (United States)

Chen, Zhuoyue; Song, Yue; Zhang, Jing; Liu, Wei; Cui, Jihong; Li, Hongmin; Chen, Fulin

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 2months 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. Copyright © 2016 Elsevier B.V. All rights reserved.

The molecular anatomy of spontaneous germline mutations in human testes.

Directory of Open Access Journals (Sweden)

Jian Qin

2007-09-01

Full Text Available The frequency of the most common sporadic Apert syndrome mutation (C755G in the human fibroblast growth factor receptor 2 gene (FGFR2 is 100-1,000 times higher than expected from average nucleotide substitution rates based on evolutionary studies and the incidence of human genetic diseases. To determine if this increased frequency was due to the nucleotide site having the properties of a mutation hot spot, or some other explanation, we developed a new experimental approach. We examined the spatial distribution of the frequency of the C755G mutation in the germline by dividing four testes from two normal individuals each into several hundred pieces, and, using a highly sensitive PCR assay, we measured the mutation frequency of each piece. We discovered that each testis was characterized by rare foci with mutation frequencies 10(3 to >10(4 times higher than the rest of the testis regions. Using a model based on what is known about human germline development forced us to reject (p < 10(-6 the idea that the C755G mutation arises more frequently because this nucleotide simply has a higher than average mutation rate (hot spot model. This is true regardless of whether mutation is dependent or independent of cell division. An alternate model was examined where positive selection acts on adult self-renewing Ap spermatogonial cells (SrAp carrying this mutation such that, instead of only replacing themselves, they occasionally produce two SrAp cells. This model could not be rejected given our observed data. Unlike the disease site, similar analysis of C-to-G mutations at a control nucleotide site in one testis pair failed to find any foci with high mutation frequencies. The rejection of the hot spot model and lack of rejection of a selection model for the C755G mutation, along with other data, provides strong support for the proposal that positive selection in the testis can act to increase the frequency of premeiotic germ cells carrying a mutation

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.

Developmental expression of "germline"- and "sex determination"-related genes in the ctenophore Mnemiopsis leidyi.

Science.gov (United States)

Reitzel, Adam M; Pang, Kevin; Martindale, Mark Q

2016-01-01

An essential developmental pathway in sexually reproducing animals is the specification of germ cells and the differentiation of mature gametes, sperm and oocytes. The "germline" genes vasa, nanos and piwi are commonly identified in primordial germ cells, suggesting a molecular signature for the germline throughout animals. However, these genes are also expressed in a diverse set of somatic stem cells throughout the animal kingdom leaving open significant questions for whether they are required for germline specification. Similarly, members of the Dmrt gene family are essential components regulating sex determination and differentiation in bilaterian animals, but the functions of these transcription factors, including potential roles in sex determination, in early diverging animals remain unknown. The phylogenetic position of ctenophores and the genome sequence of the lobate Mnemiopsis leidyi motivated us to determine the compliment of these gene families in this species and determine expression patterns during development. Our phylogenetic analyses of the vasa, piwi and nanos gene families show that Mnemiopsis has multiple genes in each family with multiple lineage-specific paralogs. Expression domains of Mnemiopsis nanos, vasa and piwi, during embryogenesis from fertilization to the cydippid stage, were diverse, with little overlapping expression and no or little expression in what we think are the germ cells or gametogenic regions. piwi paralogs in Mnemiopsis had distinct expression domains in the ectoderm during development. We observed overlapping expression domains in the apical organ and tentacle apparatus of the cydippid for a subset of "germline genes," which are areas of high cell proliferation, suggesting that these genes are involved with "stem cell" specification and maintenance. Similarly, the five Dmrt genes show diverse non-overlapping expression domains, with no clear evidence for expression in future gametogenic regions of the adult. We also

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

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.

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...

Micro/nanoscale mechanical characterization and in situ observation of cracking of laminated Si3N4/BN composites

International Nuclear Information System (INIS)

Li Xiaodong; Zou Linhua; Ni Hai; Reynolds, Anthony P.; Wang Changan; Huang Yong

2008-01-01

Micro/nanoscale mechanical characterization of laminated Si 3 N 4 /BN composites was carried out by nanoindentation techniques. A custom-designed micro mechanical tester was integrated with an optical microscope and an atomic force microscope to perform in situ three-point bending tests on notched Si 3 N 4 /BN composite bend specimens where the crack initiation and propagation were imaged simultaneously with the optical microscope and atomic force microscope during bending loading. The whole fracture process was in situ captured. It was found that crack deflection was initiated/induced by the pre-existing microvoids and microcracks in BN interfacial layers. New fracture mechanisms were proposed to provide guidelines for the design of biomimetic nacre-like composites

Germline mutation rates in mice following in utero exposure to diesel exhaust particles by maternal inhalation

DEFF Research Database (Denmark)

Ritz, Caitlin; Ruminski, Wojciech; Hougaard, Karin S.

2011-01-01

(PAPs) from industrial environments cause DNA damage and mutations in the sperm of adult male mice. Effects on the female and male germline during critical stages of development (in utero) are unknown. In mice, previous studies have shown that expanded simple tandem repeat (ESTR) loci exhibit high rates......The induction of inherited DNA sequence mutations arising in the germline (i.e., sperm or egg) of mice exposed in utero to diesel exhaust particles (DEPs) via maternal inhalation compared to unexposed controls was investigated in this study. Previous work has shown that particulate air pollutants...... of spontaneous mutation, making this endpoint a valuable tool for studying inherited mutation and genomic instability. In the present study, pregnant C57Bl/6 mice were exposed to 19mg/m3 DEP from gestational day 7 through 19, alongside air exposed controls. Male and female F1 offspring were raised to maturity...

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.

A novel molecular diagnostics platform for somatic and germline precision oncology.

Science.gov (United States)

Cabanillas, Rubén; Diñeiro, Marta; Castillo, David; Pruneda, Patricia C; Penas, Cristina; Cifuentes, Guadalupe A; de Vicente, Álvaro; Durán, Noelia S; Álvarez, Rebeca; Ordóñez, Gonzalo R; Cadiñanos, Juan

2017-07-01

Next-generation sequencing (NGS) opens new options in clinical oncology, from therapy selection to genetic counseling. However, realization of this potential not only requires succeeding in the bioinformatics and interpretation of the results, but also in their integration into the clinical practice. We have developed a novel NGS diagnostic platform aimed at detecting (1) somatic genomic alterations associated with the response to approved targeted cancer therapies and (2) germline mutations predisposing to hereditary malignancies. Next-generation sequencing libraries enriched in the exons of 215 cancer genes (97 for therapy selection and 148 for predisposition, with 30 informative for both applications), as well as selected introns from 17 genes involved in drug-related rearrangements, were prepared from 39 tumors (paraffin-embedded tissues/cytologies), 36 germline samples (blood) and 10 cell lines using hybrid capture. Analysis of NGS results was performed with specifically developed bioinformatics pipelines. The platform detects single-nucleotide variants (SNVs) and insertions/deletions (indels) with sensitivity and specificity >99.5% (allelic frequency ≥0.1), as well as copy-number variants (CNVs) and rearrangements. Somatic testing identified tailored approved targeted drugs in 35/39 tumors (89.74%), showing a diagnostic yield comparable to that of leading commercial platforms. A somatic EGFR p.E746_S752delinsA mutation in a mediastinal metastasis from a breast cancer prompted its anatomopathologic reassessment, its definite reclassification as a lung cancer and its treatment with gefitinib (partial response sustained for 15 months). Testing of 36 germline samples identified two pathogenic mutations (in CDKN2A and BRCA2 ). We propose a strategy for interpretation and reporting of results adaptable to the aim of the request, the availability of tumor and/or normal samples and the scope of the informed consent. With an adequate methodology, it is possible to

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

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

In vitro cytotoxicity of nanoparticles in mammalian germline stem cells.

Science.gov (United States)

Braydich-Stolle, Laura; Hussain, Saber; Schlager, John J; Hofmann, Marie-Claude

2005-12-01

Gametogenesis is a complex biological process that is particularly sensitive to environmental insults such as chemicals. Many chemicals have a negative impact on the germline, either by directly affecting the germ cells, or indirectly through their action on the somatic nursing cells. Ultimately, these effects can inhibit fertility, and they may have negative consequences for the development of the offspring. Recently, nanomaterials such as nanotubes, nanowires, fullerene derivatives (buckyballs), and quantum dots have received enormous national attention in the creation of new types of analytical tools for biotechnology and the life sciences. Despite the wide application of nanomaterials, there is a serious lack of information concerning their impact on human health and the environment. Thus, there are limited studies available on toxicity of nanoparticles for risk assessment of nanomaterials. The purpose of this study was to assess the suitability of a mouse spermatogonial stem cell line as a model to assess nanotoxicity in the male germline in vitro. The effects of different types of nanoparticles on these cells were evaluated by light microscopy, and by cell proliferation and standard cytotoxicity assays. Our results demonstrate a concentration-dependent toxicity for all types of particles tested, whereas the corresponding soluble salts had no significant effect. Silver nanoparticles were the most toxic while molybdenum trioxide (MoO(3)) nanoparticles were the least toxic. Our results suggest that this cell line provides a valuable model with which to assess the cytotoxicity of nanoparticles in the germ line in vitro.

A computational approach to distinguish somatic vs. germline origin of genomic alterations from deep sequencing of cancer specimens without a matched normal.

Directory of Open Access Journals (Sweden)

James X Sun

2018-02-01

Full Text Available A key constraint in genomic testing in oncology is that matched normal specimens are not commonly obtained in clinical practice. Thus, while well-characterized genomic alterations do not require normal tissue for interpretation, a significant number of alterations will be unknown in whether they are germline or somatic, in the absence of a matched normal control. We introduce SGZ (somatic-germline-zygosity, a computational method for predicting somatic vs. germline origin and homozygous vs. heterozygous or sub-clonal state of variants identified from deep massively parallel sequencing (MPS of cancer specimens. The method does not require a patient matched normal control, enabling broad application in clinical research. SGZ predicts the somatic vs. germline status of each alteration identified by modeling the alteration's allele frequency (AF, taking into account the tumor content, tumor ploidy, and the local copy number. Accuracy of the prediction depends on the depth of sequencing and copy number model fit, which are achieved in our clinical assay by sequencing to high depth (>500x using MPS, covering 394 cancer-related genes and over 3,500 genome-wide single nucleotide polymorphisms (SNPs. Calls are made using a statistic based on read depth and local variability of SNP AF. To validate the method, we first evaluated performance on samples from 30 lung and colon cancer patients, where we sequenced tumors and matched normal tissue. We examined predictions for 17 somatic hotspot mutations and 20 common germline SNPs in 20,182 clinical cancer specimens. To assess the impact of stromal admixture, we examined three cell lines, which were titrated with their matched normal to six levels (10-75%. Overall, predictions were made in 85% of cases, with 95-99% of variants predicted correctly, a significantly superior performance compared to a basic approach based on AF alone. We then applied the SGZ method to the COSMIC database of known somatic variants

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

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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

Parallel germline infiltration of a lentivirus in two Malagasy lemurs.

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Clément Gilbert

2009-03-01

Full Text Available Retroviruses normally infect the somatic cells of their host and are transmitted horizontally, i.e., in an exogenous way. Occasionally, however, some retroviruses can also infect and integrate into the genome of germ cells, which may allow for their vertical inheritance and fixation in a given species; a process known as endogenization. Lentiviruses, a group of mammalian retroviruses that includes HIV, are known to infect primates, ruminants, horses, and cats. Unlike many other retroviruses, these viruses have not been demonstrably successful at germline infiltration. Here, we report on the discovery of endogenous lentiviral insertions in seven species of Malagasy lemurs from two different genera -- Cheirogaleus and Microcebus. Combining molecular clock analyses and cross-species screening of orthologous insertions, we show that the presence of this endogenous lentivirus in six species of Microcebus is the result of one endogenization event that occurred about 4.2 million years ago. In addition, we demonstrate that this lentivirus independently infiltrated the germline of Cheirogaleus and that the two endogenization events occurred quasi-simultaneously. Using multiple proviral copies, we derive and characterize an apparently full length and intact consensus for this lentivirus. These results provide evidence that lentiviruses have repeatedly infiltrated the germline of prosimian species and that primates have been exposed to lentiviruses for a much longer time than what can be inferred based on sequence comparison of circulating lentiviruses. The study sets the stage for an unprecedented opportunity to reconstruct an ancestral primate lentivirus and thereby advance our knowledge of host-virus interactions.

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.

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

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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.

Remobilization of Sleeping Beauty transposons in the germline of Xenopus tropicalis

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Yergeau Donald A

2011-11-01

Full Text Available Abstract Background The Sleeping Beauty (SB transposon system has been used for germline transgenesis of the diploid frog, Xenopus tropicalis. Injecting one-cell embryos with plasmid DNA harboring an SB transposon substrate together with mRNA encoding the SB transposase enzyme resulted in non-canonical integration of small-order concatemers of the transposon. Here, we demonstrate that SB transposons stably integrated into the frog genome are effective substrates for remobilization. Results Transgenic frogs that express the SB10 transposase were bred with SB transposon-harboring animals to yield double-transgenic 'hopper' frogs. Remobilization events were observed in the progeny of the hopper frogs and were verified by Southern blot analysis and cloning of the novel integrations sites. Unlike the co-injection method used to generate founder lines, transgenic remobilization resulted in canonical transposition of the SB transposons. The remobilized SB transposons frequently integrated near the site of the donor locus; approximately 80% re-integrated with 3 Mb of the donor locus, a phenomenon known as 'local hopping'. Conclusions In this study, we demonstrate that SB transposons integrated into the X. tropicalis genome are effective substrates for excision and re-integration, and that the remobilized transposons are transmitted through the germline. This is an important step in the development of large-scale transposon-mediated gene- and enhancer-trap strategies in this highly tractable developmental model system.

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

Delamination Resistance Of Laminate Made With VBO MTM46/HTS Prepreg

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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.

Elucidating the impact of neurofibromatosis-1 germline mutations on neurofibromin function and dopamine-based learning.

Science.gov (United States)

Anastasaki, Corina; Woo, Albert S; Messiaen, Ludwine M; Gutmann, David H

2015-06-15

Neurofibromatosis type 1 (NF1) is a common autosomal dominant neurologic condition characterized by significant clinical heterogeneity, ranging from malignant cancers to cognitive deficits. Recent studies have begun to reveal rare genotype-phenotype correlations, suggesting that the specific germline NF1 gene mutation may be one factor underlying disease heterogeneity. The purpose of this study was to define the impact of the germline NF1 gene mutation on brain neurofibromin function relevant to learning. Herein, we employ human NF1-patient primary skin fibroblasts, induced pluripotent stem cells and derivative neural progenitor cells (NPCs) to demonstrate that NF1 germline mutations have dramatic effects on neurofibromin expression. Moreover, while all NF1-patient NPCs exhibit increased RAS activation and reduced cyclic AMP generation, there was a neurofibromin dose-dependent reduction in dopamine (DA) levels. Additionally, we leveraged two complementary Nf1 genetically-engineered mouse strains in which hippocampal-based learning and memory is DA-dependent to establish that neuronal DA levels and signaling as well as mouse spatial learning are controlled in an Nf1 gene dose-dependent manner. Collectively, this is the first demonstration that different germline NF1 gene mutations differentially dictate neurofibromin function in the brain. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Genomic hypomethylation in the human germline associates with selective structural mutability in the human genome.

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Jian Li

Full Text Available The hotspots of structural polymorphisms and structural mutability in the human genome remain to be explained mechanistically. We examine associations of structural mutability with germline DNA methylation and with non-allelic homologous recombination (NAHR mediated by low-copy repeats (LCRs. Combined evidence from four human sperm methylome maps, human genome evolution, structural polymorphisms in the human population, and previous genomic and disease studies consistently points to a strong association of germline hypomethylation and genomic instability. Specifically, methylation deserts, the ~1% fraction of the human genome with the lowest methylation in the germline, show a tenfold enrichment for structural rearrangements that occurred in the human genome since the branching of chimpanzee and are highly enriched for fast-evolving loci that regulate tissue-specific gene expression. Analysis of copy number variants (CNVs from 400 human samples identified using a custom-designed array comparative genomic hybridization (aCGH chip, combined with publicly available structural variation data, indicates that association of structural mutability with germline hypomethylation is comparable in magnitude to the association of structural mutability with LCR-mediated NAHR. Moreover, rare CNVs occurring in the genomes of individuals diagnosed with schizophrenia, bipolar disorder, and developmental delay and de novo CNVs occurring in those diagnosed with autism are significantly more concentrated within hypomethylated regions. These findings suggest a new connection between the epigenome, selective mutability, evolution, and human disease.

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)

Friction Properties of Laminated Composite Materials of Alpha-Tricalcium Phosphate–Filled Poly (Vinyl Alcohol) Hydrogels

OpenAIRE

Yamamoto, Kanae; Iwai, Tomoaki; Shoukaku, Yutaka

2015-01-01

The aim of this study was to examine the mechanical characteristics of a polyvinyl alcohol hydrogel (PVA-H) as a candidate material for artificial joint cartilage. In the study, PVA-H was filled with α-tricalcium phosphate (α-TCP) in order to improve its mechanical properties. In addition, laminated composite materials with 3 layers were prepared by laminating α-TCP–filled PVA-H and unfilled PVA-H. The samples were prepared with different numbers of repeated freeze–thaw cycles and several con...

Complete Genome Sequence of Germline Chromosomally Integrated Human Herpesvirus 6A and Analyses Integration Sites Define a New Human Endogenous Virus with Potential to Reactivate as an Emerging Infection.

OpenAIRE

Tweedy, J; Spyrou, MA; Pearson, M; Lassner, D; Kuhl, U; Gompels, UA

2016-01-01

Human herpesvirus-6A and B (HHV-6A, HHV-6B) have recently defined endogenous genomes, resulting from integration into the germline: chromosomally-integrated "CiHHV-6A/B". These affect approximately 1.0% of human populations, giving potential for virus gene expression in every cell. We previously showed that CiHHV-6A was more divergent than CiHHV-6B by examining four genes in 44 European CiHHV-6A/B cardiac/haematology patients. There was evidence for gene expression/reactivation, imp...

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...

The roles of DNA damage-dependent signals and MAPK cascades in tributyltin-induced germline apoptosis in Caenorhabditis elegans.

Science.gov (United States)

Wang, Yun; Wang, Shunchang; Luo, Xun; Yang, Yanan; Jian, Fenglei; Wang, Xuemin; Xie, Lucheng

2014-08-01

The induction of apoptosis is recognized to be a major mechanism of tributyltin (TBT) toxicity. However, the underlying signaling pathways for TBT-induced apoptosis remain unclear. In this study, using the nematode Caenorhabditis elegans, we examined whether DNA damage response (DDR) pathway and mitogen-activated protein kinase (MAPK) signaling cascades are involved in TBT-induced germline apoptosis and cell cycle arrest. Our results demonstrated that exposing worms to TBT at the dose of 10nM for 6h significantly increased germline apoptosis in N2 strain. Germline apoptosis was absent in strains that carried ced-3 or ced-4 loss-of-function alleles, indicating that both caspase protein CED-3 and Apaf-1 protein CED-4 were required for TBT-induced apoptosis. TBT-induced apoptosis was blocked in the Bcl-2 gain-of-function strain ced-9(n1950), whereas TBT induced a minor increase in the BH3-only protein EGL-1 mutated strain egl-1(n1084n3082). Checkpoint proteins HUS-1 and CLK-2 exerted proapoptotic effects, and the null mutation of cep-1, the homologue of tumor suppressor gene p53, significantly inhibited TBT-induced apoptosis. Apoptosis in the loss-of-function strains of ERK, JNK and p38 MAPK signaling pathways were completely or mildly suppressed under TBT stress. These results were supported by the results of mRNA expression levels of corresponding genes. The present study indicated that TBT-induced apoptosis required the core apoptotic machinery, and that DDR genes and MAPK pathways played essential roles in signaling the processes. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

Analysis of 3D Planar Laminations in a Welded Section of API 5L X52 Applying the Finite Element Method

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Martin. J. Fernández-Cueto

Full Text Available Abstract The mechanical behavior of API 5L X52 steel with planar type laminations was studied in the present work. Planar laminations were proposed in the base metal (BM, heat affected zone (HAZ and welding bead (WB. Three-dimensional finite element (FE models, kinematic hardening and mechanical properties for BM, HAZ, and WB were activated in the finite element program. The results showed that crack propagation corresponds to the direction of the main stress. For a crack length (2a of 10.01 mm, crack propagation may occur at the right crack tip towards the outer wall of the BM. For 2a of 15.12 mm, crack propagation was located on the right crack tip and propagates to the inner wall. For 2a of 17.12 mm, crack propagation was observed at the left crack tip and propagates to the outer wall in the BM. The results achieved by FEM agree when compared with real laminations in API 5L pipelines.

Germline Genetic Modification and Identity: the Mitochondrial and Nuclear Genomes.

Science.gov (United States)

Scott, Rosamund; Wilkinson, Stephen

2017-12-01

In a legal 'first', the UK removed a prohibition against modifying embryos in human reproduction, to enable mitochondrial replacement techniques (MRTs), a move the Government distanced from 'germline genetic modification', which it aligned with modifying the nuclear genome. This paper (1) analyzes the uses and meanings of this term in UK/US legal and policy debates; and (2) evaluates related ethical concerns about identity. It shows that, with respect to identity, MRTs and nuclear genome editing techniques such as CRISPR/Cas-9 (now a policy topic), are not as different as has been supposed. While it does not follow that the two should be treated exactly alike, one of the central reasons offered for treating MRTs more permissively than nuclear genetic modification, and for not regarding MRTs as 'germline genetic modification', is thereby in doubt. Identity cannot, by itself, do the work thus far assigned to it, explicitly or otherwise, in law and policy.

A role of BRCA1 and BRCA2 germline mutations in breast cancer susceptibility within Sardinian population

International Nuclear Information System (INIS)

Palomba, Grazia; Tanda, Francesco; Farris, Antonio; Orrù, Sandra; Floris, Carlo; Pisano, Marina; Lovicu, Mario; Santona, Maria Cristina; Landriscina, Gennaro; Crisponi, Laura; Palmieri, Giuseppe; Loi, Angela; Monne, Maria; Uras, Antonella; Fancello, Patrizia; Piras, Giovanna; Gabbas, Attilio; Cossu, Antonio; Budroni, Mario; Contu, Antonio

2009-01-01

In recent years, numerous studies have assessed the prevalence of germline mutations in BRCA1 and BRCA2 genes in various cohorts. We here extensively investigated the prevalence and geographical distribution of BRCA1-2 mutations in the entire genetically-homogeneous Sardinian population. The occurrence of phenotypic characteristics which may be predictive for the presence of BRCA1-2 germline mutations was also evaluated. Three hundred and forty-eight breast cancer patients presenting a familial recurrence of invasive breast or ovarian carcinoma with at least two affected family members were screened for BRCA1-2 mutations by DHPLC analysis and DNA sequencing. Association of BRCA1 and BRCA2 mutational status with clinical and pathological parameters was evaluated by Pearson's Chi-Squared test. Overall, 8 BRCA1 and 5 BRCA2 deleterious mutations were detected in 35/348 (10%) families; majority (23/35;66%) of mutations was found in BRCA2 gene. The geographical distribution of BRCA1-2 mutations was related to three specific large areas of Sardinia, reflecting its ancient history: a) the Northern area, linguistically different from the rest of the island (where a BRCA2 c.8764-8765delAG mutation with founder effect was predominant); b) the Middle area, land of the ancient Sardinian population (where BRCA2 mutations are still more common than BRCA1 mutations); and c) the South-Western area, with many Phoenician and Carthaginian locations (where BRCA1 mutations are prevalent). We also found that phenotypic features such as high tumor grading and lack of expression of estrogen/progesterone receptors together with age at diagnosis and presence of ovarian cancer in the family may be predictive for the presence of BRCA1-2 germline mutations

Laminated structure in internally oxidized Ru-Ta coatings

Energy Technology Data Exchange (ETDEWEB)

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.

A Mononucleotide Markers Panel to Identify hMLH1/hMSH2 Germline Mutations

Directory of Open Access Journals (Sweden)

M. Pedroni

2007-01-01

Full Text Available Hereditary NonPolyposis Colorectal Cancer (Lynch syndrome is an autosomal dominant disease caused by germline mutations in a class of genes deputed to maintain genomic integrity during cell replication, mutations result in a generalized genomic instability, particularly evident at microsatellite loci (Microsatellite Instability, MSI. MSI is present in 85–90% of colorectal cancers that occur in Lynch Syndrome. To standardize the molecular diagnosis of MSI, a panel of 5 microsatellite markers was proposed (known as the “Bethesda panel”. Aim of our study is to evaluate if MSI testing with two mononucleotide markers, such as BAT25 and BAT26, was sufficient to identify patients with hMLH1/hMSH2 germline mutations. We tested 105 tumours for MSI using both the Bethesda markers and the two mononucleotide markers BAT25 and BAT26. Moreover, immunohistochemical evaluation of MLH1 and MSH2 proteins was executed on the tumours with at least one unstable microsatellite, whereas germline hMLH1/hMSH2 mutations were searched for all cases showing two or more unstable microsatellites.

Production of germline transgenic prairie voles (Microtus ochrogaster) using lentiviral vectors.

Science.gov (United States)

Donaldson, Zoe R; Yang, Shang-Hsun; Chan, Anthony W S; Young, Larry J

2009-12-01

The study of alternative model organisms has yielded tremendous insights into the regulation of behavioral and physiological traits not displayed by more widely used animal models, such as laboratory rats and mice. In particular, comparative approaches often exploit species ideally suited for investigating specific phenomenon. For instance, comparative studies of socially monogamous prairie voles and polygamous meadow voles have been instrumental toward gaining an understanding of the genetic and neurobiological basis of social bonding. However, laboratory studies of less commonly used organisms, such as prairie voles, have been limited by a lack of genetic tools, including the ability to manipulate the genome. Here, we show that lentiviral vector-mediated transgenesis is a rapid and efficient approach for creating germline transgenics in alternative laboratory rodents. Injection of a green fluorescent protein (GFP)-expressing lentiviral vector into the perivitelline space of 23 single-cell embryos yielded three live offspring (13 %), one of which (33%) contained germline integration of a GFP transgene driven by the human ubiquitin-C promoter. In comparison, transfer of 23 uninjected embryos yielded six live offspring (26%). Green fluorescent protein is present in all tissues examined and is expressed widely in the brain. The GFP transgene is heritable and stably expressed until at least the F(2) generation. This technology has the potential to allow investigation of specific gene candidates in prairie voles and provides a general protocol to pursue germline transgenic manipulation in many different rodent species.

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)

Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer.

Science.gov (United States)

Hirasawa, Akira; Imoto, Issei; Naruto, Takuya; Akahane, Tomoko; Yamagami, Wataru; Nomura, Hiroyuki; Masuda, Kiyoshi; Susumu, Nobuyuki; Tsuda, Hitoshi; Aoki, Daisuke

2017-12-22

Pathogenic germline BRCA1 , BRCA2 ( BRCA1/2 ), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1 ), 8 (3.5%; BRCA2 ), 6 (2.6%; mismatch repair genes), 3 (1.3%; RAD51D ), 2 (0.9%; ATM ), 1 (0.4%; MRE11A ), 1 ( FANCC ), and 1 ( GABRA6 ). Carriers of BRCA1/2 or any other tested gene pathogenic variants were more likely to be diagnosed younger, have first or second-degree relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC). After adjustment for these variables, all 3 features were independent predictive factors for pathogenic variants in any tested genes whereas only the latter two remained for variants in BRCA1/2 . Our data indicate similar variant prevalence in Japanese patients with OC and other ethnic groups and suggest that HGSC and OC family history may facilitate genetic predisposition prediction in Japanese patients with OC and referring high-risk patients for genetic counseling and testing.

Experimental evidence showing that no mitotically active female germline progenitors exist in postnatal mouse ovaries.

Science.gov (United States)

Zhang, Hua; Zheng, Wenjing; Shen, Yan; Adhikari, Deepak; Ueno, Hiroo; Liu, Kui

2012-07-31

It has been generally accepted for more than half a century that, in most mammalian species, oocytes cannot renew themselves in postnatal or adult life, and that the number of oocytes is already fixed in fetal or neonatal ovaries. This assumption, however, has been challenged over the past decade. In this study, we have taken an endogenous genetic approach to this question and generated a multiple fluorescent Rosa26(rbw/+);Ddx4-Cre germline reporter mouse model for in vivo and in vitro tracing of the development of female germline cell lineage. Through live cell imaging and de novo folliculogenesis experiments, we show that the Ddx4-expressing cells from postnatal mouse ovaries did not enter mitosis, nor did they contribute to oocytes during de novo folliculogenesis. Our results provide evidence that supports the traditional view that no postnatal follicular renewal occurs in mammals, and no mitotically active Ddx4-expressing female germline progenitors exist in postnatal mouse ovaries.

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...

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...

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.

Influence of stacking sequence on scattering characteristics of the fundamental anti-symmetric Lamb wave at through holes in composite laminates.

Science.gov (United States)

Veidt, Martin; Ng, Ching-Tai

2011-03-01

This paper investigates the scattering characteristics of the fundamental anti-symmetric (A(0)) Lamb wave at through holes in composite laminates. Three-dimensional (3D) finite element (FE) simulations and experimental measurements are used to study the physical phenomenon. Unidirectional, bidirectional, and quasi-isotropic composite laminates are considered in the study. The influence of different hole diameter to wavelength aspect ratios and different stacking sequences on wave scattering characteristics are investigated. The results show that amplitudes and directivity distribution of the scattered Lamb wave depend on these parameters. In the case of quasi-isotropic composite laminates, the scattering directivity patterns are dominated by the fiber orientation of the outer layers and are quite different for composite laminates with the same number of laminae but different stacking sequence. The study provides improved physical insight into the scattering phenomena at through holes in composite laminates, which is essential to develop, validate, and optimize guided wave damage detection and characterization techniques. © 2011 Acoustical Society of America

In Genes We Trust: Germline Engineering, Eugenics, and the Future of the Human Genome.

Science.gov (United States)

Powell, Russell

2015-12-01

Liberal proponents of genetic engineering maintain that developing human germline modification technologies is morally desirable because it will result in a net improvement in human health and well-being. Skeptics of germline modification, in contrast, fear evolutionary harms that could flow from intervening in the human germline, and worry that such programs, even if well intentioned, could lead to a recapitulation of the scientifically and morally discredited projects of the old eugenics. Some bioconservatives have appealed as well to the value of retaining our "given" human biological nature as a reason for restraining the development and use of human genetic modification technologies even where they would tend to increase well-being. In this article, I argue that germline intervention will be necessary merely to sustain the levels of genetic health that we presently enjoy for future generations-a goal that should appeal to bioliberals and bioconservatives alike. This is due to the population-genetic consequences of relaxed selection pressures in human populations caused by the increasing efficacy and availability of conventional medicine. This heterodox conclusion, which I present as a problem of intergenerational justice, has been overlooked in medicine and bioethics due to certain misconceptions about human evolution, which I attempt to rectify, as well as the sordid history of Darwinian approaches to medicine and social policy, which I distinguish from the present argument. © The Author 2015. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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.

Cervical and incisal marginal discrepancy in ceramic laminate veneering materials: A SEM analysis

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Hemalatha Ranganathan

2017-01-01

Full Text Available Context: Marginal discrepancy influenced by the choice of processing material used for the ceramic laminate veneers needs to be explored further for better clinical application. Aims: This study aimed to evaluate the amount of cervical and incisal marginal discrepancy associated with different ceramic laminate veneering materials. Settings and Design: This was an experimental, single-blinded, in vitro trial. Subjects and Methods: Ten central incisors were prepared for laminate veneers with 2 mm uniform reduction and heavy chamfer finish line. Ceramic laminate veneers fabricated over the prepared teeth using four different processing materials were categorized into four groups as Group I - aluminous porcelain veneers, Group II - lithium disilicate ceramic veneers, Group III - lithium disilicate-leucite-based veneers, Group IV - zirconia-based ceramic veneers. The cervical and incisal marginal discrepancy was measured using a scanning electron microscope. Statistical Analysis Used: ANOVA and post hoc Tukey honest significant difference (HSD tests were used for statistical analysis. Results: The cervical and incisal marginal discrepancy for four groups was Group I - 114.6 ± 4.3 μm, 132.5 ± 6.5 μm, Group II - 86.1 ± 6.3 μm, 105.4 ± 5.3 μm, Group III - 71.4 ± 4.4 μm, 91.3 ± 4.7 μm, and Group IV - 123.1 ± 4.1 μm, 142.0 ± 5.4 μm. ANOVA and post hoc Tukey HSD tests observed a statistically significant difference between the four test specimens with regard to cervical marginal discrepancy. The cervical and incisal marginal discrepancy scored F = 243.408, P < 0.001 and F = 180.844, P < 0.001, respectively. Conclusion: This study concluded veneers fabricated using leucite reinforced lithium disilicate exhibited the least marginal discrepancy followed by lithium disilicate ceramic, aluminous porcelain, and zirconia-based ceramics. The marginal discrepancy was more in the incisal region than in the cervical region in all the groups.

NanoTIO2 (UV-Titan does not induce ESTR mutations in the germline of prenatally exposed female mice

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Boisen Anne Mette

2012-06-01

Full Text Available Abstract Background Particulate air pollution has been linked to an increased risk of cardiovascular disease and cancer. Animal studies have shown that inhalation of air particulates induces mutations in the male germline. Expanded simple tandem repeat (ESTR loci in mice are sensitive markers of mutagenic effects on male germ cells resulting from environmental exposures; however, female germ cells have received little attention. Oocytes may be vulnerable during stages of active cell division (e.g., during fetal development. Accordingly, an increase in germline ESTR mutations in female mice prenatally exposed to radiation has previously been reported. Here we investigate the effects of nanoparticles on the female germline. Since pulmonary exposure to nanosized titanium dioxide (nanoTiO2 produces a long-lasting inflammatory response in mice, it was chosen for the present study. Findings Pregnant C57BL/6 mice were exposed by whole-body inhalation to the nanoTiO2 UV-Titan L181 (~42.4 mg UV-Titan/m3 or filtered clean air on gestation days (GD 8–18. Female C57BL/6 F1 offspring were raised to maturity and mated with unexposed CBA males. The F2 descendents were collected and ESTR germline mutation rates in this generation were estimated from full pedigrees (mother, father, offspring of F1 female mice (192 UV-Titan-exposed F2 offspring and 164 F2 controls. ESTR mutation rates of 0.029 (maternal allele and 0.047 (paternal allele in UV-Titan-exposed F2 offspring were not statistically different from those of F2 controls: 0.037 (maternal allele and 0.061 (paternal allele. Conclusions We found no evidence for increased ESTR mutation rates in F1 females exposed in utero to UV-Titan nanoparticles from GD8-18 relative to control females.

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)

TMC-SNPdb: an Indian germline variant database derived from whole exome sequences.

Science.gov (United States)

Upadhyay, Pawan; Gardi, Nilesh; Desai, Sanket; Sahoo, Bikram; Singh, Ankita; Togar, Trupti; Iyer, Prajish; Prasad, Ratnam; Chandrani, Pratik; Gupta, Sudeep; Dutt, Amit

2016-01-01

Cancer is predominantly a somatic disease. A mutant allele present in a cancer cell genome is considered somatic when it's absent in the paired normal genome along with public SNP databases. The current build of dbSNP, the most comprehensive public SNP database, however inadequately represents several non-European Caucasian populations, posing a limitation in cancer genomic analyses of data from these populations. We present the T: ata M: emorial C: entre-SNP D: ata B: ase (TMC-SNPdb), as the first open source, flexible, upgradable, and freely available SNP database (accessible through dbSNP build 149 and ANNOVAR)-representing 114 309 unique germline variants-generated from whole exome data of 62 normal samples derived from cancer patients of Indian origin. The TMC-SNPdb is presented with a companion subtraction tool that can be executed with command line option or using an easy-to-use graphical user interface with the ability to deplete additional Indian population specific SNPs over and above dbSNP and 1000 Genomes databases. Using an institutional generated whole exome data set of 132 samples of Indian origin, we demonstrate that TMC-SNPdb could deplete 42, 33 and 28% false positive somatic events post dbSNP depletion in Indian origin tongue, gallbladder, and cervical cancer samples, respectively. Beyond cancer somatic analyses, we anticipate utility of the TMC-SNPdb in several Mendelian germline diseases. In addition to dbSNP build 149 and ANNOVAR, the TMC-SNPdb along with the subtraction tool is available for download in the public domain at the following:Database URL: http://www.actrec.gov.in/pi-webpages/AmitDutt/TMCSNP/TMCSNPdp.html. © The Author(s) 2016. Published by Oxford University Press.

A germline mutation in the BRCA1 3'UTR predicts Stage IV breast cancer.

Science.gov (United States)

Dorairaj, Jemima J; Salzman, David W; Wall, Deirdre; Rounds, Tiffany; Preskill, Carina; Sullivan, Catherine A W; Lindner, Robert; Curran, Catherine; Lezon-Geyda, Kim; McVeigh, Terri; Harris, Lyndsay; Newell, John; Kerin, Michael J; Wood, Marie; Miller, Nicola; Weidhaas, Joanne B

2014-06-10

A germline, variant in the BRCA1 3'UTR (rs8176318) was previously shown to predict breast and ovarian cancer risk in women from high-risk families, as well as increased risk of triple negative breast cancer. Here, we tested the hypothesis that this variant predicts tumor biology, like other 3'UTR mutations in cancer. The impact of the BRCA1-3'UTR-variant on BRCA1 gene expression, and altered response to external stimuli was tested in vitro using a luciferase reporter assay. Gene expression was further tested in vivo by immunoflourescence staining on breast tumor tissue, comparing triple negative patient samples with the variant (TG or TT) or non-variant (GG) BRCA1 3'UTR. To determine the significance of the variant on clinically relevant endpoints, a comprehensive collection of West-Irish breast cancer patients were tested for the variant. Finally, an association of the variant with breast screening clinical phenotypes was evaluated using a cohort of women from the High Risk Breast Program at the University of Vermont. Luciferase reporters with the BRCA1-3'UTR-variant (T allele) displayed significantly lower gene expression, as well as altered response to external hormonal stimuli, compared to the non-variant 3'UTR (G allele) in breast cancer cell lines. This was confirmed clinically by the finding of reduced BRCA1 gene expression in triple negative samples from patients carrying the homozygous TT variant, compared to non-variant patients. The BRCA1-3'UTR-variant (TG or TT) also associated with a modest increased risk for developing breast cancer in the West-Irish cohort (OR=1.4, 95% CI 1.1-1.8, p=0.033). More importantly, patients with the BRCA1-3'UTR-variant had a 4-fold increased risk of presenting with Stage IV disease (p=0.018, OR=3.37, 95% CI 1.3-11.0). Supporting that this finding is due to tumor biology, and not difficulty screening, obese women with the BRCA1-3'UTR-variant had significantly less dense breasts (p=0.0398) in the Vermont cohort. A variant in

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

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.

Static Analysis of Laminated Composite Plate using New Higher Order Shear Deformation Plate Theory

Directory of Open Access Journals (Sweden)

Ibtehal Abbas Sadiq

2017-02-01

Full Text Available In the present work a theoretical analysis depending on the new higher order . element in shear deformation theory for simply supported cross-ply laminated plate is developed. The new displacement field of the middle surface expanded as a combination of exponential and trigonometric function of thickness coordinate with the transverse displacement taken to be constant through the thickness. The governing equations are derived using Hamilton’s principle and solved using Navier solution method to obtain the deflection and stresses under uniform sinusoidal load. The effect of many design parameters such as number of laminates, aspect ratio and thickness ratio on static behavior of the laminated composite plate has been studied. The modal of the present work has been verified by comparing the results of shape functions with that were obtained by other workers. Result shows the good agreement with 3D elasticity solution and that published by other researchers.

Improving sensitivity of the polyurethane/CNT laminate strain sensor by controlled mechanical preload

International Nuclear Information System (INIS)

Slobodian, Petr; Olejnik, Robert; Matyas, Jiri; Babar, Dipak Gorakh

2016-01-01

This article describes strain detection potential of polyurethane/CNT layered composite and further possible enhance of its sensitivity to strain, expressed by value of gauge factor, GF, employing its controlled mechanical preload. In course of its fabrication a non-woven polyurethane membrane made by electro spinning was used as filtering membrane for CNT aqueous dispersion. Final CNT polyurethane laminate composite is prepared by compression molding. Produced polyurethane/CNT composite laminate is electrically conductive and high elastic. Its elongation leads to change of its macroscopic electrical resistance. Changes in resistance are further reversible, reproducible and can monitor deformation in real time. Gauge factor reaches very high values around 8 for strain reaching 3.5% comparing with conventional metallic strain gauges. Finally, controlled mechanical preload significantly increases value of GF. For example for value of 8.1% of preload value of GF reaches 23.3 for strain 3.5%. (paper)

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.

Analysis of Usability in Furniture Production of Wood Plastic Laminated Board

Directory of Open Access Journals (Sweden)

Abdullah Cemil Ilçe

2015-05-01

Full Text Available The objective of this study was to manufacture a lightweight and easily producible wood plastic laminate (WPL board that could be used in the furniture sector. Eastern beech (Fagus orientalis L. veneer papels (A and hollow polycarbonate boards (B, both with a thickness of 4 mm, were laminated in different combinations using polyurethane (PUR and polychloroprene (PCR adhesives. The physical and mechanical properties of the WPL boards obtained were determined according to the principles specified in the EN 326-1, EN 317, EN 310, ASTM D1037, and ASTM D1761 standards. Subsequently, the specimens were compared with particle boards (PB, medium density fiberboards (MDF, and okoume plywoods (PW. According to the results, the AABAA, ABABA, and ABBBA combinations of the WPL materials had better physical properties, such as weight, water absorption, and swelling thickness, compared to the other composites. Furthermore, because the WPL materials had a high bending resistance, modulus of elasticity, and nail and screw withdrawal strength, they could be used instead of PB and MDF. The WPL material obtained within the scope of this study are suitable for furniture making.

A superconducting magnet mandrel with minimum symmetry laminations for proton therapy

Science.gov (United States)

Caspi, S.; Arbelaez, D.; Brouwer, L.; Dietderich, D. R.; Felice, H.; Hafalia, R.; Prestemon, S.; Robin, D.; Sun, C.; Wan, W.

2013-08-01

The size and weight of ion-beam cancer therapy gantries are frequently determined by a large aperture, curved, ninety degree, dipole magnet. The higher fields achievable with superconducting technology promise to greatly reduce the size and weight of this magnet and therefore also the gantry as a whole. This paper reports advances in the design of winding mandrels for curved, canted cosine-theta (CCT) magnets in the context of a preliminary magnet design for a proton gantry. The winding mandrel is integral to the CCT design and significantly affects the construction cost, stress management, winding feasibility, eddy current power losses, and field quality of the magnet. A laminated mandrel design using a minimum symmetry in the winding path is introduced and its feasibility demonstrated by a rapid prototype model. Piecewise construction of the mandrel using this laminated approach allows for increased manufacturing techniques and material choices. Sectioning the mandrel also reduces eddy currents produced during field changes accommodating the scan of beam energies during treatment. This symmetry concept can also greatly reduce the computational resources needed for 3D finite element calculations. It is shown that the small region of symmetry forming the laminations combined with periodic boundary conditions can model the entire magnet geometry disregarding the ends.

Germline BAP1 inactivation is preferentially associated with metastatic ocular melanoma and cutaneous-ocular melanoma families.

Directory of Open Access Journals (Sweden)

Ching-Ni Jenny Njauw

Full Text Available BAP1 has been shown to be a target of both somatic alteration in high-risk ocular melanomas (OM and germline inactivation in a few individuals from cancer-prone families. These findings suggest that constitutional BAP1 changes may predispose individuals to metastatic OM and that familial permeation of deleterious alleles could delineate a new cancer syndrome.To characterize BAP1's contribution to melanoma risk, we sequenced BAP1 in a set of 100 patients with OM, including 50 metastatic OM cases and 50 matched non-metastatic OM controls, and 200 individuals with cutaneous melanoma (CM including 7 CM patients from CM-OM families and 193 CM patients from CM-non-OM kindreds.Germline BAP1 mutations were detected in 4/50 patients with metastatic OM and 0/50 cases of non-metastatic OM (8% vs. 0%, p = 0.059. Since 2/4 of the BAP1 carriers reported a family history of CM, we analyzed 200 additional hereditary CM patients and found mutations in 2/7 CM probands from CM-OM families and 1/193 probands from CM-non-OM kindreds (29% vs. 0.52%, p = .003. Germline mutations co-segregated with both CM and OM phenotypes and were associated with the presence of unique nevoid melanomas and highly atypical nevoid melanoma-like melanocytic proliferations (NEMMPs. Interestingly, 7/14 germline variants identified to date reside in C-terminus suggesting that the BRCA1 binding domain is important in cancer predisposition.Germline BAP1 mutations are associated with a more aggressive OM phenotype and a recurrent phenotypic complex of cutaneous/ocular melanoma, atypical melanocytic proliferations and other internal neoplasms (ie. COMMON syndrome, which could be a useful clinical marker for constitutive BAP1 inactivation.

Impact of germline and somatic missense variations on drug binding sites.

Science.gov (United States)

Yan, C; Pattabiraman, N; Goecks, J; Lam, P; Nayak, A; Pan, Y; Torcivia-Rodriguez, J; Voskanian, A; Wan, Q; Mazumder, R

2017-03-01

Advancements in next-generation sequencing (NGS) technologies are generating a vast amount of data. This exacerbates the current challenge of translating NGS data into actionable clinical interpretations. We have comprehensively combined germline and somatic nonsynonymous single-nucleotide variations (nsSNVs) that affect drug binding sites in order to investigate their prevalence. The integrated data thus generated in conjunction with exome or whole-genome sequencing can be used to identify patients who may not respond to a specific drug because of alterations in drug binding efficacy due to nsSNVs in the target protein's gene. To identify the nsSNVs that may affect drug binding, protein-drug complex structures were retrieved from Protein Data Bank (PDB) followed by identification of amino acids in the protein-drug binding sites using an occluded surface method. Then, the germline and somatic mutations were mapped to these amino acids to identify which of these alter protein-drug binding sites. Using this method we identified 12 993 amino acid-drug binding sites across 253 unique proteins bound to 235 unique drugs. The integration of amino acid-drug binding sites data with both germline and somatic nsSNVs data sets revealed 3133 nsSNVs affecting amino acid-drug binding sites. In addition, a comprehensive drug target discovery was conducted based on protein structure similarity and conservation of amino acid-drug binding sites. Using this method, 81 paralogs were identified that could serve as alternative drug targets. In addition, non-human mammalian proteins bound to drugs were used to identify 142 homologs in humans that can potentially bind to drugs. In the current protein-drug pairs that contain somatic mutations within their binding site, we identified 85 proteins with significant differential gene expression changes associated with specific cancer types. Information on protein-drug binding predicted drug target proteins and prevalence of both somatic and

Multiscale Static Analysis of Notched and Unnotched Laminates Using the Generalized Method of Cells

Science.gov (United States)

Naghipour Ghezeljeh, Paria; Arnold, Steven M.; Pineda, Evan J.; Stier, Bertram; Hansen, Lucas; Bednarcyk, Brett A.; Waas, Anthony M.

2016-01-01

The generalized method of cells (GMC) is demonstrated to be a viable micromechanics tool for predicting the deformation and failure response of laminated composites, with and without notches, subjected to tensile and compressive static loading. Given the axial [0], transverse [90], and shear [+45/-45] response of a carbon/epoxy (IM7/977-3) system, the unnotched and notched behavior of three multidirectional layups (Layup 1: [0,45,90,-45](sub 2S), Layup 2: [0,60,0](sub 3S), and Layup 3: [30,60,90,-30, -60](sub 2S)) are predicted under both tensile and compressive static loading. Matrix nonlinearity is modeled in two ways. The first assumes all nonlinearity is due to anisotropic progressive damage of the matrix only, which is modeled, using the multiaxial mixed-mode continuum damage model (MMCDM) within GMC. The second utilizes matrix plasticity coupled with brittle final failure based on the maximum principle strain criteria to account for matrix nonlinearity and failure within the Finite Element Analysis--Micromechanics Analysis Code (FEAMAC) software multiscale framework. Both MMCDM and plasticity models incorporate brittle strain- and stress-based failure criteria for the fiber. Upon satisfaction of these criteria, the fiber properties are immediately reduced to a nominal value. The constitutive response for each constituent (fiber and matrix) is characterized using a combination of vendor data and the axial, transverse, and shear responses of unnotched laminates. Then, the capability of the multiscale methodology is assessed by performing blind predictions of the mentioned notched and unnotched composite laminates response under tensile and compressive loading. Tabulated data along with the detailed results (i.e., stress-strain curves as well as damage evolution states at various ratios of strain to failure) for all laminates are presented.

Structural Laminate Aluminum-Glass-Fiber Materials 1441-Sial

Science.gov (United States)

Shestov, V. V.; Antipov, V. V.; Senatorova, O. G.; Sidel'nikov, V. V.

2014-01-01

The structure, composition and set of properties of specimens and components, and some parameters of the process of production of a promising FML class of metallic polymers based on sheets of high-modulus ( E 79 GPa) alloy 1441 with reduced density ( d 2.6 g/cm3) and an optimized glued prepreg reinforced with fibers of high-strength high-modulus VMPglass are described. Results of fire and fatigue tests of a promising 1441-SIAL structural laminate are presented.

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...

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.

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.

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.

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...

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.

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

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.

Laminae type and possible mechanisms for the formation of laminated sediments in the Shaban Deep, northern Red Sea

Directory of Open Access Journals (Sweden)

I. A. Seeberg-Elverfeldt

2005-01-01

Full Text Available Laminated sediments in the Shaban Deep, a brine-filled basin in the northern Red Sea, were analyzed with backscattered electron imagery. Here we present possible mechanisms involved in the formation of laminae of various types and homogenous intervals arising from the detailed investigation of multicore GeoB 7805-1 (26°13.9' N and 35°22.6' E; water depth 1447 m and gravity core GeoB 5836-2 (26°12.61' N, 35°21.56' E; water depth 1475 m. Sediment makeup includes six types: a a laminated structure with alternating light (mainly coccoliths and dark (diatom frustules layers, where the diatom component is indicative of the intra-annual variability between stratification and mixing events; b a pocket-like structure attributed to the sinking of particles within fecal pellets and aggregates; c a matrix of tightly packed diatoms that relates to extended stratification/mixing periods of the water column; d homogenous intervals that result from turbidity deposition; e silt accumulations which origin may lie in agglutinated foraminifers; and f pyrite layers with pyrite formation initiated at the seawater-brine interface.

Hyperthyroidism caused by a germline activating mutation of the thyrotropin receptor gene: difficulties in diagnosis and therapy.

Science.gov (United States)

Bertalan, Rita; Sallai, Agnes; Sólyom, János; Lotz, Gábor; Szabó, István; Kovács, Balázs; Szabó, Eva; Patócs, Attila; Rácz, Károly

2010-03-01

Germline activating mutations of the thyrotropin receptor (TSHR) gene have been considered as the only known cause of sporadic nonautoimmune hyperthyroidism in the pediatric population. Here we describe the long-term follow-up and evaluation of a patient with sporadic nonautoimmune primary hyperthyroidism who was found to have a de novo germline activating mutation of the TSHR gene. The patient was an infant who presented at the age of 10 months in an unconscious state with exsiccation, wet skin, fever, and tachycardia. Nonautoimmune primary hyperthyroidism was diagnosed, and brain magnetic resonance imaging and computed tomography showed also Arnold-Chiari malformation type I. Continuous propylthiouracil treatment resulted in a prolonged clinical cure lasting for 10 years. At the age of 11 years and 5 months the patient underwent subtotal thyroidectomy because of symptoms of trachea compression caused by a progressive multinodular goiter. However, 2 months after surgery, hormonal evaluation indicated recurrent hyperthyroidism and the patient was treated with propylthiouracil during the next 4 years. At the age of 15 years the patient again developed symptoms of trachea compression. Radioiodine treatment resulted in a regression of the recurrent goiter and a permanent cure of hyperthyroidism without relapse during the last 3 years of his follow-up. Sequencing of exon 10 of the TSHR gene showed a de novo heterozygous germline I630L mutation, which has been previously described as activating mutation at somatic level in toxic thyroid nodules. The I630L mutation of the TSHR gene occurs not only at somatic level in toxic thyroid nodules, but also its presence in germline is associated with nonautoimmune primary hyperthyroidism. Our case report demonstrates that in this disorder a continuous growth of the thyroid occurs without any evidence of elevated TSH due to antithyroid drug overdosing. This may justify previous recommendations for early treatment of affected

Low Base-Substitution Mutation Rate in the Germline Genome of the Ciliate Tetrahymena thermophila

Science.gov (United States)

2016-09-15

Tetrahymena thermophila, a model eukaryote. PLoS Biol. 4:e286. Farlow A, et al. 2015. The spontaneous mutation rate in the fission yeast Schizosaccharomyces...spontane- ous mutations in yeast . Proc Natl Acad Sci U S A. 105:9272–9277. Lynn DH, Doerder FP. 2012. The life and times of Tetrahymena. Methods Cell...Low Base-Substitution Mutation Rate in the Germline Genome of the Ciliate Tetrahymena thermophila Hongan Long1,2,y, David J. Winter3,*,y, Allan Y.-C

Oyster vasa-like gene as a marker of the germline cell development in Crassostrea gigas

International Nuclear Information System (INIS)

Fabioux, C.; Huvet, A.; Lelong, C.; Robert, R.; Pouvreau, S.; Daniel, J.Y.; Minguant, C.; Le Pennec, M.

2004-01-01

The oyster vasa-like gene was previously demonstrated to be specifically expressed in germline cells of adult oysters Crassostrea gigas. In the present study, this gene was used as a molecular marker to establish the developmental pattern of germline cells during oyster ontogenesis, using whole-mount in situ hybridization and real-time PCR. The Oyvlg transcripts appeared to be localized to the vegetal pole of unfertilized oocytes and maternally transmitted to embryos. At early development, these maternal transcripts were observed to segregate into a single blastomere, from the CD macromere of 2-cell stage to the 4d mesentoblast of blastula. From late blastula stage, the mesentoblast divided into two cell clumps that migrated to both sides of the larvae body and that would correspond to primordial germ cells (PGCs). Based on these results, we postulate that the germline of C. gigas is specified at early development by maternal cytoplasmic determinants including Oyvlg mRNAs, in putative PGCs that would differentiate into germinal stem cells in juvenile oysters

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...

[Participation of the piRNA pathway in recruiting a component of RNA polymerase I transcription initiation complex to germline cell nucleoli].

Science.gov (United States)

Fefelova, E A; Stolyarenko, A D; Yakushev, E Y; Gvozdev, V A; Klenov, M S

2017-01-01

Proteins of the Piwi family and short Piwi-interacting RNAs (piRNAs) ensure the protection of the genome from transposable elements. We have previously shown that nuclear Piwi protein tends to concentrate in the nucleoli of the cells of Drosophila melanogaster ovaries. It could be hypothesized that the function of Piwi in the nucleolus is associated with the repression of R1 and R2 retrotransposons inserted into the rDNA cluster. Here, we show that Piwi participates in recruiting Udd protein to nucleoli. Udd is a component of the conserved Selectivity Factor I-like (SL1-like) complex, which is required for transcription initiation by RNA polymerase I. We found that Udd localization depends on Piwi in germline cells, but not in somatic cells of the ovaries. In contrast, knockdowns of the SL1-like components (Udd or TAF1b) do not disrupt Piwi localization. We also observed that the absence of Udd or TAF1b in germline cells, as well as the impairment of Piwi nuclear localization lead to the accumulation of late stage egg chambers in the ovaries, which could be explained by reduced rRNA transcription. These results allow us to propose for the first time a role for Piwi in the nucleolus that is not directly associated with transposable element repression.

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

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

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.

Foxn1[Cre] Expression in the Male Germline.

Science.gov (United States)

Shi, Jianjun; Getun, Irina; Torres, Bivian; Petrie, Howard T

2016-01-01

Foxn1 (forkhead box N1), also known as the nude gene or winged-helix nude (Whn), is a forkhead transcription factor thought to be restricted to keratinocytes in the skin and thymus. Consistent with this tissue distribution, spontaneous or targeted mutation of Foxn1 results in the absence of both hair and a thymus. Genetic manipulation of the Foxn1 locus thus represents a powerful tool for tissue specific gene control in the skin and thymus, and tools such as Cre recombinase under control of the Foxn1 locus are widely used for this purpose. Unexpectedly, we show that Foxn1[Cre] exhibits unexpected activity in male germ cells, resulting in ubiquitous targeting of loxP-flanked alleles in all tissues in offspring from Foxn1[Cre] expressing male mice. Inheritance of recombined loxP alleles occurs independently of Cre inheritance (i.e., offspring lacking Cre nonetheless exhibit recombined alleles), suggesting that Foxn1[Cre] induced recombination in male germ cells must occur prior to meiosis in diploid germ cells. Together with previously published data, our results show that Foxn1, and alleles under its control, are expressed in the pre-meiotic male germline, revealing a new tool for germline targeting of genes, and raising important concerns for gender selection when using Foxn1 regulatory elements.

The Canonical E2Fs Are Required for Germline Development in Arabidopsis

Directory of Open Access Journals (Sweden)

Xiaozhen Yao

2018-05-01

Full Text Available A number of cell fate determinations, including cell division, cell differentiation, and programmed cell death, intensely occur during plant germline development. How these cell fate determinations are regulated remains largely unclear. The transcription factor E2F is a core cell cycle regulator. Here we show that the Arabidopsis canonical E2Fs, including E2Fa, E2Fb, and E2Fc, play a redundant role in plant germline development. The e2fa e2fb e2fc (e2fabc triple mutant is sterile, although its vegetative development appears normal. On the one hand, the e2fabc microspores undergo cell death during pollen mitosis. Microspores start to die at the bicellular stage. By the tricellular stage, the majority of the e2fabc microspores are degenerated. On the other hand, a wild type ovule often has one megaspore mother cell (MMC, whereas the majority of e2fabc ovules have two to three MMCs. The subsequent female gametogenesis of e2fabc mutant is aborted and the vacuole is severely impaired in the embryo sac. Analysis of transmission efficiency showed that the canonical E2Fs from both male and female gametophyte are essential for plant gametogenesis. Our study reveals that the canonical E2Fs are required for plant germline development, especially the pollen mitosis and the archesporial cell (AC-MMC transition.

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)

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.

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.)

Maternal Metabolic Syndrome Programs Mitochondrial Dysfunction via Germline Changes across Three Generations

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Jessica L. Saben

2016-06-01

Full Text Available Maternal obesity impairs offspring health, but the responsible mechanisms are not fully established. To address this question, we fed female mice a high-fat/high-sugar diet from before conception until weaning and then followed the outcomes in the next three generations of offspring, all fed a control diet. We observed that female offspring born to obese mothers had impaired peripheral insulin signaling that was associated with mitochondrial dysfunction and altered mitochondrial dynamic and complex proteins in skeletal muscle. This mitochondrial phenotype persisted through the female germline and was passed down to the second and third generations. Our results indicate that maternal programming of metabolic disease can be passed through the female germline and that the transfer of aberrant oocyte mitochondria to subsequent generations may contribute to the increased risk for developing insulin resistance.

A low frequency vibration energy harvester using magnetoelectric laminate composite

International Nuclear Information System (INIS)