WorldWideScience

Sample records for germ line development

  1. Understanding Mammalian Germ Line Development with In Vitro Models.

    Science.gov (United States)

    Martínez-Arroyo, Ana M; Míguez-Forján, Jose M; Remohí, Jose; Pellicer, Antonio; Medrano, Jose V

    2015-09-15

    Germ line development is crucial in organisms with sexual reproduction to complete their life cycle. In mammals, knowledge about germ line development is based mainly on the mouse model, in which genetic and epigenetic events are well described. However, little is known about how germ line development is orchestrated in humans, especially in the earliest stages. New findings derived from human in vitro models to obtain germ cells can shed light on these questions. This comprehensive review summarizes the current knowledge about mammalian germ line development, emphasizing the state of the art obtained from in vitro models for germ cell-like cell derivation. Current knowledge of the pluripotency cycle and germ cell specification has allowed different in vitro strategies to obtain germ cells with proven functionality in mouse models. Several reports during the last 10 years show that in vitro germ cell derivation with proven functionality to generate a healthy offspring is possible in mice. However, differences in the embryo development and pluripotency potential between human and mouse make it difficult to extrapolate these results. Further efforts on both human and mouse in vitro models to obtain germ cells from pluripotent stem cells may help to elucidate how human physiological events take place; therefore, therapeutic strategies can also be considered.

  2. A germ cell determinant reveals parallel pathways for germ line development in Caenorhabditis elegans.

    Science.gov (United States)

    Mainpal, Rana; Nance, Jeremy; Yanowitz, Judith L

    2015-10-15

    Despite the central importance of germ cells for transmission of genetic material, our understanding of the molecular programs that control primordial germ cell (PGC) specification and differentiation are limited. Here, we present findings that X chromosome NonDisjunction factor-1 (XND-1), known for its role in regulating meiotic crossover formation, is an early determinant of germ cell fates in Caenorhabditis elegans. xnd-1 mutant embryos display a novel 'one PGC' phenotype as a result of G2 cell cycle arrest of the P4 blastomere. Larvae and adults display smaller germ lines and reduced brood size consistent with a role for XND-1 in germ cell proliferation. Maternal XND-1 proteins are found in the P4 lineage and are exclusively localized to the nucleus in PGCs, Z2 and Z3. Zygotic XND-1 turns on shortly thereafter, at the ∼300-cell stage, making XND-1 the earliest zygotically expressed gene in worm PGCs. Strikingly, a subset of xnd-1 mutants lack germ cells, a phenotype shared with nos-2, a member of the conserved Nanos family of germline determinants. We generated a nos-2 null allele and show that nos-2; xnd-1 double mutants display synthetic sterility. Further removal of nos-1 leads to almost complete sterility, with the vast majority of animals without germ cells. Sterility in xnd-1 mutants is correlated with an increase in transcriptional activation-associated histone modification and aberrant expression of somatic transgenes. Together, these data strongly suggest that xnd-1 defines a new branch for PGC development that functions redundantly with nos-2 and nos-1 to promote germline fates by maintaining transcriptional quiescence and regulating germ cell proliferation. © 2015. Published by The Company of Biologists Ltd.

  3. Germ line determinants are not localized early in sea urchin development, but do accumulate in the small micromere lineage.

    Science.gov (United States)

    Juliano, Celina E; Voronina, Ekaterina; Stack, Christie; Aldrich, Maryanna; Cameron, Andrew R; Wessel, Gary M

    2006-12-01

    Two distinct modes of germ line determination are used throughout the animal kingdom: conditional-an inductive mechanism, and autonomous-an inheritance of maternal factors in early development. This study identifies homologs of germ line determinants in the sea urchin Strongylocentrotus purpuratus to examine its mechanism of germ line determination. A list of conserved germ-line associated genes from diverse organisms was assembled to search the S. purpuratus genome for homologs, and the expression patterns of these genes were examined during embryogenesis by whole mount in situ RNA hybridization and QPCR. Of the 14 genes tested, all transcripts accumulate uniformly during oogenesis and Sp-pumilio, Sp-tudor, Sp-MSY, and Sp-CPEB1 transcripts are also uniformly distributed during embryonic development. Sp-nanos2, Sp-seawi, and Sp-ovo transcripts, however, are enriched in the vegetal plate of the mesenchyme blastula stage and Sp-vasa, Sp-nanos2, Sp-seawi, and Sp-SoxE transcripts are localized in small micromere descendents at the tip of the archenteron during gastrulation and are then enriched in the left coelomic pouch of larvae. The results of this screen suggest that sea urchins conditionally specify their germ line, and support the hypothesis that this mechanism is the basal mode of germ line determination amongst deuterostomes. Furthermore, accumulation of germ line determinants selectively in small micromere descendents supports the hypothesis that these cells contribute to the germ line.

  4. Epigenetic reprogramming in the porcine germ line

    DEFF Research Database (Denmark)

    Matzen, Sara Maj Hyldig; Croxall, Nicola; Contreras, David A.

    2011-01-01

    BACKGROUND: Epigenetic reprogramming is critical for genome regulation during germ line development. Genome-wide demethylation in mouse primordial germ cells (PGC) is a unique reprogramming event essential for erasing epigenetic memory and preventing the transmission of epimutations to the next...... an increased proportion of cells in G2. CONCLUSIONS: Our study demonstrates that epigenetic reprogramming occurs in pig migratory and gonadal PGC, and establishes the window of time for the occurrence of these events. Reprogramming of histone H3K9me2 and H3K27me3 detected between E15-E21 precedes the dynamic...... DNA demethylation at imprinted loci and DNA repeats between E22-E42. Our findings demonstrate that major epigenetic reprogramming in the pig germ line follows the overall dynamics shown in mice, suggesting that epigenetic reprogramming of germ cells is conserved in mammals. A better understanding...

  5. Germ line mechanics – and unfinished business

    Science.gov (United States)

    Wessel, Gary M.

    2016-01-01

    Primordial germ cells are usually made early in the development of an organism. These are the mother of all stem cells that are necessary for propagation of the species, yet use highly diverse mechanisms between organisms. How they are specified, and when and where they form, are central to developmental biology. Using diverse organisms to study this development is illuminating for understanding the mechanics these cells use in this essential function, and for identifying the breadth of evolutionary changes that have occurred between species. This essay emphasizes how echinoderms may contribute to the patch-work quilt of our understanding of germ line formation during embryogenesis. PMID:26970000

  6. Environmentally induced transgenerational epigenetic reprogramming of primordial germ cells and the subsequent germ line.

    Directory of Open Access Journals (Sweden)

    Michael K Skinner

    Full Text Available A number of environmental factors (e.g. toxicants have been shown to promote the epigenetic transgenerational inheritance of disease and phenotypic variation. Transgenerational inheritance requires the germline transmission of altered epigenetic information between generations in the absence of direct environmental exposures. The primary periods for epigenetic programming of the germ line are those associated with primordial germ cell development and subsequent fetal germline development. The current study examined the actions of an agricultural fungicide vinclozolin on gestating female (F0 generation progeny in regards to the primordial germ cell (PGC epigenetic reprogramming of the F3 generation (i.e. great-grandchildren. The F3 generation germline transcriptome and epigenome (DNA methylation were altered transgenerationally. Interestingly, disruptions in DNA methylation patterns and altered transcriptomes were distinct between germ cells at the onset of gonadal sex determination at embryonic day 13 (E13 and after cord formation in the testis at embryonic day 16 (E16. A larger number of DNA methylation abnormalities (epimutations and transcriptional alterations were observed in the E13 germ cells than in the E16 germ cells. These observations indicate that altered transgenerational epigenetic reprogramming and function of the male germline is a component of vinclozolin induced epigenetic transgenerational inheritance of disease. Insights into the molecular control of germline transmitted epigenetic inheritance are provided.

  7. Germ-line gene therapy and the medical imperative.

    Science.gov (United States)

    Munson, Ronald; Davis, Lawrence H

    1992-06-01

    Somatic cell gene therapy has yielded promising results. If germ cell gene therapy can be developed, the promise is even greater: hundreds of genetic diseases might be virtually eliminated. But some claim the procedure is morally unacceptable. We thoroughly and sympathetically examine several possible reasons for this claim but find them inadequate. There is no moral reason, then, not to develop and employ germ-line gene therapy. Taking the offensive, we argue next that medicine has a prima facie moral obligation to do so.

  8. FLI-1 Flightless-1 and LET-60 Ras control germ line morphogenesis in C. elegans

    Directory of Open Access Journals (Sweden)

    Dentler William L

    2008-05-01

    Full Text Available Abstract Background In the C. elegans germ line, syncytial germ line nuclei are arranged at the cortex of the germ line as they exit mitosis and enter meiosis, forming a nucleus-free core of germ line cytoplasm called the rachis. Molecular mechanisms of rachis formation and germ line organization are not well understood. Results Mutations in the fli-1 gene disrupt rachis organization without affecting meiotic differentiation, a phenotype in C. elegans referred to here as the germ line morphogenesis (Glm phenotype. In fli-1 mutants, chains of meiotic germ nuclei spanned the rachis and were partially enveloped by invaginations of germ line plasma membrane, similar to nuclei at the cortex. Extensions of the somatic sheath cells that surround the germ line protruded deep inside the rachis and were associated with displaced nuclei in fli-1 mutants. fli-1 encodes a molecule with leucine-rich repeats and gelsolin repeats similar to Drosophila flightless 1 and human Fliih, which have been shown to act as cytoplasmic actin regulators as well as nuclear transcriptional regulators. Mutations in let-60 Ras, previously implicated in germ line development, were found to cause the Glm phenotype. Constitutively-active LET-60 partially rescued the fli-1 Glm phenotype, suggesting that LET-60 Ras and FLI-1 might act together to control germ line morphogenesis. Conclusion FLI-1 controls germ line morphogenesis and rachis organization, a process about which little is known at the molecular level. The LET-60 Ras GTPase might act with FLI-1 to control germ line morphogenesis.

  9. Multiphoton microscopy imaging of developing tooth germs

    Directory of Open Access Journals (Sweden)

    Pei-Yu Pan

    2014-01-01

    Conclusion: In this study, a novel multiphoton microscopy database of images from developing tooth germs in mice was set up. We confirmed that multiphoton laser microscopy is a powerful tool for investigating the development of tooth germ and is worthy for further application in the study of tooth regeneration.

  10. The C. elegans TPR Containing Protein, TRD-1, Regulates Cell Fate Choice in the Developing Germ Line and Epidermis.

    Directory of Open Access Journals (Sweden)

    Samantha Hughes

    Full Text Available Correct cell fate choice is crucial in development. In post-embryonic development of the hermaphroditic Caenorhabitis elegans, distinct cell fates must be adopted in two diverse tissues. In the germline, stem cells adopt one of three possible fates: mitotic cell cycle, or gamete formation via meiosis, producing either sperm or oocytes. In the epidermis, the stem cell-like seam cells divide asymmetrically, with the daughters taking on either a proliferative (seam or differentiated (hypodermal or neuronal fate. We have isolated a novel conserved C. elegans tetratricopeptide repeat containing protein, TRD-1, which is essential for cell fate determination in both the germline and the developing epidermis and has homologs in other species, including humans (TTC27. We show that trd-1(RNAi and mutant animals have fewer seam cells as a result of inappropriate differentiation towards the hypodermal fate. In the germline, trd-1 RNAi results in a strong masculinization phenotype, as well as defects in the mitosis to meiosis switch. Our data suggests that trd-1 acts downstream of tra-2 but upstream of fem-3 in the germline sex determination pathway, and exhibits a constellation of phenotypes in common with other Mog (masculinization of germline mutants. Thus, trd-1 is a new player in both the somatic and germline cell fate determination machinery, suggestive of a novel molecular connection between the development of these two diverse tissues.

  11. Doubly uniparental inheritance of mitochondria as a model system for studying germ line formation.

    Directory of Open Access Journals (Sweden)

    Liliana Milani

    Full Text Available BACKGROUND: Doubly Uniparental Inheritance (DUI of mitochondria occurs when both mothers and fathers are capable of transmitting mitochondria to their offspring, in contrast to the typical Strictly Maternal Inheritance (SMI. DUI was found in some bivalve molluscs, in which two mitochondrial genomes are inherited, one through eggs, the other through sperm. During male embryo development, spermatozoon mitochondria aggregate in proximity of the first cleavage furrow and end up in the primordial germ cells, while they are dispersed in female embryos. METHODOLOGY/PRINCIPAL FINDINGS: We used MitoTracker, microtubule staining and transmission electron microscopy to examine the mechanisms of this unusual distribution of sperm mitochondria in the DUI species Ruditapes philippinarum. Our results suggest that in male embryos the midbody deriving from the mitotic spindle of the first division concurs in positioning the aggregate of sperm mitochondria. Furthermore, an immunocytochemical analysis showed that the germ line determinant Vasa segregates close to the first cleavage furrow. CONCLUSIONS/SIGNIFICANCE: In DUI male embryos, spermatozoon mitochondria aggregate in a stable area on the animal-vegetal axis: in organisms with spiral segmentation this zone is not involved in cleavage, so the aggregation is maintained. Moreover, sperm mitochondria reach the same embryonic area in which also germ plasm is transferred. In 2-blastomere embryos, the segregation of sperm mitochondria in the same region with Vasa suggests their contribution in male germ line formation. In DUI male embryos, M-type mitochondria must be recognized by egg factors to be actively transferred in the germ line, where they become dominant replacing the Balbiani body mitochondria. The typical features of germ line assembly point to a common biological mechanism shared by DUI and SMI organisms. Although the molecular dynamics of the segregation of sperm mitochondria in DUI species are unknown

  12. Germ cell development in the Honeybee (Apis mellifera; Vasa and Nanos expression

    Directory of Open Access Journals (Sweden)

    Dearden Peter K

    2006-02-01

    Full Text Available Abstract Background Studies of specification of germ-cells in insect embryos has indicated that in many taxa the germ cells form early in development, and their formation is associated with pole plasm, germ plasm or an organelle called the oosome. None of these morphological features associated with germ cell formation have been identified in the Honeybee Apis mellifera. In this study I report the cloning and expression analysis of Honeybee homologues of vasa and nanos, germ cell markers in insects and other animals. Results Apis vasa and nanos RNAs are present in early honeybee embryos, but the RNAs clear rapidly, without any cells expressing these germ cell markers past stage 2. These genes are then only expressed in a line of cells in the abdomen from stage 9 onwards. These cells are the developing germ cells that are moved dorsally by dorsal closure and are placed in the genital ridge. Conclusion This study of the expression of germ cell markers in the honeybee implies that in this species either germ cells are formed by an inductive event, late in embryogenesis, or they are formed early in development in the absence of vasa and nanos expression. This contrasts with germ cell development in other members of the Hymenoptera, Diptera and Lepidoptera.

  13. Identification of genes expressed in the hermaphrodite germ line of C. elegans using SAGE

    Science.gov (United States)

    Wang, Xin; Zhao, Yongjun; Wong, Kim; Ehlers, Peter; Kohara, Yuji; Jones, Steven J; Marra, Marco A; Holt, Robert A; Moerman, Donald G; Hansen, Dave

    2009-01-01

    Background Germ cells must progress through elaborate developmental stages from an undifferentiated germ cell to a fully differentiated gamete. Some of these stages include exiting mitosis and entering meiosis, progressing through the various stages of meiotic prophase, adopting either a male (sperm) or female (oocyte) fate, and completing meiosis. Additionally, many of the factors needed to drive embryogenesis are synthesized in the germ line. To increase our understanding of the genes that might be necessary for the formation and function of the germ line, we have constructed a SAGE library from hand dissected C. elegans hermaphrodite gonads. Results We found that 4699 genes, roughly 21% of all known C. elegans genes, are expressed in the adult hermaphrodite germ line. Ribosomal genes are highly expressed in the germ line; roughly four fold above their expression levels in the soma. We further found that 1063 of the germline-expressed genes have enriched expression in the germ line as compared to the soma. A comparison of these 1063 germline-enriched genes with a similar list of genes prepared using microarrays revealed an overlap of 460 genes, mutually reinforcing the two lists. Additionally, we identified 603 germline-enriched genes, supported by in situ expression data, which were not previously identified. We also found >4 fold enrichment for RNA binding proteins in the germ line as compared to the soma. Conclusion Using multiple technological platforms provides a more complete picture of global gene expression patterns. Genes involved in RNA metabolism are expressed at a significantly higher level in the germ line than the soma, suggesting a stronger reliance on RNA metabolism for control of the expression of genes in the germ line. Additionally, the number and expression level of germ line expressed genes on the X chromosome is lower than expected based on a random distribution. PMID:19426519

  14. Identification of genes expressed in the hermaphrodite germ line of C. elegans using SAGE

    Directory of Open Access Journals (Sweden)

    Holt Robert A

    2009-05-01

    Full Text Available Abstract Background Germ cells must progress through elaborate developmental stages from an undifferentiated germ cell to a fully differentiated gamete. Some of these stages include exiting mitosis and entering meiosis, progressing through the various stages of meiotic prophase, adopting either a male (sperm or female (oocyte fate, and completing meiosis. Additionally, many of the factors needed to drive embryogenesis are synthesized in the germ line. To increase our understanding of the genes that might be necessary for the formation and function of the germ line, we have constructed a SAGE library from hand dissected C. elegans hermaphrodite gonads. Results We found that 4699 genes, roughly 21% of all known C. elegans genes, are expressed in the adult hermaphrodite germ line. Ribosomal genes are highly expressed in the germ line; roughly four fold above their expression levels in the soma. We further found that 1063 of the germline-expressed genes have enriched expression in the germ line as compared to the soma. A comparison of these 1063 germline-enriched genes with a similar list of genes prepared using microarrays revealed an overlap of 460 genes, mutually reinforcing the two lists. Additionally, we identified 603 germline-enriched genes, supported by in situ expression data, which were not previously identified. We also found >4 fold enrichment for RNA binding proteins in the germ line as compared to the soma. Conclusion Using multiple technological platforms provides a more complete picture of global gene expression patterns. Genes involved in RNA metabolism are expressed at a significantly higher level in the germ line than the soma, suggesting a stronger reliance on RNA metabolism for control of the expression of genes in the germ line. Additionally, the number and expression level of germ line expressed genes on the X chromosome is lower than expected based on a random distribution.

  15. On the development of extragonadal and gonadal human germ cells

    Directory of Open Access Journals (Sweden)

    A. Marijne Heeren

    2016-02-01

    Full Text Available Human germ cells originate in an extragonadal location and have to migrate to colonize the gonadal primordia at around seven weeks of gestation (W7, or five weeks post conception. Many germ cells are lost along the way and should enter apoptosis, but some escape and can give rise to extragonadal germ cell tumors. Due to the common somatic origin of gonads and adrenal cortex, we investigated whether ectopic germ cells were present in the human adrenals. Germ cells expressing DDX4 and/or POU5F1 were present in male and female human adrenals in the first and second trimester. However, in contrast to what has been described in mice, where ‘adrenal’ and ‘ovarian’ germ cells seem to enter meiosis in synchrony, we were unable to observe meiotic entry in human ‘adrenal’ germ cells until W22. By contrast, ‘ovarian’ germ cells at W22 showed a pronounced asynchronous meiotic entry. Interestingly, we observed that immature POU5F1+ germ cells in both first and second trimester ovaries still expressed the neural crest marker TUBB3, reminiscent of their migratory phase. Our findings highlight species-specific differences in early gametogenesis between mice and humans. We report the presence of a population of ectopic germ cells in the human adrenals during development.

  16. 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.

  17. 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

  18. A role for Lin28 in primordial germ cell development and germ cell malignancy

    Science.gov (United States)

    West, Jason A.; Viswanathan, Srinivas R.; Yabuuchi, Akiko; Cunniff, Kerianne; Takeuchi, Ayumu; Park, In-Hyun; Sero, Julia E.; Zhu, Hao; Perez-Atayde, Antonio; Frazier, A. Lindsay; Surani, M. Azim; Daley, George Q.

    2009-01-01

    The rarity and inaccessibility of the earliest primordial germ cells (PGCs) in the mouse embryo thwarts efforts to investigate molecular mechanisms of germ cell specification. Stella marks the minute founder population of the germ lineage1,2. Here we differentiate mouse embryonic stem cells (ESCs) carrying a Stella transgenic reporter into putative PGCs in vitro. The Stella+ cells possess a transcriptional profile similar to embryo-derived PGCs, and like their counterparts in vivo, lose imprints in a time-dependent manner. Using inhibitory RNAs to screen candidate genes for effects on the development of Stella+ cells in vitro, we discovered that Lin28, a negative regulator of let-7 microRNA processing3-6, is essential for proper PGC development. We further show that Blimp1, a let-7 target and a master regulator of PGC specification7-9, can rescue the effect of Lin28-deficiency during PGC development, thereby establishing a mechanism of action for Lin28 during PGC specification. Over-expression of Lin28 promotes formation of Stella+ cells in vitro and PGCs in chimeric embryos, and is associated with human germ cell tumours. The differentiation of putative PGCs from ESCs in vitro recapitulates the early stages of gamete development in vivo, and provides an accessible system for discovering novel genes involved in germ cell development and malignancy. PMID:19578360

  19. The ethics of germ line gene manipulation--a five dimensional debate.

    Science.gov (United States)

    Carter, Lucy

    2002-10-01

    Contributors to the debate surrounding the ethics of germ line gene manipulation have by and large concentrated their efforts on discussions of the potential risks that are associated with the use of this technology. Many international advisory committees have ruled out the acceptability of germ line gene manipulation at least for the time being. The purpose of this work is to generate much needed discussion on the many other ethical issues concerning the implementation of not only germ line gene manipulation but also other related biotechnologies. In this paper I systematically investigate and analyse the most salient issues put forward by proponents and opponents alike. I argue that if germ line manipulation proves to be a safe and effective procedure, then the principle of beneficence imposes on the medical profession a moral duty to pursue the technology.

  20. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms.

    Science.gov (United States)

    Malkin, D; Li, F P; Strong, L C; Fraumeni, J F; Nelson, C E; Kim, D H; Kassel, J; Gryka, M A; Bischoff, F Z; Tainsky, M A

    1990-11-30

    Familial cancer syndromes have helped to define the role of tumor suppressor genes in the development of cancer. The dominantly inherited Li-Fraumeni syndrome (LFS) is of particular interest because of the diversity of childhood and adult tumors that occur in affected individuals. The rarity and high mortality of LFS precluded formal linkage analysis. The alternative approach was to select the most plausible candidate gene. The tumor suppressor gene, p53, was studied because of previous indications that this gene is inactivated in the sporadic (nonfamilial) forms of most cancers that are associated with LFS. Germ line p53 mutations have been detected in all five LFS families analyzed. These mutations do not produce amounts of mutant p53 protein expected to exert a trans-dominant loss of function effect on wild-type p53 protein. The frequency of germ line p53 mutations can now be examined in additional families with LFS, and in other cancer patients and families with clinical features that might be attributed to the mutation.

  1. Lack of GNAQ and GNA11 germ-line mutations in familial melanoma pedigrees with uveal melanoma or blue nevi

    Directory of Open Access Journals (Sweden)

    Jason Ezra Hawkes

    2013-06-01

    Full Text Available Approximately 10% of melanoma cases are familial, but only 25-40% of familial melanoma cases can be attributed to germ-line mutations in the CDKN2A - the most significant high-risk melanoma susceptibility locus identified to date. The pathogenic mutation(s in most of the remaining familial melanoma pedigrees have not yet been identified. The most common mutations in nevi and sporadic melanoma are found in BRAF and NRAS, both of which result in constitutive activation of the MAPK pathway. However, these mutations are not found in uveal melanomas or the intradermal melanocytic proliferations known as blue nevi. Rather, multiple studies report a strong association between these lesions and somatic mutations in Guanine nucleotide-binding protein G(q subunit alpha (GNAQ, Guanine nucleotide-binding protein G(q subunit alpha-11 (GNA11 and BRCA1 associated protein-1 (BAP1. Recently, germ-line mutations in BAP1, the gene encoding a tumor suppressing deubiquitinating enzyme, have been associated with predisposition to a variety of cancers including uveal melanoma, but no studies have examined the association of germ-line mutations in GNAQ and GNA11 with uveal melanoma and blue nevi. We have now done so by sequencing exon 5 of both of these genes in 13 unique familial melanoma pedigrees, members of which have had either uveal or cutaneous melanoma and/or blue nevi. Germ-line DNA from a total of 22 individuals was used for sequencing; however no deleterious mutations were detected. Nevertheless, such candidate gene studies and the discovery of novel germ-line mutations associated with an increased MM susceptibility can lead to a better understanding of the pathways involved in melanocyte transformation, formulation of risk assessment, and the development of specific drug therapies.

  2. The DEAD-box protein MEL-46 is required in the germ line of the nematode Caenorhabditis elegans.

    Science.gov (United States)

    Minasaki, Ryuji; Puoti, Alessandro; Streit, Adrian

    2009-06-17

    In the hermaphrodite of the nematode Caenorhabditis elegans, the first germ cells differentiate as sperm. Later the germ line switches to the production of oocytes. This process requires the activity of a genetic regulatory network that includes among others the fem, fog and mog genes. The function of some of these genes is germline specific while others also act in somatic tissues. DEAD box proteins have been shown to be involved in the control of gene expression at different steps such as transcription and pre-mRNA processing. We show that the Caenorhabditis elegans gene mel-46 (maternal effect lethal) encodes a DEAD box protein that is related to the mammalian DDX20/Gemin3/DP103 genes. mel-46 is expressed throughout development and mutations in mel-46 display defects at multiple developmental stages. Here we focus on the role of mel-46 in the hermaphrodite germ line. mel-46(yt5) mutant hermaphrodites are partially penetrant sterile and fully penetrant maternal effect lethal. The germ line of mutants shows variable defects in oogenesis. Further, mel-46(yt5) suppresses the complete feminization caused by mutations in fog-2 and fem-3, two genes that are at the top and the center, respectively, of the genetic germline sex determining cascade, but not fog-1 that is at the bottom of this cascade. The C. elegans gene mel-46 encodes a DEAD box protein that is required maternally for early embryogenesis and zygotically for postembryonic development. In the germ line, it is required for proper oogenesis. Although it interacts genetically with genes of the germline sex determination machinery its primary function appears to be in oocyte differentiation rather than sex determination.

  3. In Vitro Modeling of Human Germ Cell Development Using Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Yuncheng Zhao

    2018-02-01

    Full Text Available Summary: Due to differences across species, the mechanisms of cell fate decisions determined in mice cannot be readily extrapolated to humans. In this study, we developed a feeder- and xeno-free culture protocol that efficiently induced human pluripotent stem cells (iPSCs into PLZF+/GPR125+/CD90+ spermatogonium-like cells (SLCs. These SLCs were enriched with key genes in germ cell development such as MVH, DAZL, GFRα1, NANOS3, and DMRT1. In addition, a small fraction of SLCs went through meiosis in vitro to develop into haploid cells. We further demonstrated that this chemically defined induction protocol faithfully recapitulated the features of compromised germ cell development of PSCs with NANOS3 deficiency or iPSC lines established from patients with non-obstructive azoospermia. Taken together, we established a powerful experimental platform to investigate human germ cell development and pathology related to male infertility. : In this article, Wang and colleagues established a feeder- and xeno-free system to robustly induce human pluripotent stem cells (PSCs into spermatogonia-like cells. This chemically defined induction protocol faithfully recapitulated the features of compromised germ cell development of PSCs with NANOS3 deficiency or iPSC lines established from patients with non-obstructive azoospermia. Keywords: pluripotent stem cells, spermatogonia, infertility, non-obstructive azoospermia

  4. Germ line transmission of a yeast artificial chromosome spanning the murine [alpha][sub 1](I) collagen locus

    Energy Technology Data Exchange (ETDEWEB)

    Strauss, W.M.; Dausman, J.; Beard, C.; Jaenisch, R. (Massachusetts Inst. of Technology, Cambridge (United States)); Johnson, C.; Lawrence, J.B. (Univ. of Massachusetts Medical School, Worcester (United States))

    1993-03-26

    Molecular complementation of mutant phenotypes by transgenic technology is a potentially important tool for gene identification. A technology was developed to allow the transfer of a physically intact yeast artificial chromosome (YAC) into the germ line of the mouse. A purified 150-kilobase YAC encompassing the murine gene Col1a1 was efficiently introduced into embryonic stem (ES) cells via lipofection. Chimeric founder mice were derived from two transfected ES cell clones. These chimeras transmitted the full length transgene through the germ line, generating two transgenic mouse strains. Transgene expression was visualized as nascent transcripts in interphase nuclei and quantitated by ribonuclease protection analysis. Both assays indicated that the transgene was expressed at levels comparable to the endogenous collagen gene. 32 refs., 3 figs., 1 tab.

  5. Spondyloepiphseal dysplasia congenita in siblings born to unaffected parents: ? germ line mosaicism

    Energy Technology Data Exchange (ETDEWEB)

    Mulla, W.; McDonald-McGinn, D.; Zackai, E. [Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)] [and others

    1994-09-01

    Germ line mosaicism has been used to explain the birth of more than one child affected with a dominantly inherited disorder born to unaffected parents. Furthermore, it has been confirmed clinically in families where recurrence in siblings was originally thought to be autosomal recessive, but were affected individuals have reproduced affected offspring. Firm evidence of germ line mosaicism using mutation analysis by molecular methods exists for some autosomal disorders. We present two siblings with spondyloepipheseal dysplasia congenita (SEDC) born to unaffected parents. This suggests the presence of germ line mosaicism in this entity. Patient 1 was born at 32 weeks gestation to a G1P1 Puerto Rican mother. The pregnancy was complicated by polyhydramnios. The neonate, a short-limbed dwarf, died at 15 hours of age from respiratory distress and a compromised thoracic cavity. Patient 2, the sibling of patient 1 was born at 37 weeks gestation after a pregnancy complicated by polyhydramnios and prenatal ultrasound diagnosis of short-limbed dwarfism. The diagnosis of SEDC was made and, after review of the sibling`s postmortem X-rays, it was felt that she was similarly affected. The family history reveals no history of dwarfism or consanguinity. The SEDC is described as an autosomal dominant form of dwarfism with variable presentation including some cases that have been lethal in the neonatal period. SEDC is now believed to represent a family of collagen II mutations. Sporadic cases that have arisen in families with no history have been ascribed to new heterozygous mutations. Other families in which SEDC and SEMD recurred without a family history most likely represent germ line mosaicism. In these cases molecular studies should be pursued to document a collagen II mutation. We believe that germ line mosaicism is the most plausible explanation for recurrence in our family.

  6. Differential expression of conserved germ line markers and delayed segregation of male and female primordial germ cells in a hermaphrodite, the leech helobdella.

    Science.gov (United States)

    Cho, Sung-Jin; Vallès, Yvonne; Weisblat, David A

    2014-02-01

    In sexually reproducing animals, primordial germ cells (PGCs) are often set aside early in embryogenesis, a strategy that minimizes the risk of genomic damage associated with replication and mitosis during the cell cycle. Here, we have used germ line markers (piwi, vasa, and nanos) and microinjected cell lineage tracers to show that PGC specification in the leech genus Helobdella follows a different scenario: in this hermaphrodite, the male and female PGCs segregate from somatic lineages only after more than 20 rounds of zygotic mitosis; the male and female PGCs share the same (mesodermal) cell lineage for 19 rounds of zygotic mitosis. Moreover, while all three markers are expressed in both male and female reproductive tissues of the adult, they are expressed differentially between the male and female PGCs of the developing embryo: piwi and vasa are expressed preferentially in female PGCs at a time when nanos is expressed preferentially in male PGCs. A priori, the delayed segregation of male and female PGCs from somatic tissues and from one another increases the probability of mutations affecting both male and female PGCs of a given individual. We speculate that this suite of features, combined with a capacity for self-fertilization, may contribute to the dramatically rearranged genome of Helobdella robusta relative to other animals.

  7. Genetic modification of the human germ line: The reasons why this project has no future.

    Science.gov (United States)

    Morange, Michel

    2015-01-01

    Modification of the human germ line has remained a distant but valuable objective for most biologists since the emergence of genetics (and even before). To study the historical transformations of this project, I have selected three periods - the 1930s, at the pinnacle of eugenics, around 1974 when molecular biology triumphed, and today - and have adopted three criteria to estimate the feasibility of this project: the state of scientific knowledge, the existence of suitable tools, and societal demands. Although the long-awaited techniques to modify the germ line are now available, I will show that most of the expectations behind this project have disappeared, or are considered as being reachable by highly different strategies. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  8. The Ovary of Tubifex tubifex (Clitellata, Naididae, Tubificinae Is Composed of One, Huge Germ-Line Cyst that Is Enriched with Cytoskeletal Components.

    Directory of Open Access Journals (Sweden)

    Anna Z Urbisz

    Full Text Available Recent studies on the ovary organization and oogenesis in Tubificinae have revealed that their ovaries are small polarized structures that are composed of germ cells in subsequent stages of oogenesis that are associated with somatic cells. In syncytial cysts, as a rule, each germ cell is connected to the central cytoplasmic mass, the cytophore, via only one stable intercellular bridge (ring canal. In this paper we present detailed data about the composition of germ-line cysts in Tubifex tubifex with special emphasis on the occurrence and distribution of the cytoskeletal elements. Using fixed material and live cell imaging techniques, we found that the entire ovary of T. tubifex is composed of only one, huge multicellular germ-line cyst, which may contain up to 2,600 cells. Its architecture is broadly similar to the cysts that are found in other clitellate annelids, i.e. a common, anuclear cytoplasmic mass in the center of the cyst and germ cells that are connected to it via intercellular bridges. The cytophore in the T. tubifex cyst extends along the long axis of the ovary in the form of elongated and branched cytoplasmic strands. Rhodamine-coupled phalloidin staining revealed that the prominent strands of actin filaments occur inside the cytophore. Similar to the cytophore, F-actin strands are branched and they are especially well developed in the middle and outermost parts of the ovary. Microfilaments are also present in the ring canals that connect the germ cells with the cytophore in the narrow end of the ovary. Using TubulinTracker, we found that the microtubules form a prominent network of loosely and evenly distributed tubules inside the cytophore as well as in every germ cell. The well-developed cytoskeletal elements in T. tubifex ovary seem to ensure the integrity of such a huge germ-line cyst of complex (germ cells-ring canals-cytophore organization. A comparison between the cysts that are described here and other well-known female

  9. Sequence and expression pattern of the germ line marker vasa in honey bees and stingless bees

    Science.gov (United States)

    2009-01-01

    Queens and workers of social insects differ in the rates of egg laying. Using genomic information we determined the sequence of vasa, a highly conserved gene specific to the germ line of metazoans, for the honey bee and four stingless bees. The vasa sequence of social bees differed from that of other insects in two motifs. By RT-PCR we confirmed the germ line specificity of Amvasa expression in honey bees. In situ hybridization on ovarioles showed that Amvasa is expressed throughout the germarium, except for the transition zone beneath the terminal filament. A diffuse vasa signal was also seen in terminal filaments suggesting the presence of germ line cells. Oocytes showed elevated levels of Amvasa transcripts in the lower germarium and after follicles became segregated. In previtellogenic follicles, Amvasa transcription was detected in the trophocytes, which appear to supply its mRNA to the growing oocyte. A similar picture was obtained for ovarioles of the stingless bee Melipona quadrifasciata, except that Amvasa expression was higher in the oocytes of previtellogenic follicles. The social bees differ in this respect from Drosophila, the model system for insect oogenesis, suggesting that changes in the sequence and expression pattern of vasa may have occurred during social evolution. PMID:21637523

  10. Sequence and expression pattern of the germ line marker vasa in honey bees and stingless bees

    Directory of Open Access Journals (Sweden)

    Érica Donato Tanaka

    2009-01-01

    Full Text Available Queens and workers of social insects differ in the rates of egg laying. Using genomic information we determined the sequence of vasa, a highly conserved gene specific to the germ line of metazoans, for the honey bee and four stingless bees. The vasa sequence of social bees differed from that of other insects in two motifs. By RT-PCR we confirmed the germ line specificity of Amvasa expression in honey bees. In situ hybridization on ovarioles showed that Amvasa is expressed throughout the germarium, except for the transition zone beneath the terminal filament. A diffuse vasa signal was also seen in terminal filaments suggesting the presence of germ line cells. Oocytes showed elevated levels of Amvasa transcripts in the lower germarium and after follicles became segregated. In previtellogenic follicles, Amvasa transcription was detected in the trophocytes, which appear to supply its mRNA to the growing oocyte. A similar picture was obtained for ovarioles of the stingless bee Melipona quadrifasciata, except that Amvasa expression was higher in the oocytes of previtellogenic follicles. The social bees differ in this respect from Drosophila, the model system for insect oogenesis, suggesting that changes in the sequence and expression pattern of vasa may have occurred during social evolution.

  11. Differentiation in Stem Cell Lineages and in Life: Explorations in the Male Germ Line Stem Cell Lineage.

    Science.gov (United States)

    Fuller, Margaret T

    2016-01-01

    I have been privileged to work on cellular differentiation during a great surge of discovery that has revealed the molecular mechanisms and genetic regulatory circuitry that control embryonic development and adult tissue maintenance and repair. Studying the regulation of proliferation and differentiation in the male germ line stem cell lineage has allowed us investigate how the developmental program imposes layers of additional controls on fundamental cellular processes like cell cycle progression and gene expression to give rise to the huge variety of specialized cell types in our bodies. We are beginning to understand how local signals from somatic support cells specify self-renewal versus differentiation in the stem cell niche at the apical tip of the testis. We are discovering the molecular events that block cell proliferation and initiate terminal differentiation at the switch from mitosis to meiosis-a signature event of the germ cell program. Our work is beginning to reveal how the developmental program that sets up the dramatic new cell type-specific transcription program that prepares germ cells for meiotic division and spermatid differentiation is turned on when cells become spermatocytes. I have had the privilege of working with incredible students, postdocs, and colleagues who have discovered, brainstormed, challenged, and refined our science and our ideas of how developmental pathways and cellular mechanisms work together to drive differentiation. © 2016 Elsevier Inc. All rights reserved.

  12. Germ cell differentiation and proliferation in the developing testis of the South American plains viscacha, Lagostomus maximus (Mammalia, Rodentia).

    Science.gov (United States)

    Gonzalez, C R; Muscarsel Isla, M L; Fraunhoffer, N A; Leopardo, N P; Vitullo, A D

    2012-08-01

    Cell proliferation and cell death are essential processes in the physiology of the developing testis that strongly influence the normal adult spermatogenesis. We analysed in this study the morphometry, the expression of the proliferation cell nuclear antigen (PCNA), cell pluripotency marker OCT-4, germ cell marker VASA and apoptosis in the developing testes of Lagostomus maximus, a rodent in which female germ line develops through abolished apoptosis and unrestricted proliferation. Morphometry revealed an increment in the size of the seminiferous cords with increasing developmental age, arising from a significant increase of PCNA-positive germ cells and a stable proportion of PCNA-positive Sertoli cells. VASA showed a widespread cytoplasmic distribution in a great proportion of proliferating gonocytes that increased significantly at late development. In the somatic compartment, Leydig cells increased at mid-development, whereas peritubular cells showed a stable rate of proliferation. In contrast to other mammals, OCT-4 positive gonocytes increased throughout development reaching 90% of germ cells in late-developing testis, associated with a conspicuous increase in circulating FSH from mid- to late-gestation. TUNEL analysis was remarkable negative, and only a few positive cells were detected in the somatic compartment. These results show that the South American plains viscacha displays a distinctive pattern of testis development characterized by a sustained proliferation of germ cells throughout development, with no signs of apoptosis cell demise, in a peculiar endocrine in utero ambiance that seems to promote the increase of spermatogonial number as a primary direct effect of FSH.

  13. Proliferation of endogenous retroviruses in the early stages of a host germ line invasion.

    Science.gov (United States)

    Ishida, Yasuko; Zhao, Kai; Greenwood, Alex D; Roca, Alfred L

    2015-01-01

    Endogenous retroviruses (ERVs) comprise 8% of the human genome and are common in all vertebrate genomes. The only retrovirus known to be currently transitioning from exogenous to endogenous form is the koala retrovirus (KoRV), making koalas (Phascolarctos cinereus) ideal for examining the early stages of retroviral endogenization. To distinguish endogenous from exogenous KoRV proviruses, we isolated koala genomic regions flanking KoRV integration sites. In three wild southern Australian koalas, there were fewer KoRV loci than in three captive Queensland koalas, consistent with reports that southern Australian koalas carry fewer KoRVs. Of 39 distinct KoRV proviral loci examined in a sire-dam-progeny triad, all proved to be vertically transmitted and endogenous; none was exogenous. Of the 39 endogenous KoRVs (enKoRVs), only one was present in the genomes of both the sire and the dam, suggesting that, at this early stage in the retroviral invasion of a host germ line, very large numbers of ERVs have proliferated at very low frequencies in the koala population. Sequence divergence between the 5'- and 3'-long terminal repeats (LTRs) of a provirus can be used as a molecular clock. Within each of ten enKoRVs, the 5'-LTR sequence was identical to the 3'-LTR sequence, suggesting a maximum age for enKoRV invasion of the koala germ line of approximately 22,200-49,900 years ago, although a much younger age is possible. Across the ten proviruses, seven LTR haplotypes were detected, indicating that at least seven different retroviral sequences had entered the koala germ line. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Proliferation of Endogenous Retroviruses in the Early Stages of a Host Germ Line Invasion

    Science.gov (United States)

    Ishida, Yasuko; Zhao, Kai; Greenwood, Alex D.; Roca, Alfred L.

    2015-01-01

    Endogenous retroviruses (ERVs) comprise 8% of the human genome and are common in all vertebrate genomes. The only retrovirus known to be currently transitioning from exogenous to endogenous form is the koala retrovirus (KoRV), making koalas (Phascolarctos cinereus) ideal for examining the early stages of retroviral endogenization. To distinguish endogenous from exogenous KoRV proviruses, we isolated koala genomic regions flanking KoRV integration sites. In three wild southern Australian koalas, there were fewer KoRV loci than in three captive Queensland koalas, consistent with reports that southern Australian koalas carry fewer KoRVs. Of 39 distinct KoRV proviral loci examined in a sire–dam–progeny triad, all proved to be vertically transmitted and endogenous; none was exogenous. Of the 39 endogenous KoRVs (enKoRVs), only one was present in the genomes of both the sire and the dam, suggesting that, at this early stage in the retroviral invasion of a host germ line, very large numbers of ERVs have proliferated at very low frequencies in the koala population. Sequence divergence between the 5′- and 3′-long terminal repeats (LTRs) of a provirus can be used as a molecular clock. Within each of ten enKoRVs, the 5′-LTR sequence was identical to the 3′-LTR sequence, suggesting a maximum age for enKoRV invasion of the koala germ line of approximately 22,200–49,900 years ago, although a much younger age is possible. Across the ten proviruses, seven LTR haplotypes were detected, indicating that at least seven different retroviral sequences had entered the koala germ line. PMID:25261407

  15. Germ-line origins of mutation in families with hemophilia B: The sex ratio varies with the type of mutation

    Energy Technology Data Exchange (ETDEWEB)

    Ketterling, R.P.; Vielhaber, E.; Bottema, C.D.K.; Schaid, D.J.; Sommer, S.S. (Mayo Clinic/Foundation, Rochester, MN (United States)); Cohen, M.P. (Vanderbilt Univ., Nashville, TN (United States)); Sexauer, C.L. (Children' s Hospital, Oklahoma City, OK (United States))

    1993-01-01

    Previous epidemiological and biochemical studies have generated conflicting estimates of the sex ratio of mutation. Direct genomic sequencing in combination with haplotype analysis extends previous analyses by allowing the precise mutation to be determined in a given family. From analysis of the factor IX gene of 260 consecutive families with hemophilia B, the authors report the germ-line origin of mutation in 25 families. When combined with 14 origins of mutation reported by others and with 4 origins previously reported by them, a total of 25 occur in the female germ line, and 18 occur in the male germ line. The excess of germ-line origins in females does not imply an overall excess mutation rate per base pair in the female germ line. Bayesian analysis of the data indicates that the sex ratio varies with the type of mutation. The aggregate of single-base substitutions shows a male predominance of germ-line mutations (P < .002). The maximum-likelihood estimate of the male predominance is 3.5-fold. Of the single-base substitutions, deletions display a sex ratio of unity. Analysis of the parental age at transmission of a new mutation suggests that germ-line mutations are associated with a small increase in parental age in females but little, if any, increase in males. Although direct genomic sequencing offers a general method for defining the origin of mutation in specific families, accurate estimates of the sex ratios of different mutational classes require large sample sizes and careful correction for multiple biases of ascertainment. The biases in the present data result in an underestimate of the enhancement of mutation in males. 62 refs., 1 fig., 5 tabs.

  16. Transgenic mice produced by retroviral transduction of male germ-line stem cells

    OpenAIRE

    Nagano, Makoto; Brinster, Clayton J.; Orwig, Kyle E.; Ryu, Buom-Yong; Avarbock, Mary R.; Brinster, Ralph L.

    2001-01-01

    Male germ-line stem cells are the only cell type in postnatal mammals that have the capability to self-renew and to contribute genes to the next generation. Genetic modification of these cells would provide an opportunity to study the biology of their complex self-renewal and differentiation processes, as well as enable the generation of transgenic animals in a wide range of species. Although retroviral vectors have been used as an efficient method to introduce genes into a variety of cell ty...

  17. Melatonin receptor genes (mel-1a, mel-1b, mel-1c) are differentially expressed in the avian germ line.

    Science.gov (United States)

    Kawashima, Takaharu; Stepińska, Urszula; Kuwana, Takashi; Olszańska, Bozenna

    2008-09-01

    The presence of melatonin receptor transcripts (mel-1a, mel-1b and mel-1c) was investigated in primordial germ cells (PGCs), immature and mature oocytes, and sperm of Japanese quail by reverse transcription--polymerase chain reaction (RT-PCR). The mel-1a transcript was detected in as few as in a thousand PGCs. Significant differences in the expression of melatonin receptor genes were found in differentiating germ cells: in PGCs only the mel-1a receptor was expressed, in blastoderms and immature oocytes all three transcripts (mel-1a, mel-1b, mel-1c) were present, while in mature ovulated oocytes the predominant transcript was mel-1c (with sporadic occurrence of mel-1a and mel-1b). In sperm, mel-1a and mel-1c were present but mel-1b was absent. This indicates that the expression of melatonin receptor genes changes throughout the differentiation of PGCs into adult gametes: during oocyte differentiation two additional transcripts, mel-1b and mel-1c, are synthesized in addition to mel-1a, but at oocyte maturation, mel-1a and mel-1b are degraded and only mel-1c remains. During male line (spermatozoa) differentiation mel-1c is transcribed in addition to mel-1a, with mel-1b being completely absent. Since melatonin and the activities of enzymes participating in melatonin synthesis are present in the avian yolk, it is reasonable to suggest a role for this molecule in early avian development and germ line differentiation. We propose that melatonin may act as a signaling molecule regulating some differentiation processes (e.g., cell proliferation, migration, etc.) before the formation of neural and hormonal systems.

  18. Mismatch repair deficiency does not enhance ENU mutagenesis in the zebrafish germ line.

    Science.gov (United States)

    Feitsma, Harma; de Bruijn, Ewart; van de Belt, Jose; Nijman, Isaac J; Cuppen, Edwin

    2008-07-01

    S(N)1-type alkylating agents such as N-ethyl-N-nitrosourea (ENU) are very potent mutagens. They act by transferring their alkyl group to DNA bases, which, upon mispairing during replication, can cause single base pair mutations in the next replication cycle. As DNA mismatch repair (MMR) proteins are involved in the recognition of alkylation damage, we hypothesized that ENU-induced mutation rates could be increased in a MMR-deficient background, which would be beneficial for mutagenesis approaches. We applied a standard ENU mutagenesis protocol to adult zebrafish deficient in the MMR gene msh6 and heterozygous controls to study the effect of MMR on ENU-induced DNA damage. Dose-dependent lethality was found to be similar for homozygous and heterozygous mutants, indicating that there is no difference in ENU resistance. Mutation discovery by high-throughput dideoxy resequencing of genomic targets in outcrossed progeny of the mutagenized fish did also not reveal any differences in germ line mutation frequency. These results may indicate that the maximum mutation load for zebrafish has been reached with the currently used, highly optimized ENU mutagenesis protocol. Alternatively, the MMR system in the zebrafish germ line may be saturated very rapidly, thereby having a limited effect on high-dose ENU mutagenesis.

  19. The perfect host: a mouse host embryo facilitating more efficient germ line transmission of genetically modified embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Robert A Taft

    Full Text Available There is a continual need to improve efficiency in creating precise genetic modifications in mice using embryonic stem cells (ESCs. We describe a novel approach resulting in 100% germline transmission from competent injected ESCs. We developed an F1 mouse host embryo (Perfect Host, PH that selectively ablates its own germ cells via tissue-specific induction of diphtheria toxin. This approach allows competent microinjected ESCs to fully dominate the germline, eliminating competition for this critical niche in the developing and adult animal. This is in contrast to conventional methods, where competition from host germ cells results in offspring derived from host cells and ESCs, necessitating extensive breeding of chimeras and genotyping to identify germline. The germline transmission process is also complicated by variability in the actual number of ESCs that colonize the germline niche and the proportion that are germline competent. To validate the PH approach we used ESC lines derived from 129 F1, BALB/cByJ, and BTBR backgrounds as well as an iPS line. Resulting chimeric males produced 194 offspring, all paternally derived from the introduced stem cells, with no offspring being derived from the host genome. We further tested this approach using eleven genetically modified C57BL/6N ESC lines (International Knockout Mouse Consortium. ESC germline transmission was observed in 9/11 (82% lines using PH blastocysts, compared to 6/11 (55% when conventional host blastocysts were used. Furthermore, less than 35% (83/240 of mice born in the first litters from conventional chimeras were confirmed to be of ESC-origin. By comparison, 100% (137/137 of the first litter offspring of PH chimeras were confirmed as ESC-derived. Together, these data demonstrate that the PH approach increases the probability of germline transmission and speeds the generation of ESC derived animals from chimeras. Collectively, this approach reduces the time and costs inherent in the

  20. Pathogenesis of germ cell neoplasia in testicular dysgenesis and disorders of sex development

    DEFF Research Database (Denmark)

    Jørgensen, Anne; Lindhardt Johansen, Marie; Juul, Anders

    2015-01-01

    in individuals with 46,XY DSD. We summarise knowledge concerning development and sex differentiation of human gonads, with focus on sex-dimorphic steps of germ cell maturation, including meiosis. We also briefly outline the histopathology of germ cell neoplasia in situ (GCNIS) and gonadoblastoma (GDB), which......Development of human gonads is a sex-dimorphic process which evolved to produce sex-specific types of germ cells. The process of gonadal sex differentiation is directed by the action of the somatic cells and ultimately results in germ cells differentiating to become functional gametes through...

  1. Insights into female germ cell biology: from in vivo development to in vitro derivations.

    Science.gov (United States)

    Jung, Dajung; Kee, Kehkooi

    2015-01-01

    Understanding the mechanisms of human germ cell biology is important for developing infertility treatments. However, little is known about the mechanisms that regulate human gametogenesis due to the difficulties in collecting samples, especially germ cells during fetal development. In contrast to the mitotic arrest of spermatogonia stem cells in the fetal testis, female germ cells proceed into meiosis and began folliculogenesis in fetal ovaries. Regulations of these developmental events, including the initiation of meiosis and the endowment of primordial follicles, remain an enigma. Studying the molecular mechanisms of female germ cell biology in the human ovary has been mostly limited to spatiotemporal characterizations of genes or proteins. Recent efforts in utilizing in vitro differentiation system of stem cells to derive germ cells have allowed researchers to begin studying molecular mechanisms during human germ cell development. Meanwhile, the possibility of isolating female germline stem cells in adult ovaries also excites researchers and generates many debates. This review will mainly focus on presenting and discussing recent in vivo and in vitro studies on female germ cell biology in human. The topics will highlight the progress made in understanding the three main stages of germ cell developments: namely, primordial germ cell formation, meiotic initiation, and folliculogenesis.

  2. Primordial germ cells and amnion development in the avian embryo

    NARCIS (Netherlands)

    De Melo Bernardo, Ana

    2016-01-01

    Primordial germ cells (PGCs) are the progenitors of the gametes, responsible for transmitting genetic information from generation to generation. Although there is a long history of gamete biology research, there is still a lot to be learned about many of the mechanisms underlying germ cell

  3. Origin of pluripotent germ cell tumours: the role of microenvironment during embryonic development

    DEFF Research Database (Denmark)

    Kristensen, David Møbjerg; Sonne, Si Brask; Ottesen, Anne Marie

    2008-01-01

    into virtually any type of tissue and form teratomas (non-seminomas). CIS cells display a close phenotypic similarity to fetal germ cells (primordial germ cells or gonocytes) suggesting an origin due to a developmental delay or arrest of differentiation of early germ cells. The pluripotency of these neoplasms...... in several tissue specific stem cells, such as TFAP2C (AP-2gamma) or KIT. CIS and seminomas highly express a number of pre-meiotic germ cell specific genes, which are down-regulated during development to non-seminomas, while the expression of other embryonic markers, such as SOX2, is up...

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

    OpenAIRE

    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-...

  5. Disrupting the male germ line to find infertility and contraception targets.

    Science.gov (United States)

    Archambeault, Denise R; Matzuk, Martin M

    2014-05-01

    Genetically-manipulated mouse models have become indispensible for broadening our understanding of genes and pathways related to male germ cell development. Until suitable in vitro systems for studying spermatogenesis are perfected, in vivo models will remain the gold standard for inquiry into testicular function. Here, we discuss exciting advances that are allowing researchers faster, easier, and more customizable access to their mouse models of interest. Specifically, the trans-NIH Knockout Mouse Project (KOMP) is working to generate knockout mouse models of every gene in the mouse genome. The related Knockout Mouse Phenotyping Program (KOMP2) is performing systematic phenotypic analysis of this genome-wide collection of knockout mice, including fertility screening. Together, these programs will not only uncover new genes involved in male germ cell development but also provide the research community with the mouse models necessary for further investigations. In addition to KOMP/KOMP2, another promising development in the field of mouse models is the advent of CRISPR (clustered regularly interspaced short palindromic repeat)-Cas technology. Utilizing 20 nucleotide guide sequences, CRISPR/Cas has the potential to introduce sequence-specific insertions, deletions, and point mutations to produce null, conditional, activated, or reporter-tagged alleles. CRISPR/Cas can also successfully target multiple genes in a single experimental step, forgoing the multiple generations of breeding traditionally required to produce mouse models with deletions, insertions, or mutations in multiple genes. In addition, CRISPR/Cas can be used to create mouse models carrying variants identical to those identified in infertile human patients, providing the opportunity to explore the effects of such mutations in an in vivo system. Both the KOMP/KOMP2 projects and the CRISPR/Cas system provide powerful, accessible genetic approaches to the study of male germ cell development in the mouse. A

  6. Optimized gene editing technology for Drosophila melanogaster using germ line-specific Cas9.

    Science.gov (United States)

    Ren, Xingjie; Sun, Jin; Housden, Benjamin E; Hu, Yanhui; Roesel, Charles; Lin, Shuailiang; Liu, Lu-Ping; Yang, Zhihao; Mao, Decai; Sun, Lingzhu; Wu, Qujie; Ji, Jun-Yuan; Xi, Jianzhong; Mohr, Stephanie E; Xu, Jiang; Perrimon, Norbert; Ni, Jian-Quan

    2013-11-19

    The ability to engineer genomes in a specific, systematic, and cost-effective way is critical for functional genomic studies. Recent advances using the CRISPR-associated single-guide RNA system (Cas9/sgRNA) illustrate the potential of this simple system for genome engineering in a number of organisms. Here we report an effective and inexpensive method for genome DNA editing in Drosophila melanogaster whereby plasmid DNAs encoding short sgRNAs under the control of the U6b promoter are injected into transgenic flies in which Cas9 is specifically expressed in the germ line via the nanos promoter. We evaluate the off-targets associated with the method and establish a Web-based resource, along with a searchable, genome-wide database of predicted sgRNAs appropriate for genome engineering in flies. Finally, we discuss the advantages of our method in comparison with other recently published approaches.

  7. Radiation-induced germ-line mutations detected by a direct comparison of parents and children DNA sequences containing SNPs

    International Nuclear Information System (INIS)

    Morimyo, M.; Hongo, E.; Higashi, T.; Wu, J.; Matsumoto, I.; Okamoto, M.; Kawano, A.; Tsuji, S.

    2003-01-01

    Full text: Germ-line mutation is detected in mice but not in humans. To estimate genetic risk of humans, a new approach to extrapolate from animal data to humans or to directly detect radiation-induced mutations in man is expected. We have developed a new method to detect germ-line mutations by directly comparing DNA sequences of parents and children. The nucleotide sequences among mouse strains are almost identical except SNP markers that are detected at 1/1000 frequency. When gamma-irradiated male mice are mated with female mice, heterogeneous nucleotide sequences induced in children DNA are a candidate of mutation, whose assignment can be done by SNP analysis. This system can easily detect all types of mutations such as transition, transversion, frameshift and deletion induced by radiation and can be applied to humans having genetically heterogeneous nucleotide sequences and many SNP markers. C3H male mice of 8 weeks of gestation were irradiated with gamma rays of 3 and 1 Gy and after 3 weeks, they were mated with the same aged C57BL female mice. After 3 weeks breeding, DNA was extracted from parents and children mice. The nucleotide sequences of 150 STS markers containing 300-900 bp and SNPs of parents and children DNA were determined by a direct sequencing; amplification of STS markers by Taq DNA polymerase, purification of PCR products, and DNA sequencing with a dye-terminator method. At each radiation dose, a total amount of 5 Mb DNA sequences were examined to detect radiation-induced mutations. We could find 6 deletions in 3 Gy irradiated mice but not in 1 Gy and control mice. The mutation frequency was about 4.0 x 10 -7 /bp/ Gy or 1.6 x 10 -4 /locus/Gy, and suggested the non-linear increase of mutation rate with dose

  8. Germ line transformation of the yellow fever mosquito, Aedes aegypti, mediated by transpositional insertion of a piggyBac vector.

    Science.gov (United States)

    Lobo, N F; Hua-Van, A; Li, X; Nolen, B M; Fraser, M J

    2002-04-01

    Mosquito-vectored diseases such as yellow fever and dengue fever continue to have a substantial impact on human populations world-wide. Novel strategies for control of these mosquito vectored diseases can arise through the development of reliable systems for genetic manipulation of the insect vector. A piggyBac vector marked with the Drosophila melanogaster cinnabar (cn) gene was used to transform the white-eyed khw strain of Aedes aegypti. Microinjection of preblastoderm embryos resulted in four families of cinnabar transformed insects. An overall transformation frequency of 4%, with a range of 0% to as high as 13% for individual experiments, was achieved when using a heat-shock induced transposase providing helper plasmid. Southern hybridizations indicated multiple insertion events in three of four transgenic lines, while the presence of duplicated target TTAA sites at either ends of individual insertions confirmed characteristic piggyBac transposition events in these three transgenic lines. The transgenic phenotype has remained stable for more than twenty generations. The transformations effected using the piggyBac element establish the potential of this element as a germ-line transformation vector for Aedine mosquitoes.

  9. Control over the morphology and segregation of Zebrafish germ cell granules during embryonic development

    Directory of Open Access Journals (Sweden)

    Nakkrasae La-Iad

    2008-05-01

    Full Text Available Abstract Background Zebrafish germ cells contain granular-like structures, organized around the cell nucleus. These structures share common features with polar granules in Drosophila, germinal granules in Xenopus and chromatoid bodies in mice germ cells, such as the localization of the zebrafish Vasa, Piwi and Nanos proteins, among others. Little is known about the structure of these granules as well as their segregation in mitosis during early germ-cell development. Results Using transgenic fish expressing a fluorescently labeled novel component of Zebrafish germ cell granules termed Granulito, we followed the morphology and distribution of the granules. We show that whereas these granules initially exhibit a wide size variation, by the end of the first day of development they become a homogeneous population of medium size granules. We investigated this resizing event and demonstrated the role of microtubules and the minus-end microtubule dependent motor protein Dynein in the process. Last, we show that the function of the germ cell granule resident protein the Tudor domain containing protein-7 (Tdrd7 is required for determination of granule morphology and number. Conclusion Our results suggest that Zebrafish germ cell granules undergo a transformation process, which involves germ cell specific proteins as well as the microtubular network.

  10. Germ-line CAG repeat instability causes extreme CAG repeat expansion with infantile-onset spinocerebellar ataxia type 2

    DEFF Research Database (Denmark)

    Vinther-Jensen, Tua; Ek, Jakob; Duno, Morten

    2013-01-01

    The spinocerebellar ataxias (SCA) are a genetically and clinically heterogeneous group of diseases, characterized by dominant inheritance, progressive cerebellar ataxia and diverse extracerebellar symptoms. A subgroup of the ataxias is caused by unstable CAG-repeat expansions in their respective ...... of paternal germ-line repeat sequence instability of the expanded SCA2 locus.European Journal of Human Genetics advance online publication, 10 October 2012; doi:10.1038/ejhg.2012.231....

  11. DAZ Family Proteins, Key Players for Germ Cell Development

    Science.gov (United States)

    Fu, Xia-Fei; Cheng, Shun-Feng; Wang, Lin-Qing; Yin, Shen; De Felici, Massimo; Shen, Wei

    2015-01-01

    DAZ family proteins are found almost exclusively in germ cells in distant animal species. Deletion or mutations of their encoding genes usually severely impair either oogenesis or spermatogenesis or both. The family includes Boule (or Boll), Dazl (or Dazla) and DAZ genes. Boule and Dazl are situated on autosomes while DAZ, exclusive of higher primates, is located on the Y chromosome. Deletion of DAZ gene is the most common causes of infertility in humans. These genes, encoding for RNA binding proteins, contain a highly conserved RNA recognition motif and at least one DAZ repeat encoding for a 24 amino acids sequence able to bind other mRNA binding proteins. Basically, Daz family proteins function as adaptors for target mRNA transport and activators of their translation. In some invertebrate species, BOULE protein play a pivotal role in germline specification and a conserved regulatory role in meiosis. Depending on the species, DAZL is expressed in primordial germ cells (PGCs) and/or pre-meiotic and meiotic germ cells of both sexes. Daz is found in fetal gonocytes, spermatogonia and spermatocytes of adult testes. Here we discuss DAZ family genes in a phylogenic perspective, focusing on the common and distinct features of these genes, and their pivotal roles during gametogenesis evolved during evolution. PMID:26327816

  12. The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations.

    Science.gov (United States)

    Senter, Leigha; Clendenning, Mark; Sotamaa, Kaisa; Hampel, Heather; Green, Jane; Potter, John D; Lindblom, Annika; Lagerstedt, Kristina; Thibodeau, Stephen N; Lindor, Noralane M; Young, Joanne; Winship, Ingrid; Dowty, James G; White, Darren M; Hopper, John L; Baglietto, Laura; Jenkins, Mark A; de la Chapelle, Albert

    2008-08-01

    Although the clinical phenotype of Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer) has been well described, little is known about disease in PMS2 mutation carriers. Now that mutation detection methods can discern mutations in PMS2 from mutations in its pseudogenes, more mutation carriers have been identified. Information about the clinical significance of PMS2 mutations is crucial for appropriate counseling. Here, we report the clinical characteristics of a large series of PMS2 mutation carriers. We performed PMS2 mutation analysis using long-range polymerase chain reaction and multiplex ligation-dependent probe amplification for 99 probands diagnosed with Lynch syndrome-associated tumors showing isolated loss of PMS2 by immunohistochemistry. Penetrance was calculated using a modified segregation analysis adjusting for ascertainment. Germ-line PMS2 mutations were detected in 62% of probands (n = 55 monoallelic; 6 biallelic). Among families with monoallelic PMS2 mutations, 65.5% met revised Bethesda guidelines. Compared with the general population, in mutation carriers, the incidence of colorectal cancer was 5.2-fold higher, and the incidence of endometrial cancer was 7.5-fold higher. In North America, this translates to a cumulative cancer risk to age 70 years of 15%-20% for colorectal cancer, 15% for endometrial cancer, and 25%-32% for any Lynch syndrome-associated cancer. No elevated risk for non-Lynch syndrome-associated cancers was observed. PMS2 mutations contribute significantly to Lynch syndrome, but the penetrance for monoallelic mutation carriers appears to be lower than that for the other mismatch repair genes. Modified counseling and cancer surveillance guidelines for PMS2 mutation carriers are proposed.

  13. A landscape of germ line mutations in a cohort of inherited bone marrow failure patients.

    Science.gov (United States)

    Bluteau, Olivier; Sebert, Marie; Leblanc, Thierry; Peffault de Latour, Régis; Quentin, Samuel; Lainey, Elodie; Hernandez, Lucie; Dalle, Jean-Hugues; Sicre de Fontbrune, Flore; Lengline, Etienne; Itzykson, Raphael; Clappier, Emmanuelle; Boissel, Nicolas; Vasquez, Nadia; Da Costa, Mélanie; Masliah-Planchon, Julien; Cuccuini, Wendy; Raimbault, Anna; De Jaegere, Louis; Adès, Lionel; Fenaux, Pierre; Maury, Sébastien; Schmitt, Claudine; Muller, Marc; Domenech, Carine; Blin, Nicolas; Bruno, Bénédicte; Pellier, Isabelle; Hunault, Mathilde; Blanche, Stéphane; Petit, Arnaud; Leverger, Guy; Michel, Gérard; Bertrand, Yves; Baruchel, André; Socié, Gérard; Soulier, Jean

    2018-02-15

    Bone marrow (BM) failure (BMF) in children and young adults is often suspected to be inherited, but in many cases diagnosis remains uncertain. We studied a cohort of 179 patients (from 173 families) with BMF of suspected inherited origin but unresolved diagnosis after medical evaluation and Fanconi anemia exclusion. All patients had cytopenias, and 12.0% presented ≥5% BM blast cells. Median age at genetic evaluation was 11 years; 20.7% of patients were aged ≤2 years and 36.9% were ≥18 years. We analyzed genomic DNA from skin fibroblasts using whole-exome sequencing, and were able to assign a causal or likely causal germ line mutation in 86 patients (48.0%), involving a total of 28 genes. These included genes in familial hematopoietic disorders ( GATA2 , RUNX1 ), telomeropathies ( TERC , TERT , RTEL1 ), ribosome disorders ( SBDS , DNAJC21 , RPL5 ), and DNA repair deficiency ( LIG4 ). Many patients had an atypical presentation, and the mutated gene was often not clinically suspected. We also found mutations in genes seldom reported in inherited BMF (IBMF), such as SAMD9 and SAMD9L (N = 16 of the 86 patients, 18.6%), MECOM/EVI1 (N = 6, 7.0%), and ERCC6L2 (N = 7, 8.1%), each of which was associated with a distinct natural history; SAMD9 and SAMD9L patients often experienced transient aplasia and monosomy 7, whereas MECOM patients presented early-onset severe aplastic anemia, and ERCC6L2 patients, mild pancytopenia with myelodysplasia. This study broadens the molecular and clinical portrait of IBMF syndromes and sheds light on newly recognized disease entities. Using a high-throughput sequencing screen to implement precision medicine at diagnosis can improve patient management and family counseling. © 2018 by The American Society of Hematology.

  14. Germ-line PHD1 and PHD2 mutations detected in patients with pheochromocytoma/paraganglioma-polycythemia.

    Science.gov (United States)

    Yang, Chunzhang; Zhuang, Zhengping; Fliedner, Stephanie M J; Shankavaram, Uma; Sun, Michael G; Bullova, Petra; Zhu, Roland; Elkahloun, Abdel G; Kourlas, Peter J; Merino, Maria; Kebebew, Electron; Pacak, Karel

    2015-01-01

    We have investigated genetic/pathogenetic factors associated with a new clinical entity in patients presenting with pheochromocytoma/paraganglioma (PHEO/PGL) and polycythemia. Two patients without hypoxia-inducible factor 2α (HIF2A) mutations, who presented with similar clinical manifestations, were analyzed for other gene mutations, including prolyl hydroxylase (PHD) mutations. We have found for the first time a germ-line mutation in PHD1 in one patient and a novel germ-line PHD2 mutation in a second patient. Both mutants exhibited reduced protein stability with substantial quantitative protein loss and thus compromised catalytic activities. Due to the unique association of patients' polycythemia with borderline or mildly elevated erythropoietin (EPO) levels, we also performed an in vitro sensitivity assay of erythroid progenitors to EPO and for EPO receptor (EPOR) expression. The results show inappropriate hypersensitivity of erythroid progenitors to EPO in these patients, indicating increased EPOR expression/activity. In addition, the present study indicates that HIF dysregulation due to PHD mutations plays an important role in the pathogenesis of these tumors and associated polycythemia. The PHD1 mutation appears to be a new member contributing to the genetic landscape of this novel clinical entity. Our results support the existence of a specific PHD1- and PHD2-associated PHEO/PGL-polycythemia disorder. • A novel germ-l i n e PHD1 mutation causing heochromocytoma/paraganglioma and polycythemia. • Increased EPOR activity and inappropriate hypersensitivity of erythroid progenitors to EPO.

  15. Analysis of the cytoskeleton organization and its possible functions in male earthworm germ-line cysts equipped with a cytophore.

    Science.gov (United States)

    Małota, Karol; Świątek, Piotr

    2016-10-01

    We studied the organization of F-actin and the microtubular cytoskeleton in male germ-line cysts in the seminal vesicles of the earthworm Dendrobaena veneta using light, fluorescent and electron microscopy along with both chemically fixed tissue and life cell imaging. Additionally, in order to follow the functioning of the cytoskeleton, we incubated the cysts in colchicine, nocodazole, cytochalasin D and latrunculin A. The male germ-line cells of D. veneta are interconnected via stable intercellular bridges (IB), and form syncytial cysts. Each germ cell has only one IB that connects it to the anuclear central cytoplasmic mass, the cytophore. During the studies, we analyzed the cytoskeleton in spermatogonial, spermatocytic and spermatid cysts. F-actin was detected in the cortical cytoplasm and forms distinct rings in the IBs. The arrangement of the microtubules changed dynamically during spermatogenesis. The microtubules are distributed evenly in whole spermatogonial and spermatocytic cysts; however, they primarily accumulate within the IBs in spermatogonia. In early spermatids, microtubules pass through the IBs and are present in whole cysts. During spermatid elongation, the microtubules form a manchette while they are absent in the cytophore and in the IBs. Use of cytoskeletal drugs did not alter the general morphology of the cysts. Detectable effects-the occurrence of nuclei in the late spermatids and manchette fragments in the cytophore-were observed only after incubation in nocodazole. Our results suggest that the microtubules are responsible for cytoplasmic/organelle transfer between the germ cells and the cytophore during spermatogenesis and for the positioning of the spermatid nuclei.

  16. Quantification of healthy and atretic germ cells and follicles in the developing and post-natal ovary of the South American plains vizcacha, Lagostomus maximus: evidence of continuous rise of the germinal reserve.

    Science.gov (United States)

    Inserra, P I F; Leopardo, N P; Willis, M A; Freysselinard, A L; Vitullo, A D

    2014-02-01

    The female germ line in mammals is subjected to massive cell death that eliminates 60-85% of the germinal reserve by birth and continues from birth to adulthood until the exhaustion of the germinal pool. Germ cell demise occurs mainly through apoptosis by means of a biased expression in favour of pro-apoptotic members of the BCL2 gene family. By contrast, the South American plains vizcacha, Lagostomus maximus, exhibits sustained expression of the anti-apoptotic BCL2 gene throughout gestation and a low incidence of germ cell apoptosis. This led to the proposal that, in the absence of death mechanisms other than apoptosis, the female germ line should increase continuously from foetal life until after birth. In this study, we quantified all healthy germ cells and follicles in the ovaries of L. maximus from early foetal life to day 60 after birth using unbiased stereological methods and detected apoptosis by labelling with TUNEL assay. The healthy germ cell population increased continuously from early-developing ovary reaching a 50 times higher population number by the end of gestation. TUNEL-positive germ cells were develops in the absence of constitutive massive germ cell elimination.

  17. Effects of chemical and physical agents on recombination events in cells of the germ line of male and female Drosophila melanogaster.

    Science.gov (United States)

    Würgler, F E

    1991-01-01

    Genotoxic agents can induce mutations as well as recombination in the genetic material. The fruit fly Drosophila melanogaster was one of the first assay systems to test physical and chemical agents for recombinogenic effects. Such effects can be observed in cells of the germ line as well as in somatic cells. At present information is available on 54 agents, among them 48 chemicals that have been tested in cells of the germ line of males and/or females. Effects on meiotic recombination in female germ cells cannot simply be classified as positive or negative since for a number of agents, depending on the chromosome region studied, recombination frequencies may be increased, unaffected or decreased. The male germ line of D. melanogaster represents a unique situation because meiotic recombination does not occur. Among 25 agents tested in male germ cells 24 did induce male recombination, among them alkylating, intercalating and cross-linking agents, direct-acting ones as well as compounds needing metabolic activation. With several compounds the frequency of induced recombination is highest in the heterochromatic regions near the centromeres. In brood pattern analyses, e.g., after exposure of adult males to ionizing radiation, the first appearance of crossover progeny is indicative of the sampling of exposed spermatocytes. In premeiotic cells of the male and the female germ line mitotic recombination can occur. Upon clonal expansion of the recombinant cells, clusters of identical crossovers can be observed.

  18. Temporal germ cell development strategy during continuous spermatogenesis within the montane lizard, Sceloporus bicanthalis (Squamata; Phrynosomatidae).

    Science.gov (United States)

    Gribbins, Kevin; Anzalone, Marla; Collier, Matthew; Granados-González, Gisela; Villagrán-Santa Cruz, Maricela; Hernández-Gallegos, Oswaldo

    2011-10-01

    Sceloporus bicanthalis is a viviparous lizard that lives at higher elevations in Mexico. Adult male S. bicanthalis were collected (n = 36) from the Nevado de Toluca, Mexico (elevation is 4200 m) during August to December, 2007 and January to July, 2008. Testes were extracted, fixed in Trumps, and dehydrated in a graded series of ethanol. Tissues were embedded, sectioned (2 μm), stained, and examined via a light microscope to determine the spermatogenic developmental strategy of S. bicanthalis. In all months examined, the testes were spermiogenically active; based on this, plus the presence of sperm in the lumina of seminiferous tubules, we inferred that S. bicanthalis had year-round or continuous spermatogenesis, unlike most reptiles that occupy a temperate or montane habitat. It was recently reported that seasonally breeding reptiles had a temporal germ cell development strategy similar to amphibians, where germ cells progress through spermatogenesis as a single population, which leads to a single spermiation event. This was much different than spatial development within the testis of other derived amniotes. We hypothesized that germ cell development was temporal in S. bicanthalis. Therefore, we wanted to determine whether reptiles that practice continuous spermatogenesis have a mammalian-like spatial germ cell development, which is different than the typical temperate reptile exhibiting a temporal development. In the present study, S. bicanthalis had a temporal development strategy, despite its continuous spermatogenic cycle, making them similar to tropical anoles. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Immunohistochemical Examination for the Distribution of Podoplanin-Expressing Cells in Developing Mouse Molar Tooth Germs

    Science.gov (United States)

    Imaizumi, Yuri; Amano, Ikuko; Tsuruga, Eichi; Kojima, Hiroshi; Sawa, Yoshihiko

    2010-01-01

    We recently reported the expression of podoplanin in the apical bud of adult mouse incisal tooth. This study was aimed to investigate the distribution of podoplanin-expressing cells in mouse tooth germs at several developing stages. At the bud stage podoplanin was expressed in oral mucous epithelia and in a tooth bud. At the cap stage podoplanin was expressed on inner and outer enamel epithelia but not in mesenchymal cells expressing the neural crest stem cell marker nestin. At the early bell stage nestin and podoplanin were expressed in cervical loop and odontoblasts. At the root formation stage both nestin and podoplanin were weakly expressed in odontoblasts generating radicular dentin. Podoplanin expression was also found in the Hertwig epithelial sheath. These results suggest that epithelial cells of developing tooth germ acquire the ability to express nestin, and that tooth germ epithelial cells maintain the ability to express podoplanin in oral mucous epithelia. The expression of podoplanin in odontoblasts was induced as tooth germ development advanced, but was suppressed with the completion of the primary dentin, suggesting that podoplanin may be involved in the cell growth of odontoblasts. Nestin may function as an intermediate filament that binds podoplanin in odontoblasts. PMID:21060740

  20. Patterns of Glycoconjugate Distribution during Molar Tooth Germ Development in Mice

    Directory of Open Access Journals (Sweden)

    AR. Varasteh

    2007-09-01

    Full Text Available Objective: The aim of the present study was to evaluate the structure and distribution of Glycoconjugates during molar tooth germ development in mice.Materials and Methods: Sixteen tooth germs were obtained from BALB/c mice embryos 15 to 18 days post-gestation and fixed in 10% formalin. After routine tissue processing, 5μm sections were cut and stained with BSA1-B4 and PNA using the lectin histochemical method. All slides were evaluated by light microscopy.Results: Both lectins showed positive reaction in the tooth germ but with spatiotemporal differences. During bell stage, the reaction was strong with BSA1-B4 but moderate with PNA. Strong PNA uptake was observed in the odontoblastic and ameloblastic nuclei alongwith the apical cytoplasm of the ameloblasts.Conclusion: Although the lectins that were used in the present study recognize the same terminal sugar residue, they reacted with different disaccharide sequences with various penaltomer sugars. Therefore it may be assumed that the pattern of affinity for different parts of the developing tooth germ such as ameloblasts and odontoblasts is different in various lectins.

  1. Germ cell tumors in patients with disorders of sex development: Risk factors, initial developmental stages and targets for early diagnosis

    NARCIS (Netherlands)

    M.B.C.M. Cools (Martine)

    2006-01-01

    textabstractThis thesis describes the origin, identification and correct diagnosis of the earliest stages of malignant germ cell tumors, i.e. intra tubular germ cell neoplasia unclassified (ITGNU) and gonadoblastoma, in patients with disorders of sex development. Special attention is given to the

  2. Germ-line mutations at a mouse ESTR (Pc-3) locus and human microsatellite loci

    International Nuclear Information System (INIS)

    Ryo, Haruko; Nakajima, Hiroo; Nomura, Taisei

    2006-01-01

    We examined the use of the mouse Pc-3 ESTR (expanded simple tandem repeat) locus and 72 human microsatellite loci as potentially sensitive biomarkers for mutagenic exposures to germ cells in mice and humans respectively. In the mouse work, we treated male mice with TCDD (2, 3, 7, 8-tetrachlo-rodibenzo-p-dioxin; a chemical known to induce congenital anomalies in humans and mice) and, analysed the F 1 fetuses for Pc-3 mutations. Although the incidence of anomalies was higher in the TCDD group, there were no induced mutations. However, respiratory distress syndrome (RDS) was observed in 3 of 7 fetuses born to male mice which were treated with TCDD and which showed abnormal length of Pc-3 allele. In the human studies, the children of Chernobyl liquidators were examined for mutations at a total of 72 (31 autosomal, 1 X-linked and 40 Y-linked) microsatellite loci. This study was prompted by earlier findings of increases in microsatellite mutations in barn swallows and wheat in the highly contaminated areas after the Chernobyl accident. We examined 64 liquidator families (70 children) and 66 control families (70 children). However, no increases in mutation rates were found. The estimated mean dose to the liquidators was about 39 mSv and this might be one possible reason why no increases of mutations could be found. (author)

  3. Transplantation of germ cells from glial cell line-derived neurotrophic factor-overexpressing mice to host testes depleted of endogenous spermatogenesis by fractionated irradiation

    NARCIS (Netherlands)

    Creemers, L. B.; Meng, X.; den Ouden, K.; van Pelt, A. M. M.; Izadyar, F.; Santoro, M.; Sariola, H.; de rooij, D. G.

    2002-01-01

    With a novel method of eliminating spermatogenesis in host animals, male germ cells isolated from mice with targeted overexpression of glial cell line-derived neurotrophic factor (GDNF) were transplanted to evaluate their ability to reproduce the phenotype previously found in the transgenic animals.

  4. Exome sequencing of bilateral testicular germ cell tumors suggests independent development lineages.

    Science.gov (United States)

    Brabrand, Sigmund; Johannessen, Bjarne; Axcrona, Ulrika; Kraggerud, Sigrid M; Berg, Kaja G; Bakken, Anne C; Bruun, Jarle; Fosså, Sophie D; Lothe, Ragnhild A; Lehne, Gustav; Skotheim, Rolf I

    2015-02-01

    Intratubular germ cell neoplasia, the precursor of testicular germ cell tumors (TGCTs), is hypothesized to arise during embryogenesis from developmentally arrested primordial germ cells (PGCs) or gonocytes. In early embryonal life, the PGCs migrate from the yolk sac to the dorsal body wall where the cell population separates before colonizing the genital ridges. However, whether the malignant transformation takes place before or after this separation is controversial. We have explored the somatic exome-wide mutational spectra of bilateral TGCT to provide novel insight into the in utero critical time frame of malignant transformation and TGCT pathogenesis. Exome sequencing was performed in five patients with bilateral TGCT (eight tumors), of these three patients in whom both tumors were available (six tumors) and two patients each with only one available tumor (two tumors). Selected loci were explored by Sanger sequencing in 71 patients with bilateral TGCT. From the exome-wide mutational spectra, no identical mutations in any of the three bilateral tumor pairs were identified. Exome sequencing of all eight tumors revealed 87 somatic non-synonymous mutations (median 10 per tumor; range 5-21), some in already known cancer genes such as CIITA, NEB, platelet-derived growth factor receptor α (PDGFRA), and WHSC1. SUPT6H was found recurrently mutated in two tumors. We suggest independent development lineages of bilateral TGCT. Thus, malignant transformation into intratubular germ cell neoplasia is likely to occur after the migration of PGCs. We reveal possible drivers of TGCT pathogenesis, such as mutated PDGFRA, potentially with therapeutic implications for TGCT patients. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.

  5. Exome Sequencing of Bilateral Testicular Germ Cell Tumors Suggests Independent Development Lineages

    Directory of Open Access Journals (Sweden)

    Sigmund Brabrand

    2015-02-01

    Full Text Available Intratubular germ cell neoplasia, the precursor of testicular germ cell tumors (TGCTs, is hypothesized to arise during embryogenesis from developmentally arrested primordial germ cells (PGCs or gonocytes. In early embryonal life, the PGCs migrate from the yolk sac to the dorsal body wall where the cell population separates before colonizing the genital ridges. However, whether the malignant transformation takes place before or after this separation is controversial. We have explored the somatic exome-wide mutational spectra of bilateral TGCT to provide novel insight into the in utero critical time frame of malignant transformation and TGCT pathogenesis. Exome sequencing was performed in five patients with bilateral TGCT (eight tumors, of these three patients in whom both tumors were available (six tumors and two patients each with only one available tumor (two tumors. Selected loci were explored by Sanger sequencing in 71 patients with bilateral TGCT. From the exome-wide mutational spectra, no identical mutations in any of the three bilateral tumor pairs were identified. Exome sequencing of all eight tumors revealed 87 somatic non-synonymous mutations (median 10 per tumor; range 5-21, some in already known cancer genes such as CIITA, NEB, platelet-derived growth factor receptor α (PDGFRA, and WHSC1. SUPT6H was found recurrently mutated in two tumors. We suggest independent development lineages of bilateral TGCT. Thus, malignant transformation into intratubular germ cell neoplasia is likely to occur after the migration of PGCs. We reveal possible drivers of TGCT pathogenesis, such as mutated PDGFRA, potentially with therapeutic implications for TGCT patients.

  6. Convergent evolution of germ granule nucleators: A hypothesis.

    Science.gov (United States)

    Kulkarni, Arpita; Extavour, Cassandra G

    2017-10-01

    Germ cells have been considered "the ultimate stem cell" because they alone, during normal development of sexually reproducing organisms, are able to give rise to all organismal cell types. Morphological descriptions of a specialized cytoplasm termed 'germ plasm' and associated electron dense ribonucleoprotein (RNP) structures called 'germ granules' within germ cells date back as early as the 1800s. Both germ plasm and germ granules are implicated in germ line specification across metazoans. However, at a molecular level, little is currently understood about the molecular mechanisms that assemble these entities in germ cells. The discovery that in some animals, the gene products of a small number of lineage-specific genes initiate the assembly (also termed nucleation) of germ granules and/or germ plasm is the first step towards facilitating a better understanding of these complex biological processes. Here, we draw on research spanning over 100years that supports the hypothesis that these nucleator genes may have evolved convergently, allowing them to perform analogous roles across animal lineages. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Ovarian germ cell tumors with rhabdomyosarcomatous components and later development of growing teratoma syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Al-Jumaily Usama

    2012-01-01

    Full Text Available Abstract Introduction Development of a sarcomatous component in a germ cell tumor is an uncommon phenomenon. Most cases reported have a grim prognosis. Growing teratoma syndrome is also an uncommon phenomenon and occurs in approximately 2% to 7% of non seminomatous germ cell tumors and should be treated surgically. Case presentation We report the case of a 12-year-old Asian girl with an ovarian mixed germ cell tumor containing a rhabdomyosarcomatous component. She was treated with a germ cell tumor chemotherapy regimen and rhabdomyosarcoma-specific chemotherapy. Towards the end of her treatment, she developed a retroperitoneal mass that was increasing in size. It was completely resected, revealing a mature teratoma, consistent with growing teratoma syndrome. She is still in complete remission approximately three years after presentation. Conclusion The presence of rhabdomyosarcoma in a germ cell tumor should be treated by a combined chemotherapy regimen (for germ cell tumor and rhabdomyosarcoma. In addition, development of a mass during or after therapy with normal serum markers should raise the possibility of growing teratoma syndrome that should be treated surgically.

  8. Isolation of oogenesis-specific genes transcribed in the germ-line of Calliphora erythrocephala and Drosophila melanogaster

    International Nuclear Information System (INIS)

    Tucker, M.A.

    1988-01-01

    Poly(A) + RNA from early or mid-stage ovarian follicles of C. erythrocephala was used to generate radiolabelled oogenesis-specific cDNA probes for screening the phage libraries. A cDNA probe made from mid-stage embryo poly(A) + RNA was used as the differential screening probe. Thus plaques hybridizing to the two oogenesis-specific probes but not the mid-stage embryo probe were selected as potentially containing oogenesis-specific genes. Two further rounds of screening were used to eliminate false positives and, after plaque purification, restriction digests of the remaining clones were screened by Southern blot hybridization to identify DNA fragments transcribed in an oogenesis-specific manner. In situ hybridization to sections of ovarian follicles has been used to determine the cell types within the follicles in which the various genes are expressed. Radiolabelled RNA probes for four of the C. erythrocephala oogenesis-specific clones and the two D. melanogaster clones have been hybridized to ovarian follicles. Further studies have been concentrated on the two germ-line transcribed, oogenesis-specific clones isolated from the D. melanogaster clone library. Detailed genetic mapping of the DA clone and of these mutations was performed to determine which mutations might represent the DA gene. cDNA clones have been isolated for the transcribed region of clone DA and have been used to further define the transcription unit from this region of the D. melanogaster genome

  9. Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences

    DEFF Research Database (Denmark)

    Dean, Afshan; van den Driesche, Sander; Wang, Yili

    2016-01-01

    Analgesics which affect prostaglandin (PG) pathways are used by most pregnant women. As germ cells (GC) undergo developmental and epigenetic changes in fetal life and are PG targets, we investigated if exposure of pregnant rats to analgesics (indomethacin or acetaminophen) affected GC development...... smaller ovaries and reduced follicle numbers during puberty/adulthood; as similar changes were found for F2 offspring of analgesic-exposed F1 fathers or mothers, we interpret this as potentially indicating an analgesic-induced change to GC in F1. Assuming our results are translatable to humans, they raise...

  10. Glial cell line-derived neurotrophic factor and endothelial cells promote self-renewal of rabbit germ cells with spermatogonial stem cell properties.

    Science.gov (United States)

    Kubota, Hiroshi; Wu, Xin; Goodyear, Shaun M; Avarbock, Mary R; Brinster, Ralph L

    2011-08-01

    Previous studies suggest that exogenous factors crucial for spermatogonial stem cell (SSC) self-renewal are conserved among several mammalian species. Since glial cell line-derived neurotrophic factor (GDNF) and fibroblast growth factor 2 (FGF2) are critical for rodent SSC self-renewal, we hypothesized that they might promote self-renewal of nonrodent SSCs. Therefore, we cultured testicular germ cells from prepubertal rabbits in the presence of GDNF and FGF2 and found they proliferated indefinitely as cellular clumps that displayed characteristics previously identified for rodent SSCs. The rabbit germ cells could not be maintained on mouse embryonic fibroblast (STO) feeders that support rodent SSC self-renewal in vitro but were rather supported on mouse yolk sac-derived endothelial cell (C166) feeder layers. Proliferation of rabbit germ cells was dependent on GDNF. Of critical importance was that clump-forming rabbit germ cells colonized seminiferous tubules of immunodeficient mice, proliferated for at least 6 mo, while retaining an SSC phenotype in the testes of recipient mice, indicating that they were rabbit SSCs. This study demonstrates that GDNF is a mitogenic factor promoting self-renewal that is conserved between rodent and rabbit SSCs; with an evolutionary separation of ∼ 60 million years. These findings provide a foundation to study the mechanisms governing SSC self-renewal in nonrodent species.

  11. Identification of 3 novel VHL germ-line mutations in Danish VHL patients

    DEFF Research Database (Denmark)

    Dandanell, Mette; Friis-Hansen, Lennart Jan; Sunde, Lone

    2012-01-01

    von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome in which the patients develop retinal and central nervous system hemangioblastomas, pheochromocytomas and clear-cell renal tumors. The autosomal dominant disease is caused by mutations in the VHL gene.......von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome in which the patients develop retinal and central nervous system hemangioblastomas, pheochromocytomas and clear-cell renal tumors. The autosomal dominant disease is caused by mutations in the VHL gene....

  12. Developing Green Line Products

    DEFF Research Database (Denmark)

    Muñoz-Marin, Ana Maria; Lassen, Astrid Heidemann; Poulsen, Søren Bolvig

    2011-01-01

    This publication is based on the Master thesis “User-driven ecoinnovation process: Towards the implementation of the Green product line at JELD-WEN” written by Ana Maria Muñoz-Marin as her Graduation Project for the MSc. Global Innovation Management degree. The company-based experiment was carried...

  13. Germ layers, the neural crest and emergent organization in development and evolution.

    Science.gov (United States)

    Hall, Brian K

    2018-04-10

    Discovered in chick embryos by Wilhelm His in 1868 and named the neural crest by Arthur Milnes Marshall in 1879, the neural crest cells that arise from the neural folds have since been shown to differentiate into almost two dozen vertebrate cell types and to have played major roles in the evolution of such vertebrate features as bone, jaws, teeth, visceral (pharyngeal) arches, and sense organs. I discuss the discovery that ectodermal neural crest gave rise to mesenchyme and the controversy generated by that finding; the germ layer theory maintained that only mesoderm could give rise to mesenchyme. A second topic of discussion is germ layers (including the neural crest) as emergent levels of organization in animal development and evolution that facilitated major developmental and evolutionary change. The third topic is gene networks, gene co-option, and the evolution of gene-signaling pathways as key to developmental and evolutionary transitions associated with the origin and evolution of the neural crest and neural crest cells. © 2018 Wiley Periodicals, Inc.

  14. MSH6 and PMS2 germ-line pathogenic variants implicated in Lynch syndrome are associated with breast cancer.

    Science.gov (United States)

    Roberts, Maegan E; Jackson, Sarah A; Susswein, Lisa R; Zeinomar, Nur; Ma, Xinran; Marshall, Megan L; Stettner, Amy R; Milewski, Becky; Xu, Zhixiong; Solomon, Benjamin D; Terry, Mary Beth; Hruska, Kathleen S; Klein, Rachel T; Chung, Wendy K

    2018-01-18

    PurposeAn association of Lynch syndrome (LS) with breast cancer has been long suspected; however, there have been insufficient data to address this question for each of the LS genes individually.MethodsWe conducted a retrospective review of personal and family history in 423 women with pathogenic or likely pathogenic germ-line variants in MLH1 (N = 65), MSH2 (N = 94), MSH6 (N = 140), or PMS2 (N = 124) identified via clinical multigene hereditary cancer testing. Standard incidence ratios (SIRs) of breast cancer were calculated by comparing breast cancer frequencies in our study population with those in the general population (Surveillance, Epidemiology, and End Results 18 data).ResultsWhen evaluating by gene, the age-standardized breast cancer risks for MSH6 (SIR = 2.11; 95% confidence interval (CI), 1.56-2.86) and PMS2 (SIR = 2.92; 95% CI, 2.17-3.92) were associated with a statistically significant risk for breast cancer whereas no association was observed for MLH1 (SIR = 0.87; 95% CI, 0.42-1.83) or MSH2 (SIR = 1.22; 95% CI, 0.72-2.06).ConclusionOur data demonstrate that two LS genes, MSH6 and PMS2, are associated with an increased risk for breast cancer and should be considered when ordering genetic testing for individuals who have a personal and/or family history of breast cancer.GENETICS in MEDICINE advance online publication, 18 January 2018; doi:10.1038/gim.2017.254.

  15. Testicular atrophy and loss of nerve growth factor-immunoreactive germ cell line in rats exposed to n-hexane and a protective effect of simultaneous exposure to toluene or xylene

    Energy Technology Data Exchange (ETDEWEB)

    Nylen, P; Johnson, A C; Hoeglund, G; Ebendal, T; Eriksdotter-Nilsson, M; Henschen, A; Olson, L; Hansson, T; Kronevi, T; Kvist, U

    1989-07-01

    Testicular and germ cell line morphology in rats were studied 2 weeks, 10 months and 14 months after cessation of a 61-day inhalation exposure to 1000 ppm n-hexane. Androgen biosynthetic capacity of testis, testosterone blood concentration, vas deferens morphology and noradrenaline (NA) concentration, epididymal sperm morphology, and fertility were also studied. Severe testicular atrophy involving the seminiferous tubules with loss of the nerve growth factor (NGF) immunoreactive germ cell line was found. Total loss of the germ cell line was found in a fraction of animals up to 14 months post-exposure, indicating permanent testicular damage. No impairment of androgen synthesis or androgen dependent accessory organs was observed. Simultaneous administration of 1000 ppm n-hexane and 1000 ppm toluene, or 1000 ppm n-hexane and 1000 ppm xylene, did not cause germ cell line alterations or testicular atrophy. Toluene and xylene were thus found to protect from n-hexane induced testicular atrophy. (orig.).

  16. Correction of mouse ornithine transcarbamylase deficiency by gene transfer into the germ line

    Energy Technology Data Exchange (ETDEWEB)

    Cavard, C; Grimber, G; Dubois, N; Chasse, J F; Bennoun, M; Minet-Thuriaux, M; Kamoun, P; Briand, P

    1988-03-25

    The sparse fur with abnormal skin and hair (Spf-ash) mouse is a model for the human x-linked hereditary disorder, ornithine transcarbamylase (OTC) deficiency. In Spf-ash mice, both OTC mRNA and enzyme activity are 5% of control values resulting in hyperammonemia, pronounced orotic aciduria and an abnormal phenotype characterized by growth retardation and sparse fur. Using microinjection, the authors introduced a construction containing rat OTC cDNA linked to the SV40 early promoter into fertilized eggs of Spf-ash mice. The expression of the transgene resulted in the development of a transgenic mouse whose phenotype and orotic acid excretion are fully normalized. Thus, the possibility of correcting hereditary enzymatic defect by gene transfer of heterologous cDNA coding for the normal enzyme has been demonstrated.

  17. 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

  18. AZFa protein DDX3Y is differentially expressed in human male germ cells during development and in testicular tumours

    DEFF Research Database (Denmark)

    Gueler, B; Sonne, S B; Zimmer, J

    2012-01-01

    are believed to originate from fetal gonocytes.METHODSDDX3Y protein expression was analysed during development in different tissues by western blotting. The localization of DDX3Y in normal fetal and prepubertal testis tissue of different ages as well as in a series of distinct TGCT tissue samples (CIS......, classical seminoma, spermatocytic seminoma, teratoma and embryonal carcinoma) was performed by immunohistochemistry.RESULTSGerm cell-specific expression of DDX3Y protein was revealed in fetal prospermatogonia but not in gonocytes and not before the 17th gestational week. After birth, DDX3Y was expressed......, but not in somatically differentiated non-seminomas, consistent with its germ-cell specific function.CONCLUSIONSThe fetal germ cell DDX3Y expression suggests a role in early spermatogonial proliferation and implies that, in men with AZFa deletion, germ cell depletion may begin prenatally. The strong expression of DDX3Y...

  19. The early human germ cell lineage does not express SOX2 during in vivo development or upon in vitro culture

    DEFF Research Database (Denmark)

    Perrett, Rebecca M; Turnpenny, Lee; Eckert, Judith J

    2008-01-01

    NANOG, POU5F1, and SOX2 are required by the inner cell mass of the blastocyst and act cooperatively to maintain pluripotency in both mouse and human embryonic stem cells. Inadequacy of any one of them causes loss of the undifferentiated state. Mouse primordial germ cells (PGCs), from which...... pluripotent embryonic germ cells (EGCs) are derived, also express POU5F1, NANOG, and SOX2. Thus, a similar expression profile has been predicted for human PGCs. Here we show by RT-PCR, immunoblotting, and immunohistochemistry that human PGCs express POU5F1 and NANOG but not SOX2, with no evidence...... of redundancy within the group B family of human SOX genes. Although lacking SOX2, proliferative human germ cells can still be identified in situ during early development and are capable of culture in vitro. Surprisingly, with the exception of FGF4, many stem cell-restricted SOX2 target genes remained detected...

  20. Towards gene banking amphibian maternal germ lines: short-term incubation, cryoprotectant tolerance and cryopreservation of embryonic cells of the frog, Limnodynastes peronii.

    Science.gov (United States)

    Lawson, Bianca; Clulow, Simon; Mahony, Michael J; Clulow, John

    2013-01-01

    Gene banking is arguably the best method available to prevent the loss of genetic diversity caused by declines in wild populations, when the causes of decline cannot be halted or reversed. For one of the most impacted vertebrate groups, the amphibians, gene banking technologies have advanced considerably, and gametes from the male line can be banked successfully for many species. However, cryopreserving the female germ line remains challenging, with attempts at cryopreserving oocytes unsuccessful due to their large size and yolk content. One possible solution is to target cryopreservation of early embryos that contain the maternal germ line, but consist of smaller cells. Here, we investigate the short term incubation, cryoprotectant tolerance, and cryopreservation of dissociated early embryonic cells from gastrulae and neurulae of the Striped Marsh Frog, Limnodynastes peronii. Embryos were dissociated and cells were incubated for up to 24 hours in various media. Viability of both gastrula and neurula cells remained high (means up to 40-60%) over 24 hours of incubation in all media, although viability was maintained at a higher level in Ca(2+)-free Simplified Amphibian Ringer; low speed centrifugation did not reduce cell viability. Tolerance of dissociated embryonic cells was tested for two cryoprotectants, glycerol and dimethyl sulphoxide; dissociated cells of both gastrulae and neurulae were highly tolerant to both-indeed, cell viability over 24 hours was higher in media containing low-to-medium concentrations than in equivalent cryoprotectant-free media. Viability over 24 hours was lower in concentrations of cryoprotectant higher than 10%. Live cells were recovered following cryopreservation of both gastrula and neurula cells, but only at low rates. Optimal cryodiluents were identified for gastrula and neurula cells. This is the first report of a slow cooling protocol for cryopreservation of amphibian embryonic cells, and sets future research directions for

  1. Towards gene banking amphibian maternal germ lines: short-term incubation, cryoprotectant tolerance and cryopreservation of embryonic cells of the frog, Limnodynastes peronii.

    Directory of Open Access Journals (Sweden)

    Bianca Lawson

    Full Text Available Gene banking is arguably the best method available to prevent the loss of genetic diversity caused by declines in wild populations, when the causes of decline cannot be halted or reversed. For one of the most impacted vertebrate groups, the amphibians, gene banking technologies have advanced considerably, and gametes from the male line can be banked successfully for many species. However, cryopreserving the female germ line remains challenging, with attempts at cryopreserving oocytes unsuccessful due to their large size and yolk content. One possible solution is to target cryopreservation of early embryos that contain the maternal germ line, but consist of smaller cells. Here, we investigate the short term incubation, cryoprotectant tolerance, and cryopreservation of dissociated early embryonic cells from gastrulae and neurulae of the Striped Marsh Frog, Limnodynastes peronii. Embryos were dissociated and cells were incubated for up to 24 hours in various media. Viability of both gastrula and neurula cells remained high (means up to 40-60% over 24 hours of incubation in all media, although viability was maintained at a higher level in Ca(2+-free Simplified Amphibian Ringer; low speed centrifugation did not reduce cell viability. Tolerance of dissociated embryonic cells was tested for two cryoprotectants, glycerol and dimethyl sulphoxide; dissociated cells of both gastrulae and neurulae were highly tolerant to both-indeed, cell viability over 24 hours was higher in media containing low-to-medium concentrations than in equivalent cryoprotectant-free media. Viability over 24 hours was lower in concentrations of cryoprotectant higher than 10%. Live cells were recovered following cryopreservation of both gastrula and neurula cells, but only at low rates. Optimal cryodiluents were identified for gastrula and neurula cells. This is the first report of a slow cooling protocol for cryopreservation of amphibian embryonic cells, and sets future research

  2. A vector-based system for the differentiation of mouse embryonic stem cells toward germ-line cells

    Directory of Open Access Journals (Sweden)

    Reza Ebrahimzadeh-Vesal

    2014-08-01

    Conclusion: In this study, we demonstrated the in vitro generation of mouse embryonic stem cells to germ cells by using a backbone vector containing the fusion gene Stra8-EGFP. The Stra8 gene is a retinoic acid-responsive protein and is able to regulate meiotic initiation.

  3. RNA-Sequencing Analyses Demonstrate the Involvement of Canonical Transient Receptor Potential Channels in Rat Tooth Germ Development

    Directory of Open Access Journals (Sweden)

    Jun Yang

    2017-06-01

    Full Text Available Tooth development depends on multiple molecular interactions between the dental epithelium and mesenchyme, which are derived from ectodermal and ectomesenchymal cells, respectively. We report on a systematic RNA sequencing analysis of transcriptional expression levels from the bud to hard tissue formation stages of rat tooth germ development. We found that GNAO1, ENO1, EFNB1, CALM1, SIAH2, ATP6V0A1, KDELR2, GTPBP1, POLR2C, SORT1, and members of the canonical transient receptor potential (TRPC channel family are involved in tooth germ development. Furthermore, Cell Counting Kit 8 (CCK8 and Transwell migration assays were performed to explore the effects of these differentially expressed genes (DEGs on the proliferation and migration of dental pulp stem cells. Immunostaining revealed that TRPC channels are expressed at varying levels during odontogenesis. The identified genes represent novel candidates that are likely to be vital for rat tooth germ development. Together, the results provide a valuable resource to elucidate the gene regulatory mechanisms underlying mammalian tooth germ development.

  4. Vulnerability of female germ cells in developing mice and monkeys to tritium, gamma rays, and polycyclic aromatic hydrocarbons

    International Nuclear Information System (INIS)

    Dobson, R.L.; Koehler, C.G.; Felton, J.S.; Kwan, T.C.; Wuebbles, B.J.; Jones, D.C.L.

    1978-01-01

    During development female germ cells in both mouse and monkey are extremely sensitive to destruction by low-level chronic tritium exposure (via 3 HOH in maternal drinking water). Practical significance of this stems from tritium's importance in nuclear energy production and as an environmental pollutant. In mice exposed from conception to 14 days of age, the LD 50 level for oocytes is only 2 μCi per mililiter of body water. The present studies indicate that, for female germ cells in squirrel monkeys exposed in utero, the LD 50 is even lower, about 0.5 μCi/ml. This striking sensitivity contrasts with reported radioresistance for primate oocytes, chiefly from acute x-irradiation experiments. The discrepancy is reconciled if germ cells in the fetal primate pass through a highly sensitive period of limited duration. In light of other data showing germ-cell loss following repeated semiweekly x-irradiation during late but not during mid gestation, these results indicate that exceedingly high sensitivity occurs probably about the middle of the last trimester, at which time the LD 50 for monkey germ cells is, as for that of the mouse, less than 5 rads. Whereas highest radiosensitivity in primates is before birth, in mice it is after birth. To define the period of sensitivity more sharply, we measured oocyte responses to standard gamma-ray exposures in Swiss-Webster mice at various ages and found them to be maximal between days 5 and 19. Polycyclic aromatic hydrocarbons (PAH's), important as pollutants, also can destroy female germ cells effectively

  5. A novel germ-line point mutation in RET exon 8 (Gly(533)Cys) in a large kindred with familial medullary thyroid carcinoma

    OpenAIRE

    Silva, Adriana Madeira Alvares da [UNIFESP; Maciel, Rui Monteiro de Barros [UNIFESP; Dias-da-Silva, Magnus Régios [UNIFESP; Toledo, Silvia Regina Caminada de [UNIFESP; De Carvalho, Marcos B.; Cerutti, Janete Maria [UNIFESP

    2003-01-01

    Familial medullary thyroid carcinoma is related to germ-line mutations in the RET oncogene, mainly in cysteine codon 10 or 11, whereas noncysteine mutations in codons 13 - 15 are rare. We now report a new missense point mutation in exon 8 of the RET gene (1597G-->T) corresponding to a Gly(533)Cys substitution in the cystein-rich domain of RET protein in 76 patients from a 6-generation Brazilian family with 229 subjects, with ascendants from Spain. It is likely that the mutation causes familia...

  6. Development of space-fertilized eggs and formation of primordial germ cells in the embryos of medaka fish

    Science.gov (United States)

    Ijiri, K.

    In the second International Microgravity Laboratory (IML-2) mission in 1994, four small Japanese killifish (Medaka, Oryzias latipes) made a space travel of 15 days aboard a space shuttle. These four adult Medaka fish successfully mated in space for the first time among vertebrate animals. Moreover, the eggs they laid developed normally, at least in their external appearance, hatching as fry (baby fish) in space. Fish mated and laid eggs every day during the first week. Near the end of the mission most of the eggs had a well-developed body with two pigmented eyes. In total, 43 eggs were laid (detected), out of which 8 fry hatched in space, as truly `space-originated' babies. A further 30 fry hatched within 3 days after landing. This is the normal hatching rate, compared with the ground-based data. Among the 8 space-originated fry, four were killed for histological sections, and germ cells at the gonadal region were counted for each fry. Their numbers were in the range of the germ cells of the normal control fry (ground-kept samples). Thus, as embryos developed normally in their external appearance, inside the embryos the formation of primordial germ cells took place normally in space, and their migration to the genital ridges was not hindered by microgravity. The two of the remaining space-originated fry have grown up and been creating their offspring in the laboratory. This proved that the primordial germ cells formed in space were also normal from a functional point of view. The four space-travelled adult fish re-started mating and laying eggs on the 7th day after landing and continued to do so every day afterward. Fertilization rate and hatchability of these eggs were as high as the eggs laid by the laboratory-kept fish. This fact implies that in gametogenesis of adult fish, there are no specific stages of germ cells extremely susceptible to microgravity.

  7. Germ line mutations of mismatch repair genes in hereditary nonpolyposis colorectal cancer patients with small bowel cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative Study

    DEFF Research Database (Denmark)

    Park, Jae-Gahb; Kim, Duck-Woo; Hong, Chang Won

    2006-01-01

    PURPOSE: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC). EXPERIMENTAL DESIGN: A questionnaire was mailed to 55 members of the Internatio......PURPOSE: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC). EXPERIMENTAL DESIGN: A questionnaire was mailed to 55 members...... of the International Society for Gastrointestinal Hereditary Tumours, requesting information regarding patients with HNPCC-associated SBC and germ line mismatch repair gene mutations. RESULTS: The study population consisted of 85 HNPCC patients with identified mismatch repair gene mutations and SBCs. SBC was the first...... HNPCC-associated malignancy in 14 of 41 (34.1%) patients for whom a personal history of HNPCC-associated cancers was available. The study population harbored 69 different germ line mismatch repair gene mutations, including 31 mutations in MLH1, 34 in MSH2, 3 in MSH6, and 1 in PMS2. We compared...

  8. Expression of FGFR3 during human testis development and in germ cell-derived tumours of young adults

    DEFF Research Database (Denmark)

    Ewen, Katherine A; Olesen, Inge A; Winge, Sofia B

    2013-01-01

    development and to ascertain whether FGFR3 signalling is linked to germ cell proliferation and the pathogenesis of testicular germ cell tumours (TGCTs) of young adult men. Using RT-PCR, immunohistochemistry and Western blotting, we examined 58 specimens of human testes throughout development for FGFR3...... expression, and then compared expression of FGFR3 with proliferation markers (PCNA or Ki67). We also analysed for FGFR3 expression 30 TGCTs and 28 testes containing the tumour precursor cell, carcinoma in situ (CIS). Fetal and adult testes expressed exclusively the FGFR3IIIc isoform. FGFR3 protein expression...... was restricted to the cytoplasm/plasma membrane of spermatogonia and was most prevalent at mid-gestation, infancy and from puberty onwards. Phosphorylated (p)FGFR was detected in pre-spermatogonia at mid-gestation and in spermatogonia during puberty and in the adult testis. Throughout normal human testis...

  9. Interaction between NANOS2 and the CCR4-NOT Deadenylation Complex Is Essential for Male Germ Cell Development in Mouse

    OpenAIRE

    Suzuki, Atsushi; Saba, Rie; Miyoshi, Kei; Morita, Yoshinori; Saga, Yumiko

    2012-01-01

    Nanos is one of the evolutionarily conserved proteins implicated in germ cell development and we have previously shown that it interacts with the CCR4-NOT deadenylation complex leading to the suppression of specific RNAs. However, the molecular mechanism and physiological significance of this interaction have remained elusive. In our present study, we identify CNOT1, a component of the CCR4-NOT deadenylation complex, as a direct factor mediating the interaction with NANOS2. We find that the f...

  10. Germ killing by ultraviolet radiation

    International Nuclear Information System (INIS)

    Wawrik, O.

    1975-01-01

    Short-wave UV radiation, in particular the range about 250 nm, has a high germ reducing effect. Corresponding UV burners which above all emit radiation at the line of 254 nm can therefore be used effectively in all cases where the least possible content of germs in the air is aimed at. Apart from this it is also possible to reduce by this process the germs on surfaces and liquids. Especially in the most various ranges of pharmaceutical production one is steadily striving for efficient and last not least economic procedures by which it is possible to reduce the germs present in the air of a room. Numerous scientific investigations have sufficiently proved that short-wave UV radiation is extremely well appropriate for such purposes. Absolutely germ-free air in a room can only be obtained under laboratory conditions. In practice, however, the aim is not to achieve a 100 per cent killing of the germs present in a room but to make sure that the germ rate in certain rooms is constantly reduced to the lowest possible level. If in this connection it is referred to a germ reduction of 100 or 99 per cent this is but theory. (orig.) [de

  11. Redeployment of germ layers related TFs shows regionalized expression during two non-embryonic developments.

    Science.gov (United States)

    Ricci, Lorenzo; Cabrera, Fabien; Lotito, Sonia; Tiozzo, Stefano

    2016-08-01

    In all non-vertebrate metazoan phyla, species that evolved non-embryonic developmental pathways as means of propagation or regeneration can be found. In this context, new bodies arise through asexual reproduction processes (such as budding) or whole body regeneration, that lack the familiar temporal and spatial cues classically associated with embryogenesis, like maternal determinants, or gastrulation. The molecular mechanisms underlying those non-embryonic developments (i.e., regeneration and asexual reproduction), and their relationship to those deployed during embryogenesis are poorly understood. We have addressed this question in the colonial ascidian Botryllus schlosseri, which undergoes an asexual reproductive process via palleal budding (PB), as well as a whole body regeneration by vascular budding (VB). We identified early regenerative structures during VB and then followed the fate of differentiating tissues during both non-embryonic developments (PB and VB) by monitoring the expression of genes known to play key functions in germ layer specification with well conserved expression patterns in solitary ascidian embryogenesis. The expression patterns of FoxA1, GATAa, GATAb, Otx, Bra, Gsc and Tbx2/3 were analysed during both PB and VB. We found that the majority of these transcription factors were expressed during both non-embryonic developmental processes, revealing a regionalization of the palleal and vascular buds. Knockdown of GATAa by siRNA in palleal buds confirmed that preventing the correct development of one of these regions blocks further tissue specification. Our results indicate that during both normal and injury-induced budding, a similar alternative developmental program operates via early commitment of epithelial regions. Copyright © 2016. Published by Elsevier Inc.

  12. Minichromosome maintenance helicase paralog MCM9 is dispensible for DNA replication but functions in germ-line stem cells and tumor suppression.

    Science.gov (United States)

    Hartford, Suzanne A; Luo, Yunhai; Southard, Teresa L; Min, Irene M; Lis, John T; Schimenti, John C

    2011-10-25

    Effective DNA replication is critical to the health and reproductive success of organisms. The six MCM2-7 proteins, which form the replicative helicase, are essential for high-fidelity replication of the genome. Many eukaryotes have a divergent paralog, MCM9, that was reported to be essential for loading MCM2-7 onto replication origins in the Xenopus oocyte extract system. To address the in vivo role of mammalian MCM9, we created and analyzed the phenotypes of mice with various mutations in Mcm9 and an intronic DNA replication-related gene Asf1a. Ablation of Mcm9 was compatible with cell proliferation and mouse viability, showing that it is nonessential for MCM2-7 loading or DNA replication. Mcm9 mutants underwent p53-independent embryonic germ-cell depletion in both sexes, with males also exhibiting defective spermatogonial stem-cell renewal. MCM9-deficient cells had elevated genomic instability and defective cell cycle reentry following replication stress, and mutant animals were prone to sex-specific cancers, most notably hepatocellular carcinoma in males. The phenotypes of mutant mice and cells suggest that MCM9 evolved a specialized but nonessential role in DNA replication or replication-linked quality-control mechanisms that are especially important for germ-line stem cells, and also for tumor suppression and genome maintenance in the soma.

  13. Quantitative analysis of fluoride-induced hypermineralization of developing enamel in neonatal hamster tooth germs

    Science.gov (United States)

    Tros, G. H. J.; Lyaruu, D. M.; Vis, R. D.

    1993-10-01

    A procedure was developed for analysing the effect of fluoride on mineralization in the enamel of neonatal hamster molars during amelogenesis by means of the quantitative determination of the mineral content. In this procedure the distribution of calcium and mineral concentration was determined in sections containing developing tooth enamel mineral embedded in an organic epoxy resin matrix by means of the micro-PIXE technique. This allowed the determination of the calcium content along preselected tracks with a spatial resolution of 2 μm using a microprobe PIXE setup with a 3 MeV proton beam of 10 to 50 pA with a spot size of 2 μm in the track direction. In this procedure the X-ray yield is used as a measure for the calcium content. The thickness of each sample section is determined independently by measuring the energy loss of α-particles from a calibration source upon passing through the sample. The sample is considered as consisting of two bulk materials, allowing the correction for X-ray self-absorption and the calculation of the calcium concentration. The procedure was applied for measuring the distribution of mineral concentration in 2 μm thick sections taken from tooth germs of hamsters administered with NaF. The measurements indicated that a single intraperitoneal administration of 20 mg NaF/kg body weight to 4-to-5-day-old hamsters leads within 24 h to hypermineralization of certain focal enamel surface areas containing cystic lesions under transitional and early secretory ameloblasts. The mineral concentration there is substantially increased due to the fluoride treatment (35%, instead of 5 to 10% as in the controls), indicating that the normal mineralization process has been seriously disturbed. Furthermore it is found that using this technique the mineral concentration peaks at about 70% at the dentine-enamel junction, which is comparable to that reported for human dentine using other techniques.

  14. Micro-PIGE determination of fluorine distribution in developing hamster tooth germs

    International Nuclear Information System (INIS)

    Lyaruu, D.M.; Lenglet, W.J.; Woeltgens, J.H.B.; Bronckers, A.L.

    1989-01-01

    A micro-PIGE (Proton-Induced gamma-ray Emission) technique based on the delayed 5/2+----1/2+ nuclear transition of fluorine (E gamma = 197 keV, t1/2 = 87 ns) emitted after 19 F(p,p', gamma) 19 F reaction was used to detect and study the distribution of fluorine in the developing enamel organ during pre-eruptive stages, i.e., the transitional to early maturation stages of enamel formation in neonatal hamsters administered a single IP dose of sodium fluoride (20 mg NaF/kg body weight). The aforementioned nuclear reaction is unique for fluorine, and therefore detection of gamma-rays emanating from this reaction in a biological specimen implies a positive identification of fluorine at that particular site. Calcium and phosphorus X-rays were also recorded and used as parameters for assessment of the relationship between the degree of mineralization and fluoride incorporation into the enamel organ. The highest fluorine concentration in the enamel organ was recorded in the dentin near the dentin-enamel junction (DEJ). In the enamel, the highest concentration of fluorine was found to be associated with the more mature areas of the enamel near the DEJ, but gradually decreased in the direction of the enamel surface. Fluorine was not detected in the control germs. These results suggest that administration of fluoride in high doses during the pre-eruptive stages of enamel formation leads to incorporation of the ion into the forming dentin and enamel mineral, and that the enamel matrix does not seem to bind fluoride avidly

  15. Effects of environmental Bisphenol A exposures on germ cell development and Leydig cell function in the human fetal testis.

    Directory of Open Access Journals (Sweden)

    Soria Eladak

    Full Text Available Using an organotypic culture system termed human Fetal Testis Assay (hFeTA we previously showed that 0.01 μM BPA decreases basal, but not LH-stimulated, testosterone secreted by the first trimester human fetal testis. The present study was conducted to determine the potential for a long-term antiandrogenic effect of BPA using a xenograft model, and also to study the effect of BPA on germ cell development using both the hFETA and xenograft models.Using the hFeTA system, first trimester testes were cultured for 3 days with 0.01 to 10 μM BPA. For xenografts, adult castrate male nude mice were injected with hCG and grafted with first trimester testes. Host mice received 10 μM BPA (~ 500 μg/kg/day in their drinking water for 5 weeks. Plasma levels of total and unconjugated BPA were 0.10 μM and 0.038 μM respectively. Mice grafted with second trimester testes received 0.5 and 50 μg/kg/day BPA by oral gavage for 5 weeks.With first trimester human testes, using the hFeTA model, 10 μM BPA increased germ cell apoptosis. In xenografts, germ cell density was also reduced by BPA exposure. Importantly, BPA exposure significantly decreased the percentage of germ cells expressing the pluripotency marker AP-2γ, whilst the percentage of those expressing the pre-spermatogonial marker MAGE-A4 significantly increased. BPA exposure did not affect hCG-stimulated androgen production in first and second trimester xenografts as evaluated by both plasma testosterone level and seminal vesicle weight in host mice.Exposure to BPA at environmentally relevant concentrations impairs germ cell development in first trimester human fetal testis, whilst gonadotrophin-stimulated testosterone production was unaffected in both first and second trimester testis. Studies using first trimester human fetal testis demonstrate the complementarity of the FeTA and xenograft models for determining the respective short-term and long term effects of environmental exposures.

  16. Expression of FGFR3 during human testis development and in germ cell-derived tumours of young adults.

    Science.gov (United States)

    Ewen, Katherine A; Olesen, Inge A; Winge, Sofia B; Nielsen, Ana R; Nielsen, John E; Graem, Niels; Juul, Anders; Rajpert-De Meyts, Ewa

    2013-01-01

    Observations in patients with an activating mutation of fibroblast growth factor receptor 3 (FGFR3) suggest a role for FGFR3 signalling in promoting proliferation or survival of germ cells. In this study, we aimed to identify the FGFR3 subtype and the ontogeny of expression during human testis development and to ascertain whether FGFR3 signalling is linked to germ cell proliferation and the pathogenesis of testicular germ cell tumours (TGCTs) of young adult men. Using RT-PCR, immunohistochemistry and Western blotting, we examined 58 specimens of human testes throughout development for FGFR3 expression, and then compared expression of FGFR3 with proliferation markers (PCNA or Ki67). We also analysed for FGFR3 expression 30 TGCTs and 28 testes containing the tumour precursor cell, carcinoma in situ (CIS). Fetal and adult testes expressed exclusively the FGFR3IIIc isoform. FGFR3 protein expression was restricted to the cytoplasm/plasma membrane of spermatogonia and was most prevalent at mid-gestation, infancy and from puberty onwards. Phosphorylated (p)FGFR was detected in pre-spermatogonia at mid-gestation and in spermatogonia during puberty and in the adult testis. Throughout normal human testis development, expression of FGFR3 did not directly correlate with proliferation markers. In preinvasive CIS cells and in TGCTs, including classical seminoma and embryonal carcinoma, FGFR3IIIc was detected only in a small number of cells, with a heterogeneous expression pattern. FGFR3 is an excellent marker for human pre-/spermatogonia throughout development. Signalling through this receptor is likely associated with spermatogonial survival rather than proliferation. FGFR3 is not expressed in gonocytes and may not be essential to the aetiology of TGCTs stemming from CIS.

  17. Primordial Germ Cell-Mediated Chimera Technology Produces Viable Pure-Line Houbara Bustard Offspring: Potential for Repopulating an Endangered Species

    Science.gov (United States)

    Wernery, Ulrich; Liu, Chunhai; Baskar, Vijay; Guerineche, Zhor; Khazanehdari, Kamal A.; Saleem, Shazia; Kinne, Jörg; Wernery, Renate

    2010-01-01

    Background The Houbara bustard (Chlamydotis undulata) is a wild seasonal breeding bird populating arid sandy semi-desert habitats in North Africa and the Middle East. Its population has declined drastically during the last two decades and it is classified as vulnerable. Captive breeding programmes have, hitherto, been unsuccessful in reviving population numbers and thus radical technological solutions are essential for the long term survival of this species. The purpose of this study was to investigate the use of primordial germ cell-mediated chimera technology to produce viable Houbara bustard offspring. Methodology/Principal Findings Embryonic gonadal tissue was dissected from Houbara bustard embryos at eight days post-incubation. Subsequently, Houbara tissue containing gonadal primordial germ cells (gPGCs) was injected into White Leghorn chicken (Gallus gallus domesticus) embryos, producing 83/138 surviving male chimeric embryos, of which 35 chimeric roosters reached sexual maturity after 5 months. The incorporation and differentiation of Houbara gPGCs in chimeric chicken testis were assessed by PCR with Houbara-specific primers and 31.3% (5/16) gonads collected from the injected chicken embryos showed the presence of donor Houbara cells. A total of 302 semen samples from 34 chimeric roosters were analyzed and eight were confirmed as germline chimeras. Semen samples from these eight roosters were used to artificially inseminate three female Houbara bustards. Subsequently, 45 Houbara eggs were obtained and incubated, two of which were fertile. One egg hatched as a male live born Houbara; the other was female but died before hatching. Genotyping confirmed that the male chick was a pure-line Houbara derived from a chimeric rooster. Conclusion This study demonstrates for the first time that Houbara gPGCs can migrate, differentiate and eventually give rise to functional sperm in the chimeric chicken testis. This approach may provide a promising tool for propagation

  18. Primordial germ cell-mediated chimera technology produces viable pure-line Houbara bustard offspring: potential for repopulating an endangered species.

    Directory of Open Access Journals (Sweden)

    Ulrich Wernery

    2010-12-01

    Full Text Available The Houbara bustard (Chlamydotis undulata is a wild seasonal breeding bird populating arid sandy semi-desert habitats in North Africa and the Middle East. Its population has declined drastically during the last two decades and it is classified as vulnerable. Captive breeding programmes have, hitherto, been unsuccessful in reviving population numbers and thus radical technological solutions are essential for the long term survival of this species. The purpose of this study was to investigate the use of primordial germ cell-mediated chimera technology to produce viable Houbara bustard offspring.Embryonic gonadal tissue was dissected from Houbara bustard embryos at eight days post-incubation. Subsequently, Houbara tissue containing gonadal primordial germ cells (gPGCs was injected into White Leghorn chicken (Gallus gallus domesticus embryos, producing 83/138 surviving male chimeric embryos, of which 35 chimeric roosters reached sexual maturity after 5 months. The incorporation and differentiation of Houbara gPGCs in chimeric chicken testis were assessed by PCR with Houbara-specific primers and 31.3% (5/16 gonads collected from the injected chicken embryos showed the presence of donor Houbara cells. A total of 302 semen samples from 34 chimeric roosters were analyzed and eight were confirmed as germline chimeras. Semen samples from these eight roosters were used to artificially inseminate three female Houbara bustards. Subsequently, 45 Houbara eggs were obtained and incubated, two of which were fertile. One egg hatched as a male live born Houbara; the other was female but died before hatching. Genotyping confirmed that the male chick was a pure-line Houbara derived from a chimeric rooster.This study demonstrates for the first time that Houbara gPGCs can migrate, differentiate and eventually give rise to functional sperm in the chimeric chicken testis. This approach may provide a promising tool for propagation and conservation of endangered avian

  19. Gut microbiota and lipopolysaccharide content of the diet influence development of regulatory T cells: studies in germ-free mice.

    Science.gov (United States)

    Hrncir, Tomas; Stepankova, Renata; Kozakova, Hana; Hudcovic, Tomas; Tlaskalova-Hogenova, Helena

    2008-11-06

    Mammals are essentially born germ-free but the epithelial surfaces are promptly colonized by astounding numbers of bacteria soon after birth. The most extensive microbial community is harbored by the distal intestine. The gut microbiota outnumber ~10 times the total number of our somatic and germ cells. The host-microbiota relationship has evolved to become mutually beneficial. Studies in germ-free mice have shown that gut microbiota play a crucial role in the development of the immune system. The principal aim of the present study was to elucidate whether the presence of gut microbiota and the quality of a sterile diet containing various amounts of bacterial contaminants, measured by lipopolysaccharide (LPS) content, can influence maturation of the immune system in gnotobiotic mice. We have found that the presence of gut microbiota and to a lesser extent also the LPS-rich sterile diet drive the expansion of B and T cells in Peyer's patches and mesenteric lymph nodes. The most prominent was the expansion of CD4+ T cells including Foxp3-expressing T cells in mesenteric lymph nodes. Further, we have observed that both the presence of gut microbiota and the LPS-rich sterile diet influence in vitro cytokine profile of spleen cells. Both gut microbiota and LPS-rich diet increase the production of interleukin-12 and decrease the production of interleukin-4. In addition, the presence of gut microbiota increases the production of interleukin-10 and interferon-gamma. Our data clearly show that not only live gut microbiota but also microbial components (LPS) contained in sterile diet stimulate the development, expansion and function of the immune system. Finally, we would like to emphasize that the composition of diet should be regularly tested especially in all gnotobiotic models as the LPS content and other microbial components present in the diet may significantly alter the outcome of experiments.

  20. Switching of dominant retrotransposon silencing strategies from posttranscriptional to transcriptional mechanisms during male germ-cell development in mice.

    Directory of Open Access Journals (Sweden)

    Kota Inoue

    2017-07-01

    Full Text Available Mammalian genomes harbor millions of retrotransposon copies, some of which are transpositionally active. In mouse prospermatogonia, PIWI-interacting small RNAs (piRNAs combat retrotransposon activity to maintain the genomic integrity. The piRNA system destroys retrotransposon-derived RNAs and guides de novo DNA methylation at some retrotransposon promoters. However, it remains unclear whether DNA methylation contributes to retrotransposon silencing in prospermatogonia. We have performed comprehensive studies of DNA methylation and polyA(+ RNAs (transcriptome in developing male germ cells from Pld6/Mitopld and Dnmt3l knockout mice, which are defective in piRNA biogenesis and de novo DNA methylation, respectively. The Dnmt3l mutation greatly reduced DNA methylation levels at most retrotransposons, but its impact on their RNA abundance was limited in prospermatogonia. In Pld6 mutant germ cells, although only a few retrotransposons exhibited reduced DNA methylation, many showed increased expression at the RNA level. More detailed analysis of RNA sequencing, nascent RNA quantification, profiling of cleaved RNA ends, and the results obtained from double knockout mice suggest that PLD6 works mainly at the posttranscriptional level. The increase in retrotransposon expression was larger in Pld6 mutants than it was in Dnmt3l mutants, suggesting that RNA degradation by the piRNA system plays a more important role than does DNA methylation in prospermatogonia. However, DNA methylation had a long-term effect: hypomethylation caused by the Pld6 or Dnmt3l mutation resulted in increased retrotransposon expression in meiotic spermatocytes. Thus, posttranscriptional silencing plays an important role in the early stage of germ cell development, then transcriptional silencing becomes important in later stages. In addition, intergenic and intronic retrotransposon sequences, in particular those containing the antisense L1 promoters, drove ectopic expression of nearby

  1. Influence of vitamin D on cisplatin sensitivity in testicular germ cell cancer-derived cell lines and in a NTera2 xenograft model

    DEFF Research Database (Denmark)

    Jørgensen, Anne; Blomberg Jensen, Martin; Nielsen, John Erik

    2013-01-01

    The active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) has anti-proliferative, pro-apoptotic, and pro-differentiating effects in somatic cancer cells in vitro and in vivo. 1,25(OH)(2)D(3) also augments the anti-tumor effects of several chemotherapeutic agents, including...... cisplatin, which may have clinical relevance. Given the pro-differentiation effect of vitamin D recently demonstrated in testicular germ cell tumors (TGCTs), we hypothesized that 1,25(OH)(2)D(3) could be a beneficial adjunctive to existing chemotherapy regime used to treat these tumors. In this study, cell...... survival effects of 1,25(OH)(2)D(3), another pro-differentiation compound, retinoic acid and cisplatin were investigated in TGCT-derived cell lines in vitro. 1,25(OH)(2)D(3) augmented the effect of cisplatin in an embryonal carcinoma-derived cell line (NTera2), possibly through downregulation...

  2. Specification of primordial germ cells in medaka (Oryzias latipes

    Directory of Open Access Journals (Sweden)

    Raz Erez

    2007-01-01

    Full Text Available Abstract Background Primordial germ cells (PGCs give rise to gametes that are responsible for the development of a new organism in the next generation. Two modes of germ line specification have been described: the inheritance of asymmetrically-localized maternally provided cytoplasmic determinants and the induction of the PGC fate by other cell types. PGCs specification in zebrafish appears to depend on inheritance of germ plasm in which several RNA molecules such as vasa and nanos reside. Whether the specification mode of PGCs found in zebrafish is general for other fish species was brought into question upon analysis of olvas expression – the vasa homologue in another teleost, medaka (Oryzias latipes. Here, in contrast to the findings in zebrafish, the PGCs are found in a predictable position relative to a somatic structure, the embryonic shield. This finding, coupled with the fact that vasa mRNA, which is localized to the germ plasm of zebrafish but does not label a similar structure in medaka opened the possibility of fundamentally different mechanisms governing PGC specification in these two fish species. Results In this study we addressed the question concerning the mode of PGC specification in medaka using embryological experiments, analysis of RNA stability in the PGCs and electron microscopy observations. Dramatic alterations in the somatic environment, i.e. induction of a secondary axis or mesoderm formation alteration, did not affect the PGC number. Furthermore, the PGCs of medaka are capable of protecting specific RNA molecules from degradation and could therefore exhibit a specific mRNA expression pattern controlled by posttrancriptional mechanisms. Subsequent analysis of 4-cell stage medaka embryos using electron microscopy revealed germ plasm-like structures located at a region corresponding to that of zebrafish germ plasm. Conclusion Taken together, these results are consistent with the idea that in medaka the inheritance of

  3. Nuclear Reprogramming in Mouse Primordial Germ Cells: Epigenetic Contribution

    Directory of Open Access Journals (Sweden)

    Massimo De Felici

    2011-01-01

    Full Text Available The unique capability of germ cells to give rise to a new organism, allowing the transmission of primary genetic information from generation to generation, depends on their epigenetic reprogramming ability and underlying genomic totipotency. Recent studies have shown that genome-wide epigenetic modifications, referred to as “epigenetic reprogramming”, occur during the development of the gamete precursors termed primordial germ cells (PGCs in the embryo. This reprogramming is likely to be critical for the germ line development itself and necessary to erase the parental imprinting and setting the base for totipotency intrinsic to this cell lineage. The status of genome acquired during reprogramming and the associated expression of key pluripotency genes render PGCs susceptible to transform into pluripotent stem cells. This may occur in vivo under still undefined condition, and it is likely at the origin of the formation of germ cell tumors. The phenomenon appears to be reproduced under partly defined in vitro culture conditions, when PGCs are transformed into embryonic germ (EG cells. In the present paper, I will try to summarize the contribution that epigenetic modifications give to nuclear reprogramming in mouse PGCs.

  4. Concurrent development of testicular seminoma and choriocarcinoma of the superior mediastinum, presented as cervical mass: a case report and implications about pathogenesis of germ-cell tumours

    Directory of Open Access Journals (Sweden)

    Bamias Aristotelis

    2006-11-01

    Full Text Available Abstract Background Synchronous presentation of more than one germ cell tumours of different histology in the same patient is considered to be very rare. In these cases of multiple germ cell tumours, strong theoretical and clinical data suggest an underlying common pathogenetic mechanism concerning genetic instability or abnormalities during the pluripotent embryonic differentiation and maturation of the germ cell. Case presentation A 25 year-old young man presented with an enlarging, slightly painful left cervical mass. Despite the initial disorientation of the diagnosis to a possible thyroid disorder, the patient underwent complete surgical resection of the mass revealing mediastinal choriocarcinoma. Subsequent ultrasound of the scrotum indicated the presence of a small lobular node in the upper pole of the left testicle and the patient underwent radical left inguinal orchiectomy disclosing a typical seminoma. Based on these results, the patient received 4 cycles of Bleomycin, Etoposide and Platinum chemotherapy experiencing only mild toxicity and resulting in complete ongoing clinical and biochemical remission. Conclusion The pathogenesis of concurrent germ cell tumours in the same patient remains an area of controversy. Although the genetic instability of the pluripotent germ cell offers an adequate explanation, the possibility of metastasis from the primary, less differentiated tumour to a distant location as a more mature subtype cannot be excluded. Possible development of a metastatic site of different histology and thus biological behaviour (e.g choriocarcinoma should be anticipated. Furthermore, urologists, pathologists and medical oncologists should be meticulous in the original pathological diagnosis in these patients, since there is a significant frequency of germ cell tumours with mixed or overlapping histological elements with diverse potential of evolution and differentiation.

  5. Human-specific subcellular compartmentalization of P-element induced wimpy testis-like (PIWIL) granules during germ cell development and spermatogenesis

    NARCIS (Netherlands)

    Gomes Fernandes, Maria; He, Nannan; Wang, Fang; Van Iperen, Liesbeth; Eguizabal, Cristina; Matorras, Roberto; Roelen, Bernard A J; Chuva de Sousa Lopes, Susana M

    2018-01-01

    STUDY QUESTION: What is the dynamics of expression of P-element induced wimpy testis-like (PIWIL) proteins in the germline during human fetal development and spermatogenesis? SUMMARY ANSWER: PIWIL1, PIWIL2, PIWIL3 and PIWIL4 were expressed in a sex-specific fashion in human germ cells (GC) during

  6. Comparative analysis of miRNA expression during the development of insects of different metamorphosis modes and germ-band types.

    Science.gov (United States)

    Ylla, Guillem; Piulachs, Maria-Dolors; Belles, Xavier

    2017-10-11

    Do miRNAs contribute to specify the germ-band type and the body structure in the insect embryo? Our goal was to address that issue by studying the changes in miRNA expression along the ontogeny of the German cockroach Blattella germanica, which is a short germ-band and hemimetabolan species. We sequenced small RNA libraries representing 11 developmental stages of B. germanica ontogeny (with especial emphasis on embryogenesis) and the changes in miRNA expression were examined. Data were compared with equivalent data for two long germ-band holometabolan species Drosophila melanogaster and Drosophila virilis, and the short germ-band holometabolan species Tribolium castaneum. The identification of B. germanica embryo small RNA sequences unveiled miRNAs not detected in previous studies, such as those of the MIR-309 family and 54 novel miRNAs. Four main waves of miRNA expression were recognized (with most miRNA changes occurring during the embryonic stages): the first from day 0 to day 1 of embryogenesis, the second during mid-embryogenesis (days 0-6), the third (with an acute expression peak) on day 2 of embryonic development, and the fourth during post-embryonic development. The second wave defined the boundaries of maternal-to-zygotic transition, with maternal mRNAs being cleared, presumably by Mir-309 and associated scavenger miRNAs. miRNAs follow well-defined patterns of expression over hemimetabolan ontogeny, patterns that are more diverse during embryonic development than during the nymphal stages. The results suggest that miRNAs play important roles in the developmental transitions between the embryonic stages of development (starting with maternal loading), during which they might influence the germ-band type and metamorphosis mode.

  7. Line-mode browser development days

    CERN Multimedia

    Anna Pantelia

    2013-01-01

    Twelve talented web developers have travelled to CERN from all over the world to recreate a piece of web history: the line-mode browser. See the line-mode browser simulator that they created here. Read more about the birth of the web here.

  8. Dependence of radiation effects in the progeny of the fist and second generation on stages of the development of germ cell of both parents at the time of irradiation: Experimental studies

    International Nuclear Information System (INIS)

    Nefyodov, I.; Nefyodova, I.; Palyga, G.

    1997-01-01

    Studies of 35199 offspring of Wistar rats showed that after irradiation of both parents (P) with doses of 0.25-4 Gy the manifestation of radiation effects in the descendants of the first (F1) and second (F2) generations in ontogenesis depended upon radiation dose and the stage of development of P germ cells at the moment of radiation exposure. After irradiation of the matured oocytes, spermatidis and spermatozoids the consequences for FI are mainly determined by a female or their aggravation takes place. After irradiation of the maturing oocytes, spermatocytes and spermatogonia the effects for F1 are mainly determined by the male. The death of F1 occurs chiefly in embryogenesis and F2 in early postnatal ontogenesis. It is more marked by the father's line (the descendants of F1 males and intact females) than by mother's line (the descendants of F1 females and intact males). (author)

  9. Regulation of proliferation in developing human tooth germs by MSX homeodomain proteins and cyclin-dependent kinase inhibitor p19INK4d.

    Science.gov (United States)

    Kero, Darko; Vukojevic, Katarina; Stazic, Petra; Sundov, Danijela; Mardesic Brakus, Snjezana; Saraga-Babic, Mirna

    2017-10-02

    Before the secretion of hard dental tissues, tooth germs undergo several distinctive stages of development (dental lamina, bud, cap and bell). Every stage is characterized by specific proliferation patterns, which is regulated by various morphogens, growth factors and homeodomain proteins. The role of MSX homeodomain proteins in odontogenesis is rather complex. Expression domains of genes encoding for murine Msx1/2 during development are observed in tissues containing highly proliferative progenitor cells. Arrest of tooth development in Msx knockout mice can be attributed to impaired proliferation of progenitor cells. In Msx1 knockout mice, these progenitor cells start to differentiate prematurely as they strongly express cyclin-dependent kinase inhibitor p19 INK4d . p19 INK4d induces terminal differentiation of cells by blocking the cell cycle in mitogen-responsive G1 phase. Direct suppression of p19 INK4d by Msx1 protein is, therefore, important for maintaining proliferation of progenitor cells at levels required for the normal progression of tooth development. In this study, we examined the expression patterns of MSX1, MSX2 and p19 INK4d in human incisor tooth germs during the bud, cap and early bell stages of development. The distribution of expression domains of p19 INK4d throughout the investigated period indicates that p19 INK4d plays active role during human tooth development. Furthermore, comparison of expression domains of p19 INK4d with those of MSX1, MSX2 and proliferation markers Ki67, Cyclin A2 and pRb, indicates that MSX-mediated regulation of proliferation in human tooth germs might not be executed by the mechanism similar to one described in developing tooth germs of wild-type mouse.

  10. Interaction between NANOS2 and the CCR4-NOT deadenylation complex is essential for male germ cell development in mouse.

    Directory of Open Access Journals (Sweden)

    Atsushi Suzuki

    Full Text Available Nanos is one of the evolutionarily conserved proteins implicated in germ cell development and we have previously shown that it interacts with the CCR4-NOT deadenylation complex leading to the suppression of specific RNAs. However, the molecular mechanism and physiological significance of this interaction have remained elusive. In our present study, we identify CNOT1, a component of the CCR4-NOT deadenylation complex, as a direct factor mediating the interaction with NANOS2. We find that the first 10 amino acids (AAs of NANOS2 are required for this binding. We further observe that a NANOS2 mutant lacking these first 10 AAs (NANOS2-ΔN10 fails to rescue defects in the Nanos2-null mouse. Our current data thus indicate that the interaction with the CCR4-NOT deadenylation complex is essential for NANOS2 function. In addition, we further demonstrate that NANOS2-ΔN10 can associate with specific mRNAs as well as wild-type NANOS2, suggesting the existence of other NANOS2-associated factor(s that determine the specificity of RNA-binding independently of the CCR4-NOT deadenylation complex.

  11. Development of the adverse outcome pathway "alkylation of DNA in male premeiotic germ cells leading to heritable mutations" using the OECD's users' handbook supplement.

    Science.gov (United States)

    Yauk, Carole L; Lambert, Iain B; Meek, M E Bette; Douglas, George R; Marchetti, Francesco

    2015-12-01

    The Organisation for Economic Cooperation and Development's (OECD) Adverse Outcome Pathway (AOP) programme aims to develop a knowledgebase of all known pathways of toxicity that lead to adverse effects in humans and ecosystems. A Users' Handbook was recently released to provide supplementary guidance on AOP development. This article describes one AOP-alkylation of DNA in male premeiotic germ cells leading to heritable mutations. This outcome is an important regulatory endpoint. The AOP describes the biological plausibility and empirical evidence supporting that compounds capable of alkylating DNA cause germ cell mutations and subsequent mutations in the offspring of exposed males. Alkyl adducts are subject to DNA repair; however, at high doses the repair machinery becomes saturated. Lack of repair leads to replication of alkylated DNA and ensuing mutations in male premeiotic germ cells. Mutations that do not impair spermatogenesis persist and eventually are present in mature sperm. Thus, the mutations are transmitted to the offspring. Although there are some gaps in empirical support and evidence for essentiality of the key events for certain aspects of this AOP, the overall AOP is generally accepted as dogma and applies broadly to any species that produces sperm. The AOP was developed and used in an iterative process to test and refine the Users' Handbook, and is one of the first publicly available AOPs. It is our hope that this AOP will be leveraged to develop other AOPs in this field to advance method development, computational models to predict germ cell effects, and integrated testing strategies. © 2015 Her Majesty the Queen in Right of Canada.

  12. Germ Cell-less Promotes Centrosome Segregation to Induce Germ Cell Formation

    Directory of Open Access Journals (Sweden)

    Dorothy A. Lerit

    2017-01-01

    Full Text Available The primordial germ cells (PGCs specified during embryogenesis serve as progenitors to the adult germline stem cells. In Drosophila, the proper specification and formation of PGCs require both centrosomes and germ plasm, which contains the germline determinants. Centrosomes are microtubule (MT-organizing centers that ensure the faithful segregation of germ plasm into PGCs. To date, mechanisms that modulate centrosome behavior to engineer PGC development have remained elusive. Only one germ plasm component, Germ cell-less (Gcl, is known to play a role in PGC formation. Here, we show that Gcl engineers PGC formation by regulating centrosome dynamics. Loss of gcl leads to aberrant centrosome separation and elaboration of the astral MT network, resulting in inefficient germ plasm segregation and aborted PGC cellularization. Importantly, compromising centrosome separation alone is sufficient to mimic the gcl loss-of-function phenotypes. We conclude Gcl functions as a key regulator of centrosome separation required for proper PGC development.

  13. Epigenetic features of testicular germ cell tumours in relation to epigenetic characteristics of foetal germ cells

    DEFF Research Database (Denmark)

    Kristensen, Dina Graae; Skakkebæk, Niels E; Rajpert-De Meyts, Ewa

    2013-01-01

    in humans. However, the common precursor of testicular cancers- the carcinoma in situ (CIS) cell- is thought to be an arrested foetal germ cell. Therefore studies of CIS cells may leverage information on human foetal germ cell development and, in particular, when neoplastic transformation is initiated....... In this review, we will focus on current knowledge of the epigenetics of CIS cells and relate it to the epigenetic changes occurring in early developing germ cells of mice during specification, migration and colonization. We will focus on DNA methylation and some of the best studied histone modifications like H3...... event in the initiation of testicular germ cell cancer. Even though only sparse information is available on epigenetic cues in human foetal germ cells, these indicate that the developmental patterns differ from the findings in mice and emphasize the need for further studies of foetal germ cell...

  14. Disorders of Sex Development : Clinical outcomes, (epi)genetic regulation and germ cell cancer

    NARCIS (Netherlands)

    Y.G. van der Zwan (Yvonne )

    2013-01-01

    markdownabstract__Abstract__ One of the most fundamental aspects of early human development is establishment of sex, which can be defined as the biological qualities that differentiate between male and female. The process of normal sex development is strictly controlled by functionality of a

  15. Nanosecond pulsed electric field suppresses development of eyes and germ cells through blocking synthesis of retinoic acid in Medaka (Oryzias latipes.

    Directory of Open Access Journals (Sweden)

    Eri Shiraishi

    Full Text Available Application of nanosecond pulsed electric fields (nsPEFs has attracted rising attention in various scientific fields including medical, pharmacological, and biological sciences, although its effects and molecular mechanisms leading to the effects remain poorly understood. Here, we show that a single, high-intensity (10-30 kV/cm, 60-ns PEF exposure affects gene expression and impairs development of eyes and germ cells in medaka (Oryzias latipes. Exposure of early blastula stage embryos to nsPEF down-regulated the expression of several transcription factors which are essential for eye development, causing abnormal eye formation. Moreover, the majority of the exposed genetic female embryos showed a fewer number of germ cells similar to that of the control (unexposed genetic male at 9 days post-fertilization (dpf. However, all-trans retinoic acid (atRA treatment following the exposure rescued proliferation of germ cells and resumption of normal eye development, suggesting that the phenotypes induced by nsPEF are caused by a decrease of retinoic acid levels. These results confirm that nsPEFs induce novel effects during embryogenesis in medaka.

  16. Fate of fluoride-induced subameloblastic cysts in developing hamster molar tooth germs

    NARCIS (Netherlands)

    Lyaruu, D.M.; Alberga, J.M.R.; Kwee, N.C.H.; Bervoets, T.J.M.; Bronckers, A.L.J.J.; Denbesten, P.K.

    2011-01-01

    White opacities and pits are developmental defects in enamel caused by high intake of fluoride (F) during amelogenesis. We tested the hypothesis that these enamel pits develop at locations where F induces the formation of sub-ameloblastic cysts. We followed the fate of these cysts during molar

  17. Dead end1 is an essential partner of NANOS2 for selective binding of target RNAs in male germ cell development.

    Science.gov (United States)

    Suzuki, Atsushi; Niimi, Yuki; Shinmyozu, Kaori; Zhou, Zhi; Kiso, Makoto; Saga, Yumiko

    2016-01-01

    RNA-binding proteins (RBPs) play important roles for generating various cell types in many developmental processes, including eggs and sperms. Nanos is widely known as an evolutionarily conserved RNA-binding protein implicated in germ cell development. Mouse NANOS2 interacts directly with the CCR4-NOT (CNOT) deadenylase complex, resulting in the suppression of specific RNAs. However, the mechanisms involved in target specificity remain elusive. We show that another RBP, Dead end1 (DND1), directly interacts with NANOS2 to load unique RNAs into the CNOT complex. This interaction is mediated by the zinc finger domain of NANOS2, which is essential for its association with target RNAs. In addition, the conditional deletion of DND1 causes the disruption of male germ cell differentiation similar to that observed in Nanos2-KO mice. Thus, DND1 is an essential partner for NANOS2 that leads to the degradation of specific RNAs. We also present the first evidence that the zinc finger domain of Nanos acts as a protein-interacting domain for another RBP, providing a novel insight into Nanos-mediated germ cell development. © 2015 The Authors.

  18. Dearth and Delayed Maturation of Testicular Germ Cells in Fanconi Anemia E Mutant Male Mice.

    Directory of Open Access Journals (Sweden)

    Chun Fu

    Full Text Available After using a self-inactivating lentivirus for non-targeted insertional mutagenesis in mice, we identified a transgenic family with a recessive mutation that resulted in reduced fertility in homozygous transgenic mice. The lentiviral integration site was amplified by inverse PCR. Sequencing revealed that integration had occurred in intron 8 of the mouse Fance gene, which encodes the Fanconi anemia E (Fance protein. Fanconi anemia (FA proteins play pivotal roles in cellular responses to DNA damage and Fance acts as a molecular bridge between the FA core complex and Fancd2. To investigate the reduced fertility in the mutant males, we analyzed postnatal development of testicular germ cells. At one week after birth, most tubules in the mutant testes contained few or no germ cells. Over the next 2-3 weeks, germ cells accumulated in a limited number of tubules, so that some tubules contained germ cells around the full periphery of the tubule. Once sufficient numbers of germ cells had accumulated, they began to undergo the later stages of spermatogenesis. Immunoassays revealed that the Fancd2 protein accumulated around the periphery of the nucleus in normal developing spermatocytes, but we did not detect a similar localization of Fancd2 in the Fance mutant testes. Our assays indicate that although Fance mutant males are germ cell deficient at birth, the extant germ cells can proliferate and, if they reach a threshold density, can differentiate into mature sperm. Analogous to previous studies of FA genes in mice, our results show that the Fance protein plays an important, but not absolutely essential, role in the initial developmental expansion of the male germ line.

  19. Regulation of germ cell development by intercellular signaling in the mammalian ovarian follicle.

    Science.gov (United States)

    Clarke, Hugh J

    2018-01-01

    Prior to ovulation, the mammalian oocyte undergoes a process of differentiation within the ovarian follicle that confers on it the ability to give rise to an embryo. Differentiation comprises two phases-growth, during which the oocyte increases more than 100-fold in volume as it accumulates macromolecules and organelles that will sustain early embryogenesis; and meiotic maturation, during which the oocyte executes the first meiotic division and prepares for the second division. Entry of an oocyte into the growth phase appears to be triggered when the adjacent granulosa cells produce specific growth factors. As the oocyte grows, it elaborates a thick extracellular coat termed the zona pellucida. Nonetheless, cytoplasmic extensions of the adjacent granulosa cells, termed transzonal projections (TZPs), enable them to maintain contact-dependent communication with the oocyte. Through gap junctions located where the TZP tips meet the oocyte membrane, they provide the oocyte with products that sustain its metabolic activity and signals that regulate its differentiation. Conversely, the oocyte secretes diffusible growth factors that regulate proliferation and differentiation of the granulosa cells. Gap junction-permeable products of the granulosa cells prevent precocious initiation of meiotic maturation, and the gap junctions also enable oocyte maturation to begin in response to hormonal signals received by the granulosa cells. Development of the oocyte or the somatic compartment may also be regulated by extracellular vesicles newly identified in follicular fluid and at TZP tips, which could mediate intercellular transfer of macromolecules. Oocyte differentiation thus depends on continuous signaling interactions with the somatic cells of the follicle. WIREs Dev Biol 2018, 7:e294. doi: 10.1002/wdev.294 This article is categorized under: Gene Expression and Transcriptional Hierarchies > Cellular Differentiation Signaling Pathways > Cell Fate Signaling Early Embryonic

  20. X-ray micro-analysis of the mineralization patterns in developing enamel in hamster tooth germs exposed to fluoride in vitro during the secretory phase of amelogenesis

    International Nuclear Information System (INIS)

    Lyaruu, D.M.; Blijleven, N.; Hoeben-Schornagel, K.; Bronckers, A.L.; Woeltgens, J.H.

    1989-01-01

    The developing enamel from three-day-old hamster first maxillary (M1) molar tooth germs exposed to fluoride (F-) in vitro was analyzed for its mineral content by means of the energy-dispersive x-ray microanalysis technique. The aim of this study was to obtain semi-quantitative data on the F(-)-induced hypermineralization patterns in the enamel and to confirm that the increase in electron density observed in micrographs of F(-)-treated enamel is indeed due to an increase in mineral content in the fluorotic enamel. The tooth germs were explanted during the early stages of secretory amelogenesis and initially cultured for 24 hr in the presence of 10 ppm F- in the culture medium. The germs were then cultured for another 24 hr without F-. In order to compare the ultrastructural results directly with the microprobe data, we used the same specimens for both investigations. The net calcium counts (measurement minus background counts) in the analyses were used as a measure of the mineral content in the enamel. The aprismatic pre-exposure enamel, deposited in vivo before the onset of culture, was the most hypermineralized region in the fluorotic enamel, i.e., it contained the highest amount of calcium measured. The degree of the F(-)-induced hypermineralization gradually decreased (but was not abolished) in the more mature regions of the enamel. The unmineralized enamel matrix secreted during the initial F- treatment in vitro mineralized during the subsequent culture without F-. The calcium content in this enamel layer was in the same order of magnitude as that recorded for the newly deposited enamel in control tooth germs cultured without F-

  1. Generation of germ cells in vitro in the era of induced pluripotent stem cells.

    Science.gov (United States)

    Imamura, Masanori; Hikabe, Orie; Lin, Zachary Yu-Ching; Okano, Hideyuki

    2014-01-01

    Induced pluripotent stem cells (iPSCs) are stem cells that can be artificially generated via "cellular reprogramming" using gene transduction in somatic cells. iPSCs have enormous potential in stem-cell biology as they can give rise to numerous cell lineages, including the three germ layers. An evaluation of germ-line competency by blastocyst injection or tetraploid complementation, however, is critical for determining the developmental potential of mouse iPSCs towards germ cells. Recent studies have demonstrated that primordial germ cells obtained by the in vitro differentiation of iPSCs produce functional gametes as well as healthy offspring. These findings illustrate not only that iPSCs are developmentally similar to embryonic stem cells (ESCs), but also that somatic cells from adult tissues can produce gametes in vitro, that is, if they are reprogrammed into iPSCs. In this review, we discuss past and recent advances in the in vitro differentiation of germ cells using pluripotent stem cells, with an emphasis on ESCs and iPSCs. While this field of research is still at a stage of infancy, it holds great promises for investigating the mechanisms of germ-cell development, especially in humans, and for advancing reproductive and developmental engineering technologies in the future. © 2013 Wiley Periodicals, Inc.

  2. Development of buffalo (Bubalus bubalis embryonic stem cell lines from somatic cell nuclear transferred blastocysts

    Directory of Open Access Journals (Sweden)

    Syed Mohmad Shah

    2015-11-01

    Full Text Available We developed buffalo embryonic stem cell lines from somatic cell nuclear transfer derived blastocysts, produced by hand-guided cloning technique. The inner cell mass of the blastocyst was cut mechanically using a Microblade and cultured onto feeder cells in buffalo embryonic stem (ES cell culture medium at 38 °C in a 5% CO2 incubator. The stem cell colonies were characterized for alkaline phosphatase activity, karyotype, pluripotency and self-renewal markers like OCT4, NANOG, SOX2, c-Myc, FOXD3, SSEA-1, SSEA-4, TRA-1-60, TRA-1-81 and CD90. The cell lines also possessed the capability to differentiate across all the three germ layers under spontaneous differentiation conditions.

  3. TOPAZ1, a novel germ cell-specific expressed gene conserved during evolution across vertebrates.

    Directory of Open Access Journals (Sweden)

    Adrienne Baillet

    Full Text Available BACKGROUND: We had previously reported that the Suppression Subtractive Hybridization (SSH approach was relevant for the isolation of new mammalian genes involved in oogenesis and early follicle development. Some of these transcripts might be potential new oocyte and granulosa cell markers. We have now characterized one of them, named TOPAZ1 for the Testis and Ovary-specific PAZ domain gene. PRINCIPAL FINDINGS: Sheep and mouse TOPAZ1 mRNA have 4,803 bp and 4,962 bp open reading frames (20 exons, respectively, and encode putative TOPAZ1 proteins containing 1,600 and 1653 amino acids. They possess PAZ and CCCH domains. In sheep, TOPAZ1 mRNA is preferentially expressed in females during fetal life with a peak during prophase I of meiosis, and in males during adulthood. In the mouse, Topaz1 is a germ cell-specific gene. TOPAZ1 protein is highly conserved in vertebrates and specifically expressed in mouse and sheep gonads. It is localized in the cytoplasm of germ cells from the sheep fetal ovary and mouse adult testis. CONCLUSIONS: We have identified a novel PAZ-domain protein that is abundantly expressed in the gonads during germ cell meiosis. The expression pattern of TOPAZ1, and its high degree of conservation, suggests that it may play an important role in germ cell development. Further characterization of TOPAZ1 may elucidate the mechanisms involved in gametogenesis, and particularly in the RNA silencing process in the germ line.

  4. Primordial germ cell biology at the beginning of the XXI century.

    Science.gov (United States)

    De Felici, Massimo

    2009-01-01

    At the XIV Workshop on the Development and Function of the Reproductive Organs held at the Congress Centre of the University of Rome Tor Vergata, Monteporzio Catone, Rome, Italy, the introduction to the first session entitled Mammalian primordial germ cells dedicated to the memory of Anne McLaren, was the occasion for a concise review of the state of art of research on the biology of primordial germ cells (PGCs). This great, unforgettable scientist, who died in a car accident in July 2007, dedicated most of her studies to this field over the last 25 years. Topics briefly reviewed in this Meeting Report are: 1) how the germ line is determined; 2) what are the mechanisms underlying PGC migration; 3) to what extent PGC survival, proliferation and differentiation are cell autonomous or environmentally controlled processes and 4) how the potential for totipotency is retained in PGCs.

  5. High power RF transmission line component development

    International Nuclear Information System (INIS)

    Hong, B. G.; Hwang, C. K.; Bae, Y. D.; Yoon, J. S.; Wang, S. J.; Gu, S. H.; Yang, J. R.; Hahm, Y. S.; Oh, G. S.; Lee, J. R.; Lee, W. I.; Park, S. H.; Kang, M. S.; Oh, S. H.; Lee, W.I.

    1999-12-01

    We developed the liquid stub and phase shifter which are the key high RF power transmission line components. They show reliable operation characteristics and increased insulation capability, and reduced the size by using liquid (silicon oil, dielectric constant ε=2.72) instead of gas for insulating dielectric material. They do not have finger stock for the electric contact so the local temperature rise due to irregular contact and RF breakdown due to scratch in conductor are prevented. They can be utilized in broadcasting, radar facility which require high RF power transmission. Moreover, they are key components in RF heating system for fusion reactor. (author)

  6. High power RF transmission line component development

    Energy Technology Data Exchange (ETDEWEB)

    Hong, B. G.; Hwang, C. K.; Bae, Y. D.; Yoon, J. S.; Wang, S. J.; Gu, S. H.; Yang, J. R.; Hahm, Y. S.; Oh, G. S.; Lee, J. R.; Lee, W. I.; Park, S. H.; Kang, M. S.; Oh, S. H.; Lee, W.I

    1999-12-01

    We developed the liquid stub and phase shifter which are the key high RF power transmission line components. They show reliable operation characteristics and increased insulation capability, and reduced the size by using liquid (silicon oil, dielectric constant {epsilon}=2.72) instead of gas for insulating dielectric material. They do not have finger stock for the electric contact so the local temperature rise due to irregular contact and RF breakdown due to scratch in conductor are prevented. They can be utilized in broadcasting, radar facility which require high RF power transmission. Moreover, they are key components in RF heating system for fusion reactor. (author)

  7. Lin28a regulates germ cell pool size and fertility

    Science.gov (United States)

    Shinoda, Gen; de Soysa, T. Yvanka; Seligson, Marc T.; Yabuuchi, Akiko; Fujiwara, Yuko; Huang, Pei Yi; Hagan, John P.; Gregory, Richard I.; Moss, Eric G.; Daley, George Q.

    2013-01-01

    Overexpression of LIN28A is associated with human germ cell tumors and promotes primordial germ cell (PGC) development from embryonic stem cells in vitro and in chimeric mice. Knockdown of Lin28a inhibits PGC development in vitro, but how constitutional Lin28a deficiency affects the mammalian reproductive system in vivo remains unknown. Here, we generated Lin28a knockout (KO) mice and found that Lin28a deficiency compromises the size of the germ cell pool in both males and females by affecting PGC proliferation during embryogenesis. Interestingly however, in Lin28a KO males the germ cell pool partially recovers during postnatal expansion, while fertility remains impaired in both males and females mated to wild type mice. Embryonic overexpression of let-7, a microRNA negatively regulated by Lin28a, reduces the germ cell pool, corroborating the role of the Lin28a/let-7 axis in regulating the germ lineage. PMID:23378032

  8. Extragonadal Germ Cell Cancer (EGC)

    Science.gov (United States)

    The Testicular Cancer Resource Center Extragonadal Germ Cell Cancer (EGC) 95% of all testicular tumors are germ cell tumors. That is, the tumors originate in the sperm forming cells in the testicles ( ...

  9. Evidence against a germ plasm in the milkweed bug Oncopeltus fasciatus, a hemimetabolous insect

    Directory of Open Access Journals (Sweden)

    Ben Ewen-Campen

    2013-04-01

    Primordial germ cell (PGC formation in holometabolous insects like Drosophila melanogaster relies on maternally synthesised germ cell determinants that are asymmetrically localised to the oocyte posterior cortex. Embryonic nuclei that inherit this “germ plasm” acquire PGC fate. In contrast, historical studies of basally branching insects (Hemimetabola suggest that a maternal requirement for germ line genes in PGC specification may be a derived character confined principally to Holometabola. However, there have been remarkably few investigations of germ line gene expression and function in hemimetabolous insects. Here we characterise PGC formation in the milkweed bug Oncopeltus fasciatus, a member of the sister group to Holometabola, thus providing an important evolutionary comparison to members of this clade. We examine the transcript distribution of orthologues of 19 Drosophila germ cell and/or germ plasm marker genes, and show that none of them localise asymmetrically within Oncopeltus oocytes or early embryos. Using multiple molecular and cytological criteria, we provide evidence that PGCs form after cellularisation at the site of gastrulation. Functional studies of vasa and tudor reveal that these genes are not required for germ cell formation, but that vasa is required in adult males for spermatogenesis. Taken together, our results provide evidence that Oncopeltus germ cells may form in the absence of germ plasm, consistent with the hypothesis that germ plasm is a derived strategy of germ cell specification in insects.

  10. Evidence against a germ plasm in the milkweed bug Oncopeltus fasciatus, a hemimetabolous insect.

    Science.gov (United States)

    Ewen-Campen, Ben; Jones, Tamsin E M; Extavour, Cassandra G

    2013-06-15

    Primordial germ cell (PGC) formation in holometabolous insects like Drosophila melanogaster relies on maternally synthesised germ cell determinants that are asymmetrically localised to the oocyte posterior cortex. Embryonic nuclei that inherit this "germ plasm" acquire PGC fate. In contrast, historical studies of basally branching insects (Hemimetabola) suggest that a maternal requirement for germ line genes in PGC specification may be a derived character confined principally to Holometabola. However, there have been remarkably few investigations of germ line gene expression and function in hemimetabolous insects. Here we characterise PGC formation in the milkweed bug Oncopeltus fasciatus, a member of the sister group to Holometabola, thus providing an important evolutionary comparison to members of this clade. We examine the transcript distribution of orthologues of 19 Drosophila germ cell and/or germ plasm marker genes, and show that none of them localise asymmetrically within Oncopeltus oocytes or early embryos. Using multiple molecular and cytological criteria, we provide evidence that PGCs form after cellularisation at the site of gastrulation. Functional studies of vasa and tudor reveal that these genes are not required for germ cell formation, but that vasa is required in adult males for spermatogenesis. Taken together, our results provide evidence that Oncopeltus germ cells may form in the absence of germ plasm, consistent with the hypothesis that germ plasm is a derived strategy of germ cell specification in insects.

  11. AiGERM: A logic programming front end for GERM

    Science.gov (United States)

    Hashim, Safaa H.

    1990-01-01

    AiGerm (Artificially Intelligent Graphical Entity Relation Modeler) is a relational data base query and programming language front end for MCC (Mission Control Center)/STP's (Space Test Program) Germ (Graphical Entity Relational Modeling) system. It is intended as an add-on component of the Germ system to be used for navigating very large networks of information. It can also function as an expert system shell for prototyping knowledge-based systems. AiGerm provides an interface between the programming language and Germ.

  12. Molecular biological features of male germ cell differentiation

    Science.gov (United States)

    HIROSE, MIKA; TOKUHIRO, KEIZO; TAINAKA, HITOSHI; MIYAGAWA, YASUSHI; TSUJIMURA, AKIRA; OKUYAMA, AKIHIKO; NISHIMUNE, YOSHITAKE

    2007-01-01

    Somatic cell differentiation is required throughout the life of a multicellular organism to maintain homeostasis. In contrast, germ cells have only one specific function; to preserve the species by conveying the parental genes to the next generation. Recent studies of the development and molecular biology of the male germ cell have identified many genes, or isoforms, that are specifically expressed in the male germ cell. In the present review, we consider the unique features of male germ cell differentiation. (Reprod Med Biol 2007; 6: 1–9) PMID:29699260

  13. Guns, Germs and Steel

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 6; Issue 1. Guns, Germs and Steel - A Short History of Everybody for the Last 13,000 years. Suri Venkatachalam. Book Review Volume 6 Issue 1 January 2001 pp 84-88. Fulltext. Click here to view fulltext PDF. Permanent link:

  14. Foodborne Germs and Illnesses

    Science.gov (United States)

    ... Español (Spanish) Recommend on Facebook Tweet Share Compartir What Causes Food Poisoning? Many different disease-causing germs can contaminate ... email address: Enter Email Address What’s this? Submit What's this? Submit Button ... of Foodborne Illness in the U.S. Food Safety is a CDC Winnable Battle Foodborne Illness ...

  15. Theoretical Atomic Physics code development IV: LINES, A code for computing atomic line spectra

    International Nuclear Information System (INIS)

    Abdallah, J. Jr.; Clark, R.E.H.

    1988-12-01

    A new computer program, LINES, has been developed for simulating atomic line emission and absorption spectra using the accurate fine structure energy levels and transition strengths calculated by the (CATS) Cowan Atomic Structure code. Population distributions for the ion stages are obtained in LINES by using the Local Thermodynamic Equilibrium (LTE) model. LINES is also useful for displaying the pertinent atomic data generated by CATS. This report describes the use of LINES. Both CATS and LINES are part of the Theoretical Atomic PhysicS (TAPS) code development effort at Los Alamos. 11 refs., 9 figs., 1 tab

  16. Antagonistic effects of gestational dietary exposure to low-dose vinclozolin and genistein on rat fetal germ cell development.

    Science.gov (United States)

    Lehraiki, Abdelali; Messiaen, Sébastien; Berges, Raymond; Canivenc-Lavier, Marie-Chantal; Auger, Jacques; Habert, René; Levacher, Christine

    2011-05-01

    Continuous, low-dose exposure to a phytoestrogen (1 mg/kg/day genistein) and/or to an antiandrogenic food contaminant (1 mg/kg/day vinclozolin) has been recently reported to affect male reproductive tract and fertility [1] in adults. We investigated whether alterations of the testis are already present at the end of in utero exposure using the same rat model and doses following exposure from conception to delivery. After vinclozolin exposure, we observed in the neonate a slight but significant alteration of steroidogenesis and gametogenesis with a reduction of testosterone secretion and of the number of gonocytes. In contrast, genistein exposure had no effect. While the vinclozolin-genistein mixture acts in a synergistic manner to induce the most significant alterations in the adult, interestingly, genistein antagonized the deleterious effect of vinclozolin on germ cells in the neonate. This difference emphasizes the importance of studying the effects of endocrine disruptors during various developmental stages to understand their effects. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Immunofluorescence Analysis of Testicular Biopsies With Germ Cell and Sertoli Cell Markers Shows Significant MVH Negative Germ Cell Depletion With Older Age of Orchidopexy

    DEFF Research Database (Denmark)

    Li, Ruili; Thorup, Jørgen Mogens; Sun, Cong

    2014-01-01

    Undescended testis is the most common defect in newborn boys. It is associated with increased risks of infertility and testicular malignancy due to abnormal germ cell development in these testes. Early surgery may limit such risks. The aim of our study was to analyse germ cell development verses ...... age of orchidopexy using a germ cell marker and a Sertoli cell marker on testicular biopsies.......Undescended testis is the most common defect in newborn boys. It is associated with increased risks of infertility and testicular malignancy due to abnormal germ cell development in these testes. Early surgery may limit such risks. The aim of our study was to analyse germ cell development verses...

  18. Development of a Handheld Line Information Reader and Generator for Efficient Management of Optical Communication Lines.

    Science.gov (United States)

    Lee, Jaeyul; Kwon, Hyungwoo; Song, Jaewon; Jeon, Mansik; Kim, Jeehyun

    2017-08-24

    A handheld line information reader and a line information generator were developed for the efficient management of optical communication lines. The line information reader consists of a photo diode, trans-impedance amplifier, voltage amplifier, microcontroller unit, display panel, and communication modules. The line information generator consists of a laser diode, laser driving circuits, microcontroller unit, and communication modules. The line information reader can detect the optical radiation field of the test line by bending the optical fiber. To enhance the sensitivity of the line information reader, an additional lens was used with a focal length of 4.51 mm. Moreover, the simulation results obtained through BeamPROP ® software from Synopsys, Inc. demonstrated a stronger optical radiation field of the fiber due to a longer transmission wavelength and larger bending angle of the fiber. Therefore, the developed devices can be considered as useful tools for the efficient management of optical communication lines.

  19. Establishment of the Vertebrate Germ Layers.

    Science.gov (United States)

    Tseng, Wei-Chia; Munisha, Mumingjiang; Gutierrez, Juan B; Dougan, Scott T

    2017-01-01

    The process of germ layer formation is a universal feature of animal development. The germ layers separate the cells that produce the internal organs and tissues from those that produce the nervous system and outer tissues. Their discovery in the early nineteenth century transformed embryology from a purely descriptive field into a rigorous scientific discipline, in which hypotheses could be tested by observation and experimentation. By systematically addressing the questions of how the germ layers are formed and how they generate overall body plan, scientists have made fundamental contributions to the fields of evolution, cell signaling, morphogenesis, and stem cell biology. At each step, this work was advanced by the development of innovative methods of observing cell behavior in vivo and in culture. Here, we take an historical approach to describe our current understanding of vertebrate germ layer formation as it relates to the long-standing questions of developmental biology. By comparing how germ layers form in distantly related vertebrate species, we find that highly conserved molecular pathways can be adapted to perform the same function in dramatically different embryonic environments.

  20. Identifying a novel role for X-prolyl aminopeptidase (Xpnpep) 2 in CrVI-induced adverse effects on germ cell nest breakdown and follicle development in rats.

    Science.gov (United States)

    Banu, Sakhila K; Stanley, Jone A; Sivakumar, Kirthiram K; Arosh, Joe A; Barhoumi, Rola; Burghardt, Robert C

    2015-03-01

    Environmental exposure to endocrine-disrupting chemicals (EDCs) is one cause of premature ovarian failure (POF). Hexavalent chromium (CrVI) is a heavy metal EDC widely used in more than 50 industries, including chrome plating, welding, wood processing, and tanneries. Recent data from U.S. Environmental Protection Agency indicate increased levels of Cr in drinking water from several American cities, which potentially predispose residents to various health problems. Recently, we demonstrated that gestational exposure to CrVI caused POF in F1 offspring. The current study was performed to identify the molecular mechanism behind CrVI-induced POF. Pregnant rats were treated with 25 ppm of potassium dichromate from Gestational Day (GD) 9.5 to GD 14.5 through drinking water, and the fetuses were exposed to CrVI through transplacental transfer. Ovaries were removed from the fetuses or pups on Embryonic Day (ED) 15.5, ED 17.5, Postnatal Day (PND) 1, PND 4, or PND 25, and various analyses were performed. Results showed that gestational exposure to CrVI: 1) increased germ cell/oocyte apoptosis and advanced germ cell nest (GCN) breakdown; 2) increased X-prolyl aminopeptidase (Xpnpep) 2, a POF marker in humans, during GCN breakdown; 3) decreased Xpnpep2 during postnatal follicle development; and 4) increased colocalization of Xpnpep2 with Col3 and Col4. We also found that Xpnpep2 inversely regulated the expression of Col1, Col3, and Col4 in all the developmental stages studied. Thus, CrVI advanced GCN breakdown and increased follicle atresia in F1 female progeny by targeting Xpnpep2. © 2015 by the Society for the Study of Reproduction, Inc.

  1. In vivo functional requirement of the mouse Ifitm1 gene for germ cell development, interferon mediated immune response and somitogenesis.

    Directory of Open Access Journals (Sweden)

    Ingeborg Klymiuk

    Full Text Available The mammalian Interferon induced transmembrane protein 1 (Ifitm1 gene was originally identified as a member of a gene family highly inducible by type I and type II interferons. Based on expression analyses, it was suggested to be required for normal primordial germ cell migration. The knockdown of Ifitm1 in mouse embryos provided evidence for a role in somitogenesis. We generated the first targeted knockin allele of the Ifitm1 gene to systematically reassess all inferred functions. Sperm motility and the fertility of male and female mutant mice are as in wild type littermates. Embryonic somites and the adult vertebral column appear normal in homozygous Ifitm1 knockout mice, demonstrating that Ifitm1 is not essential for normal segmentation of the paraxial mesoderm. Proportions of leucocyte subsets, including granulocytes, monocytes, B-cells, T-cells, NK-cells, and NKT-cells, are unchanged in mutant mice. Based on a normal immune response to Listeria monocytogenes infection, there is no evidence for a dysfunction in downstream IFNγ signaling in Ifitm1 mutant mice. Expression from the Ifitm1 locus from E8.5 to E14.5 is highly dynamic. In contrast, in adult mice, Ifitm1 expression is highly restricted and strong in the bronchial epithelium. Intriguingly, IFITM1 is highly overexpressed in tumor epithelia cells of human squamous cell carcinomas and in adenocarcinomas of NSCLC patients. These analyses underline the general importance of targeted in vivo studies for the functional annotation of the mammalian genome. The first comprehensive description of the Ifitm1 expression pattern provides a rational basis for the further examination of Ifitm1 gene functions. Based on our data, the fact that IFITM1 can function as a negative regulator of cell proliferation, and because the gene maps to chromosome band 11p15.5, previously associated with NSCLC, it is likely that IFITM1 in man has a key role in tumor formation.

  2. Carcinoma in situ testis displays permissive chromatin modifications similar to immature foetal germ cells

    DEFF Research Database (Denmark)

    Almstrup, K; Nielsen, J E; Mlynarska, O

    2010-01-01

    The majority of testicular germ cell cancers develop through a pre-invasive carcinoma in situ (CIS) stage. The CIS cell is a neoplastic counterpart of foetal germ cells. During their development, foetal germ cells undergo extensive and essential epigenetic modifications, but little is known about...

  3. The genome of the Hi5 germ cell line from Trichoplusia ni, an agricultural pest and novel model for small RNA biology.

    Science.gov (United States)

    Fu, Yu; Yang, Yujing; Zhang, Han; Farley, Gwen; Wang, Junling; Quarles, Kaycee A; Weng, Zhiping; Zamore, Phillip D

    2018-01-29

    We report a draft assembly of the genome of Hi5 cells from the lepidopteran insect pest, Trichoplusia ni , assigning 90.6% of bases to one of 28 chromosomes and predicting 14,037 protein-coding genes. Chemoreception and detoxification gene families reveal T. ni -specific gene expansions that may explain its widespread distribution and rapid adaptation to insecticides. Transcriptome and small RNA data from thorax, ovary, testis, and the germline-derived Hi5 cell line show distinct expression profiles for 295 microRNA- and >393 piRNA-producing loci, as well as 39 genes encoding small RNA pathway proteins. Nearly all of the W chromosome is devoted to piRNA production, and T. ni siRNAs are not 2´- O -methylated. To enable use of Hi5 cells as a model system, we have established genome editing and single-cell cloning protocols. The T. ni genome provides insights into pest control and allows Hi5 cells to become a new tool for studying small RNAs ex vivo. © 2018, Fu et al.

  4. Childhood Central Nervous System Germ Cell Tumors Treatment (PDQ®)—Patient Version

    Science.gov (United States)

    Childhood central nervous system (CNS) germ cell tumors form from germ cells (a type of cell that forms as a fetus develops and later becomes sperm in the testicles or eggs in the ovaries). Learn about the signs, tests to diagnose, and treatment of pediatric germ cell tumors in the brain in this expert-reviewed summary.

  5. A novel puf-A gene predicted from evolutionary analysis is involved in the development of eyes and primordial germ-cells.

    Directory of Open Access Journals (Sweden)

    Ming-Wei Kuo

    Full Text Available Although the human genome project has been completed for some time, the issue of the number of transcribed genes with identifiable biological functions remains unresolved. We used zebrafish as a model organism to study the functions of Ka/Ks-predicted novel human exons, which were identified from a comparative evolutionary genomics analysis.In this study, a novel gene, designated as puf-A, was cloned and functionally characterized, and its homologs in zebrafish, mouse, and human were identified as one of the three homolog clusters which were consisted of 14 related proteins with Puf repeats. Computer modeling of human Puf-A structure and a pull-down assay for interactions with RNA targets predicted that it was a RNA-binding protein. Specifically, Puf-A contained a special six Puf-repeat domain, which constituted a unique superhelix half doughnut-shaped Puf domain with a topology similar to, but different from the conventional eight-repeat Pumilio domain. Puf-A transcripts were uniformly distributed in early embryos, but became restricted primarily to eyes and ovaries at a later stage of development. In mice, puf-A expression was detected primarily in retinal ganglion and pigmented cells. Knockdown of puf-A in zebrafish embryos resulted in microphthalmia, a small head, and abnormal primordial germ-cell (PGC migration. The latter was confirmed by microinjecting into embryos puf-A siRNA containing nanos 3' UTR that expressed in PGC only. The importance of Puf-A in the maturation of germline stem cells was also implicated by its unique expression in the most primitive follicles (stage I in adult ovaries, followed by a sharp decline of expression in later stages of folliculogenesis. Taken together, our study shows that puf-A plays an important role not only in eye development, but also in PGC migration and the specification of germ cell lineage. These studies represent an exemplary implementation of a unique platform to uncover unknown function(s of

  6. On-Line Maintenance Methodology Development

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyo Won; Kim, Jae Ho; Jae, Moo Sung [Hanyang University, Seoul (Korea, Republic of)

    2012-05-15

    Most of domestic maintenance activities for nuclear power plants are performed while overhaul. Therefore, On-Line Maintenance (OLM) is one of the proper risks informed application techniques for diffusing maintenance burden during overhaul with safety of the plant is secured. The NUMARC 93-01 (Rev.3) presents the OLM state of the art and it provides methodology. This study adopts NUMARC 93-01 (Rev.3) and present OLM. The reference component is Emergency Diesel Generator (EDG) of Ulchin 3, 4

  7. Linearization of germs of hyperbolic vector fields

    NARCIS (Netherlands)

    Bonckaert, P; Naudot, [No Value; Yang, JZ

    2003-01-01

    We develop a normal form to express asymptotically a conjugacy between a germ of resonant vector field and its linear part. We show that such an asymptotic expression can be written in terms of functions of the Logarithmic Mourtada type. To cite this article: P Bonckaert et al., C. R. Acad. Sci.

  8. The proteasome inhibitor bortezomib induces testicular toxicity by upregulation of oxidative stress, AMP-activated protein kinase (AMPK) activation and deregulation of germ cell development in adult murine testis

    International Nuclear Information System (INIS)

    Li, Wei; Fu, Jianfang; Zhang, Shun; Zhao, Jie; Xie, Nianlin; Cai, Guoqing

    2015-01-01

    Understanding how chemotherapeutic agents mediate testicular toxicity is crucial in light of compelling evidence that male infertility, one of the severe late side effects of intensive cancer treatment, occurs more often than they are expected to. Previous study demonstrated that bortezomib (BTZ), a 26S proteasome inhibitor used to treat refractory multiple myeloma (MM), exerts deleterious impacts on spermatogenesis in pubertal mice via unknown mechanisms. Here, we showed that intermittent treatment with BTZ resulted in fertility impairment in adult mice, evidenced by testicular atrophy, desquamation of immature germ cells and reduced caudal sperm storage. These deleterious effects may originate from the elevated apoptosis in distinct germ cells during the acute phase and the subsequent disruption of Sertoli–germ cell anchoring junctions (AJs) during the late recovery. Mechanistically, balance between AMP-activated protein kinase (AMPK) activation and Akt/ERK pathway appeared to be indispensable for AJ integrity during the late testicular recovery. Of particular interest, the upregulated testicular apoptosis and the following disturbance of Sertoli–germ cell interaction may both stem from the excessive oxidative stress elicited by BTZ exposure. We also provided the in vitro evidence that AMPK-dependent mechanisms counteract follicle-stimulating hormone (FSH) proliferative effects in BTZ-exposed Sertoli cells. Collectively, BTZ appeared to efficiently prevent germ cells from normal development via multiple mechanisms in adult mice. Employment of antioxidants and/or AMPK inhibitor may represent an attractive strategy of fertility preservation in male MM patients exposed to conventional BTZ therapy and warrants further investigation. - Highlights: • Intermittent treatment with BTZ caused fertility impairment in adult mice. • BTZ treatment elicited apoptosis during early phase of testicular recovery. • Up-regulation of oxidative stress by BTZ treatment

  9. The proteasome inhibitor bortezomib induces testicular toxicity by upregulation of oxidative stress, AMP-activated protein kinase (AMPK) activation and deregulation of germ cell development in adult murine testis

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wei [Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi' an 710032 (China); Fu, Jianfang [Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Zhang, Shun [Reproductive Medicine Center, Department of Gynecology and Obstetrics, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Zhao, Jie [Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi' an 710032 (China); Xie, Nianlin, E-mail: xienianlin@126.com [Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Cai, Guoqing, E-mail: firstchair@fmmu.edu.cn [Department of Gynaecology and Obstetrics, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China)

    2015-06-01

    Understanding how chemotherapeutic agents mediate testicular toxicity is crucial in light of compelling evidence that male infertility, one of the severe late side effects of intensive cancer treatment, occurs more often than they are expected to. Previous study demonstrated that bortezomib (BTZ), a 26S proteasome inhibitor used to treat refractory multiple myeloma (MM), exerts deleterious impacts on spermatogenesis in pubertal mice via unknown mechanisms. Here, we showed that intermittent treatment with BTZ resulted in fertility impairment in adult mice, evidenced by testicular atrophy, desquamation of immature germ cells and reduced caudal sperm storage. These deleterious effects may originate from the elevated apoptosis in distinct germ cells during the acute phase and the subsequent disruption of Sertoli–germ cell anchoring junctions (AJs) during the late recovery. Mechanistically, balance between AMP-activated protein kinase (AMPK) activation and Akt/ERK pathway appeared to be indispensable for AJ integrity during the late testicular recovery. Of particular interest, the upregulated testicular apoptosis and the following disturbance of Sertoli–germ cell interaction may both stem from the excessive oxidative stress elicited by BTZ exposure. We also provided the in vitro evidence that AMPK-dependent mechanisms counteract follicle-stimulating hormone (FSH) proliferative effects in BTZ-exposed Sertoli cells. Collectively, BTZ appeared to efficiently prevent germ cells from normal development via multiple mechanisms in adult mice. Employment of antioxidants and/or AMPK inhibitor may represent an attractive strategy of fertility preservation in male MM patients exposed to conventional BTZ therapy and warrants further investigation. - Highlights: • Intermittent treatment with BTZ caused fertility impairment in adult mice. • BTZ treatment elicited apoptosis during early phase of testicular recovery. • Up-regulation of oxidative stress by BTZ treatment

  10. Ovarian Sertoli-Leydig Cell Tumor with Elevated Inhibin B as a Cause of Secondary Amenorrhea in an Adolescent with Germ Line DICER1 Mutation.

    Science.gov (United States)

    Luke, Amy M; Moroney, John W; Snitchler, Andrea; Whiteway, Susan L

    2017-10-01

    Ovarian tumors, although uncommon in children, can retain endocrine function that disrupts normal feedback mechanisms leading to amenorrhea. Inheritance of germline DICER1 mutations can lead to increased risk for development of ovarian Sertoli-Leydig cell tumors (SLCTs). We report, to our knowledge, the first case of secondary amenorrhea due to elevated inhibin B levels in a female adolescent with an ovarian SLCT. Ovarian tumors should be included in the differential diagnosis for pediatric patients who present with menstrual irregularities. Early evaluation of the hypothalamic-pituitary-ovarian axis and inhibin levels is appropriate. Our case also emphasizes the need for testing for DICER1 mutations in pediatric patients with ovarian SLCTs. Published by Elsevier Inc.

  11. Overview of the Graphical User Interface for the GERM Code (GCR Event-Based Risk Model

    Science.gov (United States)

    Kim, Myung-Hee; Cucinotta, Francis A.

    2010-01-01

    The descriptions of biophysical events from heavy ions are of interest in radiobiology, cancer therapy, and space exploration. The biophysical description of the passage of heavy ions in tissue and shielding materials is best described by a stochastic approach that includes both ion track structure and nuclear interactions. A new computer model called the GCR Event-based Risk Model (GERM) code was developed for the description of biophysical events from heavy ion beams at the NASA Space Radiation Laboratory (NSRL). The GERM code calculates basic physical and biophysical quantities of high-energy protons and heavy ions that have been studied at NSRL for the purpose of simulating space radiobiological effects. For mono-energetic beams, the code evaluates the linear-energy transfer (LET), range (R), and absorption in tissue equivalent material for a given Charge (Z), Mass Number (A) and kinetic energy (E) of an ion. In addition, a set of biophysical properties are evaluated such as the Poisson distribution of ion or delta-ray hits for a specified cellular area, cell survival curves, and mutation and tumor probabilities. The GERM code also calculates the radiation transport of the beam line for either a fixed number of user-specified depths or at multiple positions along the Bragg curve of the particle. The contributions from primary ion and nuclear secondaries are evaluated. The GERM code accounts for the major nuclear interaction processes of importance for describing heavy ion beams, including nuclear fragmentation, elastic scattering, and knockout-cascade processes by using the quantum multiple scattering fragmentation (QMSFRG) model. The QMSFRG model has been shown to be in excellent agreement with available experimental data for nuclear fragmentation cross sections, and has been used by the GERM code for application to thick target experiments. The GERM code provides scientists participating in NSRL experiments with the data needed for the interpretation of their

  12. Germ-line variants identified by next generation sequencing in a panel of estrogen and cancer associated genes correlate with poor clinical outcome in Lynch syndrome patients.

    Science.gov (United States)

    Jóri, Balazs; Kamps, Rick; Xanthoulea, Sofia; Delvoux, Bert; Blok, Marinus J; Van de Vijver, Koen K; de Koning, Bart; Oei, Felicia Trups; Tops, Carli M; Speel, Ernst Jm; Kruitwagen, Roy F; Gomez-Garcia, Encarna B; Romano, Andrea

    2015-12-01

    The risk to develop colorectal and endometrial cancers among subjects testing positive for a pathogenic Lynch syndrome mutation varies, making the risk prediction difficult. Genetic risk modifiers alter the risk conferred by inherited Lynch syndrome mutations, and their identification can improve genetic counseling. We aimed at identifying rare genetic modifiers of the risk of Lynch syndrome endometrial cancer. A family based approach was used to assess the presence of genetic risk modifiers among 35 Lynch syndrome mutation carriers having either a poor clinical phenotype (early age of endometrial cancer diagnosis or multiple cancers) or a neutral clinical phenotype. Putative genetic risk modifiers were identified by Next Generation Sequencing among a panel of 154 genes involved in endometrial physiology and carcinogenesis. A simple pipeline, based on an allele frequency lower than 0.001 and on predicted non-conservative amino-acid substitutions returned 54 variants that were considered putative risk modifiers. The presence of two or more risk modifying variants in women carrying a pathogenic Lynch syndrome mutation was associated with a poor clinical phenotype. A gene-panel is proposed that comprehends genes that can carry variants with putative modifying effects on the risk of Lynch syndrome endometrial cancer. Validation in further studies is warranted before considering the possible use of this tool in genetic counseling.

  13. Characterization of a rabbit germ-line VH gene that is a candidate donor for VH gene conversion in mutant Alicia rabbits.

    Science.gov (United States)

    Chen, H T; Alexander, C B; Mage, R G

    1995-06-15

    Normal rabbits preferentially rearrange the 3'-most VH gene, VH1, to encode Igs with VHa allotypes, which constitute the majority of rabbit serum Igs. A gene conversion-like mechanism is employed to diversify the primary Ab repertoire. In mutant Alicia rabbits that derived from a rabbit with VHa2 allotype, the VH1 gene was deleted. Our previous studies showed that the first functional gene (VH4) or VH4-like genes were rearranged in 2- to 8-wk-old homozygous Alicia. The VH1a2-like sequences that were found in splenic mRNA from 6-wk and older Alicia rabbits still had some residues that were typical of VH4. The appearances of sequences resembling that of VH1a2 may have been caused by gene conversions that altered the sequences of the rearranged VH or there may have been rearrangement of upstream VH1a2-like genes later in development. To investigate this further, we constructed a cosmid library and isolated a VH1a2-like gene, VH12-1-6, with a sequence almost identical to VH1a2. This gene had a deleted base in the heptamer of its recombination signal sequence. However, even if this defect diminished or eliminated its ability to rearrange, the a2-like gene could have acted as a donor for gene-conversion-like alteration of rearranged VH genes. Sequence comparisons suggested that this gene or a gene like it could have acted as a donor for gene conversion in mutant Alicia and in normal rabbits.

  14. Homozygous germ-line mutation of the PMS2 mismatch repair gene: a unique case report of constitutional mismatch repair deficiency (CMMRD).

    Science.gov (United States)

    Ramchander, N C; Ryan, N A J; Crosbie, E J; Evans, D G

    2017-04-05

    Constitutional mismatch repair deficiency syndrome results from bi-allelic inheritance of mutations affecting the key DNA mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. Individuals with bi-allelic mutations have a dysfunctional mismatch repair system from birth; as a result, constitutional mismatch repair deficiency syndrome is characterised by early onset malignancies. Fewer than 150 cases have been reported in the literature over the past 20 years. This is the first report of the founder PMS2 mutation - NM_000535.5:c.1500del (p.Val501TrpfsTer94) in exon 11 and its associated cancers in this family. The proband is 30 years old and is alive today. She is of Pakistani ethnic origin and a product of consanguinity. She initially presented aged 24 with painless bleeding per-rectum from colorectal polyps and was referred to clinical genetics. Clinical examination revealed two café-au-lait lesions, lichen planus, and a dermoid cyst. Her sister had been diagnosed in childhood with an aggressive brain tumour followed by colorectal cancer. During follow up, the proband developed 37 colorectal adenomatous polyps, synchronous ovarian and endometrial adenocarcinomas, and ultimately a metachronous gastric adenocarcinoma. DNA sequencing of peripheral lymphocytes revealed a bi-allelic inheritance of the PMS2 mutation NM_000535.5:c.1500del (p.Val501TrpfsTer94) in exon 11. Ovarian tumour tissue demonstrated low microsatellite instability. To date, she has had a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and a total gastrectomy. Aspirin and oestrogen-only hormone replacement therapy provide some chemoprophylaxis and manage postmenopausal symptoms, respectively. An 18-monthly colonoscopy surveillance programme has led to the excision of three high-grade dysplastic colorectal tubular adenomatous polyps. The proband's family pedigree displays multiple relatives with cancers including a likely case of 'true' Turcot syndrome. Constitutional mismatch repair

  15. Distribution of Cathepsin K in Late Stage of Tooth Germ Development and Its Function in Degrading Enamel Matrix Proteins in Mouse.

    Directory of Open Access Journals (Sweden)

    Tao Jiang

    Full Text Available Cathepsin K (CTSK is a member of cysteine proteinase family, and is predominantly expressed in osteoclastsfor degradationof bone matrix proteins. Given the similarity in physical properties of bone and dental mineralized tissues, including enamel, dentin and cementum, CTSK is likely to take part in mineralization process during odontogenesis. On the other hand, patients with pycnodysostosis caused by mutations of the CTSK gene displayedmultipledental abnormalities, such as hypoplasia of the enamel, obliterated pulp chambers, hypercementosis and periodontal disease. Thereforeitis necessary to study the metabolic role of CTSK in tooth matrix proteins. In this study, BALB/c mice at embryonic day 18 (E18, post-natal day 1 (P1, P5, P10 and P20 were used (5 mice at each time pointfor systematic analyses of CTSK expression in the late stage of tooth germ development. We found that CTSK was abundantly expressed in the ameloblasts during secretory and maturation stages (P5 and P10 by immunohistochemistry stainings.During dentinogenesis, the staining was also intense in the mineralization stage (P5 and P10,but not detectable in the early stage of dentin formation (P1 and after tooth eruption (P20.Furthermore, through zymography and digestion test in vitro, CTSK was proved to be capable of hydrolyzing Emdogain and also cleaving Amelogenininto multiple products. Our resultsshed lights on revealing new functions of CTSK and pathogenesis of pycnodysostosis in oral tissues.

  16. Great migration: epigenetic reprogramming and germ cell-oocyte metamorphosis determine individual ovarian reserve.

    Science.gov (United States)

    Celik, Onder; Aygun, Banu Kumbak; Celik, Nilufer; Aydin, Suleyman; Haberal, Esra Tustas; Sahin, Levent; Yavuz, Yasemin; Celik, Sudenaz

    2016-01-01

    Emigration is defined as a synchronized movement of germ cells between the yolk sack and genital ridges. The miraculous migration of germ cells resembles the remigration of salmon traveling from one habitat to other. This migration of germ cells is indispensible for the development of new generations. It is not, however, clear why germ cells differentiate during migration but not at the place of origin. In order to escape harmful somatic signals which might disturb the proper establishment of germ cells forced germ cell migration may be necessary. Another reason may be to benefit from the opportunities of new habitats. Therefore, emigration may have powerful effects on the population dynamics of the immigrant germ cells. While some of these cells do reach their target, some others die or reach to wrong targets. Only germ cell precursors with genetically, and structurally powerful can reach their target. Likewise, epigenetic reprogramming in both migratory and post-migratory germ cells is essential for the establishment of totipotency. During this journey some germ cells may sacrifice themselves for the goodness of the others. The number and quality of germ cells reaching the genital ridge may vary depending on the problems encountered during migration. If the aim in germ cell specification is to provide an optimal ovarian reserve for the continuity of the generation, then this cascade of events cannot be only accomplished at the same level for every one but also are manifested by several outcomes. This is significant evidence supporting the possibility of unique individual ovarian reserve.

  17. Critical Function of PRDM2 in the Neoplastic Growth of Testicular Germ Cell Tumors

    Directory of Open Access Journals (Sweden)

    Erika Di Zazzo

    2016-12-01

    Full Text Available Testicular germ cell tumors (TGCTs derive from primordial germ cells. Their maturation is blocked at different stages, reflecting histological tumor subtypes. A common genetic alteration in TGCT is a deletion of the chromosome 1 short arm, where the PRDM2 gene, belonging to the Positive Regulatory domain gene (PRDM family, is located. Expression of PRDM2 gene is shifted in different human tumors, where the expression of the two principal protein forms coded by PRDM2 gene, RIZ1 and RIZ2, is frequently unbalanced. Therefore, PRDM2 is actually considered a candidate tumor suppressor gene in different types of cancer. Although recent studies have demonstrated that PRDM gene family members have a pivotal role during the early stages of testicular development, no information are actually available on the involvement of these genes in TGCTs. In this article we show by qRT-PCR analysis that PRDM2 expression level is modulated by proliferation and differentiation agents such as estradiol, whose exposure during fetal life is probably an important risk factor for TGCTs development in adulthood. Furthermore in normal and cancer germ cell lines, PRDM2 binds estradiol receptor α (ERα and influences proliferation, survival and apoptosis, as previously reported using MCF-7 breast cancer cell line, suggesting a potential tumor-suppressor role in TGCT formation.

  18. Human-specific subcellular compartmentalization of P-element induced wimpy testis-like (PIWIL) granules during germ cell development and spermatogenesis.

    Science.gov (United States)

    Gomes Fernandes, Maria; He, Nannan; Wang, Fang; Van Iperen, Liesbeth; Eguizabal, Cristina; Matorras, Roberto; Roelen, Bernard A J; Chuva De Sousa Lopes, Susana M

    2018-02-01

    What is the dynamics of expression of P-element induced wimpy testis-like (PIWIL) proteins in the germline during human fetal development and spermatogenesis? PIWIL1, PIWIL2, PIWIL3 and PIWIL4 were expressed in a sex-specific fashion in human germ cells (GC) during development and adulthood. PIWILs showed a mutually exclusive pattern of subcellular localization. PIWILs were present in the intermitochondrial cement and a single large granule in meiotic GC and their expression was different from that observed in mice, highlighting species-differences. In mice, PIWIL proteins play prominent roles in male infertility. PIWIL mouse mutants show either post-meiotic arrest at the round spermatid stage (PIWIL1) or arrest at the zygotene-pachytene stage of meiosis I (PIWIL2 and PIWIL4) in males, while females remain fertile. Recent studies have reported a robust piRNA pool in human fetal ovary. This is a qualitative analysis of PIWILs expression in paraffin-embedded fetal human male (N = 8), female gonads (N = 6) and adult testes (N = 5), and bioinformatics analysis of online available single-cell transcriptomics data of human fetal germ cells (n = 242). Human fetal gonads from elective abortion without medical indication and adult testes biopsies were donated for research with informed consent. Samples were fixed, paraffin-embedded and analyzed by immunofluorescence to study the temporal and cellular localization of PIWIL1, PIWIL2, PIWIL3 and PIWIL4. PIWIL1, PIWIL2 and PIWIL4 showed a mutually exclusive pattern of subcellular localization, particularly in female oocytes. To our surprise, PIWIL1 immunostaining revealed the presence of a single dense paranuclear body, resembling the chromatoid body of haploid spermatocytes, in meiotic oocytes. Moreover, in contrast to mice, PIWIL4, but not PIWIL2, localized to the intermitochondrial cement. PIWIL3 was not expressed in GC during development. The upregulation of PIWIL transcripts correlated with the transcription of markers

  19. Development of Flexible Software Process Lines with Variability Operations

    DEFF Research Database (Denmark)

    Dohrmann, Patrick; Schramm, Joachim; Kuhrmann, Marco

    2016-01-01

    the development of flexible software process lines. Method: We conducted a longitudinal study in which we studied 5 variants of the V-Modell XT process line for 2 years. Results: Our results show the variability operation instrument feasible in practice. We analyzed 616 operation exemplars addressing various...

  20. From miasmas to germs: discovery of the etiologic mentality and its genesis and development in Antioquia, Colombia De los miasmas al german: el descubrimiento de la mentalidad etiológica: génesis y desarrollo en Antioquia

    Directory of Open Access Journals (Sweden)

    Carlos Enrique Escobar Gónima

    1996-01-01

    Full Text Available

    Medical mentality is the way of seing and understanding disease at a given historical period. Louis Pasteur was the father of the so called etiologic mentalíty that proposes ";germs as causes for diseases";; his contemporaries, Lister and Koch, worked on the same line, proposed new theories and carried them to practical implications. This paper explains the development of etiologic mentality and how medicine in Antioquia, Colombia, at the end of the XIX century and the beginning of the present one received and assimilated its influence and became one of its protagonists.

    La medicina, como actividad humana, está sujeta al pensar y actuar de cada época. Actualmente, la sociedad naufraga en el ";consumismo"; y la medicina corre el riesgo de caer en el mismo error. La mentalidad médica es una forma de ver y entender la enfermedad en un momento histórico definido. Louis Pasteur fue el padre de la mentalidad etiológica que propone ";el germen como causa de las enfermedades";. Sus coetáneos, como Lister y Koch, trabajaron en el mismo sentido y llevaron a la práctica nuevas teorías. Este artículo explica el desarrollo de dicha mentalidad y cómo la medicina antioqueña de finales del siglo XIX y comienzos del XX recibió y asimiló su influencia y llegó a ser su protagonista.

  1. Molecular biology of testicular germ cell tumors.

    Science.gov (United States)

    Gonzalez-Exposito, R; Merino, M; Aguayo, C

    2016-06-01

    Testicular germ cell tumors (TGCTs) are the most common solid tumors in young adult men. They constitute a unique pathology because of their embryonic and germ origin and their special behavior. Genetic predisposition, environmental factors involved in their development and genetic aberrations have been under study in many works throughout the last years trying to explain the susceptibility and the transformation mechanism of TGCTs. Despite the high rate of cure in this type of tumors because its particular sensitivity to cisplatin, there are tumors resistant to chemotherapy for which it is needed to find new therapies. In the present work, it has been carried out a literature review on the most important molecular aspects involved in the onset and development of such tumors, as well as a review of the major developments regarding prognostic factors, new prognostic biomarkers and the possibility of new targeted therapies.

  2. Esrp1 is a marker of mouse fetal germ cells and differentially expressed during spermatogenesis.

    Directory of Open Access Journals (Sweden)

    Shaghayegh Saeidi

    Full Text Available ESRP1 regulates alternative splicing, producing multiple transcripts from its target genes in epithelial tissues. It is upregulated during mesenchymal to epithelial transition associated with reprogramming of fibroblasts to iPS cells and has been linked to pluripotency. Mouse fetal germ cells are the founders of the adult gonadal lineages and we found that Esrp1 mRNA was expressed in both male and female germ cells but not in gonadal somatic cells at various stages of gonadal development (E12.5-E15.5. In the postnatal testis, Esrp1 mRNA was highly expressed in isolated cell preparations enriched for spermatogonia but expressed at lower levels in those enriched for pachytene spermatocytes and round spermatids. Co-labelling experiments with PLZF and c-KIT showed that ESRP1 was localized to nuclei of both Type A and B spermatogonia in a speckled pattern, but was not detected in SOX9+ somatic Sertoli cells. No co-localization with the nuclear speckle marker, SC35, which has been associated with post-transcriptional splicing, was observed, suggesting that ESRP1 may be associated with co-transcriptional splicing or have other functions. RNA interference mediated knockdown of Esrp1 expression in the seminoma-derived Tcam-2 cell line demonstrated that ESRP1 regulates alternative splicing of mRNAs in a non-epithelial cell germ cell tumour cell line.

  3. On-line methanol sensor system development for recombinant ...

    African Journals Online (AJOL)

    On-line methanol sensor system development for recombinant human serum ... of the methanol sensor system was done in a medium environment with yeast cells ... induction at a low temperature and a pH where protease does not function.

  4. Gene manipulation: churches against germ changes.

    Science.gov (United States)

    Budiansky, S

    An immediate ban on human genetic engineering that alters germ cells is called for in a resolution, written by activist Jeremy Rifkin, that was released last week over the signatures of 21 Catholic bishops, a broad spectrum of Protestant and Jewish religious leaders, and three scientists. The resolution takes a much harder line than was espoused by religious leaders in a letter to the now-defunct President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. Several of the signers indicated that they did not fully agree with the resolution, but saw it as a good vehicle to encourage public discussion.

  5. Germ Cells are Made Semiotically Competent During Evolution

    DEFF Research Database (Denmark)

    Giorgi, Franco; Bruni, Luis Emilio

    2016-01-01

    Germ cells are cross-roads of development and evolution. They define the origin of every new generation and, at the same time, represent the biological end-product of any mature organism. Germ cells are endowed with the following capacities: (1) to store a self-descriptive program, (2......) to accumulate a protein-synthesizing machinery (ribosomes), and (3) to incorporate enough nourishment to sustain embryonic development (yolk). To accomplish this goal, germ cells do not simply unfold a pre-determined program or realize a sole instructive role. On the contrary, due to the complexity...... milieu and experience the compatibility of selected developmental sequences. The question of which signaling pathways are activated at each developmental stage does not result from a strictly predetermined program instructing germ cell stemness. Rather, each developmental sequence is an open...

  6. Human DAZL, DAZ and BOULE genes modulate primordial germ cell and haploid gamete formation

    Science.gov (United States)

    Kee, Kehkooi; Angeles, Vanessa T; Flores, Martha; Nguyen, Ha Nam; Pera, Renee A Reijo

    2009-01-01

    The leading cause of infertility in men and women is quantitative and qualitative defects in human germ cell (oocyte and sperm) development. Yet, it has not been possible to examine the unique developmental genetics of human germ cell formation and differentiation due to inaccessibility of germ cells during fetal development. Although several studies have shown that germ cells can be differentiated from mouse and human embryonic stem cells, human germ cells differentiated in these studies generally did not develop beyond the earliest stages1-8. Here we used a germ cell reporter to quantitate and isolate primordial germ cells derived from both male and female hESCs. Then, by silencing and overexpressing genes that encode germ cell-specific cytoplasmic RNA-binding proteins (not transcription factors), we modulated human germ cell formation and developmental progression. We observed that human DAZL (Deleted in AZoospermia-Like) functions in primordial germ cell formation, whereas closely-related genes, DAZ and BOULE, promote later stages of meiosis and development of haploid gametes. These results are significant to the generation of gametes for future basic science and potential clinical applications. PMID:19865085

  7. Role of Axumin PET Scan in Germ Cell Tumor

    Science.gov (United States)

    2018-05-01

    Testis Cancer; Germ Cell Tumor; Testicular Cancer; Germ Cell Tumor of Testis; Germ Cell Tumor, Testicular, Childhood; Testicular Neoplasms; Testicular Germ Cell Tumor; Testicular Yolk Sac Tumor; Testicular Choriocarcinoma; Testicular Diseases; Germ Cell Cancer Metastatic; Germ Cell Neoplasm of Retroperitoneum; Germ Cell Cancer, Nos

  8. The diversity of nanos expression in echinoderm embryos supports different mechanisms in germ cell specification.

    Science.gov (United States)

    Fresques, Tara; Swartz, Steven Zachary; Juliano, Celina; Morino, Yoshiaki; Kikuchi, Mani; Akasaka, Koji; Wada, Hiroshi; Yajima, Mamiko; Wessel, Gary M

    2016-07-01

    Specification of the germ cell lineage is required for sexual reproduction in all animals. However, the timing and mechanisms of germ cell specification is remarkably diverse in animal development. Echinoderms, such as sea urchins and sea stars, are excellent model systems to study the molecular and cellular mechanisms that contribute to germ cell specification. In several echinoderm embryos tested, the germ cell factor Vasa accumulates broadly during early development and is restricted after gastrulation to cells that contribute to the germ cell lineage. In the sea urchin, however, the germ cell factor Vasa is restricted to a specific lineage by the 32-cell stage. We therefore hypothesized that the germ cell specification program in the sea urchin/Euechinoid lineage has evolved to an earlier developmental time point. To test this hypothesis we determined the expression pattern of a second germ cell factor, Nanos, in four out of five extant echinoderm clades. Here we find that Nanos mRNA does not accumulate until the blastula stage or later during the development of all other echinoderm embryos except those that belong to the Echinoid lineage. Instead, Nanos is expressed in a restricted domain at the 32-128 cell stage in Echinoid embryos. Our results support the model that the germ cell specification program underwent a heterochronic shift in the Echinoid lineage. A comparison of Echinoid and non-Echinoid germ cell specification mechanisms will contribute to our understanding of how these mechanisms have changed during animal evolution. © 2016 Wiley Periodicals, Inc.

  9. Localization of trefoil factor family peptide 3 (TFF3) in epithelial tissues originating from the three germ layers of developing mouse embryo.

    Science.gov (United States)

    Bijelić, Nikola; Belovari, Tatjana; Tolušić Levak, Maja; Baus Lončar, Mirela

    2017-08-20

    Trefoil factor family (TFF) peptides are involved in the maintenance of epithelial integrity and epithelial restitution. Mature epithelial tissues originate from different embryonic germ layers. The objective of this research was to explore the presence and localization of TFF3 peptide in mouse embryonic epithelia and to examine if the occurrence of TFF3 peptide is germ layer-dependent. Mouse embryos (14-18 days old) were fixed in 4% paraformaldehyde and embedded in paraffin. Immunohistochemistry was performed with affinity purified rabbit anti-TFF3 antibody, goat anti-rabbit biotinylated secondary antibody and streptavidin-horseradish peroxidase, followed by 3,3'-diaminobenzidine. TFF3 peptide was present in the gastric and intestinal mucosa, respiratory mucosa in the upper and lower airways, pancreas, kidney tubules, epidermis, and oral cavity. The presence and localization of TFF3 peptide was associated with the embryonic stage and tissue differentiation. TFF3 peptide distribution specific to the germ layers was not observed. The role of TFF3 peptide in cell migration and differentiation, immune response, and apoptosis might be associated with specific embryonic epithelial cells. TFF3 peptide may also be considered as a marker for mucosal maturation.

  10. Localization of trefoil factor family peptide 3 (TFF3 in epithelial tissues originating from the three germ layers of developing mouse embryo

    Directory of Open Access Journals (Sweden)

    Nikola Bijelić

    2017-08-01

    Full Text Available Trefoil factor family (TFF peptides are involved in the maintenance of epithelial integrity and epithelial restitution. Mature epithelial tissues originate from different embryonic germ layers. The objective of this research was to explore the presence and localization of TFF3 peptide in mouse embryonic epithelia and to examine if the occurrence of TFF3 peptide is germ layer-dependent. Mouse embryos (14-18 days old were fixed in 4% paraformaldehyde and embedded in paraffin. Immunohistochemistry was performed with affinity purified rabbit anti-TFF3 antibody, goat anti-rabbit biotinylated secondary antibody and streptavidin-horseradish peroxidase, followed by 3,3'-diaminobenzidine. TFF3 peptide was present in the gastric and intestinal mucosa, respiratory mucosa in the upper and lower airways, pancreas, kidney tubules, epidermis, and oral cavity. The presence and localization of TFF3 peptide was associated with the embryonic stage and tissue differentiation. TFF3 peptide distribution specific to the germ layers was not observed. The role of TFF3 peptide in cell migration and differentiation, immune response, and apoptosis might be associated with specific embryonic epithelial cells. TFF3 peptide may also be considered as a marker for mucosal maturation.

  11. Development of Flexible Software Process Lines with Variability Operations

    DEFF Research Database (Denmark)

    Schramm, Joachim; Dohrmann, Patrick; Kuhrmann, Marco

    2015-01-01

    families of processes and, as part of this, variability operations provide means to modify and reuse pre-defined process assets. Objective: Our goal is to evaluate the feasibility of variability operations to support the development of flexible software process lines. Method: We conducted a longitudinal......Context: Software processes evolve over time and several approaches were proposed to support the required flexibility. Yet, little is known whether these approaches sufficiently support the development of large software processes. A software process line helps to systematically develop and manage...

  12. Repair and mutation induction in mouse germ cells: a summary and some thoughts

    International Nuclear Information System (INIS)

    Russell, L.B.

    1979-01-01

    The various lines of evidence for repair of premutational damage in mouse germ cells are reviewed with the implications for future experiment planning. Relation between mutagenicity and carcinogenicity are discussed

  13. Differentiation of primordial germ cells from induced pluripotent stem cells of primary ovarian insufficiency.

    Science.gov (United States)

    Leng, Lizhi; Tan, Yueqiu; Gong, Fei; Hu, Liang; Ouyang, Qi; Zhao, Yan; Lu, Guangxiu; Lin, Ge

    2015-03-01

    Can the induced pluripotent stem cells (iPSCs) derived from women with primary ovarian insufficiency (POI) differentiate into germ cells for potential disease modeling in vitro? The iPSC lines derived from POI patients with 46, X, del(X)(q26) or 46, X, del(X)(q26)9qh+ could differentiate into germ cells and expressed lower levels of genes in the deletion region of the X chromosome. iPSC technology has been envisioned as an approach for generating patient-specific stem cells for disease modeling and for developing novel therapies. It has also been confirmed that iPSCs differentiate into germ cells. We compared the differentiation ability of germ cells and the gene expression level of germ cell-related genes in the X chromosome deletion region of iPSC lines derived from POI patients (n = 2) with an iPSC line derived from normal fibroblasts (n = 1). We established three iPSC lines from two patients with partial Xq deletion-induced POI and normal fibroblasts by overexpressing four factors: octamer-binding transcription factor 4 (OCT4), sex-determining region Y-box 2 (SOX2), Nanog homeobox (NANOG), and lin-28 homolog (LIN28), using lentiviral vectors. We then generated stable-transfected fluorescent reporter cell lines under the control of the Asp-Glu-Ala-Asp box polypeptide 4 (DDX4, also called VASA) promoter, and selected clonal derived sublines. We induced subline differentiation into germ cells by adding Wnt3a (30 ng/ml) and bone morphogenetic protein 4 (100 ng/ml). After 12 days of differentiation, green fluorescent protein (GFP)-positive and GFP-negative cells were isolated via fluorescence-activated cell sorting and analyzed for endogenous VASA protein (immunostaining) and for germ cell markers and genes expressed in the deleted region of the X chromosome (quantitative RT-PCR). The POI- and normal fibroblast-derived iPSCs had typical self-renewal and pluripotency characteristics. After stable transfection with the VASA-GFP construct, the sublines POI1-iPS-V.1

  14. Towards Product Lining Model-Driven Development Code Generators

    OpenAIRE

    Roth, Alexander; Rumpe, Bernhard

    2015-01-01

    A code generator systematically transforms compact models to detailed code. Today, code generation is regarded as an integral part of model-driven development (MDD). Despite its relevance, the development of code generators is an inherently complex task and common methodologies and architectures are lacking. Additionally, reuse and extension of existing code generators only exist on individual parts. A systematic development and reuse based on a code generator product line is still in its inf...

  15. Development of automobile brake lining using pulverized cow hooves

    Directory of Open Access Journals (Sweden)

    Katsina C. BALA

    2016-06-01

    Full Text Available Asbestos has been used for so long as automobile brake lining material because of its good physical and chemical properties. However, due to the health hazard associated with its handling, it has lost favour and several alternative materials are being increasingly used. Asbestos-free brake lining was developed in this work using pulverized cow hooves along with epoxy resin, barium sulphate, graphite and aluminium oxide. This was with a view to exploiting the characteristics of cow hooves, which are largely discarded as waste materials to replace asbestos which has been found to be carcinogenic. Samples of brake linings were produced using compressive moulding in which the physical and mechanical properties of the samples were studied. The results obtained showed that proper bonding was achieved as the percentage by weight of epoxy resin increased and percentage by weight of pulverized cow hooves decreased. The hardness, compressive strength, coefficient of friction, water and oil absorption, relative density and wear rate of the brake linings were determined and compared with existing brake lining properties. The result indicates that pulverized cow hooves can be used as brake lining material for automobiles.

  16. Development of sealing plug for sweep gas line

    International Nuclear Information System (INIS)

    Kikuchi, Taiji; Yamada, Hirokazu; Saitoh, Takashi; Nakamichi, Masaru; Tsuchiya, Kunihiko; Kawamura, Hiroshi

    2004-03-01

    On the irradiation capsule for neutron irradiation test of the tritium breeder, the sealing plug is necessary to prevent a leak of tritium gas when the tritium breeder is picked up from the irradiation capsule after irradiation test. However, the general valve and plug cannot apply to sealing of the sweep gas line because of the following factors, the neutron irradiation effect, limited space in the irradiation capsule, high sealing efficiency, simple method and operation for control. Therefore, the sealing plug for sweep gas line has to be developed. This paper reports the development of the sealing plug for sweep gas line and the operating procedure of the sealing plug in the irradiation capsule. (author)

  17. Project development and commercialization of on-line analysis systems

    International Nuclear Information System (INIS)

    Watt, J.S.

    1997-01-01

    A project team first in the Australian Atomic Energy Commission (AAEC) and since 1982 in CSIRO has developed many on-line analysis systems for the mineral and energy industries. The development of these projects has followed a common pattern of laboratory R and D, field trials, commercialisation and technology transfer. This successful pattern is illustrated using examples of the development of systems for the on-line analysis of mineral slurries, for determination of the ash content of coal on conveyors, and for determination of the flow rates of oil, water and gas in pipelines. The first two systems are licensed to Australian companies, Amdel Ltd and Mineral Control Instrumentation Ltd. Both systems are used by industry worldwide, and are the market leaders for radioisotope gauges in their application field. The third system, the multiphase flow meter, was licensed in 1997 to Kvaerner FSSL Ltd of Aberdeen. This meter has even greater potential than the other two systems for economic benefit from its used and for numbers of installations. The on-line analysis systems have been developed to increase the productivity of the Australian mineral and energy industries, and to provide economic benefit to Australia. The economic benefit sought is predominantly improved process control based on use of the instrument, rather than from its sale. Sales of instruments are significant, however, with about A$80 million from the analysis systems and their derivatives since the 1970s. Some of the issues associated with the development of the on-line analysis system are outlined

  18. Development of putative transgenic lines of cassava variety H-226 ...

    African Journals Online (AJOL)

    CMD) caused by the Indian cassava mosaic virus (ICMV) and Sri Lankan cassava mosaic virus (SLCMV). An attempt was done to develop transgenic cassava lines resistant to SLCMV through RNAi vector targeting a conserved 440 bp of 5' end ...

  19. Developing Product Lines with 3rd-party components

    NARCIS (Netherlands)

    De Jonge, M.

    2007-01-01

    The trends toward product line development and toward adopting more 3rd-party software are hard to combine. The reason is that productlines demand fine control over the software (e.g., for diversity management), while 3rd-party software (almost by definition) provides only little or no control. A

  20. Novel strong tissue specific promoter for gene expression in human germ cells

    Directory of Open Access Journals (Sweden)

    Kuzmin Denis

    2010-08-01

    Full Text Available Abstract Background Tissue specific promoters may be utilized for a variety of applications, including programmed gene expression in cell types, tissues and organs of interest, for developing different cell culture models or for use in gene therapy. We report a novel, tissue-specific promoter that was identified and engineered from the native upstream regulatory region of the human gene NDUFV1 containing an endogenous retroviral sequence. Results Among seven established human cell lines and five primary cultures, this modified NDUFV1 upstream sequence (mNUS was active only in human undifferentiated germ-derived cells (lines Tera-1 and EP2102, where it demonstrated high promoter activity (~twice greater than that of the SV40 early promoter, and comparable to the routinely used cytomegaloviral promoter. To investigate the potential applicability of the mNUS promoter for biotechnological needs, a construct carrying a recombinant cytosine deaminase (RCD suicide gene under the control of mNUS was tested in cell lines of different tissue origin. High cytotoxic effect of RCD with a cell-death rate ~60% was observed only in germ-derived cells (Tera-1, whereas no effect was seen in a somatic, kidney-derived control cell line (HEK293. In further experiments, we tested mNUS-driven expression of a hyperactive Sleeping Beauty transposase (SB100X. The mNUS-SB100X construct mediated stable transgene insertions exclusively in germ-derived cells, thereby providing further evidence of tissue-specificity of the mNUS promoter. Conclusions We conclude that mNUS may be used as an efficient promoter for tissue-specific gene expression in human germ-derived cells in many applications. Our data also suggest that the 91 bp-long sequence located exactly upstream NDUFV1 transcriptional start site plays a crucial role in the activity of this gene promoter in vitro in the majority of tested cell types (10/12, and an important role - in the rest two cell lines.

  1. Development of Live-working Robot for Power Transmission Lines

    Science.gov (United States)

    Yan, Yu; Liu, Xiaqing; Ren, Chengxian; Li, Jinliang; Li, Hui

    2017-07-01

    Dream-I, the first reconfigurable live-working robot for power transmission lines successfully developed in China, has the functions of autonomous walking on lines and accurately positioning. This paper firstly described operation task and object of the robot; then designed a general platform, an insulator replacement end and a drainage plate bolt fastening end of the robot, presented a control system of the robot, and performed simulation analysis on operation plan of the robot; and finally completed electrical field withstand voltage tests in a high voltage hall as well as online test and trial on actual lines. Experimental results show that by replacing ends of manipulators, the robot can fulfill operation tasks of live replacement of suspension insulators and live drainage plate bolt fastening.

  2. The development of mathematics courseware for learning line and angle

    Science.gov (United States)

    Halim, Noor Dayana Abd; Han, Ong Boon; Abdullah, Zaleha; Yusup, Junaidah

    2015-05-01

    Learning software is a teaching aid which is often used in schools to increase students' motivation, attract students' attention and also improve the quality of teaching and learning process. However, the development of learning software should be followed the phases in Instructional Design (ID) Model, therefore the process can be carried out systematic and orderly. Thus, this concept paper describes the application of ADDIE model in the development of mathematics learning courseware for learning Line and Angle named CBL-Math. ADDIE model consists of five consecutive phases which are Analysis, Design, Development, Implementation and Evaluation. Each phase must be properly planned in order to achieve the objectives stated. Other than to describe the processes occurring in each phase, this paper also demonstrating how cognitive theory of multimedia learning principles are integrated in the developed courseware. The principles that applied in the courseware reduce the students' cognitive load while learning the topic of line and angle. With well prepared development process and the integration of appropriate principles, it is expected that the developed software can help students learn effectively and also increase students' achievement in the topic of Line and Angle.

  3. "Mixed germ cell testicular tumor" in an adult female

    Directory of Open Access Journals (Sweden)

    Udasimath Shivakumarswamy

    2012-01-01

    Full Text Available The androgen insensitivity (testicular feminization syndrome was described by Morris in phenotypic females with 46XY karyotype, presenting with primary amenorrhea, adequate breast development, and absent or scanty pubic or axillary hair. Gonads consist usually of seminiferous tubules without spermatogenesis. These patients have a 5-10% risk of developing germ cell tumors, usually after the complete development of secondary female sexual characteristics. We hereby report a case considered as a female with married life of 15 years, who was operated for severe abdominal pain. Phenotype characters were that of female. Microscopic examination of the tumor from the abdomen revealed germinoma and yolk sac tumor with adjacent seminiferous tubules. Karyotyping showed 46XY. Final diagnosis of malignant mixed germ cell tumor in androgen insensitivity syndrome was made. Surveillance may be the most appropriate option when these conditions are initially diagnosed in adulthood to prevent development of germ cell tumors.

  4. Risk and prognostic significance of metachronous contralateral testicular germ cell tumours

    NARCIS (Netherlands)

    Schaapveld, M.; van den Belt-Dusebout, A. W.; Gietema, J. A.; de Wit, R.; Horenblas, S.; Witjes, J. A.; Hoekstra, H. J.; Kiemeney, L. A. L. M.; Louwman, W. J.; Ouwens, G. M.; Aleman, B. M. P.; van Leeuwen, F. E.

    2012-01-01

    BACKGROUND: Testicular germ cell tumour (TGCT) patients are at increased risk of developing a contralateral testicular germ cell tumour (CTGCT). It is unclear whether TGCT treatment affects CTGCT risk. METHODS: The risk of developing a metachronous CTGCT (a CTGCT diagnosed >= 6 months after a

  5. Developmental arrest of germ cells in the pathogenesis of germ cell neoplasia

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, E; Jørgensen, N; Brøndum-Nielsen, K

    1998-01-01

    Clinical observations and epidemiological evidence suggest that important aetiopathological events that cause neoplastic transformation of the male germ cell may occur in fetal life or early infancy. The incidence of germ cell neoplasia is high in individuals with various disorders of gonadal...... development and sexual differentiation, such as gonadal dysgenesis or androgen insensitivity syndrome. Increased risk has also been noted in individuals with trisomy 21, idiopathic infertility and low birth weight. Infertility is sometimes associated with small aberrations of sex chromosomes (e.g. low...... frequency mosaicism XY/XO) which can also be found in patients with testicular cancer. The variety of conditions that predispose to testicular neoplasia and the rise in its incidence in many countries speaks for the influence of environmental factors which may affect genetically predisposed individuals. We...

  6. Germ cell regeneration-mediated, enhanced mutagenesis in the ascidian Ciona intestinalis reveals flexible germ cell formation from different somatic cells.

    Science.gov (United States)

    Yoshida, Keita; Hozumi, Akiko; Treen, Nicholas; Sakuma, Tetsushi; Yamamoto, Takashi; Shirae-Kurabayashi, Maki; Sasakura, Yasunori

    2017-03-15

    The ascidian Ciona intestinalis has a high regeneration capacity that enables the regeneration of artificially removed primordial germ cells (PGCs) from somatic cells. We utilized PGC regeneration to establish efficient methods of germ line mutagenesis with transcription activator-like effector nucleases (TALENs). When PGCs were artificially removed from animals in which a TALEN pair was expressed, somatic cells harboring mutations in the target gene were converted into germ cells, this germ cell population exhibited higher mutation rates than animals not subjected to PGC removal. PGC regeneration enables us to use TALEN expression vectors of specific somatic tissues for germ cell mutagenesis. Unexpectedly, cis elements for epidermis, neural tissue and muscle could be used for germ cell mutagenesis, indicating there are multiple sources of regenerated PGCs, suggesting a flexibility of differentiated Ciona somatic cells to regain totipotency. Sperm and eggs of a single hermaphroditic, PGC regenerated animal typically have different mutations, suggesting they arise from different cells. PGCs can be generated from somatic cells even though the maternal PGCs are not removed, suggesting that the PGC regeneration is not solely an artificial event but could have an endogenous function in Ciona. This study provides a technical innovation in the genome-editing methods, including easy establishment of mutant lines. Moreover, this study suggests cellular mechanisms and the potential evolutionary significance of PGC regeneration in Ciona. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Germ cells are not required to establish the female pathway in mouse fetal gonads.

    Directory of Open Access Journals (Sweden)

    Danielle M Maatouk

    Full Text Available The fetal gonad is composed of a mixture of somatic cell lineages and germ cells. The fate of the gonad, male or female, is determined by a population of somatic cells that differentiate into Sertoli or granulosa cells and direct testis or ovary development. It is well established that germ cells are not required for the establishment or maintenance of Sertoli cells or testis cords in the male gonad. However, in the agametic ovary, follicles do not form suggesting that germ cells may influence granulosa cell development. Prior investigations of ovaries in which pre-meiotic germ cells were ablated during fetal life reported no histological changes during stages prior to birth. However, whether granulosa cells underwent normal molecular differentiation was not investigated. In cases where germ cell loss occurred secondary to other mutations, transdifferentiation of granulosa cells towards a Sertoli cell fate was observed, raising questions about whether germ cells play an active role in establishing or maintaining the fate of granulosa cells. We developed a group of molecular markers associated with ovarian development, and show here that the loss of pre-meiotic germ cells does not disrupt the somatic ovarian differentiation program during fetal life, or cause transdifferentiation as defined by expression of Sertoli markers. Since we do not find defects in the ovarian somatic program, the subsequent failure to form follicles at perinatal stages is likely attributable to the absence of germ cells rather than to defects in the somatic cells.

  8. Germ Cells Are Not Required to Establish the Female Pathway in Mouse Fetal Gonads

    Science.gov (United States)

    Maatouk, Danielle M.; Mork, Lindsey; Hinson, Ashley; Kobayashi, Akio; McMahon, Andrew P.; Capel, Blanche

    2012-01-01

    The fetal gonad is composed of a mixture of somatic cell lineages and germ cells. The fate of the gonad, male or female, is determined by a population of somatic cells that differentiate into Sertoli or granulosa cells and direct testis or ovary development. It is well established that germ cells are not required for the establishment or maintenance of Sertoli cells or testis cords in the male gonad. However, in the agametic ovary, follicles do not form suggesting that germ cells may influence granulosa cell development. Prior investigations of ovaries in which pre-meiotic germ cells were ablated during fetal life reported no histological changes during stages prior to birth. However, whether granulosa cells underwent normal molecular differentiation was not investigated. In cases where germ cell loss occurred secondary to other mutations, transdifferentiation of granulosa cells towards a Sertoli cell fate was observed, raising questions about whether germ cells play an active role in establishing or maintaining the fate of granulosa cells. We developed a group of molecular markers associated with ovarian development, and show here that the loss of pre-meiotic germ cells does not disrupt the somatic ovarian differentiation program during fetal life, or cause transdifferentiation as defined by expression of Sertoli markers. Since we do not find defects in the ovarian somatic program, the subsequent failure to form follicles at perinatal stages is likely attributable to the absence of germ cells rather than to defects in the somatic cells. PMID:23091613

  9. Design and development of radiation absorber for sighting beam line

    International Nuclear Information System (INIS)

    Sridhar, R.; Shukla, S.K.

    2005-01-01

    During the commissioning of Indus-2 , it is necessary to view the synchrotron radiation that will be emanating from the dipole exit ports. The 10 0 beam line from dipole 11 was earmarked for sighting beam line. The synchrotron radiation power density would be around 340 watts on the photon absorber inside the radiation absorber module, at the specified beam power of Indus-2. The beam striking on this photon absorber produces x-rays and Bremsstrahlung radiation. These are to be stopped and absorbed by radiation absorber. The photon absorber and the radiation absorber are integrated in a single vacuum chamber and actuated by a pneumatic cylinder connected using a bellow. Radiation absorber was needed to isolate the diagnostic components and to protect them from radiation a well as heat when they were not in use. The paper describes the design, calculation and development of the dynamic photon cum radiation absorber. The ultimate vacuum performance is also described. (author)

  10. Characterization of germ cell-specific expression of the orphan nuclear receptor, germ cell nuclear factor.

    Science.gov (United States)

    Katz, D; Niederberger, C; Slaughter, G R; Cooney, A J

    1997-10-01

    Nuclear receptors, such as those for androgens, estrogens, and progesterones, control many reproductive processes. Proteins with structures similar to these receptors, but for which ligands have not yet been identified, have been termed orphan nuclear receptors. One of these orphans, germ cell nuclear factor (GCNF), has been shown to be germ cell specific in the adult and, therefore, may also participate in the regulation of reproductive functions. In this paper, we examine more closely the expression patterns of GCNF in germ cells to begin to define spatio-temporal domains of its activity. In situ hybridization showed that GCNF messenger RNA (mRNA) is lacking in the testis of hypogonadal mutant mice, which lack developed spermatids, but is present in the wild-type testis. Thus, GCNF is, indeed, germ cell specific in the adult male. Quantitation of the specific in situ hybridization signal in wild-type testis reveals that GCNF mRNA is most abundant in stage VII round spermatids. Similarly, Northern analysis and specific in situ hybridization show that GCNF expression first occurs in testis of 20-day-old mice, when round spermatids first emerge. Therefore, in the male, GCNF expression occurs postmeiotically and may participate in the morphological changes of the maturing spermatids. In contrast, female expression of GCNF is shown in growing oocytes that have not completed the first meiotic division. Thus, GCNF in the female is expressed before the completion of meiosis. Finally, the nature of the two different mRNAs that hybridize to the GCNF complementary DNA was studied. Although both messages contain the DNA binding domain, only the larger message is recognized by a probe from the extreme 3' untranslated region. In situ hybridization with these differential probes demonstrates that both messages are present in growing oocytes. In addition, the coding region and portions of the 3' untranslated region of the GCNF complementary DNA are conserved in the rat.

  11. Molecular mechanisms governing primordial germ cell migration in zebrafish

    NARCIS (Netherlands)

    Doitsidou, M.

    2005-01-01

    In most sexually reproducing organisms primordial germ cells (pGCs) are specified early in development in places that are distinct from the region where the somatic part of the gonad develops. From their places of specification they have to migrate towards the site where they associate with somatic

  12. Germs and Staying Healthy

    Science.gov (United States)

    ... Active Cycle of Breathing Technique Airway Clearance Techniques Autogenic Drainage Basics of Lung Care Chest Physical Therapy ... care. Clinician Awards Clinician Career Development Awards Clinician Training Awards Mutation Analysis Program Network News Network News: ...

  13. Thermal Properties of Starch From New Corn Lines as Impacted by Environment and During Line Development

    Energy Technology Data Exchange (ETDEWEB)

    Lenihan, Elizabeth M [Iowa State Univ., Ames, IA (United States)

    2003-01-01

    The objectives of this research were to further characterize exotic by adapted corn inbreds by studying the impact of environment on their starch thermal properties, and investigating the development of starch thermal properties during kernel maturation by using differential scanning calorimetry (DSC). A method to expedite identification of unusual starch thermal traits was investigated by examining five corn kernels at a time, instead of one kernel, which the previous screening methods used. Corn lines with known thermal functions were blended with background starch (control) in ratios of unique starch to control starch, and analyzed by using DSC. Control starch was representative of typical corn starch. The values for each ratio within a mutant type were unique (α < 0.01) for most DSC measurements. These results supported the five-kernel method for rapidly screening large amounts of corn germplasm to identify unusual starch traits. The effects of 5 growing locations on starch thermal properties from exotic by adapted corn and Corn Belt lines were studied using DSC. The warmest location, Missouri, generally produced starch with greater gelatinization onset temperature (ToG), narrower range of gelatinization (RG), and greater enthalpy of gelatinization (ΔHG). The coolest location, Illinois, generally resulted in starch with lower ToG, wider RG, and lower ΔHG. Starch from the Ames 1 farm had thermal properties similar to those of Illinois, whereas starch from the Ames 2 farm had thermal properties similar to those of Missouri. The temperature at Ames 2 may have been warmer since it was located near a river; however, soil type and quality also were different. Final corn starch structure and function change during development and maturity. Thus, the changes in starch thermal properties during 5 stages of endosperm development from exotic by adapted corn and Corn Belt lines at two locations were

  14. LINES

    Directory of Open Access Journals (Sweden)

    Minas Bakalchev

    2015-10-01

    Full Text Available The perception of elements in a system often creates their interdependence, interconditionality, and suppression. The lines from a basic geometrical element have become the model of a reductive world based on isolation according to certain criteria such as function, structure, and social organization. Their traces are experienced in the contemporary world as fragments or ruins of a system of domination of an assumed hierarchical unity. How can one release oneself from such dependence or determinism? How can the lines become less “systematic” and forms more autonomous, and less reductive? How is a form released from modernistic determinism on the new controversial ground? How can these elements or forms of representation become forms of action in the present complex world? In this paper, the meaning of lines through the ideas of Le Corbusier, Leonidov, Picasso, and Hitchcock is presented. Spatial research was made through a series of examples arising from the projects of the architectural studio “Residential Transformations”, which was a backbone for mapping the possibilities ranging from playfulness to exactness, as tactics of transformation in the different contexts of the contemporary world.

  15. Development of an on-line radon monitoring system

    International Nuclear Information System (INIS)

    Guo Huiping; Shang Aiguo; Liu Junfeng; Zhou Chunlin; Di Yuming

    2004-01-01

    Of the actual demand by the strategic missile troops, the author has successfully developed a specially designed passive diffusion collecting chamber to collect the decay products of radon by high voltage static electricity, and using the single-chip microcomputer to reckon the radon concentration in air, which is actually a portable, continuous and automatic on-line monitoring instrument. It was made into a four-slot standard plug-in board of a NIM, and it functions as auto data memory, data process, display, over-threshold alarming and so on. (authors)

  16. Project development and commercialisation of on-line analysis systems

    International Nuclear Information System (INIS)

    Watt, J.S.

    2000-01-01

    A project team first in the Australian Atomic Energy Commission (AAEC) and since 1982 in CSIRO has developed many on-line analysis systems for the mineral and energy industries. The development of these projects, usually lasting 7-10 years, has followed a common pattern of laboratory R and D, field trials, commercialisation and technology transfer. This successful pattern is illustrated using examples of the development of systems for the on-line analysis of mineral slurries, for determination of the ash content of coal on conveyors, and for determination of the flow rates of oil, water and gas in pipelines. The first two systems, licensed to Australian companies, are used world-wide. They are now the market leaders for radioisotope gauges in their application field. The third, the multiphase flow meter, was licensed in 1997 to an international company. This meter has even greater potential than the other two systems for economic benefit from its use and for numbers of installations. (author)

  17. MIWI2 as an Effector of DNA Methylation and Gene Silencing in Embryonic Male Germ Cells

    Directory of Open Access Journals (Sweden)

    Kanako Kojima-Kita

    2016-09-01

    Full Text Available During the development of mammalian embryonic germ cells, global demethylation and de novo DNA methylation take place. In mouse embryonic germ cells, two PIWI family proteins, MILI and MIWI2, are essential for the de novo DNA methylation of retrotransposons, presumably through PIWI-interacting RNAs (piRNAs. Although piRNA-associated MIWI2 has been reported to play critical roles in the process, its molecular mechanisms have remained unclear. To identify the mechanism, transgenic mice were produced; they contained a fusion protein of MIWI2 and a zinc finger (ZF that recognized the promoter region of a type A LINE-1 gene. The ZF-MIWI2 fusion protein brought about DNA methylation, suppression of the type A LINE-1 gene, and a partial rescue of the impaired spermatogenesis of MILI-null mice. In addition, ZF-MIWI2 was associated with the proteins involved in DNA methylation. These data indicate that MIWI2 functions as an effector of de novo DNA methylation of the retrotransposon.

  18. Development of one control and one tumor-specific induced pluripotent stem cell line from laryngeal carcinoma patient

    Directory of Open Access Journals (Sweden)

    Yamin Zhang

    2017-12-01

    Full Text Available Skin fibroblasts and tumor fibroblasts were extracted from a 64-year old male patient clinically diagnosed with laryngeal carcinoma. Control and tumor specific induced pluripotent stem cells were reprogrammed with 5 reprogramming factors, Klf-4, c-Myc, Oct-4, Sox-2, and Lin-28, using the messenger RNA reprogramming system. The transgene-free iPSC lines showed pluripotency, confirmed by immunofluorescence staining. The iPSC lines also showed normal karyotype, and could form embryoid bodies in vitro and differentiate into the 3 germ layers in vivo. This in vitro cellular model can be used to study the oncogenesis and pathogenesis of laryngeal carcinoma.

  19. PHEBUS on-line aerosol monitor development test program

    International Nuclear Information System (INIS)

    Sprenger, M.H.; Pentecost, C.G.

    1992-03-01

    EG ampersand G Idaho, Inc. developed an on-line aerosol monitor (OLAM) for the French PHEBUS Fission Product Project. Part of the development was to manufacture and test an OLAM prototype. This report presents the results of the testing which determined the mechanical integrity of the monitor at operating temperature and pressure and performed a preliminary test of the optical system. A series of twenty different tests was conducted during the prototype testing sequence. Since no leaks were detected, the OLAM demonstrated that it could provide a pressure boundary at required test conditions. The optical and electrical system also proved its integrity by exceeding the design requirement of less than 105 optical signal drift during an actual two-hour test sequence

  20. Don Germán

    OpenAIRE

    Juan Luis Mejía

    1991-01-01

    El veranillo de San Juan hace soportable el mediodía. Los "chorros d'oro" inundan de amarillo los antejardines del Prado. Las golondrinas veraneras invaden, al atardecer, los alrededores de la Biblioteca Departamental. Los voceadores de la suerte del paseo Bolívar claman a los cuatro vientos el número que cambiará su destino . Pero algo falta definitivamente en esta Barranquilla. De alguna manera la ciudad ya no es la misma. Falta Don Germán.

  1. Don Germán

    Directory of Open Access Journals (Sweden)

    Juan Luis Mejía

    1991-01-01

    Full Text Available El veranillo de San Juan hace soportable el mediodía. Los "chorros d'oro" inundan de amarillo los antejardines del Prado. Las golondrinas veraneras invaden, al atardecer, los alrededores de la Biblioteca Departamental. Los voceadores de la suerte del paseo Bolívar claman a los cuatro vientos el número que cambiará su destino . Pero algo falta definitivamente en esta Barranquilla. De alguna manera la ciudad ya no es la misma. Falta Don Germán.

  2. Economic Development Benefits of New Transit Service: RiverLINE

    Science.gov (United States)

    2010-06-01

    This report documents the economic impacts of the RiverLINE, a light rail line connecting Trenton and Camden, New Jersey. The study examined whether and how the line impacted local land use, residential property values, travel behaviors and firm perf...

  3. Stopping the Spread of Germs at Home, Work and School

    Science.gov (United States)

    ... Pandemic Other Stopping the Spread of Germs at Home, Work & School Language: English (US) Español Recommend on Facebook ... everyone from getting germs or spreading germs at home, work, or school. Clean and disinfect surfaces or objects. ...

  4. Development of on-line monitoring system using smart material

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jin Kyung; Lee, Sang Pill; Park, Yi Hyun [Dongeui Univ., Busan (Korea, Republic of); Park, Young Chul [Donga Univ., Busan (Korea, Republic of)

    2003-07-01

    A hot press method was used to create the optimal fabrication condition for a Shape Memory Alloy(SMA) composite. The bonding strength between the matrix and the reinforcement within the SMA composite by the hot press method was more increased by cold rolling. In this study, the objective was to develop an on-line monitoring system in order to prevent the crack initiation and propagation by shape memory effect in SMA composite. Shape memory effect was used to prevent the SMA composite from crack propagation. For this system an optimal AE parameter should be determined according to the degree of damage and crack initiation. When the SMA composite was heated by the plate heater attached at the composite, the propagating cracks could be controlled by the compressive force of SMA.

  5. Development of on-line monitoring system using smart material

    International Nuclear Information System (INIS)

    Lee, Jin Kyung; Lee, Sang Pill; Park, Yi Hyun; Park, Young Chul

    2003-01-01

    A hot press method was used to create the optimal fabrication condition for a Shape Memory Alloy(SMA) composite. The bonding strength between the matrix and the reinforcement within the SMA composite by the hot press method was more increased by cold rolling. In this study, the objective was to develop an on-line monitoring system in order to prevent the crack initiation and propagation by shape memory effect in SMA composite. Shape memory effect was used to prevent the SMA composite from crack propagation. For this system an optimal AE parameter should be determined according to the degree of damage and crack initiation. When the SMA composite was heated by the plate heater attached at the composite, the propagating cracks could be controlled by the compressive force of SMA

  6. Development of Elite BPH-Resistant Wide-Spectrum Restorer Lines for Three and Two Line Hybrid Rice.

    Science.gov (United States)

    Fan, Fengfeng; Li, Nengwu; Chen, Yunping; Liu, Xingdan; Sun, Heng; Wang, Jie; He, Guangcun; Zhu, Yingguo; Li, Shaoqing

    2017-01-01

    Hybrid rice has contributed significantly to the world food security. Breeding of elite high-yield, strong-resistant broad-spectrum restorer line is an important strategy for hybrid rice in commercial breeding programs. Here, we developed three elite brown planthopper (BPH)-resistant wide-spectrum restorer lines by pyramiding big-panicle gene Gn8.1 , BPH-resistant genes Bph6 and Bph9 , fertility restorer genes Rf3, Rf4, Rf5 , and Rf6 through molecular marker assisted selection. Resistance analysis revealed that the newly developed restorer lines showed stronger BPH-resistance than any of the single-gene donor parent Luoyang-6 and Luoyang-9. Moreover, the three new restorer lines had broad spectrum recovery capabilities for Honglian CMS, Wild abortive CMS and two-line GMS sterile lines, and higher grain yields than that of the recurrent parent 9,311 under nature field conditions. Importantly, the hybrid crosses also showed good performance for grain yield and BPH-resistance. Thus, the development of elite BPH-resistant wide-spectrum restorer lines has a promising future for breeding of broad spectrum BPH-resistant high-yield varieties.

  7. Germ Cell Proteins in Melanoma: Prognosis, Diagnosis, Treatment, and Theories on Expression

    International Nuclear Information System (INIS)

    Rosa, A. M.; Dabas, N.; Byrnes, D. M.; Eller, M. S.; Grichnik, J. M.; Grichnik, J M.; Grichnik, J M.

    2012-01-01

    Germ cell protein expression in melanoma has been shown to correlate with malignancy, severity of disease and to serve as an immunologic target for therapy. However, very little is known about the role that germ cell proteins play in cancer development. Unique germ cell pathways include those involved in immortalization, genetic evolution, and energy metabolism. There is an ever increasing recognition that within tumors there is a subpopulation of cells with stem-cell-like characteristics that play a role in driving tumor genesis. Stem cell and germ cell biology is intertwined. Given the enormous potential and known expression of germ cell proteins in melanoma, it is possible that they represent a largely untapped resource that may play a fundamental role in tumor development and progression. The purpose of this paper is to provide an update on the current value of germ cell protein expression in melanoma diagnosis, prognosis, and therapy, as well as to review critical germ cell pathways and discuss the potential roles these pathways may play in malignant transformation

  8. Stereotactic radiotherapy for pediatric intracranial germ cell tumors

    International Nuclear Information System (INIS)

    Zissiadis, Yvonne; Dutton, Sharon; Kieran, Mark; Goumnerova, Liliana; Scott, R. Michael; Kooy, Hanne M.; Tarbell, Nancy J.

    2001-01-01

    Purpose: Intracranial germ cell tumors are rare, radiosensitive tumors seen most commonly in the second and third decades of life. Radiotherapy alone has been the primary treatment modality for germinomas, and is used with chemotherapy for nongerminomatous tumors. Stereotactic radiotherapy techniques minimize the volume of surrounding normal tissue irradiated and, hence, the late radiation morbidity. This study reports our experience with stereotactic radiotherapy in this group of tumors. Methods and Materials: Between December 1992 and December 1998, 18 patients with intracranial germ cell tumors were treated with stereotactic radiotherapy. A total of 23 histologically proven tumors were treated. Thirteen patients had a histologic diagnosis of germinoma, and 5 patients had germinoma with nongerminomatous elements. Of those patients with a histologic diagnosis of germinoma, 5 had multiple midline tumors. The median age of the patients was 12.9 years (range, 5.6-17.5 years). Results: A boost using stereotactic radiotherapy was delivered to 19 tumors following whole-brain radiation in 8 cases and craniospinal radiation in 11 cases. Three tumors were treated with stereotactic radiotherapy to the tumor volume alone following chemotherapy, and 1 tumor received a boost using stereotactic radiosurgery following craniospinal radiation. A median dose of 2520 cGy (range, 1500-3600) cGy was given to the whole brain, and a median dose of 2160 (range, 2100-2600) cGy was given to the spinal field. The median boost dose to the tumor was 2600 (range, 2160-3600) cGy, given by stereotactic radiotherapy delivered to the 95% isodose line. At a median follow-up time of 40 (range, 12-73) months, no local or marginal recurrences were reported in patients with germinoma. Two patients with nongerminomatous tumors have relapsed. One had elevation of tumor markers only at 37 months following treatment, and the other had persistent disease following chemotherapy and radiation therapy. Eight

  9. Intracranial germ-cell tumors

    International Nuclear Information System (INIS)

    Baker, L.L.; Kollias, S.S.; Cogen, P.H.; Barkovich, A.J.

    1991-01-01

    This paper reports on the MR characteristics together with the clinical and histologic features of cerebral germ-cell tumors were investigated to augment data regarding this rare, diverse class of neoplasms. Germinomas were homogeneous or heterogeneous masses, predominantly isointense to normal brain on T1-weighted images, and hyperintense and heterogeneous on T2-weighted images; three showed adjacent brain edema. Enhancement was prominent, either homogeneous or heterogeneous. One had spinal drop metastases. Teratomas, more common in young patients, were more heterogeneous than germinomas on T1-weighted and T2-weighted images. Five showed hyper- and hypointense foci on T1-weighted images that corresponded to fat and calcium, respectively, at CT. Teratomas did not enhance or enhanced heterogeneously. Two had intratumoral hemorrhage; there were no metastases. Both patients with choriocarcinoma had hemorrhagic masses

  10. Radiosensitivity of mouse germ cells

    International Nuclear Information System (INIS)

    Matsuda, Yoichi; Takeuchi, Toyoko; Maemori, Mamiko; Seki, Naohiko; Tobari, Izuo

    1991-01-01

    To estimate radiosensitivity of mouse germ cells the analysis of chromosome aberrations was performed at diakinesis-metaphase I of spermatocytes and first-cleavage metaphase of one-cell embryos after exposure to radiations at various stages of primary spermatocytes and spermatids. The result provided evidence that there are two major types of DNA damage in X-irradiated sperm : (1) short-lived DNA lesions ; the lesions are subject to repair inhibition by agents added in G 1 , and are converted into chromosome-type aberrations during G 1 , and (2) long-lived DNA lesions ; the lesions persist until S phase and repair of the lesions is inhibited by caffeine, hydroxyurea and arabinofuranosyl cytosine in G 2 . The characteristic of X-ray damage induced in spermiogenic stage and repair mechanism for the damage in the fertilized egg were discussed comparing with the results with two chemicals, methyl methanesulfonate (MMS) and mitomycin C (MMC). (J.P.N.)

  11. DNA methylation analysis reveals distinct methylation signatures in pediatric germ cell tumors

    International Nuclear Information System (INIS)

    Amatruda, James F; Frazier, A Lindsay; Poynter, Jenny N; Ross, Julie A; Christensen, Brock; Fustino, Nicholas J; Chen, Kenneth S; Hooten, Anthony J; Nelson, Heather; Kuriger, Jacquelyn K; Rakheja, Dinesh

    2013-01-01

    Aberrant DNA methylation is a prominent feature of many cancers, and may be especially relevant in germ cell tumors (GCTs) due to the extensive epigenetic reprogramming that occurs in the germ line during normal development. We used the Illumina GoldenGate Cancer Methylation Panel to compare DNA methylation in the three main histologic subtypes of pediatric GCTs (germinoma, teratoma and yolk sac tumor (YST); N = 51) and used recursively partitioned mixture models (RPMM) to test associations between methylation pattern and tumor and demographic characteristics. We identified genes and pathways that were differentially methylated using generalized linear models and Ingenuity Pathway Analysis. We also measured global DNA methylation at LINE1 elements and evaluated methylation at selected imprinted loci using pyrosequencing. Methylation patterns differed by tumor histology, with 18/19 YSTs forming a distinct methylation class. Four pathways showed significant enrichment for YSTs, including a human embryonic stem cell pluripotency pathway. We identified 190 CpG loci with significant methylation differences in mature and immature teratomas (q < 0.05), including a number of CpGs in stem cell and pluripotency-related pathways. Both YST and germinoma showed significantly lower methylation at LINE1 elements compared with normal adjacent tissue while there was no difference between teratoma (mature and immature) and normal tissue. DNA methylation at imprinted loci differed significantly by tumor histology and location. Understanding methylation patterns may identify the developmental stage at which the GCT arose and the at-risk period when environmental exposures could be most harmful. Further, identification of relevant genetic pathways could lead to the development of new targets for therapy

  12. Interaction of NANOS2 and NANOS3 with different components of the CNOT complex may contribute to the functional differences in mouse male germ cells

    Directory of Open Access Journals (Sweden)

    Atsushi Suzuki

    2014-11-01

    Full Text Available NANOS2 and NANOS3 belong to the Nanos family of proteins that contain a conserved zinc finger domain, which consists of two consecutive CCHC-type zinc finger motifs, and contribute to germ cell development in mice. Previous studies indicate that there are redundant and distinct functions of these two proteins. NANOS2 rescues NANOS3 functions in the maintenance of primordial germ cells, whereas NANOS3 fails to replace NANOS2 functions in the male germ cell pathway. However, the lack of a conditional allele of Nanos3 has hampered delineation of each contribution of NANOS2 and NANOS3 to the male germ cell pathway. In addition, the molecular mechanism underlying the distinct functions of these proteins remains unexplored. Here, we report an unexpected observation of a transgenic mouse line expressing a NANOS2 variant harboring mutations in the zinc finger domain. Transcription of Nanos2 and Nanos3 was strongly compromised in the presence of this transgene, which resulted in the mimicking of the Nanos2/Nanos3 double-null condition in the male gonad. In these transgenic mice, P-bodies involved in RNA metabolism had disappeared and germ cell differentiation was more severely affected than that in Nanos2-null mice, indicating that NANOS3 partially substitutes for NANOS2 functions. In addition, similar to NANOS2, we found that NANOS3 associated with the CCR4-NOT deadenylation complex but via a direct interaction with CNOT8, unlike CNOT1 in the case of NANOS2. This alternate interaction might account for the molecular basis of the functional redundancy and differences in NANOS2 and NANOS3 functions.

  13. Development of an On-Line Uranium Enrichment Monitor

    International Nuclear Information System (INIS)

    Xuesheng, L.; Guorong, L.; Yonggang, Z.; Xueyuan, H. X.-Y.

    2015-01-01

    An on-line enrichment monitor was developed to measure the enrichment of UF6 flowing through the processing pipes in centrifuge uranium enrichment plant. A NaI(Tl) detector was used to measure the count rates of the 186 keV gamma ray emitted from 235U, and the total quantity of uranium was determined from thermodynamic characteristics of gaseous uranium hexafluoride. The results show that the maximum relative standard deviation is less than 1% when the measurement time is 120 s or more and the pressure is more than 2 kPa in the measurement chamber. There are two working models for the monitor. The monitor works normally in the continuous model, When the gas's pressure in the pipe fluctuates greatly, it can work in the intermittent model, and the measurement result is very well. The background of the monitor can be measured automatically periodically. It can control automatically electromagnetic valves open and close, so as to change the gas's quantity in the chamber. It is a kind of unattended and remote monitor, all of data can be transfer to central control room. It should be effective for nuclear materials accountability verifications and materials balance verification at uranium enrichment plant by using the monitor to monitor Uranium enrichment of gaseous uranium hexafluoride in the output end of cascade continuously. (author)

  14. A phase II single institution single arm prospective study with paclitaxel, ifosfamide and cisplatin (TIP) as first-line chemotherapy in high-risk germ cell tumor patients with more than ten years follow-up and retrospective correlation with ERCC1, Topoisomerase 1, 2A, p53 and HER-2 expression.

    Science.gov (United States)

    Ligia Cebotaru, Cristina; Zenovia Antone, Nicoleta; Diana Olteanu, Elena; Bejinariu, Nona; Buiga, Rares; Todor, Nicolae; Ioana Iancu, Dana; Eliade Ciuleanu, Tudor; Nagy, Viorica

    2016-01-01

    One half of high-risk germ cell tumor (HRGCT) patients relapse after standard chemotherapy. This phase II study evaluated prospectively the toxicity and efficacy in first-line of the paclitaxel-ifosfamide-cisplatin combination (TIP) in HRGCT patients and tried to identify biomarkers that may allow patient-tailored treatments. Between October 1997- September 2000, 28 chemo-naive HRGCT patients were enrolled. Patients received 4 cycles of TIP (paclitaxel 175 mg/m(2) day 1/; ifosfamide 1.2 g/m(2)/day, days 1-5; Mesna 1.2 g/m(2)/day, days 1-5; and cisplatin 20 mg/m(2)/day, days 1-5 every 3 weeks). A non-randomized comparison was made between HRGCT patients treated in the same period with first-line TIP and bleomycin-etoposide-cisplatin (BEP) (28 patients vs 20). In 17 HRGCT patients treated between 1998-2006, ERCC1, Topoisomerase 1 and 2A, p53 and HER-2 expression was retrospectively analysed by immunohistochemistry (IHC) (7 patients with TIP, 10 with BEP), and correlations were made with response to chemotherapy and survival. With a median follow-up of 72 months [range 48+...89+], 5-year disease free survival (DFS) was 55%, with 95% CI 36-72, and the overall survival (OS) was 63%, with 95% CI 44-78. In June 2015, with a median follow-up of 196.47 months (range 177.30-209.27) (>15 years), 12 [%?] patients were alive and disease-free, and 16 [%?] had died (12 specific causes). There was no significant correlation between the expression of ERCC1, Topoisomerase 1 and 2A, HER-2 and p53 and response to treatment. Long-term follow-up showed no difference in OS between TIP vs BEP as first-line therapy. Both regimens had mild toxicity.

  15. Micro-PIXE (proton-induced X-ray emission) study of the effects of fluoride on mineral distribution patterns in enamel and dentin in the developing hamster tooth germ

    International Nuclear Information System (INIS)

    Lyaruu, D.M.; Tros, G.H.; Bronckers, A.L.; Woeltgens, J.H.

    1990-01-01

    Micro-PIXE (proton-induced X-ray emission) analysis was performed on unfixed and anhydrously prepared sections from developing enamel and dentin from hamsters injected with a single dose of 20 mg NaF/kg body weight. Fluoride, apart from inducing the formation of the characteristic paired response in the enamel (i.e., a hyper- followed by a hypomineralized band in the secretory enamel), also induces the formation of sub-ameloblastic cystic lesions under the transitional and early secretory enamel accompanied by relatively intense hypermineralization of the underlying cystic enamel surface. These cystic lesions, however, were only found to be associated with certain isolated populations of these cells. In addition, these lesions were restricted to the smooth surfaces of the tooth germ only. Cystic lesions such as those seen under the transitional and early secretory ameloblasts were not observed under the fully secretory or maturation stage ameloblasts. Why fluoride induces the formation of cystic lesions in some ameloblast populations while other cells in the same stage of development apparently remain unaffected, is a matter which needs further investigation

  16. The role of sex chromosomes in mammalian germ cell differentiation: can the germ cells carrying X and Y chromosomes differentiate into fertile oocytes?

    Directory of Open Access Journals (Sweden)

    Teruko Taketo

    2015-06-01

    Full Text Available The sexual differentiation of germ cells into spermatozoa or oocytes is strictly regulated by their gonadal environment, testis or ovary, which is determined by the presence or absence of the Y chromosome, respectively. Hence, in normal mammalian development, male germ cells differentiate in the presence of X and Y chromosomes, and female germ cells do so in the presence of two X chromosomes. However, gonadal sex reversal occurs in humans as well as in other mammalian species, and the resultant XX males and XY females can lead healthy lives, except for a complete or partial loss of fertility. Germ cells carrying an abnormal set of sex chromosomes are efficiently eliminated by multilayered surveillance mechanisms in the testis, and also, though more variably, in the ovary. Studying the molecular basis for sex-specific responses to a set of sex chromosomes during gametogenesis will promote our understanding of meiotic processes contributing to the evolution of sex determining mechanisms. This review discusses the fate of germ cells carrying various sex chromosomal compositions in mouse models, the limitation of which may be overcome by recent successes in the differentiation of functional germ cells from embryonic stem cells under experimental conditions.

  17. Light and electron microscopic analyses of Vasa expression in adult germ cells of the fish medaka.

    Science.gov (United States)

    Yuan, Yongming; Li, Mingyou; Hong, Yunhan

    2014-07-15

    Germ cells of diverse animal species have a unique membrane-less organelle called germ plasm (GP). GP is usually associated with mitochondria and contains RNA binding proteins and mRNAs of germ genes such as vasa. GP has been described as the mitochondrial cloud (MC), intermitochondrial cement (IC) and chromatoid body (CB). The mechanism underlying varying GP structures has remained incompletely understood. Here we report the analysis of GP through light and electron microscopy by using Vasa as a marker in adult male germ cells of the fish medaka (Oryzias latipes). Immunofluorescence light microscopy revealed germ cell-specific Vasa expression. Vasa is the most abundant in mitotic germ cells (oogonia and spermatogonia) and reduced in meiotic germ cells. Vasa in round spermatids exist as a spherical structure reminiscent of CB. Nanogold immunoelectron microscopy revealed subcellular Vasa redistribution in male germ cells. Vasa in spermatogonia concentrates in small areas of the cytoplasm and is surrounded by mitochondria, which is reminiscent of MC. Vasa is intermixed with mitochondria to form IC in primary spermatocytes, appears as the free cement (FC) via separation from mitochondria in secondary spermatocyte and becomes condensed in CB at the caudal pole of round spermatids. During spermatid morphogenesis, Vasa redistributes and forms a second CB that is a ring-like structure surrounding the dense fiber of the flagellum in the midpiece. These structures resemble those described for GP in various species. Thus, Vasa identifies GP and adopts varying structures via dynamic reorganization at different stages of germ cell development. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Involvement of epigenetic modifiers in the pathogenesis of testicular dysgenesis and germ cell cancer

    DEFF Research Database (Denmark)

    Lawaetz, Andreas C.; Almstrup, Kristian

    2015-01-01

    Testicular germ cell cancer manifests mainly in young adults as a seminoma or non-seminoma. The solid tumors are preceded by the presence of a non-invasive precursor cell, the carcinoma in situ cell (CIS), which shows great similarity to fetal germ cells. It is therefore hypothesized that the CIS...... of epigenetic modifiers with a focus on jumonji C enzymes in the development of testicular dysgenesis and germ cell cancer in men....... cell is a fetal germ cell that has been arrested during development due to testicular dysgenesis. CIS cells retain a fetal and open chromatin structure, and recently several epigenetic modifiers have been suggested to be involved in testicular dysgenesis in mice. We here review the possible involvement...

  19. Treatment Option Overview (Ovarian Germ Cell Tumors)

    Science.gov (United States)

    ... Germ Cell Tumors Treatment (PDQ®)–Patient Version Treatment Option Overview Go to Health Professional Version Key Points ... and restore) the body’s blood cells. New treatment options Combination chemotherapy (the use of more than one ...

  20. Treatment Option Overview (Extragonadal Germ Cell Tumors)

    Science.gov (United States)

    ... Cell Tumors Treatment Testicular Cancer Treatment Age and gender can affect the risk of extragonadal germ cell ... Headache. Change in bowel habits. Feeling very tired. Trouble walking. Trouble in seeing or moving the eyes. ...

  1. General Information about Extragonadal Germ Cell Tumors

    Science.gov (United States)

    ... Cell Tumors Treatment Testicular Cancer Treatment Age and gender can affect the risk of extragonadal germ cell ... Headache. Change in bowel habits. Feeling very tired. Trouble walking. Trouble in seeing or moving the eyes. ...

  2. Development of slow positron beam lines and applications

    Science.gov (United States)

    Mondal, Nagendra Nath

    2018-05-01

    A positron is an antiparticle of an electron that can be formed in diverse methods: natural or artificial β-decay process, fission and fusion reactions, and a pair production of electron-positron occurred in the reactor and the high energy accelerator centers. Usually a long-lifetime radio isotope is customized for the construction of a slow positron beam lines in many laboratories. The typical intensity of this beam depends upon the strength of the positron source, moderator efficiency, and guiding, pulsing, focusing and detecting systems. This article will review a few positron beam lines and their potential applications in research, especially in the Positronium Bose-Einstein Condensation.

  3. Pluripotency Factors in Embryonic Stem Cells Regulate Differentiation into Germ Layers

    OpenAIRE

    Thomson, Matt; Liu, Siyuan John; Zou, Ling-Nan; Smith, Zack; Meissner, Alexander; Ramanathan, Sharad

    2011-01-01

    Cell fate decisions are fundamental for development, but we do not know how transcriptional networks reorganize during the transition from a pluripotent to a differentiated cell state. Here, we asked how mouse embryonic stem cells (ESCs) leave the pluripotent state and choose between germ layer fates. By analyzing the dynamics of the transcriptional circuit that maintains pluripotency, we found that Oct4 and Sox2, proteins that maintain ESC identity, also orchestrate germ layer fate selection...

  4. Technology, Pedagogy and On line materials: Keywords in developing On line Education

    DEFF Research Database (Denmark)

    Georgsen, Marianne; Bennedsen, Jens

    2003-01-01

    , meaning that technology itself and the use of technology are are interrelated relationship between technology and the use of technology s a dialectic are culturally and contextually situated activities. Furthermore, the and teaching is characterized by the fact that learning and teaching The development...... of ICT-based learning and are presented. Two empirical cases are described, and lessons learned from the project .(learned in a pedagogical and organisational development project (Flexnet teaching and learning. The model is developed on the basis of lessons presents a model for planning and developing...... flexible ICT-supported and reflective and critical thinking about use of technology. This paper and learning, development must be based on systematic pedagogical reflections a high degree of flexibility in online education....

  5. Origins and molecular biology of testicular germ cell tumors.

    Science.gov (United States)

    Reuter, Victor E

    2005-02-01

    Testicular germ cell tumors can be divided into three groups (infantile/prepubertal, adolescent/young adult and spermatocytic seminoma), each with its own constellation of clinical histology, molecular and clinical features. They originate from germ cells at different stages of development. The most common testicular cancers arise in postpubertal men and are characterized genetically by having one or more copies of an isochromosome of the short arm of chromosome 12 [i(12p)] or other forms of 12p amplification and by aneuploidy. The consistent gain of genetic material from chromosome 12 seen in these tumors suggests that it has a crucial role in their development. Intratubular germ cell neoplasia, unclassified type (IGCNU) is the precursor to these invasive tumors. Several factors have been associated with their pathogenesis, including cryptorchidism, elevated estrogens in utero and gonadal dysgenesis. Tumors arising in prepubertal gonads are either teratomas or yolk sac tumors, tend to be diploid and are not associated with i(12p) or with IGCNU. Spermatocytic seminoma (SS) arises in older patients. These benign tumors may be either diploid or aneuploid and have losses of chromosome 9 rather than i(12p). Intratubular SS is commonly encountered but IGCNU is not. The pathogenesis of prepubertal GCT and SS is poorly understood.

  6. On the number of founding germ cells in humans

    Directory of Open Access Journals (Sweden)

    Byers Breck

    2005-08-01

    Full Text Available Abstract Background The number of founding germ cells (FGCs in mammals is of fundamental significance to the fidelity of gene transmission between generations, but estimates from various methods vary widely. In this paper we obtain a new estimate for the value in humans by using a mathematical model of germ cell development that depends on available oocyte counts for adult women. Results The germline-development model derives from the assumption that oogonial proliferation in the embryonic stage starts with a founding cells at t = 0 and that the subsequent proliferation can be defined as a simple stochastic birth process. It follows that the population size X(t at the end of germline expansion (around the 5th month of pregnancy in humans; t = 0.42 years is a random variable with a negative binomial distribution. A formula based on the expectation and variance of this random variable yields a moment-based estimate of a that is insensitive to the progressive reduction in oocyte numbers due to their utilization and apoptosis at later stages of life. In addition, we describe an algorithm for computing the maximum likelihood estimation of the FGC population size (a, as well as the rates of oogonial division and loss to apoptosis. Utilizing both of these approaches to evaluate available oocyte-counting data, we have obtained an estimate of a = 2 – 3 for Homo sapiens. Conclusion The estimated number of founding germ cells in humans corresponds well with values previously derived from chimerical or mosaic mouse data. These findings suggest that the large variation in oocyte numbers between individual women is consistent with a smaller founding germ cell population size than has been estimated by cytological analyses.

  7. Endogenous DNA Damage and Risk of Testicular Germ Cell Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Cook, M B; Sigurdson, A J; Jones, I M; Thomas, C B; Graubard, B I; Korde, L; Greene, M H; McGlynn, K A

    2008-01-18

    Testicular germ cell tumors (TGCT) are comprised of two histologic groups, seminomas and nonseminomas. We postulated that the possible divergent pathogeneses of these histologies may be partially explained by variable endogenous DNA damage. To assess our hypothesis, we conducted a case-case analysis of seminomas and nonseminomas using the alkaline comet assay to quantify single-strand DNA breaks and alkali-labile sites. The Familial Testicular Cancer study and the U.S. Radiologic Technologists cohort provided 112 TGCT cases (51 seminomas & 61 nonseminomas). A lymphoblastoid cell line was cultured for each patient and the alkaline comet assay was used to determine four parameters: tail DNA, tail length, comet distributed moment (CDM) and Olive tail moment (OTM). Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using logistic regression. Values for tail length, tail DNA, CDM and OTM were modeled as categorical variables using the 50th and 75th percentiles of the seminoma group. Tail DNA was significantly associated with nonseminoma compared to seminoma (OR{sub 50th percentile} = 3.31, 95%CI: 1.00, 10.98; OR{sub 75th percentile} = 3.71, 95%CI: 1.04, 13.20; p for trend=0.039). OTM exhibited similar, albeit statistically non-significant, risk estimates (OR{sub 50th percentile} = 2.27, 95%CI: 0.75, 6.87; OR{sub 75th percentile} = 2.40, 95%CI: 0.75, 7.71; p for trend=0.12) whereas tail length and CDM showed no association. In conclusion, the results for tail DNA and OTM indicate that endogenous DNA damage levels are higher in patients who develop nonseminoma compared with seminoma. This may partly explain the more aggressive biology and younger age-of-onset of this histologic subgroup compared with the relatively less aggressive, later-onset seminoma.

  8. The status of the technical development for the Yamanashi Maglev test line

    Energy Technology Data Exchange (ETDEWEB)

    Nakashima, Hiroshi [Maglev Systems Development Dept., Railway Technical Research Inst., Tokyo (Japan); Seki, Akio [Linear Express Research Development Div., Central Japan Railway Co. Ltd., Tokyo (Japan)

    1996-12-31

    The superconducting maglev system has been under development for the past 25 years in Japan. In last 17 years, running test on the 7 km Miyazaki test track has yielded important data for the maglev system development. In 1990, the maglev system gained the status of one of the national - funded projects in Japan. The government authorized the 42.8 km test line in Yamanashi Prefecture and R and D entered into a new phase. This new test line is planned to go through near Tokyo on the supposed Chuo line, which is expected to be a new important line connecting Tokyo and Osaka, the central part of Japan. This fact clearly explains the role of Yamanashi test line in the future. The construction of the Yamanashi test line is energetically promoted, to start running tests in spring of 1997. The situation of the technical development of the Yamanashi test line is reviewed here. (orig.)

  9. New evidence for the origin of intracranial germ cell tumours from primordial germ cells

    DEFF Research Database (Denmark)

    Hoei-Hansen, C E; Sehested, A; Juhler, M

    2006-01-01

    that it is not required for the initiation of malignant germ cell transformation. The expression of genes associated with embryonic stem cell pluripotency in CNS germ cell tumours strongly suggests that these tumours are derived from cells that retain, at least partially, an embryonic stem cell-like phenotype, which...... germ cell tumours and analysed expression of a wide panel of stem cell-related proteins (C-KIT, OCT-3/4 (POU5F1), AP-2gamma (TFAP2C), and NANOG) and developmentally regulated germ cell-specific proteins (including MAGE-A4, NY-ESO-1, and TSPY). Expression at the protein level was analysed in 21 children...... and young adults with intracranial germinomas and non-germinomas, contributing to a careful description of these unusual tumours and adding to the understanding of pathogenesis. Stem cell related proteins were highly expressed in intracranial germ cell tumours, and many similarities were detected...

  10. The development of an on-line gold analyser

    International Nuclear Information System (INIS)

    Robert, R.V.D.; Ormrod, G.T.W.

    1982-01-01

    An on-line analyser to monitor the gold in solutions from the carbon-in-pulp process is described. The automatic system is based on the delivery of filtered samples of the solutions to a distribution valve for measurement by flameless atomic-absorption spectrophotometry. The samples is introduced by the aerosol-deposition method. Operation of the analyser on a pilot plant and on a full-scale carbon-in-pulp plant has shown that the system is economically feasible and capable of providing a continuous indication of the efficiency of the extraction process

  11. Development of a possible nonmammalian test system for radiation-induced germ-cell mutagenesis using a fish, the Japanese medaka (Oryzias latipes)

    International Nuclear Information System (INIS)

    Shima, A.; Shimada, A.

    1991-01-01

    To develop a specific-locus test (SLT) system for environmental mutagenesis using vertebrate species other than the mouse, we first established a tester stock of the fish medaka (Oryzias latipes) that is homozygous recessive at three loci. The phenotypic expression of these loci can be easily recognized early in embryonic development by observation through the transparent egg membrane. We irradiated wild-type males with 137Cs gamma-rays to determine the dose-response relationships for dominant lethal and specific-locus mutations induced in sperm, spermatids, and spermatogonia. Through observation of 322,666 loci in control offspring and 374,026 loci in offspring obtained from 0.64-, 4.75-, or 9.50-Gy-irradiated gametes, specific-locus mutations were phenotypically detected during early development. These putative mutations, designated total mutation, can be recognized only in embryos of oviparous animals. The developmental fate of these mutant embryos was precisely followed. During subsequent embryonic development, a large fraction died and thus was unavailable for test-crossing, which was used to identify viable mutations. Our medaka SLT system demonstrates that the vast majority of total mutations is associated with dominant lethal mutations. Thus far only one spontaneous viable mutation has been observed, so that all doubling calculations involving this endpoint carry a large error. With these reservations, however, we conclude that the quantitative data so far obtained from the medaka SLT are quite comparable to those from the mouse SLT and, hence, indicate the validity of the medaka SLT as a possible nonmammalian test system

  12. Germs, genomics and global public health: How can advances in genomic sciences be integrated into public health in the developing world to deal with infectious diseases?

    Science.gov (United States)

    Pang, T

    2009-12-01

    Scientific and technological advances derived from the genomics revolution have a central role to play in dealing with continuing infectious disease threats in the developing world caused by emerging and re-emerging pathogens. These techniques, coupled with increasing knowledge of host-pathogen interactions, can assist in the early identification and containment of outbreaks as well as in the development of preventive vaccination and therapeutic interventions, including the urgent need for new antibiotics. However, the effective application of genomics technologies faces key barriers and challenges which occur at three stages: from the research to the products, from the products to individual patients, and, finally, from patients to entire populations. There needs to be an emphasis on research in areas of greatest need, in facilitating the translation of research into interventions and, finally, the effective delivery of such interventions to those in greatest need. Ultimate success will depend on bringing together science, society and policy to develop effective public health implementation strategies to provide health security and health equity for all peoples.

  13. POMB/ACE chemotherapy for mediastinal germ cell tumours.

    Science.gov (United States)

    Bower, M; Brock, C; Holden, L; Nelstrop, A; Makey, A R; Rustin, G J; Newlands, E S

    1997-05-01

    Mediastinal germ cell tumours (MGCT) are rare and most published series reflect the experiences of individual institutions over many years. Since 1979, we have treated 16 men (12 non-seminomatous germ cell tumours and 4 seminomas) with newly diagnosed primary MGCT with POMB/ACE chemotherapy and elective surgical resection of residual masses. This approach yielded complete remissions in 15/16 (94%) patients. The median follow-up was 6.0 years and no relapses occurred more than 2 years after treatment. The 5 year overall survival in the non-seminomatous germ cell tumours (NSGCT) is 73% (95% confidence interval 43-90%). One patient with NSGCT developed drug-resistant disease and died without achieving remission and 2 patients died of relapsed disease. In addition, 4 patients with bulky and/or metastatic seminoma were treated with POMB/ACE. One died of treatment-related neutropenic sepsis in complete remission and one died of relapsed disease. Finally, 4 patients (2 NSGCT and 2 seminomas) referred at relapse were treated with POMB/ACE and one was successfully salvaged. The combination of POMB/ACE chemotherapy and surgery is effective management for MGCT producing high long-term survival rates.

  14. Development of an in vitro test battery for assessing chemical effects on bovine germ cells under the ReProTect umbrella

    International Nuclear Information System (INIS)

    Lazzari, Giovanna; Tessaro, Irene; Crotti, Gabriella; Galli, Cesare; Hoffmann, Sebastian; Bremer, Susanne; Pellizzer, Cristian

    2008-01-01

    Current European legislation for the registration and authorisation of chemicals (REACH) will require a dramatic increase in the use of animals for reproductive toxicity testing. Since one objective of REACH is to use vertebrates only as last resort, the development and validation of alternative methods is urgently needed. For this purpose ReProTect, an integrated research project funded by the European Union, joining together 33 partners with complementary expertise in reproductive toxicology, was designed. The study presented here describes a battery of two tests developed within ReProTect. The objective of these tests is the detection of chemical effects during the processes of oocyte maturation and fertilisation in a bovine model. The corresponding toxicological endpoints are the reaching of metaphase II and the formation of the pronuclei respectively. Fifteen chemicals have been tested (Benzo[a]pyrene, Busulfan, Butylparaben, Cadmium Chloride, Carbendazim, Cycloheximide, Diethylstilbestrol, Genistein, Ionomycin, Ketoconazole, Lindane, Methylacetoacetate, Mifepristone, Nocodazole and DMSO as solvent) demonstrating high intra-laboratory reproducibility of the tests. Furthermore, the responses obtained in both tests, for several substances, had a good correlation with the available in vivo and in vitro data. These tests therefore, could predictably become part of an integrated testing strategy that combines the bovine models with additional in vitro tests, in order to predict chemical hazards on mammalian fertility

  15. Development of Some Organs Derived from the Three Embryonic Germ Layer in a Degus Ectopic Pregnancy and Presence of a Cytotrophoblast That Mimics Human Chorionic Placenta

    Directory of Open Access Journals (Sweden)

    C. Bosco

    2014-01-01

    Full Text Available This report describes a case of abdominal pregnancy in an adult female degu from which we recovered two large tissular masses from the peritoneal cavity. The bigger one showed a number of thin vascular connections to the serosa layer of the small intestine. It was also directly connected to the smaller mass by a thin membranous process. The surface of the bigger mass facing the small intestine wall showed the presence of chorionic villous that resembled a villous human chorionic placenta, rather than the hemomonochorial labyrinthine placenta, characteristic of this species. This unusual finding leads us to postulate that in the degu’s uterus the cytotrophoblast is exposed to a number of factors that will activate cascades of cellular and molecular events that ultimately will be signaling the cytotrophoblast to develop into a labyrinthine hemomonochorial placenta. In absence of the proper uterine environment, as is the case of the abdominal pregnancy in the peritoneal cavity reported here, the lack of signaling will lead the cytotrophoblast to develop into a villous chorionic placenta, similar to that observed in human.

  16. Baldness, acne and testicular germ cell tumors

    Science.gov (United States)

    Trabert, Britton; Sigurdson, Alice J.; Sweeney, Anne M.; Amato, Robert J.; Strom, Sara S.; McGlynn, Katherine A.

    2013-01-01

    Androgen levels during critical periods of testicular development may be involved in the etiology of testicular germ cell tumors (TGCT). We evaluated the roles of adolescent and early adult life correlates of androgen exposure and TGCT in a hospital-based case control study. TGCT cases (n=187) and controls (n=148), matched on age, race and state of residence, participated in the study. Unconditional logistic regression was used to estimate associations between TGCT and male pattern baldness, severe acne, markers of puberty onset and body size. Cases were significantly less likely to report hair loss than controls (OR, 0.6; 95% CI, 0.4, 1.0). Amount of hair loss, increasing age at onset and increasing rate of loss were all inversely associated with TGCT (rate of hair loss: p-trend=0.03; age at onset: p-trend=0.03; amount of hair loss: p-trend=0.01). History of severe acne was inversely associated with TGCT (OR, 0.5; 95% CI, 0.3, 0.9) and height was positively associated with TGCT (p-trend=0.02). Increased endogenous androgen levels during puberty and early adulthood may be associated with decreased risk of TGCT. Additional studies of endogenous hormone levels during puberty and early adult life are warranted, especially studies evaluating the role of androgen synthesis, metabolism and uptake. PMID:21128977

  17. Differential Nanos 2 protein stability results in selective germ cell accumulation in the sea urchin.

    Science.gov (United States)

    Oulhen, Nathalie; Wessel, Gary M

    2016-10-01

    Nanos is a translational regulator required for the survival and maintenance of primordial germ cells. In the sea urchin, Strongylocentrotus purpuratus (Sp), Nanos 2 mRNA is broadly transcribed but accumulates specifically in the small micromere (sMic) lineage, in part because of the 3'UTR element GNARLE leads to turnover in somatic cells but retention in the sMics. Here we found that the Nanos 2 protein is also selectively stabilized; it is initially translated throughout the embryo but turned over in the future somatic cells and retained only in the sMics, the future germ line in this animal. This differential stability of Nanos protein is dependent on the open reading frame (ORF), and is independent of the sumoylation and ubiquitylation pathways. Manipulation of the ORF indicates that 68 amino acids in the N terminus of the Nanos protein are essential for its stability in the sMics whereas a 45 amino acid element adjacent to the zinc fingers targets its degradation. Further, this regulation of Nanos protein is cell autonomous, following formation of the germ line. These results are paradigmatic for the unique presence of Nanos in the germ line by a combination of selective RNA retention, distinctive translational control mechanisms (Oulhen et al., 2013), and now also by defined Nanos protein stability. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Radiotherapy of patients with germ cell tumor

    International Nuclear Information System (INIS)

    Inomata, Taisuke; Maeda, Tomoho; Yoshida, Shoji; Ogawa, Yasuhiro; Hamada, Fumio; Imajo, Yoshinari; Gose, Kyuhei; Fujiwara, Kiyoshi.

    1986-01-01

    Twenty-one patients with germ cell tumor who received radiotherapy were discussed. There were eight patients with germinoma, two patients with malignant teratoma, three patients with pineocytoma (out of category of germ cell tumor today) and eight unverified patients. Irradiated dose was mostly from 50 Gy to 60 Gy and local irradiation was performed after whole brain irradiation in many cases. The effect of radiotherapy was not so good in patients with malignant teratoma. On the contrary, it was relatively good in patients with germinoma and five out of eight patients are alive with no symptoms of recurrence. Six out of eight unverified patients are also alive. Among them, several patients with germinoma are considered to be included. Germinoma occupies many cases of germ cell tumor and has a good response to radiotherapy. Against spinal cord metastasis and late recurrence, additional therapy, such as chemotherapy, seems to be useful to improve cure ratio. (author)

  19. [Germ cell membrane lipids in spermatogenesis].

    Science.gov (United States)

    Wang, Ting; Shi, Xiao; Quan, Song

    2016-05-01

    Spermatogenesis is a complex developmental process in which a diploid progenitor germ cell transforms into highly specialized spermatozoa. During spermatogenesis, membrane remodeling takes place, and cell membrane permeability and liquidity undergo phase-specific changes, which are all associated with the alteration of membrane lipids. Lipids are important components of the germ cell membrane, whose volume and ratio fluctuate in different phases of spermatogenesis. Abnormal lipid metabolism can cause spermatogenic dysfunction and consequently male infertility. Germ cell membrane lipids are mainly composed of cholesterol, phospholipids and glycolipids, which play critical roles in cell adhesion and signal transduction during spermatogenesis. An insight into the correlation of membrane lipids with spermatogenesis helps us to better understand the mechanisms of spermatogenesis and provide new approaches to the diagnosis and treatment of male infertility.

  20. Dielectric window development for the ITER ICRF vacuum transmission line

    International Nuclear Information System (INIS)

    Heikinheimo, L.; Heikkinen, J.; Hytoenen, Y.

    1998-08-01

    A vacuum window block design is presented for the ITER (International Thermonuclear Experimental Reactor) ion cyclotron radio frequency heating vacuum transmission line. The vacuum windows in various auxiliaries of the present fusion facilities and in future fusion reactors are essential and most vulnerable components, as they provide ultimate vacuum and tritium containment. Various existing windows, e.g. those at the ASDEX Upgrade tokamak (IPP, Garching), Tore Supra (CEA, Cadarache), and at JET Tokamak (Euratom, Culham), have provided a starting point for the present work, but the large size, remote handling and cooling requirements, as well as the strong neutron radiation in the fusion reactors have called a new design, where new material combinations for the dielectric and conductor have deemed to be necessary. Conventional and well tested design solutions have been chosen wherever possible. A preprototype construction has been launched to test the design principles, in particular the joining of the ceramics to a titanium conductor by brazing which has not been possible so far in this size and geometry. First results of the preprototype tests are reported here. The present final report is a combination of the results achieved with the support of two different projects; an industrial project funded by EFET and a NET Research and Design project funded by the Euratom/TEKES within the Euratom fusion programme. (orig.)

  1. Tooth-germ damage by ionizing radiation

    International Nuclear Information System (INIS)

    Sobkowiak, E.M.; Beetke, E.; Bienengraeber, V.; Held, M.; Kittner, K.H.

    1977-01-01

    Experiments on animals (four-week-old dogs) were conducted in an investigation made to study the possibility of dose-dependent tooth-germ damage produced by ionizing radiation. The individual doses were 50 R and 200 R, respectively, and they were administered once to three times at weekly intervals. Hyperemia and edemata could be observed on tooth-germ pulps from 150 R onward. Both of these conditions became more acute as the radiation dose increased (from 150 R to 600 R). Possible damage to both the dentin and enamel is pointed out. (author)

  2. Development and use of dynamic product-line architectures

    NARCIS (Netherlands)

    Andersson, J; Bosch, J

    Software product families are used to shorten time-to-market, improve quality and lower cost, by means of effective reuse. The paper presents the results of case study conducted at four Swedish companies that are involved in either the development of or development with a software product family.

  3. Development of a Short Line Railroad Safety Institute : phase I - job analysis.

    Science.gov (United States)

    2014-04-01

    The Federal Railroad Administrations (FRA) : Office of Research and Development (R&D) is : supporting the American Short Line and : Regional Railroad Association (ASLRRA) in the : development, implementation, and evaluation of : a proposed Short L...

  4. Stability of wheat germ oil obtained by supercritical carbon dioxide ...

    African Journals Online (AJOL)

    심정은

    accumulated gas volume passing through the apparatus were measured using a gas flow meter. Wheat germ oil was ..... of rancidity in wheat germ analyzed by headspace gas chromatography and sensory analysis. J. Agric. Food Chem.

  5. On-line professional staff development: An evaluation study

    NARCIS (Netherlands)

    de Vries, Linda; Naidu, Som; Jegede, Olugbemiro; Collis, Betty

    1995-01-01

    This paper reports the design, implementation, and evaluation of a teleseminar on instructional design (ID) and computer-mediated communication (CMC) for the purposes of staff development at The University of Southern Queensland, Toowoomba, Australia. Participation was open to any staff with an

  6. Stages of Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... tumors: Yolk sac tumors make a hormone called alpha-fetoprotein (AFP). They can form in the ovary, testicle, ... are used to detect extracranial germ cell tumors: Alpha-fetoprotein (AFP). Beta-human chorionic gonadotropin (β-hCG). For ...

  7. Photogrammetry in the line: recent developments in industrial photogrammetry

    Science.gov (United States)

    Boesemann, Werner

    2003-05-01

    In recent years industrial photogrammetry has emerged from a highly specialized niche technology to a well established tool in industrial coordinate measurement applications with numerous installations in a significantly growing market of flexible and portable optical measurement systems. This is due to the development of powerful, but affordable video and computer technology. The increasing industrial requirements for accuracy, speed, robustness and ease of use of these systems together with a demand for the highest possible degree of automation have forced universities and system manufacturers to develop hard- and software solutions to meet these requirements. The presentation will show the latest trends in hardware development, especially new generation digital and/or intelligent cameras, aspects of image engineering like use of controlled illumination or projection technologies,and algorithmic and software aspects like automation strategies or new camera models. The basic qualities of digital photogrammetry-like portability and flexibility on one hand and fully automated quality control on the other -- sometimes lead to certain conflicts in the design of measurement systems for different online, offline or real-time solutions. The presentation will further show, how these tools and methods are combined in different configurations to be able to cover the still growing demands of the industrial end-users.

  8. Cell line development for biomanufacturing processes: recent advances and an outlook.

    Science.gov (United States)

    Le, Huong; Vishwanathan, Nandita; Jacob, Nitya M; Gadgil, Mugdha; Hu, Wei-Shou

    2015-08-01

    At the core of a biomanufacturing process for recombinant proteins is the production cell line. It influences the productivity and product quality. Its characteristics also dictate process development, as the process is optimized to complement the producing cell to achieve the target productivity and quality. Advances in the past decade, from vector design to cell line screening, have greatly expanded our capability to attain producing cell lines with certain desired traits. Increasing availability of genomic and transcriptomic resources for industrially important cell lines coupled with advances in genome editing technology have opened new avenues for cell line development. These developments are poised to help biosimilar manufacturing, which requires targeting pre-defined product quality attributes, e.g., glycoform, to match the innovator's range. This review summarizes recent advances and discusses future possibilities in this area.

  9. Involvement of the DNA mismatch repair system in cisplatin sensitivity of testicular germ cell tumours.

    Science.gov (United States)

    Rudolph, Christiane; Melau, Cecilie; Nielsen, John E; Vile Jensen, Kristina; Liu, Dekang; Pena-Diaz, Javier; Rajpert-De Meyts, Ewa; Rasmussen, Lene Juel; Jørgensen, Anne

    2017-08-01

    Testicular germ cell tumours (TGCT) are highly sensitive to cisplatin-based chemotherapy, but patients with tumours containing differentiated teratoma components are less responsive to this treatment. The cisplatin sensitivity in TGCT has previously been linked to the embryonic phenotype in the majority of tumours, although the underlying mechanism largely remains to be elucidated. The aim of this study was to investigate the role of the DNA mismatch repair (MMR) system in the cisplatin sensitivity of TGCT. The expression pattern of key MMR proteins, including MSH2, MSH6, MLH1 and PMS2, were investigated during testis development and in the pathogenesis of TGCT, including germ cell neoplasia in situ (GCNIS). The TGCT-derived cell line NTera2 was differentiated using retinoic acid (10 μM, 6 days) after which MMR protein expression and activity, as well as cisplatin sensitivity, were investigated in both undifferentiated and differentiated cells. Finally, the expression of MSH2 was knocked down by siRNA in NTera2 cells after which the effect on cisplatin sensitivity was examined. MMR proteins were expressed in proliferating cells in the testes, while in malignant germ cells MMR protein expression was found to coincide with the expression of the pluripotency factor OCT4, with no or low expression in the more differentiated yolk sac tumours, choriocarcinomas and teratomas. In differentiated NTera2 cells we found a significantly (p cisplatin sensitivity, compared to undifferentiated NTera2 cells. Also, we found that partial knockdown of MSH2 expression in undifferentiated NTera2 cells resulted in a significantly (p cisplatin sensitivity. This study reports, for the first time, expression of the MMR system in fetal gonocytes, from which GCNIS cells are derived. Our findings in primary TGCT specimens and TGCT-derived cells suggest that a reduced sensitivity to cisplatin in differentiated TGCT components could result from a reduced expression of MMR proteins, in

  10. EMMPRIN (basigin/CD147) is involved in the morphogenesis of tooth germ in mouse molars.

    Science.gov (United States)

    Xie, Ming; Jiao, Ting; Chen, Yuqin; Xu, Chun; Li, Jing; Jiang, Xinquan; Zhang, Fuqiang

    2010-05-01

    The pattern of gene expression for extracellular matrix metalloproteinase inducer (EMMPRIN) was revealed in the tooth germ of mouse mandibular molars using quantitative real-time PCR. In situ hybridization and immunohistochemical study demonstrated the characteristic distribution of EMMPRIN in the different stages of tooth germ development. To investigate the functional role played by EMMPRIN in tooth germ development, EMMPRIN siRNA interference approach was carried out in cultured mouse mandibles at embryonic day 11.0 (E11.0). The results showed that EMMPRIN siRNA-treated explants exhibited a marked growth inhibition of tooth germ compared to the control and scrambled siRNA-treated explants. Meanwhile, a significant increase in MT1-MMP mRNA expression and a reduction in MMP-2, MMP-3, MMP-9, MMP-13 and MT2-MMP mRNA expression were observed in the mouse mandibles following EMMPRIN abrogation. The current results indicate that EMMPRIN could thus be involved in the early stage of tooth germ development and morphogenesis, possibly by regulating the expression of MMP genes.

  11. Longitudinal development of number line estimation and mathematics performance in primary school children

    NARCIS (Netherlands)

    Friso-van den Bos, I.; Kroesbergen, E.H.; van Luit, J.E.H.; Xenidou-Dervou, I.; Jonkman, L.M.; van der Schoot, M.; van Lieshout, E.C.D.M.

    2015-01-01

    Children's ability to relate number to a continuous quantity abstraction visualized as a number line is widely accepted to be predictive of mathematics achievement. However, a debate has emerged with respect to how children's placements are distributed on this number line across development. In the

  12. Longitudinal development of number line estimation and mathematics performance in primary school children

    NARCIS (Netherlands)

    Friso - van den Bos, Ilona; Kroesbergen, Evelyn; van Luit, Hans; Xenidou-Dervou, Iro; Jonkman, Lisa M.; Van der Schoot, Menno; Van Lieshout, Ernest C. D. M.

    2015-01-01

    Children’s ability to relate number to a continuous quantity abstraction visualized as a number line is widely accepted to be predictive of mathematics achievement. However, a debate has emerged with respect to how children’s placements are distributed on this number line across development. In the

  13. A Role-Playing Game for a Software Engineering Lab: Developing a Product Line

    Science.gov (United States)

    Zuppiroli, Sara; Ciancarini, Paolo; Gabbrielli, Maurizio

    2012-01-01

    Software product line development refers to software engineering practices and techniques for creating families of similar software systems from a basic set of reusable components, called shared assets. Teaching how to deal with software product lines in a university lab course is a challenging task, because there are several practical issues that…

  14. Development of vitrification line technology and the manufacture of equipment

    International Nuclear Information System (INIS)

    Alexa, J.

    1989-01-01

    The development is described of technology and the production of equipment for the vitrification of liquid radioactive wastes. For vitrification, frit Frita F270 is used containing up to 20% titanium and featuring a corrosion effect lower by one order than that of lead glass. The liquid waste is discharged in a measuring tank where it is mixed with formic acid. It is then pumped into an evaporator. Breed vapor is carried via a condenser to a condensate tank. The evaporator concentrate is transported to a homogenizer where it is gradually mixed with Frita. The viscous mush thus produced is carried into a furnace where the remaining water is evaporated. The furnace decontamination factor is 10 2 to 10 3 . At a temperature of up to 1,050 degC the frit melts and is discharged into a case. Currently, technology has been developed of mush preparation and the design has been completed of a vitrification furnace featuring remote lid opening and closing, and of equipment for processing furnace emissions. (J.B.). 3 figs., 1 tab., 1 ref

  15. Predicting retroperitoneal histology in postchemotherapy testicular germ cell cancer : A model update and multicentre validation with more than 1000 patients

    NARCIS (Netherlands)

    Vergouwe, Yvonne; Steyerberg, Ewout W.; Foster, Richard S.; Sleijfer, Dirk T.; Fossa, Sophie D.; Gerl, Arthur; de Wit, Ronald; Roberts, J. Trevor; Habbema, J. Dik F.

    Objectives: Surgical resection of postchemotherapy retroperitoneal lymph nodes is often performed in patients with advanced nonseminomatous testicular germ cell cancer. We previously developed a model to predict the probability that the lymph nodes contain only necrotic or fibrotic (benign) tissue

  16. Development and validation of a novel patient-reported treatment satisfaction measure for hyperfunctional facial lines: facial line satisfaction questionnaire.

    Science.gov (United States)

    Pompilus, Farrah; Burgess, Somali; Hudgens, Stacie; Banderas, Benjamin; Daniels, Selena

    2015-12-01

    Facial lines or wrinkles are among the most visible signs of aging, and minimally invasive cosmetic procedures are becoming increasingly popular. The aim of this study was to develop and validate the Facial Line Satisfaction Questionnaire (FLSQ) for use in adults with upper facial lines (UFL). A literature review, concept elicitation interviews (n = 33), and cognitive debriefing interviews (n = 23) of adults with UFL were conducted to develop the FLSQ. The FLSQ comprises Baseline and Follow-up versions and was field-tested with 150 subjects in a US observational study designed to assess its psychometric performance. Analyses included acceptability (item and scale distribution [i.e. missingness, floor, and ceiling effects]), reliability, and validity (including concurrent validity). In total, 69 concepts were elicited during patient interviews. Following cognitive debriefing interviews, the FLSQ-Baseline version included 11 items and the Follow-up version included 13 items. Response rates for the FLSQ were 100% and 73% at baseline and follow-up, respectively; no items had excessive missing data. Questionnaire scale scores were normally distributed. Most domain scores demonstrated good internal consistency reliability (Cronbach's α ≥ 0.70). Most items within their respective domains exhibited good convergent (item-scale correlations > 0.40) and discriminant (items had higher correlation with their hypothesized scales than other scales) validity. Concurrent validity correlation coefficients of the FLSQ domain scores with the associated concurrent measures were acceptable (range: r = 0.40-0.70). Six FLSQ items demonstrated reliability and validity as stand-alone items outside their domains. The FLSQ is a valid questionnaire for assessing treatment expectations, satisfaction, impact, and preference in adults with UFL. © 2015 The Authors. Journal of Cosmetic Dermatology Published by Wiley Periodicals, Inc.

  17. The effects of humanin and its analogues on male germ cell apoptosis induced by chemotherapeutic drugs.

    Science.gov (United States)

    Jia, Yue; Ohanyan, Aikoui; Lue, Yan-He; Swerdloff, Ronald S; Liu, Peter Y; Cohen, Pinchas; Wang, Christina

    2015-04-01

    Human (HN) prevents stress-induced apoptosis in many cells/tissues. In this study we showed that HN ameliorated chemotherapy [cyclophosphamide (CP) and Doxorubicin (DOX)]-induced male germ cell apoptosis both ex vivo in seminiferous tubule cultures and in vivo in the testis. HN acts by several putative mechanisms via binding to: an IL-12 like trimeric membrane receptor; BAX; or insulin-like growth factor binding protein-3 (IGFBP-3, a proapoptotic factor). To understand the mechanisms of HN on male germ cell apoptosis, we studied five HN analogues including: HNG (HN-S14G, a potent agonist), HNG-F6A (no binding to IGFBP-3), HN-S7A (no self-dimerization), HN-C8P (no binding to BAX), and HN-L12A (a HN antagonist) on CP-induced male germ cell apoptosis in mice. CP-induced germ cell apoptosis was inhibited by HN, HNG, HNG-F6A, HN-S7A, and HN-C8P (less effective); but not by HN-L12A. HN-L12A, but not HN-S7A or HN-C8P, blocked the protective effect of HN against CP-induced male germ cell apoptosis. HN, HN-S7A, and HN-C8P restored CP-suppressed STAT3 phosphorylation. These results suggest that HN: (1) decreases DOX (ex vivo) and CP (in vivo) induced male germ cell apoptosis; (2) action is mediated by the membrane receptor/STAT3 with minor contribution by BAX-binding pathway; (3) self-dimerization or binding to IGFBP-3 may not be involved in HN's effect in testis. HN is an important molecule in the regulation of germ cell homeostasis after injury and agonistic analogues may be developed for treating male infertility or protection against chemotherapy side effects.

  18. Development of Blumlein Line Generator and Reactor for Wastewater Treatment

    Directory of Open Access Journals (Sweden)

    Zainuddin Nawawi

    2013-11-01

    Full Text Available Nowadays the harm effects of wastewater from industrial sectors toward the environment become one of public major concern. There are several wastewater treatment methods and techniques which have been introduced such as by using biological, chemical, and physical process. However, it is found that there are some shortcomings in the current available methods and techniques. For instance, the application of chlorine can cause bacterial disinfection but produce secondary harmful carcinogenic disinfection.  And the application of ozone treatment –  which is one of the most reliable technique – requires improvement in term of ozone production and treatment system. In order to acquire a better understanding in wastewater treatment process, a study of wastewater treatment system and Hybrid Discharge reactor – to acquire gas-liquid phase corona like discharge – is carried out. In addition to the laboratory experiment, designing and development of the Blumlein pulse power circuit, and modification of reactor for wastewater treatment are accomplished as well.

  19. Conceptual design and development of a superconducting bus-line for the Large Helical Device

    International Nuclear Information System (INIS)

    Mito, T.; Takahata, K.; Yamada, S.; Yamamoto, J.; Uede, T.; Ikeda, M.

    1993-01-01

    A superconducting bus-line is proposed and preliminarily tested as an electrical feeder between the superconducting coils of the Large Helical Device (LHD) and their electrical power supply. The bus-line consists of a superconductor and its cryogenic transfer-line. The superconductor is a specially developed aluminum stabilized NbTi wire, which is installed in the innermost channel of the transfer-line. The vacuum insulated transfer-line consists of four corrugated tubes assembled coaxially. Liquid helium flows through the innermost channel and shield gas flows through another annular channel in the line. We are completing the conceptual design of the bus-line and the installation plan for the LHD experimental hall and are carrying out development of wires, including an investigation of their mechanical properties and electrical insulation. This report describes the conceptual design of the superconducting bus-line for the LHD, and the results we obtained recently during the design and development of a full-scale demonstration facility. (orig.)

  20. Coastal Ocean Ecosystem Dynamics Imager Pointing Line-of-Sight Solution Development and Testing

    Data.gov (United States)

    National Aeronautics and Space Administration — A stable pointing line of sight solution is developed and tested in support of the Coastal Ocean Ecosystem Dynamics Imager for the GEOstationary Coastal and Air...

  1. Pathobiology of germ cell tumors - applying the gossip test!

    Science.gov (United States)

    Looijenga, Leendert H J; Oosterhuis, J Wolter

    2013-01-01

    Residual mature teratoma, a frequent finding in clinical pathology since the introduction of cisplatin-based chemotherapy, put Wolter Oosterhuis on the track of germ cell tumors (GCTs). These neoplasms in the borderland between developmental biology and oncology have fascinated him ever since. He tells the story on how GCTs brought him in contact with leading investigators in the field like Ivan Damjanov, Peter Andrews, and Niels Skakkebaek. His fruitful line of research was made possible through a longstanding collaboration with Bauke de Jong and, to this day, Leendert Looijenga who joined his group as a student in 1988. Probably their most important contribution to the field of GCTs is an integrated approach to GCTs, combining epidemiology, pathology, (cyto)genetics and molecular biology, that has resulted in a pathobiology-based classification of GCTs in five types. It has clinical relevance and stimulates further research on these intriguing neoplasms and their corresponding animal models.

  2. Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 5: intercellular junctions and contacts between germs cells and Sertoli cells and their regulatory interactions, testicular cholesterol, and genes/proteins associated with more than one germ cell generation.

    Science.gov (United States)

    Hermo, Louis; Pelletier, R-Marc; Cyr, Daniel G; Smith, Charles E

    2010-04-01

    In the testis, cell adhesion and junctional molecules permit specific interactions and intracellular communication between germ and Sertoli cells and apposed Sertoli cells. Among the many adhesion family of proteins, NCAM, nectin and nectin-like, catenins, and cadherens will be discussed, along with gap junctions between germ and Sertoli cells and the many members of the connexin family. The blood-testis barrier separates the haploid spermatids from blood borne elements. In the barrier, the intercellular junctions consist of many proteins such as occludin, tricellulin, and claudins. Changes in the expression of cell adhesion molecules are also an essential part of the mechanism that allows germ cells to move from the basal compartment of the seminiferous tubule to the adluminal compartment thus crossing the blood-testis barrier and well-defined proteins have been shown to assist in this process. Several structural components show interactions between germ cells to Sertoli cells such as the ectoplasmic specialization which are more closely related to Sertoli cells and tubulobulbar complexes that are processes of elongating spermatids embedded into Sertoli cells. Germ cells also modify several Sertoli functions and this also appears to be the case for residual bodies. Cholesterol plays a significant role during spermatogenesis and is essential for germ cell development. Lastly, we list genes/proteins that are expressed not only in any one specific generation of germ cells but across more than one generation. Copyright 2009 Wiley-Liss, Inc.

  3. Defining project scenarios for the agile requirements engineering product-line development questionnaire

    OpenAIRE

    Feng, Kunwu; Lempert, Meli; Tang, Yan; Tian, Kun; Cooper, Kendra M.L.; Franch Gutiérrez, Javier

    2007-01-01

    Current agile methods are focused on practices of small, rapid developing and iteration, more people oriented, less documentation projects, and the use of the methods in large, product line projects are somehow difficult. UTD and GESSI have started a project to develop an expert system that can assist a requirements enginer in selecting a requirements engineering process that is well suited for their project, in particular with respect to the use of agile and product line engineering methods....

  4. Developing a survey to collect expertise in agile product line requirements engineering processes

    OpenAIRE

    Feng, Kunwu; Lempert, Meli; Tang, Yan; Tian, Kun; Cooper, Kendra M.L.; Franch Gutiérrez, Javier

    2007-01-01

    Current agile methods are focused on practices of small, rapid developing and iteration, more people oriented, less documentation projects, and the use of the methods in large, product line projects are somehow difficult. UTD and GESSI have started a project to develop an expert system that can assist a requirements enginer in selecting a requirements engineering process that is well suited for their project, in particular with respect to the use of agile and product line engineering methods....

  5. Development and Implementation of an Electric Circuits On-Line Course

    Directory of Open Access Journals (Sweden)

    Ahmed Hussain

    2009-02-01

    Full Text Available An electric circuit on-line course has been developed at KFUPM to support student centered learning. The course has been used in the first stage to supplement the class room face-to-face instruction. This paper describes the development stages of the on-line course and highlights its fundamental features that are not available in the traditional methods of instruction. The paper also includes the results of a survey conducted among students who have utilized the on-line material to supplement their traditional study of the electric circuits’ course. The results of the survey showed a general satisfaction with the course content and the instructional effectiveness.

  6. Developing an expert system to control a beam line at the Los Alamos Meson Physics Facility

    International Nuclear Information System (INIS)

    Clearwater, S.H.; Papcun, G.; Clark, D.A.

    1985-01-01

    High energy particle experiments require an accelerator as a source of high energy particles. To increase the productivity of an accelerator facility, we wish to develop an expert system to control beam lines. Expert Systems are a branch of Artificial Intelligence where a computer program performs tasks requiring human expertise. Unlike most expert systems we have a physical model underlying our beam line and this model can be used with the expert system to improve performance. The development of the expert system will lead to an increased understanding of the beam line as well as the possibility of state-of-the-art expert system building

  7. NANOG priming before full reprogramming may generate germ cell tumours

    Directory of Open Access Journals (Sweden)

    I Grad

    2011-11-01

    Full Text Available Reprogramming somatic cells into a pluripotent state brings patient-tailored, ethical controversy-free cellular therapy closer to reality. However, stem cells and cancer cells share many common characteristics; therefore, it is crucial to be able to discriminate between them. We generated two induced pluripotent stem cell (iPSC lines, with NANOG pre-transduction followed by OCT3/4, SOX2, and LIN28 overexpression. One of the cell lines, CHiPS W, showed normal pluripotent stem cell characteristics, while the other, CHiPS A, though expressing pluripotency markers, failed to differentiate and gave rise to germ cell-like tumours in vivo. Comparative genomic hybridisation analysis of the generated iPS lines revealed that they were genetically more stable than human embryonic stem cell counterparts. This analysis proved to be predictive for the differentiation potential of analysed cells. Moreover, the CHiPS A line expressed a lower ratio of p53/p21 when compared to CHiPS W. NANOG pre-induction followed by OCT3/4, SOX2, MYC, and KLF4 induction resulted in the same tumour-inducing phenotype. These results underline the importance of a re-examination of the role of NANOG during reprogramming. Moreover, this reprogramming method may provide insights into primordial cell tumour formation and cancer stem cell transformation.

  8. Prolonged expression of the c-kit receptor in germ cells of intersex fetal testes

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, Ewa; Jørgensen, N; Müller, Jørn

    1996-01-01

    conditions which included 45,X/46,XY mosaicism; androgen insensitivity syndrome; and 46,XY/iso(p)Y mosaicism. Individuals with such disorders of sexual differentiation and Y-chromosome material carry a very high risk of developing testicular neoplasms. Fetal testicular germ cells of the intersex subjects...... expressed Kit at a later developmental age than controls, in which no Kit protein was detectable beyond the 15th week of gestation. This finding may indicate a disturbance of the chronology of germ cell development, or it may suggest a change of the regulation of c-kit expression in subjects with disorders...

  9. Human iPS Cell-Derived Germ Cells: Current Status and Clinical Potential

    Directory of Open Access Journals (Sweden)

    Tetsuya Ishii

    2014-10-01

    Full Text Available Recently, fertile spermatozoa and oocytes were generated from mouse induced pluripotent (iPS cells using a combined in vitro and in vivo induction system. With regard to germ cell induction from human iPS cells, progress has been made particularly in the male germline, demonstrating in vitro generation of haploid, round spermatids. Although iPS-derived germ cells are expected to be developed to yield a form of assisted reproductive technology (ART that can address unmet reproductive needs, genetic and/or epigenetic instabilities abound in iPS cell generation and germ cell induction. In addition, there is still room to improve the induction protocol in the female germline. However, rapid advances in stem cell research are likely to make such obstacles surmountable, potentially translating induced germ cells into the clinical setting in the immediate future. This review examines the current status of the induction of germ cells from human iPS cells and discusses the clinical potential, as well as future directions.

  10. Identity of M2A (D2-40) antigen and gp36 (Aggrus, T1A-2, podoplanin) in human developing testis, testicular carcinoma in situ and germ-cell tumours

    DEFF Research Database (Denmark)

    Sonne, Si Brask; Herlihy, Amy S; Hoei-Hansen, Christina E

    2006-01-01

    Testicular germ-cell tumours of young adults are derived from a pre-invasive intratubular lesion, carcinoma in situ (CIS). In a recent genome-wide gene expression screening using cDNA microarrays, we found PDPN over-expressed in CIS compared to normal adult testis. PDPN encodes podoplanin (Aggrus...... gonocytes and immature Sertoli cells, similar to the expression pattern of M2A antigen, a previously identified marker for CIS and seminoma. This reinforced our previous proposal that M2A (D2-40) antigen was identical to gp36 (podoplanin, Aggrus, T1A-2). Our findings also suggest that podoplanin has...

  11. Multi-modality treatment in males with advanced malignant germ cell tumours

    International Nuclear Information System (INIS)

    Fossaa, S.D.; Klepp, O.; Ous, S.; Lien, H.; Stenwig, J.T.; Abeler, V.; Eliasson, G.; Hoest, H.

    1984-01-01

    After chemotherapy with cis-platinum, vinblastine and bleomycin, 33 surgical prosedures were performed in 29 patients with advanced malignant germ-cell tumours. The tumour masses could be completely resected macroscopially in 26 patients. Patients with fibros/necrosis or completely resected mature teratoma had an excellent prognosis, whereas only 5 of the 11 patients with vital malignant tumour survived in spite of second-line treatment with chemotherapy/radiotherapy. Preoperatively elevated serum levels of AFP, β-HCG and/or LDH indicated the presence of residual germ cell tumour. Eight of 14 patients were rendered tumour-free by radiotherapy given as second- or third-line treatment. In general, tumour masses, remaining after cis-platinum-based induction chemotherapy should be resected as completely as possible even in the case of mature teratoma or fibrosis/necrosis. Radiotherapy should be considered as second -and thirdline treatment

  12. Prognostic Factors and Treatment Results After Bleomycin, Etoposide, and Cisplatin in Germ Cell Cancer

    DEFF Research Database (Denmark)

    Kier, Maria G; Lauritsen, Jakob; Mortensen, Mette S

    2017-01-01

    BACKGROUND: First-line treatment for patients with disseminated germ cell cancer (GCC) is bleomycin, etoposide, and cisplatin (BEP). A prognostic classification of patients receiving chemotherapy was published by the International Germ Cell Cancer Collaborative Group (IGCCCG) in 1997, but only...... a small proportion of the patients received BEP. OBJECTIVE: To estimate survival probabilities after BEP, evaluate the IGCCCG prognostic classification, and propose new prognostic factors for outcome. DESIGN, SETTING, AND PARTICIPANTS: Of a Danish population-based cohort of GCC patients (1984-2007), 1889...... received first-line BEP, with median follow-up of 15 yr. Covariates evaluated as prognostic factors were age, year of treatment, primary site, non-pulmonary visceral metastases, pulmonary metastases, and tumor markers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes measured were 5-yr progression...

  13. YKL-40 is differentially expressed in human embryonic stem cells and in cell progeny of the three germ layers

    DEFF Research Database (Denmark)

    Brøchner, Christian B; Johansen, Julia S; Larsen, Lars A

    2012-01-01

    oxygen tension, in culture medium with or without basic fibroblast growth factor, and on feeder layers comprising mouse embryonic fibroblasts or human foreskin fibroblasts to evaluate whether hESCs and their progeny produced YKL-40 and to characterize YKL-40 expression during differentiation. Secreted......The secreted glycoprotein YKL-40 participates in cell differentiation, inflammation, and cancer progression. High YKL-40 expression is reported during early human development, but its functions are unknown. Six human embryonic stem cell (hESC) lines were cultured in an atmosphere of low or high...... YKL-40 protein and YKL-40 mRNA expression were measured by enzyme-linked immunosorbent assay (ELISA) and quantitative RT-PCR. Serial-sectioned colonies were stained for YKL-40 protein and for pluripotent hESC (OCT4, NANOG) and germ layer (HNF-3ß, PDX1, CD34, p63, nestin, PAX6) markers. Double...

  14. Neurl4 contributes to germ cell formation and integrity in Drosophila

    Directory of Open Access Journals (Sweden)

    Jennifer Jones

    2015-08-01

    Full Text Available Primordial germ cells (PGCs form at the posterior pole of the Drosophila embryo, and then migrate to their final destination in the gonad where they will produce eggs or sperm. Studies of the different stages in this process, including assembly of germ plasm in the oocyte during oogenesis, specification of a subset of syncytial embryonic nuclei as PGCs, and migration, have been informed by genetic analyses. Mutants have defined steps in the process, and the identities of the affected genes have suggested biochemical mechanisms. Here we describe a novel PGC phenotype. When Neurl4 activity is reduced, newly formed PGCs frequently adopt irregular shapes and appear to bud off vesicles. PGC number is also reduced, an effect exacerbated by a separate role for Neurl4 in germ plasm formation during oogenesis. Like its mammalian homolog, Drosophila Neurl4 protein is concentrated in centrosomes and downregulates centrosomal protein CP110. Reducing CP110 activity suppresses the abnormal PGC morphology of Neurl4 mutants. These results extend prior analyses of Neurl4 in cultured cells, revealing a heightened requirement for Neurl4 in germ-line cells in Drosophila.

  15. DNA repair studies in mammalian germ cells

    International Nuclear Information System (INIS)

    Sega, G.A.; Owens, J.G.

    1984-01-01

    In submammalian test systems, nitrosocarbamates (NEC) are 100-fold more mutagenic than are their corresponding nitrosourea homologues. To learn more about its interaction with germ-cell DNA in the mouse testis, male mice were given i.p. injections of NEC. Testicular injections of [ 3 H]dThd were given along with the NEC. Sixteen days after treatment, sperm were recovered from the caudal epididymides and assayed for an unscheduled-DNA-synthesis

  16. Diagnostic markers for germ cell neoplasms

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, Ewa; Nielsen, John E; Skakkebaek, Niels E

    2015-01-01

    This concise review summarises tissue and serum markers useful for differential diagnosis of germ cell tumours (GCTs), with focus on the most common testicular GCTs (TGCTs). GCTs are characterised by phenotypic heterogeneity due to largely retained embryonic pluripotency and aberrant somatic diff...... of molecular markers, which allow specific diagnosis of various subtypes of GCT and are very useful for early detection at the precursor stage and for monitoring of patients during the follow-up....

  17. Irinotecan in patients with relapsed or cisplatin-refractory germ cell cancer: a phase II study of the German Testicular Cancer Study Group

    OpenAIRE

    Kollmannsberger, C; Rick, O; Klaproth, H; Kubin, T; Sayer, H G; Hentrich, M; Welslau, M; Mayer, F; Kuczyk, M; Spott, C; Kanz, L; Bokemeyer, C

    2002-01-01

    Despite generally high cure rates in patients with metastatic germ cell cancer, patients with progressive disease on first-line cisplatin-based chemotherapy or with relapsed disease following high-dose salvage therapy exhibit a very poor prognosis. Irinotecan has shown antitumour activity in human testicular tumour xenografts in nude mice. We have performed a phase II study examining the single agent activity of irinotecan in patients with metastatic relapsed or cisplatin-refractory germ cell...

  18. Radiation Therapy of Suprasellar Germ Cell Tumors

    International Nuclear Information System (INIS)

    Park, Woo Yoon; Choi, Doo Ho; Choi, Eun Kyung; Kim, Il Han; Ha, Sung Whan; Park, Charn Il

    1988-01-01

    A retrospective study was performed on 15 patients with suprasellar germ cell tumors treated by megavoltage external beam irradiation between Feb. 1979 and Dec. 1985. Follow-up period of survivors was 30 to 91 months. Histologic diagnosis was obtained before radiation therapy in 10 patients (9 germinomas and 1 mixed). Five patients were treated without histologic verification. In 9 patients with biopsy-proven germinomas radiation therapy was delivered to the craniospinal axis in 6, to the whole brain in 3. In 5 patients with mixed germ cell tumor or elevated tumor marker, irradiation was delivered to the craniospinal axis in 2, to the whole brain in 2, and to the primary site only in 1. Total doses ranged from 5,000 to 5,500 cGy to the primary site, 3,000 to 4,400 cGy to the whole brain, and 1,300 to 3,000 cGy to the spine. In these 14, local tumor was controlled and primary or spinal failure was not observed. One patient without elevated tumor marker was treated to the whole brain, The tumor was not controlled and he had spinal recurrence. It is proven that radiation therapy is an effective treatment for suprasellar germ cell tumors. The neuroendocrinologic presentation, tumor marker status, early response to radiation measured on CT seem to be useful means for selecting patients for radiation therapy when tissue diagnosis is not available

  19. Dnd Is a Critical Specifier of Primordial Germ Cells in the Medaka Fish

    Directory of Open Access Journals (Sweden)

    Ni Hong

    2016-03-01

    Full Text Available Primordial germ cell (PGC specification occurs early in development. PGC specifiers have been identified in Drosophila, mouse, and human but remained elusive in most animals. Here we identify the RNA-binding protein Dnd as a critical PGC specifier in the medaka fish (Oryzias latipes. Dnd depletion specifically abolished PGCs, and its overexpression boosted PGCs. We established a single-cell culture procedure enabling lineage tracing in vitro. We show that individual blastomeres from cleavage embryos at the 32- and 64-cell stages are capable of PGC production in culture. Importantly, Dnd overexpression increases PGCs via increasing PGC precursors. Strikingly, dnd RNA forms prominent particles that segregate asymmetrically. Dnd concentrates in germ plasm and stabilizes germ plasm RNA. Therefore, Dnd is a critical specifier of fish PGCs and utilizes particle partition as a previously unidentified mechanism for asymmetric segregation. These findings offer insights into PGC specification and manipulation in medaka as a lower vertebrate model.

  20. Congenital Cerebellar Mixed Germ Cell Tumor Presenting with Hemorrhage in a Newborn

    International Nuclear Information System (INIS)

    Kim, Sung Mok; Kim, Ji Hye; Yoo, So Young; Park, Won Soon; Jang, Yun Sil; Shin, Hyung Jin; Suh, Yeon Lim

    2008-01-01

    We report here on a neonate with congenital cerebellar mixed germ cell tumor, and this initially presented as cerebellar hemorrhage. Postnatal cranial ultrasonography revealed an echogenic cerebellar mass that exhibited the signal characteristics of hemorrhage rather than tumor on MR images. The short-term follow-up images also suggested a resolving cerebellar hemorrhage. One month later, the neonate developed vomiting. A second set of MR images demonstrated an enlarged mass that exhibited changed signal intensity at the same site, which suggested a neoplasm. Histological examination after the surgical resection revealed a mixed germ cell tumor

  1. Development of at-line assay to monitor charge variants of MAbs during production.

    Science.gov (United States)

    St Amand, M M; Ogunnaike, B A; Robinson, A S

    2014-01-01

    One major challenge currently facing the biopharmaceutical industry is to understand how MAb microheterogeneity affects therapeutic efficacy, potency, immunogenicity, and clearance. MAb micro-heterogeneity can result from post-translational modifications such as sialylation, galactosylation, C-terminal lysine cleavage, glycine amidation, and tryptophan oxidation, each of which can generate MAb charge variants; such heterogeneity can affect pharmacokinetics (PK) considerably. Implementation of appropriate on-line quality control strategies may help to regulate bioprocesses, thus enabling more homogenous material with desired post-translational modifications and PK behavior. However, one major restriction to implementation of quality control strategies is the availability of techniques for obtaining on-line or at-line measurements of these attributes. In this work, we describe the development of an at-line assay to separate MAb charge variants in near real-time, which could ultimately be used to implement on-line quality control strategies for MAb production. The assay consists of a 2D-HPLC method with sequential in-line Protein A and WCX-10 HPLC column steps. To perform the 2D-HPLC assay at-line, the two columns steps were integrated into a single method using a novel system configuration that allowed parallel flow over column 1 or column 2 or sequential flow from column 1 to column 2. A bioreactor system was also developed such that media samples could be removed automatically from bioreactor vessels during production and delivered to the 2D-HPLC for analysis. With this at-line HPLC assay, we have demonstrated that MAb microheterogeneity occurs throughout the cell cycle whether the host cell line is grown under different or the same nominal culture conditions. © 2013 American Institute of Chemical Engineers.

  2. Germ Cell Cancer and Multiple Relapses: Toxicity and Survival

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Kier, Maria G.G.; Mortensen, Mette S.

    2015-01-01

    Purpose: A small number of patients with germ cell cancer (GCC) receive more than one line of treatment for disseminated disease. The purpose of this study was to evaluate late toxicity and survival in an unselected cohort of patients who experienced relapse after receiving first-line treatment...... for disseminated disease. Methods: From the Danish Testicular Cancer database, we identified all patients who received more than one line of treatment for disseminated disease. Information about late toxicity and mortality was obtained by means of linkage to national registers. Prognostic factors for relapse......, compared with patients treated with only orchiectomy, had an increased risk for a second cancer (hazard ratio [HR], 3.2; 95% CI, 1.9 to 5.5), major cardiovascular disease (HR, 1.9; 95% CI, 1.0 to 3.3), pulmonary disease (HR, 2.0; 95% CI, 1.0 to 3.8), GI disease (HR, 7.3; 95% CI, 3.6 to 14.8), renal...

  3. Development of a fast multi-line x-ray CT detector for NDT

    International Nuclear Information System (INIS)

    Hofmann, T.; Nachtrab, F.; Schlechter, T.; Mühlbauer, J.; Schröpfer, S.; Firsching, M.; Uhlmann, N.; Neubauer, H.; Ernst, J.; Schweiger, T.; Oberst, M.; Meyer, A.

    2015-01-01

    Typical X-ray detectors for non-destructive testing (NDT) are line detectors or area detectors, like e.g. flat panel detectors. Multi-line detectors are currently only available in medical Computed Tomography (CT) scanners. Compared to flat panel detectors, line and multi-line detectors can achieve much higher frame rates. This allows time-resolved 3D CT scans of an object under investigation. Also, an improved image quality can be achieved due to reduced scattered radiation from object and detector themselves. Another benefit of line and multi-line detectors is that very wide detectors can be assembled easily, while flat panel detectors are usually limited to an imaging field with a size of approx. 40 × 40 cm 2 at maximum. The big disadvantage of line detectors is the limited number of object slices that can be scanned simultaneously. This leads to long scan times for large objects. Volume scans with a multi-line detector are much faster, but with almost similar image quality. Due to the promising properties of multi-line detectors their application outside of medical CT would also be very interesting for NDT. However, medical CT multi-line detectors are optimized for the scanning of human bodies. Many non-medical applications require higher spatial resolutions and/or higher X-ray energies. For those non-medical applications we are developing a fast multi-line X-ray detector.In the scope of this work, we present the current state of the development of the novel detector, which includes several outstanding properties like an adjustable curved design for variable focus-detector-distances, conserving nearly uniform perpendicular irradiation over the entire detector width. Basis of the detector is a specifically designed, radiation hard CMOS imaging sensor with a pixel pitch of 200 μ m. Each pixel has an automatic in-pixel gain adjustment, which allows for both: a very high sensitivity and a wide dynamic range. The final detector is planned to have 256 lines of

  4. Effect of UV irradiation on the early development of silkworm embryos, (2). Development of irradiated eggs

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Y. (Hokkaido Univ., Sapporo (Japan). Faculty of Agriculture)

    1981-02-01

    The development of silkworm eggs irradiated with UV was compared with that of normal eggs. When the eggs were irradiated with UV from the lateral side immediately after oviposition, development was decelerated, but the germ band was produced. The side of the germ band that was irradiated with UV was abnormal with holes, but the opposite side was hole-free and normal. The normal half of the germ band splits longitudinally, but developed along with the abnormal half to form various malformations. When the eggs were irradiated from the ventral side, the ventral part of the germ band was abnormal at the early stage, the germ band did not concentrate to one place, and produced the half-embryos longitudinally divided by the median line. The UV irradiation at the beginning of the blastoderm stage produced similar results. In the areas irradiated by UV, cleavage nuclei invaded into the surrounding protoplasm, and mitotic figures were observed, but the cell number did not increase even with the advance of development unlike normal cells, whereas the sizes of the cells, their nuclei and nucleoli were enlarged, and intercellular space widened so that the cells were no longer in close contact. The germ band cells produced in the non-irradiated area were normal. The above results suggest that when either the protoplasm or the nucleus of a silkworm egg is damaged by UV, the effect first appears as the inhibition of cell division in the germ band, and as the enlargement of the cell, nucleus and nucleoli. It is presumed that this induces the subsequent inhibition of cell differentiation or abnormalities.

  5. Calling line managers in employee continuous professional development in South East Asia

    Directory of Open Access Journals (Sweden)

    Anubama Ramachandra

    2011-11-01

    Full Text Available Purpose: The paper aims to study the relationship of Line Managers’ (LMs Human Resource (HR role and its facets within employee’s Continuous Professional Development (CPD.Design/methodology/approach: A quantitative approach using 100 questionnaires were distributed to line managers in a South East Asia with a response rate of 87%.Findings: Results depict that LMs are actively involved in Strategic Partner, Employee Champion, and Change Agent roles. Study also shows that these three HR roles correlate with employee CPD. LMs’ are neither involved in Administrative Expert role, nor it correlates with employee Continuous Professional Development.Research limitations: Inability of the line managers to be fully involved with the four HR roles constraints the process of line manager deployment of HR roles specifically to employee CPD.Practical implications: Argues that the importance of strategic partner, employee champion, and change agent roles are the most important barrier and enabler of employee CPD, thus indirectly promoting organizational success and productivity.Social implications: Highlights the difficulties of managing organisations by getting the line managers directly involve in the development of employee CPD. Many line managers have to be made and given opportunities to develop their capabilities on this platform. Contends that HR can help an organization to succeed, provided that all line managers understand their roles, work together and take responsibility for their contribution. In addition is the adoption of the HR roles for the smooth delivery of HR functions which aligns with the overall organizational success.Originality/value: Specific HR roles are significant importance to the development of employee CPD within the setting of this South East Asian organization.

  6. Development and characterization of a cell line WAF from freshwater shark Wallago attu.

    Science.gov (United States)

    Dubey, Akhilesh; Goswami, Mukunda; Yadav, Kamalendra; Sharma, Bhagwati S

    2014-02-01

    A new epithelial cell line, WAF was developed from caudal fin of freshwater shark, Wallago attu. The cell line was optimally maintained at 28 °C in Leibovitz-15 (L-15) medium supplemented with 20 % fetal bovine serum. The cell line was characterized by various cytogenetic and molecular markers. The cytogenetic analysis revealed a diploid count of 86 chromosomes at different passages. The origin of the cell lines was confirmed by the amplification of 547 and 654 bp sequences of 16S rRNA and cytochrome oxidase subunit I genes of mitochondrial DNA, respectively. WAF cells were characterized for their growth characteristics at different temperature and serum concentration. Epithelial morphology of the cell line was confirmed using immunocytochemistry. Further cell plating efficiency, transfection efficiency and viability of cryopreserved WAF cells was also determined. Cytotoxicity and genotoxicity assessment of cadmium salts on WAF cells by MTT, NR and comet assay illustrated the utility of this cell line as an in vitro model for aquatic toxicological studies. The cell line will be further useful for studying oxidative stress markers against aquatic pollutants.

  7. DEVELOPMENT OF MELON F1 SEEDS BASED ON LINES WITH GENIC MALE STERILITY

    Directory of Open Access Journals (Sweden)

    A. S. Sokolov

    2014-01-01

    Full Text Available The perspective technology of development of melon of F1hybrids seeds by use maternal lines with an original form of genic mail sterility and marker trait (lobed leaves was studied. Elements of technology allow developing hybrid seeds of melon with hybridity of 90-95%.

  8. Lipase inactivation in wheat germ by gamma irradiation

    International Nuclear Information System (INIS)

    Jha, Pankaj Kumar; Kudachikar, V.B.; Kumar, Sourav

    2013-01-01

    An attempt was made to improve the shelf life of wheat germ by optimizing processing conditions involving γ-irradiation. Studies were carried out to investigate the effect of γ-irradiation (0–30 kGy doses) on the chemical composition of wheat germ with respect to variation in moisture, total ash, crude fat, free fatty acid, protein and lipase activity. The results demonstrate that shelf stability of wheat germ was achieved by inactivation of lipase at doses of γ-irradiation greater than 12 kGy. - Highlights: Ø γ-irradiation was found to inactivate Lipase present in Wheat Germ. Ø The treatment did not result in significant changes in Total Ash, Moisture and Protein Content of Wheat Germ. Ø The irradiation at 30 kGy resulted in 31.2 % inactivation of Lipase in Wheat Germ

  9. Epigenetic Transgenerational Actions of Vinclozolin on the Development of Disease and Cancer

    Science.gov (United States)

    Skinner, Michael K.; Anway, Matthew D.

    2018-01-01

    Exposure to an environmental endocrine disruptor (e.g., vinclozolin) during embryonic gonadal sex determination appears to alter the male germ line epigenome and subsequently promotes transgenerational adult onset disease. The epigenetic mechanism involves the induction of new imprinted-like genes/DNA sequences in the germ line that appear to transmit disease phenotypes. The disease phenotypes include testis abnormalities, prostate disease, kidney disease, immune abnormalities, and tumor development. This epigenetic transgenerational disease mechanism provides a unique perspective from which to view inheritable adult onset disease states, such as cancer, and ultimately offers new insights into novel diagnostic and therapeutic strategies. PMID:17956218

  10. Issues in identifying germ tube positive yeasts by conventional methods.

    Science.gov (United States)

    Yazdanpanah, Atta; Khaithir, Tzar Mohd Nizam

    2014-01-01

    Candida speciation is vital for epidemiology and management of candidiasis. Nonmolecular conventional methods often fail to identify closely related germ tube positive yeasts from clinical specimens. The present study was conducted to identify these yeasts and to highlight issues in conventional versus molecular methods of identification. A total of 98 germ tube positive yeasts from high vaginal swabs were studied over a 12-month period. Isolates were examined with various methods including growth at 42 °C and 45 °C on Sabouraud dextrose agar (SDA), color development on CHROMagar Candida medium, chlamydospore production on corn meal agar at 25 °C, carbohydrate assimilation using ID 32C system, and polymerase chain reaction using a single pair of primers targeting the hyphal wall protein 1 (Hwp1) gene. Of all the isolates studied, 97 were molecularly confirmed as C. albicans and one isolate was identified as C. dubliniensis. No C. africana was detected in this study. The molecular method used in our study was an accurate and useful tool for discriminating C. albicans, C. dubliniensis, and C. africana. The conventional methods, however, were less accurate and riddled with many issues that will be discussed in further details. © 2013 Wiley Periodicals, Inc.

  11. Germ Plasm Biogenesis--An Oskar-Centric Perspective.

    Science.gov (United States)

    Lehmann, Ruth

    2016-01-01

    Germ granules are the hallmark of all germ cells. These membrane-less, electron-dense structures were first observed over 100 years ago. Today, their role in regulating and processing transcripts critical for the establishment, maintenance, and protection of germ cells is well established, and pathways outlining the biochemical mechanisms and physical properties associated with their biogenesis are emerging. © 2016 Elsevier Inc. All rights reserved.

  12. Development of the advanced on-line BWR core monitoring system TiARA

    International Nuclear Information System (INIS)

    Kobayashi, Yoko; Yamazaki, Hiroshi

    1996-01-01

    Development of an integrated computer environment to support plant operators and station nuclear engineers is a recent activity. In achieving this goal, an advanced on-line boiling water reactor (BWR) core monitoring system: TiARA has been developed by Toden Software. An integrated design approach was performed through the introduction of recent computer technologies, a sophisticated human/machine interface (HMI) and an advanced nodal method. The first prototype of TiARA was ready in early 1996. This prototype is now undergoing a field test at Kashiwazaki-Kariwa unit 6. After successful completion of this test, the authors will have achieved the following goals: (1) consistency between on-line core monitoring system and off-line core management system; (2) an enhanced HMI and database; (3) user-friendly operability and maintainability; (4) system development from the utilities' standpoint to fully satisfy operator needs

  13. Grinding and cooking dry-mill germ to optimize aqueous enzymatic oil extraction

    Science.gov (United States)

    The many recent dry grind plants that convert corn to ethanol are potential sources of substantial amounts of corn oil. This report describes an aqueous enzymatic extraction (AEE) method to separate oil from dry-mill corn germ (DMG). The method is an extension of AEE previously developed for wet...

  14. Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts

    DEFF Research Database (Denmark)

    Kraggerud, Sigrid Marie; Hoei-Hansen, Christina E; Alagaratnam, Sharmini

    2013-01-01

    This review focuses on the molecular characteristics and development of rare malignant ovarian germ cell tumors (mOGCTs). We provide an overview of the genomic aberrations assessed by ploidy, cytogenetic banding, and comparative genomic hybridization. We summarize and discuss the transcriptome pr...

  15. Burden of testicular, paratesticular and extragonadal germ cell tumours in Europe

    NARCIS (Netherlands)

    Trama, A.; Mallone, S.; Nicolai, N.; Necchi, A.; Schaapveld, M.; Gietema, J.; Znaor, A.; Ardanaz, E.; Berrino, F.

    We provide updated estimates of survival, incidence, complete prevalence, and proportion cured for patients with testicular/paratesticular and extragonadal germ cell cancers in Europe, grouped according to the new list of cancer types developed by RARECARE. We collected data, archived in European

  16. Cytokeratin expression in mouse lacrimal gland germ epithelium.

    Science.gov (United States)

    Hirayama, Masatoshi; Liu, Ying; Kawakita, Tetsuya; Shimmura, Shigeto; Tsubota, Kazuo

    2016-05-01

    The lacrimal gland secretes tear fluids that protect the ocular surface epithelium, and its dysfunction leads to dry eye disease (DED). The functional restoration of the lacrimal gland by engraftment of a bioengineered lacrimal gland using lacrimal gland germ epithelial cells has been proposed to cure DED in mice. Here, we investigate the expression profile of cytokeratins in the lacrimal gland germ epithelium to clarify their unique characteristics. We performed quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry (IHC) analysis to clarify the expression profile of cytokeratin in the lacrimal gland germ epithelium. The mRNA expression of keratin (KRT) 5, KRT8, KRT14, KRT15, and KRT18 in the lacrimal gland germ epithelium was increased compared with that in mouse embryonic stem cells and the lacrimal gland germ mesenchyme, as analyzed by Q-PCR. The expression level of KRT15 increased in the transition from stem cells to lacrimal gland germ epithelium, then decreased as the lacrimal gland matured. IHC revealed that the expression set of these cytokeratins in the lacrimal gland germ epithelium was different from that in the adult lacrimal gland. The expression of KRT15 was observed in the lacrimal gland germ epithelium, and it segmentalized into some of the basal cells in the intercanulated duct in mature gland. We determined the expression profile of cytokeratins in the lacrimal gland epithelium, and identified KRT15 as a candidate unique cellular marker for the lacrimal gland germ epithelium. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Cross-talk between miR-471-5p and autophagy component proteins regulates LC3-associated phagocytosis (LAP) of apoptotic germ cells.

    Science.gov (United States)

    Panneerdoss, Subbarayalu; Viswanadhapalli, Suryavathi; Abdelfattah, Nourhan; Onyeagucha, Benjamin C; Timilsina, Santosh; Mohammad, Tabrez A; Chen, Yidong; Drake, Michael; Vuori, Kristiina; Kumar, T Rajendra; Rao, Manjeet K

    2017-09-19

    Phagocytic clearance of apoptotic germ cells by Sertoli cells is vital for germ cell development and differentiation. Here, using a tissue-specific miRNA transgenic mouse model, we show that interaction between miR-471-5p and autophagy member proteins regulates clearance of apoptotic germ cells via LC3-associated phagocytosis (LAP). Transgenic mice expressing miR-471-5p in Sertoli cells show increased germ cell apoptosis and compromised male fertility. Those effects are due to defective engulfment and impaired LAP-mediated clearance of apoptotic germ cells as miR-471-5p transgenic mice show lower levels of Dock180, LC3, Atg12, Becn1, Rab5 and Rubicon in Sertoli cells. Our results reveal that Dock180 interacts with autophagy member proteins to constitute a functional LC3-dependent phagocytic complex. We find that androgen regulates Sertoli cell phagocytosis by controlling expression of miR-471-5p and its target proteins. These findings suggest that recruitment of autophagy machinery is essential for efficient clearance of apoptotic germ cells by Sertoli cells using LAP.Although phagocytic clearance of apoptotic germ cells by Sertoli cells is essential for spermatogenesis, little of the mechanism is known. Here the authors show that Sertoli cells employ LC3-associated phagocytosis (LAP) by recruiting autophagy member proteins to clear apoptotic germ cells.

  18. Advances in Mammalian Cell Line Development Technologies for Recombinant Protein Production

    Directory of Open Access Journals (Sweden)

    Say Kong Ng

    2013-04-01

    Full Text Available From 2006 to 2011, an average of 15 novel recombinant protein therapeutics have been approved by US Food and Drug Administration (FDA annually. In addition, the expiration of blockbuster biologics has also spurred the emergence of biosimilars. The increasing numbers of innovator biologic products and biosimilars have thus fuelled the demand of production cell lines with high productivity. Currently, mammalian cell line development technologies used by most biopharmaceutical companies are based on either the methotrexate (MTX amplification technology or the glutamine synthetase (GS system. With both systems, the cell clones obtained are highly heterogeneous, as a result of random genome integration by the gene of interest and the gene amplification process. Consequently, large numbers of cell clones have to be screened to identify rare stable high producer cell clones. As such, the cell line development process typically requires 6 to 12 months and is a time, capital and labour intensive process. This article reviews established advances in protein expression and clone screening which are the core technologies in mammalian cell line development. Advancements in these component technologies are vital to improve the speed and efficiency of generating robust and highly productive cell line for large scale production of protein therapeutics.

  19. Supporting Development of Satellite's Guidance Navigation and Control Software: A Product Line Approach

    Science.gov (United States)

    McComas, David; Stark, Michael; Leake, Stephen; White, Michael; Morisio, Maurizio; Travassos, Guilherme H.; Powers, Edward I. (Technical Monitor)

    2000-01-01

    The NASA Goddard Space Flight Center Flight Software Branch (FSB) is developing a Guidance, Navigation, and Control (GNC) Flight Software (FSW) product line. The demand for increasingly more complex flight software in less time while maintaining the same level of quality has motivated us to look for better FSW development strategies. The GNC FSW product line has been planned to address the core GNC FSW functionality very similar on many recent low/near Earth missions in the last ten years. Unfortunately these missions have not accomplished significant drops in development cost since a systematic approach towards reuse has not been adopted. In addition, new demands are continually being placed upon the FSW which means the FSB must become more adept at providing GNC FSW functionality's core so it can accommodate additional requirements. These domain features together with engineering concepts are influencing the specification, description and evaluation of FSW product line. Domain engineering is the foundation for emerging product line software development approaches. A product line is 'A family of products designed to take advantage of their common aspects and predicted variabilities'. In our product line approach, domain engineering includes the engineering activities needed to produce reusable artifacts for a domain. Application engineering refers to developing an application in the domain starting from reusable artifacts. The focus of this paper is regarding the software process, lessons learned and on how the GNC FSW product line manages variability. Existing domain engineering approaches do not enforce any specific notation for domain analysis or commonality and variability analysis. Usually, natural language text is the preferred tool. The advantage is the flexibility and adapt ability of natural language. However, one has to be ready to accept also its well-known drawbacks, such as ambiguity, inconsistency, and contradictions. While most domain analysis

  20. GAGE cancer-germline antigens are recruited to the nuclear envelope by germ cell-less (GCL)

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Rösner, Heike I; Pedersen, Christina B

    2012-01-01

    GAGE proteins are highly similar, primate-specific molecules with unique primary structure and undefined cellular roles. They are restricted to cells of the germ line in adult healthy individuals, but are broadly expressed in a wide range of cancers. In a yeast two-hybrid screen we identified the...... different dsDNA fragments, suggesting sequence-nonspecific binding. Dual association of GAGE family members with GCL at the nuclear envelope inner membrane in cells, and with dsDNA in vitro, implicate GAGE proteins in chromatin regulation in germ cells and cancer cells....... the metazoan transcriptional regulator, Germ cell-less (GCL), as an interaction partner of GAGE12I. GCL directly binds LEM-domain proteins (LAP2β, emerin, MAN1) at the nuclear envelope, and we found that GAGE proteins were recruited to the nuclear envelope inner membrane by GCL. Based on yeast two...

  1. Longitudinal development of number line estimation and mathematics performance in primary school children.

    Science.gov (United States)

    Friso-van den Bos, Ilona; Kroesbergen, Evelyn H; Van Luit, Johannes E H; Xenidou-Dervou, Iro; Jonkman, Lisa M; Van der Schoot, Menno; Van Lieshout, Ernest C D M

    2015-06-01

    Children's ability to relate number to a continuous quantity abstraction visualized as a number line is widely accepted to be predictive of mathematics achievement. However, a debate has emerged with respect to how children's placements are distributed on this number line across development. In the current study, different models were applied to children's longitudinal number placement data to get more insight into the development of number line representations in kindergarten and early primary school years. In addition, longitudinal developmental relations between number line placements and mathematical achievement, measured with a national test of mathematics, were investigated using cross-lagged panel modeling. A group of 442 children participated in a 3-year longitudinal study (ages 5-8 years) in which they completed a number-to-position task every 6 months. Individual number line placements were fitted to various models, of which a one-anchor power model provided the best fit for many of the placements at a younger age (5 or 6 years) and a two-anchor power model provided better fit for many of the children at an older age (7 or 8 years). The number of children who made linear placements also grew with age. Cross-lagged panel analyses indicated that the best fit was provided with a model in which number line acuity and mathematics performance were mutually predictive of each other rather than models in which one ability predicted the other in a non-reciprocal way. This indicates that number line acuity should not be seen as a predictor of math but that both skills influence each other during the developmental process. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Germ cell specification and ovary structure in the rotifer Brachionus plicatilis.

    Science.gov (United States)

    Smith, James M; Cridge, Andrew G; Dearden, Peter K

    2010-08-02

    The segregation of the germline from somatic tissues is an essential process in the development of all animals. Specification of the primordial germ cells (PGCs) takes place via different strategies across animal phyla; either specified early in embryogenesis by the inheritance of maternal determinants in the cytoplasm of the oocyte ('preformation') or selected later in embryonic development from undifferentiated precursors by a localized inductive signal ('epigenesis'). Here we investigate the specification and development of the germ cells in the rotifer Brachionus plicatilis, a member of the poorly-characterized superphyla Lophotrochozoa, by isolating the Brachionus homologues of the conserved germ cell markers vasa and nanos, and examining their expression using in situ hybridization. Bpvasa and Bpnos RNA expression have very similar distributions in the Brachionus ovary, showing ubiquitous expression in the vitellarium, with higher levels in the putative germ cell cluster. Bpvas RNA expression is present in freshly laid eggs, remaining ubiquitous in embryos until at least the 96 cell stage after which expression narrows to a small cluster of cells at the putative posterior of the embryo, consistent with the developing ovary. Bpnos RNA expression is also present in just-laid eggs but expression is much reduced by the four-cell stage and absent by the 16-cell stage. Shortly before hatching of the juvenile rotifer from the egg, Bpnos RNA expression is re-activated, located in a subset of posterior cells similar to those expressing Bpvas at the same stage. The observed expression of vasa and nanos in the developing B. plicatilis embryo implies an epigenetic origin of primordial germ cells in Rotifer.

  3. Germ cell specification and ovary structure in the rotifer Brachionus plicatilis

    Directory of Open Access Journals (Sweden)

    Smith James M

    2010-08-01

    Full Text Available Abstract Background The segregation of the germline from somatic tissues is an essential process in the development of all animals. Specification of the primordial germ cells (PGCs takes place via different strategies across animal phyla; either specified early in embryogenesis by the inheritance of maternal determinants in the cytoplasm of the oocyte ('preformation' or selected later in embryonic development from undifferentiated precursors by a localized inductive signal ('epigenesis'. Here we investigate the specification and development of the germ cells in the rotifer Brachionus plicatilis, a member of the poorly-characterized superphyla Lophotrochozoa, by isolating the Brachionus homologues of the conserved germ cell markers vasa and nanos, and examining their expression using in situ hybridization. Results Bpvasa and Bpnos RNA expression have very similar distributions in the Brachionus ovary, showing ubiquitous expression in the vitellarium, with higher levels in the putative germ cell cluster. Bpvas RNA expression is present in freshly laid eggs, remaining ubiquitous in embryos until at least the 96 cell stage after which expression narrows to a small cluster of cells at the putative posterior of the embryo, consistent with the developing ovary. Bpnos RNA expression is also present in just-laid eggs but expression is much reduced by the four-cell stage and absent by the 16-cell stage. Shortly before hatching of the juvenile rotifer from the egg, Bpnos RNA expression is re-activated, located in a subset of posterior cells similar to those expressing Bpvas at the same stage. Conclusions The observed expression of vasa and nanos in the developing B. plicatilis embryo implies an epigenetic origin of primordial germ cells in Rotifer.

  4. Using Logistic Approximations of Marginal Trace Lines to Develop Short Assessments

    Science.gov (United States)

    Stucky, Brian D.; Thissen, David; Edelen, Maria Orlando

    2013-01-01

    Test developers often need to create unidimensional scales from multidimensional data. For item analysis, "marginal trace lines" capture the relation with the general dimension while accounting for nuisance dimensions and may prove to be a useful technique for creating short-form tests. This article describes the computations needed to obtain…

  5. Ectopic Expression of Testis Germ Cell Proteins in Cancer and Its Potential Role in Genomic Instability

    Directory of Open Access Journals (Sweden)

    Aaraby Yoheswaran Nielsen

    2016-06-01

    Full Text Available Genomic instability is a hallmark of human cancer and an enabling factor for the genetic alterations that drive cancer development. The processes involved in genomic instability resemble those of meiosis, where genetic material is interchanged between homologous chromosomes. In most types of human cancer, epigenetic changes, including hypomethylation of gene promoters, lead to the ectopic expression of a large number of proteins normally restricted to the germ cells of the testis. Due to the similarities between meiosis and genomic instability, it has been proposed that activation of meiotic programs may drive genomic instability in cancer cells. Some germ cell proteins with ectopic expression in cancer cells indeed seem to promote genomic instability, while others reduce polyploidy and maintain mitotic fidelity. Furthermore, oncogenic germ cell proteins may indirectly contribute to genomic instability through induction of replication stress, similar to classic oncogenes. Thus, current evidence suggests that testis germ cell proteins are implicated in cancer development by regulating genomic instability during tumorigenesis, and these proteins therefore represent promising targets for novel therapeutic strategies.

  6. Exposure to endocrine disruptor induces transgenerational epigenetic deregulation of microRNAs in primordial germ cells.

    Directory of Open Access Journals (Sweden)

    Miguel A Brieño-Enríquez

    Full Text Available In mammals, germ cell differentiation is initiated in the Primordial Germ Cells (PGCs during fetal development. Prenatal exposure to environmental toxicants such as endocrine disruptors may alter PGC differentiation, development of the male germline and induce transgenerational epigenetic disorders. The anti-androgenic compound vinclozolin represents a paradigmatic example of molecule causing transgenerational effects on germ cells. We performed prenatal exposure to vinclozolin in mice and analyzed the phenotypic and molecular changes in three successive generations. A reduction in the number of embryonic PGCs and increased rate of apoptotic cells along with decrease of fertility rate in adult males were observed in F1 to F3 generations. Blimp1 is a crucial regulator of PGC differentiation. We show that prenatal exposure to vinclozolin deregulates specific microRNAs in PGCs, such as miR-23b and miR-21, inducing disequilibrium in the Lin28/let-7/Blimp1 pathway in three successive generations of males. As determined by global maps of cytosine methylation, we found no evidence for prominent changes in DNA methylation in PGCs or mature sperm. Our data suggest that embryonic exposure to environmental endocrine disruptors induces transgenerational epigenetic deregulation of expression of microRNAs affecting key regulatory pathways of germ cells differentiation.

  7. Development of TGMS lines with improved floral traits through mutation breeding in rice

    International Nuclear Information System (INIS)

    Thiyagarajan, K.; Abirami, S.; Robin, S.; Manonmani, S.; Jambhulkar, S.J.

    2006-01-01

    Mutation breeding is now accepted as an useful means of adding valuable attributes to a variety. Plant breeders have used this tool for the improvement of some cultivated crop varieties. The current investigation is aimed to develop mutants with respect to temperature sensitivity and good floral traits for use in two line breeding. The putative Thermosensitive Genic Male Sterile lines viz,, TS 6 and CBTS 0282 were subjected to induce mutagenesis with gamma rays (300 and 350 Gy) and EMS (0.5 and 0.6%) for developing new TGMS lines with desirable floral traits. The seeds treated with gamma ray and EMS were raised in M1 generation and seeds collected from this population were raised in M2 generation as plant to progeny rows for screening the best TGMS lines with desirable floral traits. In the M2 generation a total of 469 progeny rows of CBTS 0282 and 854 progeny rows of TS 6 were raised. A population of 128, 975 plants in CBTS 0282 and 1,28,100 plants in TS 6 were raised. In M2 generation 361 sterile, uniform stable individual plants with good stigma exertion percentage and wide angle of glume opening were selected and stubble planted at HREC, Gudalur, a low temperature region. At HREC, again the same screening process was carried out and 13 stubbles with excellent stigma exertion percentage were selected and their progenies were raised in M3 generation along with control and check IR 58025 A. A total of 63 sterile and stable M3 plants with good stigma exertion percentage wider angle of glume opening excelling over the check and control were identified and raised in M4 generation along with control and check IR 58025 A. In the M4 generation a total of 16 progeny rows were found to be uniform and homozygous with good floral traits. These lines can be utilized for developing new two line hybrids

  8. Radiation- induced aneuploidy in mammalian germ cells

    International Nuclear Information System (INIS)

    Tease, C.

    1989-01-01

    The ability of ionizing radiation to induce aneuploidy in mammalian germ cells has been investigated experimentally in the laboratory mouse using a variety of cytogenetic and genetic methods. These studies have provided unambiguous evidence of induced nondisjunction in both male and female germ cells when the effect of irradiation is screened in meiotic cells or preimplantation embryos. In contrast, however, cytogenetic analyses of post-implantation embryos and genetic assays for induced chromosome gains have not found a significant radiation effect. These apparently contradictory findings may be reconciled if (a) radiation induces tertiary rather than primary trisomy, or (b) induces embryo-lethal genetic damage, such as deletions, in addition to numerical anomalies. Either or both of these explanations may account for the apparent loss during gestation of radiation-induced trisomic embryos. Extrapolating from the information so far available, it seems unlikely that environmental exposure to low doses if low dose rate radiation will result in a detectable increase in the rate of aneuploidy in the human population. (author)

  9. Intestinal obstruction in germ-free dogs.

    Science.gov (United States)

    Heneghan, J B; Robinson, J W; Menge, H; Winistörfer, B

    1981-08-01

    Mechanical occlusions were created in the intestines of four germ-free dogs. At the time of the operation, a control loop of mid-intestine was perfused in vivo and then excised for examinations in vitro, which included the determination of the equilibrium uptake of phenylalanine and of beta-methyl-glucoside, the influx kinetics of phenylalanine and morphometric analysis of the mucosa by microdissection and stereological techniques. Seven days after establishment of the occlusion the abdomen was reopened, and loops above and below the occlusion were perfused, and then excised for the same tests in vitro. Unlike occluded loops of conventional dogs, the intestine of the germ-free animal above the occlusion does not secrete water and electrolytes into the lumen. Its transport properties in vitro do not differ from those of the control loop, and the morphometric analyses reveal only slight changes in villus structure. The loop below the obstruction undergoes marked atrophy, as has been observed in conventional dogs. The results suggest that the copious secretion that occurs above an intestinal obstruction in normal animals is due to the presence of an abundant bacterial population in the obstruction fluid.

  10. Male Hypogonadism and Germ Cell Loss Caused by a Mutation in Polo-Like Kinase 4

    Science.gov (United States)

    Harris, Rebecca M.; Weiss, Jeffrey

    2011-01-01

    The genetic etiologies of male infertility remain largely unknown. To identify genes potentially involved in spermatogenesis and male infertility, we performed genome-wide mutagenesis in mice with N-ethyl-N-nitrosourea and identified a line with dominant hypogonadism and patchy germ cell loss. Genomic mapping and DNA sequence analysis identified a novel heterozygous missense mutation in the kinase domain of Polo-like kinase 4 (Plk4), altering an isoleucine to asparagine at residue 242 (I242N). Genetic complementation studies using a gene trap line with disruption in the Plk4 locus confirmed that the putative Plk4 missense mutation was causative. Plk4 is known to be involved in centriole formation and cell cycle progression. However, a specific role in mammalian spermatogenesis has not been examined. PLK4 was highly expressed in the testes both pre- and postnatally. In the adult, PLK4 expression was first detected in stage VIII pachytene spermatocytes and was present through step 16 elongated spermatids. Because the homozygous Plk4I242N/I242N mutation was embryonic lethal, all analyses were performed using the heterozygous Plk4+/I242N mice. Testis size was reduced by 17%, and histology revealed discrete regions of germ cell loss, leaving only Sertoli cells in these defective tubules. Testis cord formation (embryonic day 13.5) was normal. Testis histology was also normal at postnatal day (P)1, but germ cell loss was detected at P10 and subsequent ages. We conclude that the I242N heterozygous mutation in PLK4 is causative for patchy germ cell loss beginning at P10, suggesting a role for PLK4 during the initiation of spermatogenesis. PMID:21791561

  11. Genetic dissection of black grain rice by the development of a near isogenic line

    OpenAIRE

    Maeda, Hiroaki; Yamaguchi, Takuya; Omoteno, Motoyasu; Takarada, Takeshi; Fujita, Kenji; Murata, Kazumasa; Iyama, Yukihide; Kojima, Yoichiro; Morikawa, Makiko; Ozaki, Hidenobu; Mukaino, Naoyuki; Kidani, Yoshinori; Ebitani, Takeshi

    2014-01-01

    Rice (Oryza sativa L.) can produce black grains as well as white. In black rice, the pericarp of the grain accumulates anthocyanin, which has antioxidant activity and is beneficial to human health. We developed a black rice introgression line in the genetic background of Oryza sativa L. ‘Koshihikari’, which is a leading variety in Japan. We used Oryza sativa L. ‘Hong Xie Nuo’ as the donor parent and backcrossed with ‘Koshihikari’ four times, resulting in a near isogenic line (NIL) for black g...

  12. Childhood Central Nervous System Germ Cell Tumors Treatment

    Science.gov (United States)

    ... make hormones. Yolk sac tumors make the hormone alpha-fetoprotein (AFP). Mixed germ cell tumors are made of ... used to diagnose some CNS germ cell tumors: Alpha-fetoprotein (AFP). Beta-human chorionic gonadotropin (β-hCG). Blood ...

  13. Is Tobacco Smoke a Germ-Cell Mutagen?

    Science.gov (United States)

    Although no international organization exists to declare whether an agent is a germ-cell mutagen, tobacco smoke may be a human germ-cell mutagen. In the mouse, tobacco smoke induces a significant increase in the mutation frequency at an expanded simple tandem repeat (ESTR) locus....

  14. Germ cell transplantation in an azoospermic Klinefelter bull.

    Science.gov (United States)

    Joerg, Hannes; Janett, Fredi; Schlatt, Stefan; Mueller, Simone; Graphodatskaya, Daria; Suwattana, Duangsmorn; Asai, Mika; Stranzinger, Gerald

    2003-12-01

    Germ cell transplantation is a technique that transfers donor testicular cells into recipient testes. A population of germ cells can colonize the recipient testis, initiate spermatogenesis, and produce sperm capable of fertilization. In the present study, a nonmosaic Klinefelter bull was used as a germ cell recipient. The donor cell suspension was introduced into the rete testis using ultrasound-guided puncture. A pulsatile administration of GnRH was performed to stimulate spermatogenesis. The molecular approach to detect donor cells was done by a quantitative polymerase chain reaction with allele discrimination based on a genetic mutation between donor and recipient. Therefore, a known genetic mutation, associated with coat-color phenotype, was used to calculate the ratio of donor to recipient cells in the biopsy specimens and ejaculates for 10 mo. After slaughtering, meiotic preparations were performed. The injected germ cells did not undergo spermatogenesis. Six months after germ cell transplantation, the donor cells were rejected, which indicates that the donor cells could not incorporate in the testis. The hormone stimulation showed that the testosterone-producing Leydig cells were functionally intact. Despite subfertility therapy, neither the recipient nor the donor cells underwent spermatogenesis. Therefore, nonmosaic Klinefelter bulls are not suitable as germ cell recipients. Future germ cell recipients in cattle could be mosaic Klinefelters, interspecies hybrids, bulls with Sertoli cell-only syndrome, or bulls with disrupted germ cell migration caused by RNA interference.

  15. Editorial Introduction [to Female Germ Cells: Biology and Genetic Risk

    Science.gov (United States)

    This is an editorial introduction to the special issue of utation Research, titled, emale Germ Cells: Biology and Genetic isk, which is an attempt to present a collection of papers that emphasize the distinct properties of female germ cells and their characteristic response to mu...

  16. Who will bear the torch tomorrow? Charismatic leadership and second-line leaders in development NGOs

    OpenAIRE

    M. Shameem Siddiqi

    2001-01-01

    Competent leadership has always been considered vital in every organisation and there has been considerable research on mainstream leadership issues in the corporate sector and in politics.1 But there has been very little research on leadership issues in the emerging sector of development NGOs. The issue of second-line leadership development2 is an important one not only for the NGOs themselves but also for the aid industry, the poor and vulnerable people for whom they work and for society as...

  17. Development of an accurate transmission line fault locator using the global positioning system satellites

    Science.gov (United States)

    Lee, Harry

    1994-01-01

    A highly accurate transmission line fault locator based on the traveling-wave principle was developed and successfully operated within B.C. Hydro. A transmission line fault produces a fast-risetime traveling wave at the fault point which propagates along the transmission line. This fault locator system consists of traveling wave detectors located at key substations which detect and time tag the leading edge of the fault-generated traveling wave as if passes through. A master station gathers the time-tagged information from the remote detectors and determines the location of the fault. Precise time is a key element to the success of this system. This fault locator system derives its timing from the Global Positioning System (GPS) satellites. System tests confirmed the accuracy of locating faults to within the design objective of +/-300 meters.

  18. Molecular Evolution of Two Distinct dmrt1 Promoters for Germ and Somatic Cells in Vertebrate Gonads.

    Science.gov (United States)

    Mawaribuchi, Shuuji; Musashijima, Masato; Wada, Mikako; Izutsu, Yumi; Kurakata, Erina; Park, Min Kyun; Takamatsu, Nobuhiko; Ito, Michihiko

    2017-03-01

    The transcription factor DMRT1 has important functions in two distinct processes, somatic-cell masculinization and germ-cell development in mammals. However, it is unknown whether the functions are conserved during evolution, and what mechanism underlies its expression in the two cell lineages. Our analysis of the Xenopus laevis and Silurana tropicalis dmrt1 genes indicated the presence of two distinct promoters: one upstream of the noncoding first exon (ncEx1), and one within the first intron. In contrast, only the ncEx1-upstream promoter was detected in the dmrt1 gene of the agnathan sand lamprey, which expressed dmrt1 exclusively in the germ cells. In X. laevis, the ncEx1- and exon 2-upstream promoters were predominantly used for germ-cell and somatic-cell transcription, respectively. Importantly, knockdown of the ncEx1-containing transcript led to reduced germ-cell numbers in X. laevis gonads. Intriguingly, two genetically female individuals carrying the knockdown construct developed testicles. Analysis of the reptilian leopard gecko dmrt1 revealed the absence of ncEx1. We propose that dmrt1 regulated germ-cell development in the vertebrate ancestor, then acquired another promoter in its first intron to regulate somatic-cell masculinization during gnathostome evolution. In the common ancestor of reptiles and mammals, only one promoter got function for both the two cell lineages, accompanied with the loss of ncEx1. In addition, we found a conserved noncoding sequence (CNS) in the dmrt1 5'-flanking regions only among amniote species, and two CNSs in the introns among most vertebrates except for agnathans. Finally, we discuss relationships between these CNSs and the promoters of dmrt1 during vertebrate evolution. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Perceptions Towards On-line Banking Security: An Empirical Investigation of a Developing Country`s Banking Sector, how secure is On-line Banking

    OpenAIRE

    Bongani Ngwenya; Khanyisa Malufu

    2012-01-01

    The increase in computer crime has led to scepticism about themove made by the banks to introduce on-line banking. Someview this as a noble move which has made the banking systemmore efficient, reliable and secure, while others view it as arisky and insecure way of banking. The aim of this study wasto assess whether on-line banking in the developing countriesis secure or not. The researcher chose a descriptive-quantitativeresearch design. Data was collected using a self constructedquestionnai...

  20. Oocyte toxicity: female germ-cell loss from radiation and chemical exposures

    International Nuclear Information System (INIS)

    Dobson, R.L.

    1984-01-01

    In some mammals, female germ cells are extraordinarily sensitive to killing by exposure to ionizing radiation, especially during development. Immature oocytes, which constitute the lifetime germ-cell pool of the female, have an LD 50 in juvenile mice of only 6 rad (compared with typical LD 50 s of 100-300 rad for most other cell types studied). Essentially, the entire germ-cell supply in female squirrel monkeys is destroyed prenatally by exposure of only 0.7 rad/day. Severe but lesser destruction has been found in other species. However, evidence suggests (though not ruled out for all developmental stages) that unusually high sensitivity probably does not occur in the human female. Germ cells can also be killed by certain chemicals, and similarities exist between chemical and radiation effects. More than 75 compounds have been quantitatively studied in mice, with determination of OTI values (OTI = oocyte toxicity index = mouse LD 50 /oocyte LD 50 ) to measure the degree of preferential oocyte killing. High sensitivity in mice does not mean necessarily high sensitivity in women. Of special interest is the recent discovery that the lethal target in the extremely sensitive mouse immature oocyte is probably the plasma membrane, not DNA. Since mouse data form the main basis from which human genetic hazard (for both radiation and chemicals) is estimated, this has important implications for the determination of genetic risk in women

  1. Latest developments in on- and off-line inspection of bank notes during production

    Science.gov (United States)

    Brown, Stephen C.

    2004-06-01

    The inspection of bank notes is a highly labour intensive process where traditionally every note on every sheet is inspected manually. However with the advent of more and more sophisticated security features, both visible and invisible, and the requirement of cost reduction in the printing process, it is clear that automation is required. Machines for the automatic inspection of bank notes have been on the market for the past 10 to 12 years, but recent developments in technology have enabled a new generation of detectors and machines to be developed. This paper focuses on the latest developments in both the off-line and on-line inspection of bank notes covering not only the visible spectrum but also a new range of detectors for inspection some of the more common invisible features used as covert features in today's bank notes.

  2. Design and development of graphite/epoxy feed line for use of cryogenic propulsion systems

    International Nuclear Information System (INIS)

    Kremer, J.S.; Kreiner, J.H.; Mosallam, A.S.

    1998-01-01

    The development of lightweight composite cryogenic ines is a critical technology for single-stage-to-orbit launch vehicles such as the Reusable Launch Vehicle (RLV). To achieve weight goals, a significant effort will be required to develop feed line designs that can reliably replace today's stainless steel configurations. A number of technical problems exist, including the large coefficient of thermal expansion (CTE) differential between the composite and interfacing metallic materials and the ability to seal against composite materials in a cryogenic environment. This paper reports the results of a development efforts undertaken to design, build, and test a graphite/epoxy propellant feed line to carry liquid hydrogen (-423 degree F). The design incorporates a reusable cryogenic insulation system and a secondarily bonded/co-cured splice joint

  3. California-Oregon 500-kV transmission line development of design criteria

    International Nuclear Information System (INIS)

    Simpson, K.D.

    1990-01-01

    The California-Oregon Transmission Project (COTP) encompassed the design and construction of a third 500-kV ac intertie between California and the Pacific Northwest Transmission system. Sargent ampersand Lundy's (S ampersand L) scope of work in the COTP includes the design of approximately 150 miles of new single-circuit, 500-kV transmission line from southern Oregon to the vicinity of Redding, California. This paper presents the development of the design criteria for this segment of the project, which crosses diverse topographic and climatic regions. This project is an example of the increasing utilization of computers in transmission line engineering. Almost all aspects of design involved the use of the computer. Also, the development of the design criteria for this project coincided with an early release of the TLWorkstation software package by EPRI. TLWorkstation is an engineering workstation containing a family of programs for various aspects of transmission line design. This engineering software allows for increasing refinement in the design and economic optimization of transmission lines and is becoming an important design tool for transmission engineers

  4. Balancing development costs and sales to optimize the development time of product line additions

    NARCIS (Netherlands)

    Langerak, F.; Griffin, A.; Hultink, E.J.

    2010-01-01

    Development teams often use mental models to simplify development time decision making because a comprehensive empirical assessment of the trade-offs across the metrics of development time, development costs, proficiency in market-entry timing, and new product sales is simply not feasible.

  5. PRDM14 is expressed in germ cell tumors with constitutive overexpression altering human germline differentiation and proliferation

    Directory of Open Access Journals (Sweden)

    Joanna J. Gell

    2018-03-01

    Full Text Available Germ cell tumors (GCTs are a heterogeneous group of tumors occurring in gonadal and extragonadal locations. GCTs are hypothesized to arise from primordial germ cells (PGCs, which fail to differentiate. One recently identified susceptibility loci for human GCT is PR (PRDI-BF1 and RIZ domain proteins 14 (PRDM14. PRDM14 is expressed in early primate PGCs and is repressed as PGCs differentiate. To examine PRDM14 in human GCTs we profiled human GCT cell lines and patient samples and discovered that PRDM14 is expressed in embryonal carcinoma cell lines, embryonal carcinomas, seminomas, intracranial germinomas and yolk sac tumors, but is not expressed in teratomas. To model constitutive overexpression in human PGCs, we generated PGC-like cells (PGCLCs from human pluripotent stem cells (PSCs and discovered that elevated expression of PRDM14 does not block early PGC formation. Instead, we show that elevated PRDM14 in PGCLCs causes proliferation and differentiation defects in the germline. Keywords: Germ cell tumor, PRDM14, Cell differentiation, Primordial germ cell, Proliferation

  6. Generation of an integration-free induced pluripotent stem cell line (CSC-43 from a patient with sporadic Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Ana Marote

    2018-03-01

    Full Text Available An induced pluripotent stem cell (iPSC line was generated from a 36-year-old patient with sporadic Parkinson's disease (PD. Skin fibroblasts were reprogrammed using the non-integrating Sendai virus technology to deliver OCT3/4, SOX2, c-MYC and KLF4 factors. The generated cell line (CSC-43 exhibits expression of common pluripotency markers, in vitro differentiation into three germ layers and normal karyotype. This iPSC line can be used to study the mechanisms underlying the development of PD.

  7. Drawing ability in typical and atypical development; colour cues and the effect of oblique lines.

    Science.gov (United States)

    Farran, E K; Dodd, G F

    2015-06-01

    Individuals with Williams syndrome (WS) have poor drawing ability. Here, we investigated whether colour could be used as a facilitation cue during a drawing task. Participants with WS and non-verbal ability matched typically developing (TD) children were shown line figures presented on a 3 by 3 dot matrix, and asked to replicate the figures by drawing on an empty dot matrix. The dots of the matrix were either all black (control condition), or nine different coloured dots (colour condition). In a third condition, which also used coloured dots, participants were additionally asked to verbalise the colours of the dots prior to replicating the line drawings (colour-verbal condition). Performance was stronger in both WS and TD groups on the two coloured conditions, compared with the control condition. However, the facilitation effect of colour was significantly weaker in the WS group than in the TD group. Replication of oblique line segments was less successful than replication of non-oblique line segments for both groups; this effect was reduced by colour facilitation in the TD group only. Verbalising the colours had no additional impact on performance in either group. We suggest that colour acted as a cue to individuate the dots, thus enabling participants to better ascertain the spatial relationships between the parts of each figure, to determine the start and end points of component lines, and to determine the correspondence between the model and their replication. The reduced facilitation in the WS group is discussed in relation to the effect of oblique versus non-oblique lines, the use of atypical drawing strategies, and reduced attention to the model when drawing the replication. © 2014 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

  8. MRI of intracranial germ cell tumours

    International Nuclear Information System (INIS)

    Sumida, M.; Uozumi, T.; Kiya, K.; Mukada, K.; Arita, K.; Kurisu, K.; Sugiyama, K.; Onda, J.; Satoh, H.; Ikawa, F.; Migita, K.

    1995-01-01

    We reviewed MRI findings in proven intracranial germ cell tumours in 22 cases, 12 of whom received Gd-DTPA. On T1-weighted images, the signal intensity of the tumour parenchyma was moderately low in 19 cases and isointense in 3; on T2-weighted images, it was high in all cases. Regions of different intensity thought to be cysts were found in 17 (77 %): 7 of 12 patients with germinoma (58 %) and in all other cases. Of the 13 patients with pineal lesions T1-weighted sagittal images showed the aqueduct to be obstructed in 5, stenotic in 7 and normal in 1. Strong contrast enhancement was observed in all 12 cases. Of the 14 patients with suprasellar lesions, 5 were found to have an intrasellar extension, and in 3 of these, the normal pituitary gland, which could be distinguished from the tumour, was displaced anteriorly. Ten patients (45 %) had multiple lesions. (orig.)

  9. Tritium effects on germ cells and fertility

    International Nuclear Information System (INIS)

    Dobson, R.L.; Kwan, T.C.; Straume, T.

    1982-01-01

    Primordial oocytes in juvenile mice show acute gamma-ray LD 50 as low as 6 rad. This provides opportunities for determining dose-response relations at low doses and chronic exposure in the intact animal - conditions of particular interest for hazard evaluation. Examined in this way, 3 HOH in body water is found to kill murine oocytes exponentially with dose, the LD 50 level for chronic exposure being only 2μCi/ml (delivering 0.4 rad/day). At very low doses and dose rates, where comparisons between tritium and other radiations are of special significance for radiological protection, the RBE of tritium compared with 60 Co gamma radiation reaches approximately 3. Effects on murine fertility from tritium-induced oocyte loss have been quantified by reproductive capacity measurements. Chronic low-level exposure has been examined also in three primate species - squirrel, rhesus, and bonnet monkeys. In squirrel monkeys the ovarian germ-cell supply is 99% destroyed by the time of birth from prenatal exposure to body-water levels of 3 HOH (administered in maternal drinking water) of only 3 μCi/ml, the LD 50 level being 0.5 μCi/ml (giving 0.1 rad/day), one fourth that in mice. Though not completely ruled out, similar high sensitivity of female germ cells has not been found in macaques; and it probably does not occur in man. The exquisite radiosensitivity of primordial oocytes in mice is apparently due to vulnerability of the plasma membrane (or something of similar geometry and location), not DNA. Evidence for this comes from tritium data as well as neutron studies. Tritium administered as 3 HOH, and therefore generally distributed, is much more effective in killing murine oocytes than is tritium administered as 3 H-TdR, localized in the nucleus. This situation in the mouse may have implications for estimating radiation genetic risk in the human female

  10. Development of ATC for High Speed and High Density Commuter Line

    Science.gov (United States)

    Okutani, Tamio; Nakamura, Nobuyuki; Araki, Hisato; Irie, Shouji; Osa, Hiroki; Sano, Minoru; Ikeda, Keigo; Ozawa, Hiroyuki

    A new ATC (Automatic Train Control) system has been developed with solutions to realize short train headway by assured braking utilizing digital data transmission via rails; the digital data for the ATP (Automatic Train Protection) function; and to achieve EMC features for both AC and DC sections. The DC section is of the unprecedented DC traction power supply system utilizing IGBT PWM converter at all DC substations. Within the AC section, train traction force is controlled by PWM converter/inverters. The carrier frequencies of the digital data signals and chopping frequency of PWM traction power converters on-board are decided via spectral analysis of noise up to degraded mode cases of equipment. Developed system was equipped to the Tukuba Express Line, new commuter line of Tokyo metropolitan area, and opened since Aug. 2005.

  11. Sensitivity of spore germination and germ tube elongation of Saccharina japonica to metal exposure.

    Science.gov (United States)

    Han, Taejun; Kong, Jeong-Ae; Kang, Hee-Gyu; Kim, Seon-Jin; Jin, Gyo-Sun; Choi, Hoon; Brown, Murray T

    2011-11-01

    The sensitivity of early life stages of the brown seaweed Saccharina japonica to six metals (Cd, Cu, Hg, Ni, Pb, Zn) and two waste-water samples were investigated and a new toxicity bioassay developed. The two endpoints used were spore germination and germ tube elongation with an exposure time of 24 h. Optimal test conditions determined for photon irradiance, pH, salinity and temperature were darkness, pH 8, 35‰ and 15°C, respectively. The toxicity ranking of five metals was: Hg (EC(50) of 41 and 42 μg l(-1)) > Cu (120 and 81 μg l(-1)) > Ni (2,009 and 1,360 μg l(-1)) > Zn (3,024 and 3,897 μg l(-1)) > Pb (4,760 and 4,429 μg l(-1)) > Cd (15,052 and 7,541 μg l(-1)) for germination and germ tube elongation, respectively. The sensitivities to Cd, Cu and Ni were greater in germ tube elongation than in germination process. When tested against two different waste-water samples (processed animal and printed circuit board waste-water) values of EC(50) were between 21.29 and 32.02% for germination and between 5.33 and 8.98% for germ tube elongation. Despite differences in their chemical composition, the toxic effects of waste-water samples, as indicated by EC(50) values, did not differ significantly for the same endpoints. The CV range for both germination and germ tube elongation was between 4.61 and 37.69%, indicating high levels of precision of the tests. The results compare favourably with those from more established test procedures employing micro- and macroalgae. The advantages and potential limitations of the bioassay for the assessment of anthropogenic impacts on coastal ecosystems and commercial cultivation areas in near-shore environments are discussed.

  12. Development of an in-line grout meter for improved quality control

    International Nuclear Information System (INIS)

    Del Cul, G.D.; Gilliam, T.M.

    1991-05-01

    This report documents progress to date on the development of an in-line grout meter and demonstration of its applicability at operating temperature of 50 degree C. The grout meter, which is based on measurement of grout electrical resistance/capacitance, is intended to provide real-time measurements of grout mix ratio (ratio of dry-solids-blend materials to waste). 4 refs., 6 figs., 5 tabs

  13. The development of an expert system to tune a beam line

    International Nuclear Information System (INIS)

    Schultz, D.E.; Brown, P.A.; British Columbia Univ., Vancouver, BC

    1989-01-01

    The experience of developing an Expert System to aid in the tuning of the Ion Source Injection beam line at TRIUMF is described. The challenging and complex task of introducing Expert System technology into an established accelerator operation is outlined. Success in this environment depends strongly on the choice of project, the choice of experts, the choice of tools, and the methods used to represent the expertise. All these choices are discussed

  14. Flexible adaptation of male germ cells from female iPSCs of endangered Tokudaia osimensis.

    Science.gov (United States)

    Honda, Arata; Choijookhuu, Narantsog; Izu, Haruna; Kawano, Yoshihiro; Inokuchi, Mizuho; Honsho, Kimiko; Lee, Ah-Reum; Nabekura, Hiroki; Ohta, Hiroshi; Tsukiyama, Tomoyuki; Ohinata, Yasuhide; Kuroiwa, Asato; Hishikawa, Yoshitaka; Saitou, Mitinori; Jogahara, Takamichi; Koshimoto, Chihiro

    2017-05-01

    In mammals, the Y chromosome strictly influences the maintenance of male germ cells. Almost all mammalian species require genetic contributors to generate testes. An endangered species, Tokudaia osimensis , has a unique sex chromosome composition XO/XO, and genetic differences between males and females have not been confirmed. Although a distinctive sex-determining mechanism may exist in T. osimensis , it has been difficult to examine thoroughly in this rare animal species. To elucidate the discriminative sex-determining mechanism in T. osimensis and to find a strategy to prevent its possible extinction, we have established induced pluripotent stem cells (iPSCs) and derived interspecific chimeras using mice as the hosts and recipients. Generated iPSCs are considered to be in the so-called "true naïve" state, and T. osimensis iPSCs may contribute as interspecific chimeras to several different tissues and cells in live animals. Surprisingly, female T. osimensis iPSCs not only contributed to the female germ line in the interspecific mouse ovary but also differentiated into spermatocytes and spermatids that survived in the adult interspecific mouse testes. Thus, T. osimensis cells have high sexual plasticity through which female somatic cells can be converted to male germline cells. These findings suggest flexibility in T. osimensis cells, which can adapt their germ cell sex to the gonadal niche. The probable reduction of the extinction risk of an endangered species through the use of iPSCs is indicated by this study.

  15. Stage line diagram: an age-conditional reference diagram for tracking development.

    Science.gov (United States)

    van Buuren, Stef; Ooms, Jeroen C L

    2009-05-15

    This paper presents a method for calculating stage line diagrams, a novel type of reference diagram useful for tracking developmental processes over time. Potential fields of applications include: dentistry (tooth eruption), oncology (tumor grading, cancer staging), virology (HIV infection and disease staging), psychology (stages of cognitive development), human development (pubertal stages) and chronic diseases (stages of dementia). Transition probabilities between successive stages are modeled as smoothly varying functions of age. Age-conditional references are calculated from the modeled probabilities by the mid-P value. It is possible to eliminate the influence of age by calculating standard deviation scores (SDS). The method is applied to the empirical data to produce reference charts on secondary sexual maturation. The mean of the empirical SDS in the reference population is close to zero, whereas the variance depends on age. The stage line diagram provides quick insight into both status (in SDS) and tempo (in SDS/year) of development of an individual child. Other measures (e.g. height SDS, body mass index SDS) from the same child can be added to the chart. Diagrams for sexual maturation are available as a web application at http://vps.stefvanbuuren.nl/puberty. The stage line diagram expresses status and tempo of discrete changes on a continuous scale. Wider application of these measures scores opens up new analytic possibilities. (c) 2009 John Wiley & Sons, Ltd.

  16. Interaction of NANOS2 and NANOS3 with different components of the CNOT complex may contribute to the functional differences in mouse male germ cells

    OpenAIRE

    Atsushi Suzuki; Yuki Niimi; Yumiko Saga

    2014-01-01

    ABSTRACT NANOS2 and NANOS3 belong to the Nanos family of proteins that contain a conserved zinc finger domain, which consists of two consecutive CCHC-type zinc finger motifs, and contribute to germ cell development in mice. Previous studies indicate that there are redundant and distinct functions of these two proteins. NANOS2 rescues NANOS3 functions in the maintenance of primordial germ cells, whereas NANOS3 fails to replace NANOS2 functions in the male germ cell pathway. However, the lack o...

  17. Differential developmental expression of transcription factors GATA-4 and GATA-6, their cofactor FOG-2 and downstream target genes in testicular carcinoma in situ and germ cell tumors

    DEFF Research Database (Denmark)

    Salonen, Jonna; Rajpert-De Meyts, E; Mannisto, Susanna

    2010-01-01

    Testicular germ cell cancer is the most common malignancy among young males. The pre-invasive precursor, carcinoma in situ testis (CIS), presumably originates from arrested and transformed fetal gonocytes. Given that GATA transcription factors have essential roles in embryonic and testicular deve...... development, we explored the expression of GATA-4, GATA-6, cofactor friend of GATA (FOG)-2, and downstream target genes during human testis development and addressed the question whether changes in this pathway may contribute to germ cell neoplasms....

  18. Genome-Wide Epigenetic Characterization of Tissues from Three Germ Layers Isolated from Sheep Fetuses

    OpenAIRE

    Capra, Emanuele; Toschi, Paola; Del Corvo, Marcello; Lazzari, Barbara; Scapolo, Pier A.; Loi, Pasqualino; Williams, John L.; Stella, Alessandra; Ajmone-Marsan, Paolo

    2017-01-01

    DNA methylation of regulatory and growth-related genes contributes to fetal programming which is important for maintaining the correct development of three germ layers of the embryo that develope into different tissues and organs, and which persists into adult life. In this study, a preliminary epigenetic screen was performed to define genomic regions that are involved in fetal epigenome remodeling. Embryonic ectodermic tissues (origin of nervous tissue), mesenchymal tissues (origin of connec...

  19. Mutation in cpsf6/CFIm68 (Cleavage and Polyadenylation Specificity Factor Subunit 6 causes short 3'UTRs and disturbs gene expression in developing embryos, as revealed by an analysis of primordial germ cell migration using the medaka mutant naruto.

    Directory of Open Access Journals (Sweden)

    Takao Sasado

    Full Text Available Our previous studies analyzing medaka mutants defective in primordial germ cell (PGC migration identified cxcr4b and cxcr7, which are both receptors of the chemokine sdf1/cxcl12, as key regulators of PGC migration. Among PGC migration mutants, naruto (nar is unique in that the mutant phenotype includes gross morphological abnormalities of embryos, suggesting that the mutation affects a broader range of processes. A fine genetic linkage mapping and genome sequencing showed the nar gene encodes Cleavage and Polyadenylation Specificity Factor subunit 6 (CPSF6/CFIm68. CPSF6 is a component of the Cleavage Factor Im complex (CFIm which plays a key role in pre-mRNA 3'-cleavage and polyadenylation. 3'RACE of sdf1a/b and cxcr7 transcripts in the mutant embryos indicated shorter 3'UTRs with poly A additions occurring at more upstream positions than wild-type embryos, suggesting CPSF6 functions to prevent premature 3'UTR cleavage. In addition, expression of the coding region sequences of sdf1a/b in nar mutants was more anteriorly extended in somites than wild-type embryos, accounting for the abnormally extended distribution of PGCs in nar mutants. An expected consequence of shortening 3'UTR is the escape from the degradation mechanism mediated by microRNAs interacting with distal 3'UTR sequence. The abnormal expression pattern of sdf1a coding sequence may be at least partially accounted for by this mechanism. Given the pleiotropic effects of nar mutation, further analysis using the nar mutant will reveal processes in which CPSF6 plays essential regulatory roles in poly A site selection and involvement of 3'UTRs in posttranscriptional gene regulation in various genes in vivo.

  20. Mutation in cpsf6/CFIm68 (Cleavage and Polyadenylation Specificity Factor Subunit 6) causes short 3'UTRs and disturbs gene expression in developing embryos, as revealed by an analysis of primordial germ cell migration using the medaka mutant naruto.

    Science.gov (United States)

    Sasado, Takao; Kondoh, Hisato; Furutani-Seiki, Makoto; Naruse, Kiyoshi

    2017-01-01

    Our previous studies analyzing medaka mutants defective in primordial germ cell (PGC) migration identified cxcr4b and cxcr7, which are both receptors of the chemokine sdf1/cxcl12, as key regulators of PGC migration. Among PGC migration mutants, naruto (nar) is unique in that the mutant phenotype includes gross morphological abnormalities of embryos, suggesting that the mutation affects a broader range of processes. A fine genetic linkage mapping and genome sequencing showed the nar gene encodes Cleavage and Polyadenylation Specificity Factor subunit 6 (CPSF6/CFIm68). CPSF6 is a component of the Cleavage Factor Im complex (CFIm) which plays a key role in pre-mRNA 3'-cleavage and polyadenylation. 3'RACE of sdf1a/b and cxcr7 transcripts in the mutant embryos indicated shorter 3'UTRs with poly A additions occurring at more upstream positions than wild-type embryos, suggesting CPSF6 functions to prevent premature 3'UTR cleavage. In addition, expression of the coding region sequences of sdf1a/b in nar mutants was more anteriorly extended in somites than wild-type embryos, accounting for the abnormally extended distribution of PGCs in nar mutants. An expected consequence of shortening 3'UTR is the escape from the degradation mechanism mediated by microRNAs interacting with distal 3'UTR sequence. The abnormal expression pattern of sdf1a coding sequence may be at least partially accounted for by this mechanism. Given the pleiotropic effects of nar mutation, further analysis using the nar mutant will reveal processes in which CPSF6 plays essential regulatory roles in poly A site selection and involvement of 3'UTRs in posttranscriptional gene regulation in various genes in vivo.

  1. Development of a portable computed tomographic scanner for on-line imaging of industrial piping systems

    International Nuclear Information System (INIS)

    Jaafar Abdullah; Mohd Arif Hamzah; Mohd Soyapi Mohd Yusof; Mohd Fitri Abdul Rahman; Fadil IsmaiI; Rasif Mohd Zain

    2003-01-01

    Computed tomography (CT) technology is being increasingly developed for industrial application. This paper presents the development of a portable computed tomographic scanner for on?line imaging of industrial piping systems. The theoretical approach, the system hardware, the data acquisition system and the adopted algorithm for image reconstruction are discussed. The scanner has large potential to be used to determine the extent of corrosion under insulation (CUI), to detect blockages, to measure the thickness of deposit/materials built-up on the walls and to improve understanding of material flow in pipelines. (Author)

  2. Research on cotton anther development of three male-sterile lines

    International Nuclear Information System (INIS)

    Dou Liping; Tang Canming; Yue Jieyu; Wang Qingya

    2009-01-01

    Pollens of Sumian 22 were irradiated by 60 Co γ-rays at a dose of 20Gy, then fertilized to pistil and harvested seed. Three male-sterile lines were selected from M 1 plants, their anther observed by paraffin slice technique. Although there were some different characteristics during the abortion anther development, the abortion was consistent: the abortion stage from the development periods of pollen mother cells to microspore, pollen mother cells, tapetum, middle layer cells and the shape of anther were affected, the results contained micronucleus and double nucleus, cytoplasm expansion during the period of meiosis, tapetum and middle layer cells and so on were abnormal. (authors)

  3. FEDIX on-line information service: Design, develop, test, and implement an on-line research and education information service. Annual status report, September 1992--August 1993

    Energy Technology Data Exchange (ETDEWEB)

    Rodman, J.A.

    1993-08-01

    Federal Information Exchange, Inc. (FIE) is a diversified information services company that is recognized as the major electronic link between the higher education community and the Federal government in the field of research administration. FIE provides a range of information related services to the government, academic and private sectors, including database management, software development and technical support. FEDIX is the on-line information service designed, developed and implemented by FIE to accomplish the following objectives: (1). Broaden the participation of the education community in Federal research and education programs by providing free and unrestricted on-line access to information from all participating Federal agencies; and (2). Provide the education community with on-line access to a single keyword-searchable system for research and educational funding opportunities at the participating Federal agencies.

  4. Development of a low-level, in-line alpha counter (LLILAC)

    International Nuclear Information System (INIS)

    Gritzo, R.E.; Farnham, J.E.; Fowler, M.M.; Wouters, J.

    1996-01-01

    This is the final report of a two-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). With the increasing awareness of water contamination issues and the rising consequences of any form of contamination, real-time continuous monitoring is rapidly becoming a necessity. In particular, monitoring for the presence of any radioactive material is paramount. The most difficult of such monitoring tasks is that of detecting alpha-emitting radionuclides in water. Our development of the Low Level In-Line Alpha Counter (LLILAC) addresses the need for on-line, near real-time monitoring of alpha-emitting radionuclides in aqueous streams in a wide variety of applications. Although primarily designed as an on-line instrument for real-time applications, the detector can also be used for long-term in situ/post-closure monitoring. This detection system operates by allowing the stream to be monitored to come in contact with a large number of small rods or tubes made of scintillation material. By maximizing the surface to volume ratio of the scintillator, the response to alpha particles is favored over other types of radiation. Several configurations of scintillator and light collection schemes have been investigated to optimize the detection efficiency. We have also written several Monte Carlo codes to help to predict and understand the detector performance

  5. Design and development of line type modulators for high impedance electron gun

    Energy Technology Data Exchange (ETDEWEB)

    Dixit, Kavita P.; Tillu, Abhijit; Chavan, Ramchandra; Yadav, Vivek; Sarukte, Hemant, E-mail: kavidi@barc.gov.in [Accelerator and Pulse Power Division, Bhabha Atomic Research Centre, Mumbai (India)

    2014-07-01

    Conventional line type modulators are routinely used for powering pulsed power microwave devices such as magnetrons and klystrons used for radar, medical and scientific applications. The load impedance (operating point) is fairly well defined in these cases, and makes the design of the discharging circuit of the modulator straight forward. This paper describes the Line type modulators that have been developed and being routinely used for powering the Triode Electron Gun of industrial electron linacs. The beam parameters of such guns are user defined and the pulse current varies from few mA to 800mA (typ). The beam energies requirement varies from 40 keV to 80 keV. Hence the impedance offered by the electron gun to the power source (modulator) is not well defined. The load capacitance which is inclusive of the various stray capacitances along with the intrinsic gun capacitance is ∼ 200-400 pF. This capacitance, which depends on the configuration, shunts the load and makes the effective load highly capacitive with the resistive part varying over a wide range. The paper describes the design and development of conventional line type modulators for powering Electron gun load of the type described above. (author)

  6. 'Fluorescent Cell Chip' for immunotoxicity testing: Development of the c-fos expression reporter cell lines

    International Nuclear Information System (INIS)

    Trzaska, Dominika; Zembek, Patrycja; Olszewski, Maciej; Adamczewska, Violetta; Ulleras, Erik; Dastych, JarosIaw

    2005-01-01

    The Fluorescent Cell Chip for in vitro immunotoxicity testing employs cell lines derived from lymphocytes, mast cells, and monocytes-macrophages transfected with various EGFP cytokine reporter gene constructs. While cytokine expression is a valid endpoint for in vitro immunotoxicity screening, additional marker for the immediate-early response gene expression level could be of interest for further development and refinement of the Fluorescent Cell Chip. We have used BW.5147.3 murine thymoma transfected with c-fos reporter constructs to obtain reporter cell lines expressing ECFP under the control of murine c-fos promoter. These cells upon serum withdrawal and readdition and incubation with heavy metal compounds showed paralleled induction of c-Fos expression as evidenced by Real-Time PCR and ECFP fluorescence as evidenced by computer-supported fluorescence microscopy. In conclusion, we developed fluorescent reporter cell lines that could be employed in a simple and time-efficient screening assay for possible action of chemicals on c-Fos expression in lymphocytes. The evaluation of usefulness of these cells for the Fluorescent Cell Chip-based detection of immunotoxicity will require additional testing with a larger number of chemicals

  7. Development of an on-line tritium monitor with gamma-ray rejection and energy discrimination

    International Nuclear Information System (INIS)

    Cox, S.A.; Yule, T.J.; Bennett, E.F.

    1981-01-01

    With the prospect of large fusion facilities coming on-line in the not-too-distant future, it is becoming increasingly important that an on-line tritium-monitoring system be developed which is capable of detecting small amounts of released tritium. Since tritium oxide is some 400 times as hazardous as elemental tritium, it is necessary to distinguish between the two in order to properly evaluate the hazard. Presently available on-line instrumentation has marginal sensitivity, is unable to distinguish between the two forms of tritium, and has poor discrimination against background gamma radiation and air activation products. The objective of our program is to develop a monitoring system with the capability of distinguishing between the two forms of tritium, detecting tritium with a sensitivity of a fraction of an MPC/sub a/ (1 MPC/sub a/ = 5. x 10 - 6 Ci/M 3 ) for the oxide, and discriminating against gamma activity and airborne activity other than tritium

  8. Development of the integrated core on-line monitoring and protection aid surveillance system

    International Nuclear Information System (INIS)

    Cho, Byung Oh; In, Wang Kee; Song, Jae Seung; Zee, Sung Quun

    1998-01-01

    The integrated Core On-line Monitoring and Protection Aid Surveillance System (COMPASS) is developed for the purpose of supporting the reactor operation, based on the three-dimensional nodal design code, MASTER. The heart of COMPASS is an adaptive nodal core simulator for the on-line calculation of three-dimensional assembly and pin power distributions which are used for the evaluation of the thermal margins and for the guide in operation. In this paper, the overall structures and the solution methods of COMPASS are described. The uncertainty of COMPASS for SMART core was also evaluated by comparing that of MASTER. The results showed that COMPASS uncertainty in power shape prediction is identical to that of the design code system, MASTER. The application of COMPASS to the analysis of peaking factor for SMART core resulted with about 4% gain in peaking factor margin when compared to COLSS

  9. Development of on-line monitoring device to detect the presence/absence of sodium vapor

    International Nuclear Information System (INIS)

    Wolson, R.D.; McPheeters, C.C.; Kremesec, V.J.; Kolba, V.M.

    1983-03-01

    A process is being developed by the Sodium Waste Technology Program at ANL-W to remove metallic sodium from scrap and waste. The final step in the process is the removal of residual metallic sodium by evaporation at temperatures up to 482 0 C (900 0 F) and at pressures of about 10 - 2 torr (1.3 Pa). Efficient operation of this process requires that the operators have a method to indicate the completion of the evaporation. This end point would signify when the chamber and scrap and waste is free of metallic sodium. It was determined that a measure of the vacuum was not sufficiently sensitive, and a research effort was undertaken to select an on-line monitoring device. In this effort, three promising methods were reviewed. The use of quadrupole mass spectrometer was recommended and an on-line device was designed for use in a Sodium Process Demonstration (SPD) Plant

  10. Development of an Ethernet enabled microcontroller based module for Superconducting Cyclotron ECR beam line control

    International Nuclear Information System (INIS)

    Chatterjee, M.; Koley, D.; Nabhiraj, P.Y.

    2012-01-01

    An Ethernet enabled control and data acquisition module is developed for remote control and monitoring of the ECR beam line equipment of the Superconducting Cyclotron. The PIC microcontroller based module supports multiple general purpose analog and digital inputs and outputs for interfacing with various equipments and an embedded web server. The remote monitoring and control of the equipment are achieved through the web based user interface. The user authenticated access to control parameters and module configuration parameters ensures the operational safety of the equipment under control. This module is installed in Superconducting Cyclotron ECR beam line for the control and monitoring of vacuum pumping modules, comprising of pumps, gate valves and dual vacuum gauges. The installation of these modules results in a distributed control with localised field cabling and hence better fault diagnosis. (author)

  11. Development of a wheat-Aegilops searsii substitution line with positively affecting Chinese steamed bread quality.

    Science.gov (United States)

    Du, Xuye; Ma, Xin; Min, Jingzhi; Zhang, Xiaocun; Jia, Zhenzhen

    2018-03-01

    A wheat- Aegilops searsii substitution line GL1402, in which chromosome 1B was substituted with 1S s from Ae. searsii , was developed and detected using SDS-PAGE and GISH. The SDS-PAGE analysis showed that the HMW-GS encoded by the Glu-B1 loci of Chinese Spring was replaced by the HMW-GS encoded by the Glu-1S s loci of Ae. searsii . Glutenin macropolymer (GMP) investigation showed that GL1402 had a much higher GMP content than Chinese Spring did. A dough quality comparison of GL1402 and Chinese Spring indicated that GL1402 showed a significantly higher protein content and middle peak time (MPT), and a smaller right peak slope (RPS). Quality tests of Chinese steamed bread (CSB) showed that the GL1402 also produced good steamed bread quality. These results suggested that the substitution line is a valuable breeding material for improving the wheat processing quality.

  12. Strategic Lines of Communication in Development of Management and Human Skills

    Directory of Open Access Journals (Sweden)

    Rider Antonio Moreno Guillen

    2017-02-01

    Full Text Available The objective of this study is to propose strategic lines of communication in the development of managerial and human skills at the Rural School Nucleus (NER 187, Calderas parish, Bolívar municipality of Barinas state. The nature of the study was embedded in the quantitative paradigm, the type of research in the Feasible Project modality and the research design focused on a field study. The population and the sample were made up of thirty (30 teachers. For the collection of information, a questionnaire survey was designed with Likert scaling with five (05 response alternatives: Always, Almost Always, Sometimes, Almost Never and Never. The study concludes: infrequently the passive communication style is developed for the development of managerial and human skills. They consider that moderately the manager uses aggressive communication style to develop managerial skills. In addition, it lacks the use of assertive communication to develop managerial skills. Likewise, they lack technical skills, human skills and conceptual skills. These are relevant for the proposal of strategic lines in communication because it will accede to the strengthening of the managerial and human abilities of both the teacher and the school manager.

  13. Development of a Indica rice restorer line Fuhui838 and its derivative lines with strong restoring ability and their utilization

    International Nuclear Information System (INIS)

    Deng Dasheng; Chen Hao; Deng Wenmin; Feng Lei; Yang Xuefeng; Ma Anlu; Liu Minghai

    2009-01-01

    Fuhui 838 and its derivative restorer lines (Fuhui 718, Fuhui 305, Zhongfu 218, Mianhui 3728, Nuoyou 1...) have the ability of strong restoring, high combining, and good resisting, which were bred and released by combined techniques of radiation-induced mutation, polymerization hybridization, and temperature tolerance screening. At present, about 43 combinations were registered and released to commercial production, the series of combinations present high seed setting rate, good tolerance to chilling and heat stress, wide adaptability, high and stable yield, the accumulated area added up to 40 million hm 2 . II you 838, which is famous one of these combinations, proved to be the best in long term and wide planting after Sanyou 63, and it is also one of the main hybrid rice for exporting in China. (authors)

  14. Diet Matters: Endotoxin in the Diet Impacts the Level of Allergic Sensitization in Germ-Free Mice.

    Directory of Open Access Journals (Sweden)

    Martin Schwarzer

    Full Text Available Germ-free animals have been used to define the vital role of commensal bacteria on the maturation of the host immune system. However, the role of bacterial residues in diet in this setting is poorly understood. Here we investigated the effect of bacterial contamination in sterile diet on the level of allergic sensitization in germ-free mice. Sterile grain-based diets ST1 and R03 were tested for the level of bacterial contamination. ST1 contained higher amount of bacterial DNA, approximately ten times more endotoxin, and induced higher, TLR4-dependent, cytokine production in dendritic cells compared to R03. In a germ-free mouse model of sensitization to the major birch pollen allergen Bet v 1, feeding on ST1 for at least two generations was associated with decreased production of allergen-specific IgE and IgG1 antibodies in sera in comparison to R03. Furthermore, reduced levels of allergen-specific and ConA-induced cytokines IL-4, IL-5 and IL-13 accompanied by increased levels of IFN-γ were detected in splenocytes cultures of these mice. Our results show that contamination of experimental diet with bacterial residues, such as endotoxin, significantly affects the development of allergic sensitization in germ-free mice. Therefore, careful selection of sterile food is critical for the outcomes of germ-free or gnotobiotic experimental models of immune-deviated diseases.

  15. The effect of UV irradiation on the early development of silkworm embryos, (2)

    International Nuclear Information System (INIS)

    Kobayashi, Yoshihiro

    1981-01-01

    The development of silkworm eggs irradiated with UV was compared with that of normal eggs. When the eggs were irradiated with UV from the lateral side immediately after oviposition, development was decelerated, but the germ band was produced. The side of the germ band that was irradiated with UV was abnormal with holes, but the opposite side was hole-free and normal. The normal half of the germ band splits longitudinally, but developed along with the abnormal half to form various malformations. When the eggs were irradiated from the ventral side, the ventral part of the germ band was abnormal at the early stage, the germ band did not concentrate to one place, and produced the half-embryos longitudinally divided by the median line. The UV irradiation at the beginning of the blastoderm stage produced similar results. In the areas irradiated by UV, cleavage nuclei invaded into the surrounding protoplasm, and mitotic figures were observed, but the cell number did not increase even with the advance of development unlike normal cells, whereas the sizes of the cells, their nuclei and nucleoli were enlarged, and intercellular space widened so that the cells were no longer in close contact. The germ band cells produced in the non-irradiated area were normal. The above results suggest that when either the protoplasm or the nucleus of a silkworm egg is damaged by UV, the effect first appears as the inhibition of cell division in the germ band, and as the enlargement of the cell, nucleus and nucleoli. It is presumed that this induces the subsequent inhibition of cell differentiation or abnormalities. (Kaihara, S.)

  16. Lipid phosphate phosphatase activity regulates dispersal and bilateral sorting of embryonic germ cells in Drosophila

    Science.gov (United States)

    Renault, Andrew D.; Kunwar, Prabhat S.; Lehmann, Ruth

    2010-01-01

    In Drosophila, germ cell survival and directionality of migration are controlled by two lipid phosphate phosphatases (LPP), wunen (wun) and wunen-2 (wun2). wun wun2 double mutant analysis reveals that the two genes, hereafter collectively called wunens, act redundantly in primordial germ cells. We find that wunens mediate germ cell-germ cell repulsion and that this repulsion is necessary for germ cell dispersal and proper transepithelial migration at the onset of migration and for the equal sorting of the germ cells between the two embryonic gonads during their migration. We propose that this dispersal function optimizes adult fecundity by assuring maximal germ cell occupancy of both gonads. Furthermore, we find that the requirement for wunens in germ cell survival can be eliminated by blocking germ cell migration. We suggest that this essential function of Wunen is needed to maintain cell integrity in actively migrating germ cells. PMID:20431117

  17. Treatment Options By Stage (Ovarian Germ Cell Tumors)

    Science.gov (United States)

    ... Germ Cell Tumors Treatment (PDQ®)–Patient Version Treatment Option Overview Go to Health Professional Version Key Points ... and restore) the body’s blood cells. New treatment options Combination chemotherapy (the use of more than one ...

  18. Profiling of androgen response in rainbow trout pubertal testis: relevance to male gonad development and spermatogenesis.

    Directory of Open Access Journals (Sweden)

    Antoine D Rolland

    Full Text Available The capacity of testicular somatic cells to promote and sustain germ cell differentiation is largely regulated by sexual steroids and notably androgens. In fish species the importance of androgens is emphasized by their ability to induce sex reversal of the developing fries and to trigger spermatogenesis. Here we studied the influence of androgens on testicular gene expression in trout testis using microarrays. Following treatment of immature males with physiological doses of testosterone or 11-ketotestosterone, 418 genes that exhibit changes in expression were identified. Interestingly, the activity of testosterone appeared stronger than that of 11-ketotestosterone. Expression profiles of responsive genes throughout testis development and in isolated germ cells confirmed androgens to mainly affect gene expression in somatic cells. Furthermore, specific clusters of genes that exhibit regulation coincidently with changes in the natural circulating levels of androgens during the reproductive cycle were highlighted, reinforcing the physiological significance of these data. Among somatic genes, a phylogenetic footprinting study identified putative androgen response elements within the proximal promoter regions of 42 potential direct androgen target genes. Finally, androgens were also found to alter the germ line towards meiotic expression profiles, supporting the hypothesis of a role for the somatic responsive genes in driving germ cell fate. This study significantly increases our understanding of molecular pathways regulated by androgens in vertebrates. The highly cyclic testicular development in trout together with functions associated with regulated genes reveal potential mechanisms for androgen actions in tubule formation, steroid production, germ cell development and sperm secretion.

  19. Germ Cell Origins of Posttraumatic Stress Disorder Risk: The Transgenerational Impact of Parental Stress Experience.

    Science.gov (United States)

    Rodgers, Ali B; Bale, Tracy L

    2015-09-01

    Altered stress reactivity is a predominant feature of posttraumatic stress disorder (PTSD) and may reflect disease vulnerability, increasing the probability that an individual will develop PTSD following trauma exposure. Environmental factors, particularly prior stress history, contribute to the developmental programming of the hypothalamic-pituitary-adrenal stress axis. Critically, the consequences of stress experiences are transgenerational, with parental stress exposure impacting stress reactivity and PTSD risk in subsequent generations. Potential molecular mechanisms underlying this transmission have been explored in rodent models that specifically examine the paternal lineage, identifying epigenetic signatures in male germ cells as possible substrates of transgenerational programming. Here, we review the role of these germ cell epigenetic marks, including posttranslational histone modifications, DNA methylation, and populations of small noncoding RNAs, in the development of offspring stress axis sensitivity and disease risk. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  20. The seeds and the worms: Ludwik Fleck and the early history of germ theories

    DEFF Research Database (Denmark)

    Brorson, Stig

    2006-01-01

    -scientific "proto-ideas." In 1935, Fleck proposed that the history of germ theories could be approached through his thesis on proto-ideas. His proposal, however, remained little more than a vague suggestion and was never developed in further detail. This paper introduces the concept of proto-ideas and discusses...... the central epistemological and historiographical implications of Fleck's thesis. The Fleckian approach offers an attractive alternative to positivist reconstructions of the early history of germ theories and provides a useful framework for a deeper understanding of the sociocultural background......The Polish microbiologist and philosopher of science, Ludwik Fleck (1896-1961), was a pioneer in constructivist history and philosophy of science. Based on studies in the history of syphilis, Fleck hypothesized that many established scientific facts are linked, in their development, to pre...

  1. Structural evaluation method study and procedure development for pressurizer surge line subjected to thermal stratification phenomenon

    International Nuclear Information System (INIS)

    Zhang Yixiong; Yu Xiaofei; Ai Honglei

    2014-01-01

    Thermal stratification phenomenon of pressurizer surge line can lead potential threaten to plant safety. Base on the mechanism of thermal stratification occurrence, Fr number is used to judge whether the stratification occurs or not. Also the method of calculating heat transfer coefficient is investigated. Theoretically the 3-dimension thermal stress induced by thermal stratification is decoupled to 1-dimension global stress and 2-dimension local stress, and the complex 3-dimension problem is simplified into a combination of 1-dimension and 2-dimension to compute the stress. Comply with criterion RCC-M, the complete structure integrity evaluation is accomplished after combining the stress produced by thermal stratification and the stresses produced by the other loadings. In order to match the above combined analysis method, Code SYSTUS and ROCOCO are developed. By means of aforesaid evaluation method and corresponding analysis program, surge line thermal stratification of Qinshan Phase II Extension project is investigated in this paper. And the results show that structural integrity of the pressurizer surge line affected by thermal stratification still satisfies criterion RCC-M. (authors)

  2. Genetic dissection of black grain rice by the development of a near isogenic line.

    Science.gov (United States)

    Maeda, Hiroaki; Yamaguchi, Takuya; Omoteno, Motoyasu; Takarada, Takeshi; Fujita, Kenji; Murata, Kazumasa; Iyama, Yukihide; Kojima, Yoichiro; Morikawa, Makiko; Ozaki, Hidenobu; Mukaino, Naoyuki; Kidani, Yoshinori; Ebitani, Takeshi

    2014-06-01

    Rice (Oryza sativa L.) can produce black grains as well as white. In black rice, the pericarp of the grain accumulates anthocyanin, which has antioxidant activity and is beneficial to human health. We developed a black rice introgression line in the genetic background of Oryza sativa L. 'Koshihikari', which is a leading variety in Japan. We used Oryza sativa L. 'Hong Xie Nuo' as the donor parent and backcrossed with 'Koshihikari' four times, resulting in a near isogenic line (NIL) for black grains. A whole genome survey of the introgression line using DNA markers suggested that three regions, on chromosomes 1, 3 and 4 are associated with black pigmentation. The locus on chromosome 3 has not been identified previously. A mapping analysis with 546 F2 plants derived from a cross between the black rice NIL and 'Koshihikari' was evaluated. The results indicated that all three loci are essential for black pigmentation. We named these loci Kala1, Kala3 and Kala4. The black rice NIL was evaluated for eating quality and general agronomic traits. The eating quality was greatly superior to that of 'Okunomurasaki', an existing black rice variety. The isogenicity of the black rice NIL to 'Koshihikari' was very high.

  3. Development of a hydrological model for simulation of runoff from catchments unbounded by ridge lines

    Science.gov (United States)

    Vema, Vamsikrishna; Sudheer, K. P.; Chaubey, I.

    2017-08-01

    Watershed hydrological models are effective tools for simulating the hydrological processes in the watershed. Although there are a plethora of hydrological models, none of them can be directly applied to make water conservation decisions in irregularly bounded areas that do not confirm to topographically defined ridge lines. This study proposes a novel hydrological model that can be directly applied to any catchment, with or without ridge line boundaries. The model is based on the water balance concept, and a linear function concept to approximate the cross-boundary flow from upstream areas to the administrative catchment under consideration. The developed model is tested in 2 watersheds - Riesel Experimental Watershed and a sub-basin of Cedar Creek Watershed in Texas, USA. Hypothetical administrative catchments that did not confirm to the location of ridge lines were considered for verifying the efficacy of the model for hydrologic simulations. The linear function concept used to account the cross boundary flow was based on the hypothesis that the flow coming from outside the boundary to administrative area was proportional to the flow generated in the boundary grid cell. The model performance was satisfactory with an NSE and r2 of ≥0.80 and a PBIAS of administrative catchments of the watersheds were in good agreement with the observed hydrographs, indicating a satisfactory performance of the model in the administratively bounded areas.

  4. Development of a tilting system for electric multiple unit to speed up on conventional lines

    International Nuclear Information System (INIS)

    Seo, Sung Il; Kim, Nam Po; Lee, Soo Gil; Kim, Seok Won

    2008-01-01

    An advanced tilting system for KTT (Korean Tilting Train) was developed and a performance test of the system has been completed. KTT has been constructed to speed up and promise a significant enhancement in service quality on a conventional line. KTT is an electric multiple unit composed of 6 cars running at the design speed of 200 km/h. The tilting system is the core technology of KTT and combined with the conventional bogie system. It has a self-steering mechanism and a swing link. The self-steering mechanism of Z-bar type is free to rotate on the curve and stable to run on a straight line. The swing link mechanism of the bolster enables the carbody to tilt up to 8 .deg.. A tilting control system detects a curve with sensors and commands the electro-mechanical actuators to move the bolster through the computer network system. GPS collaborates with the tilting system to perceive the curve previously and enables gradual tilting so as not to violate passenger comfort. The performance of the tilting system has been verified by a trial test running of KTT on a commercial conventional line. The tilting system is ready for commercial use

  5. Development of Betalain Producing Callus Lines from Colored Quinoa Varieties (Chenopodium quinoa Willd).

    Science.gov (United States)

    Henarejos-Escudero, Paula; Guadarrama-Flores, Berenice; Guerrero-Rubio, M Alejandra; Gómez-Pando, Luz Rayda; García-Carmona, Francisco; Gandía-Herrero, Fernando

    2018-01-17

    Betalains are water-soluble plant pigments of hydrophilic nature with promising bioactive potential. Among the scarce edible sources of betalains is the grain crop quinoa (Chenopodium quinoa Willd), with violet, red, and yellow grains being colored by these pigments. In this work, callus cultures have been developed from differently colored plant varieties. Stable callus lines exhibited color and pigment production when maintained on Murashige and Skoog medium supplemented with the plant growth regulators 6-benzylaminopurine (8.88 μM) and 2,4-dichlorophenoxyacetic acid (6.79 μM) with a reduction of the nitrogen source to 5.91 mM. Pigment analysis by HPLC-DAD and ESI-MS/MS fully describes the content of individual pigments in the cell lines and allows the first report on the pigments present in quinoa seedlings. Phyllocactin and vulgaxanthin I are described as novel pigments in the species and show the potential of C. quinoa culture lines in the production of compounds of nutritional value.

  6. Primary pleuro-pulmonary malignant germ cell tumours.

    Directory of Open Access Journals (Sweden)

    Vaideeswar P

    2002-01-01

    Full Text Available Lungs and pleura are rare sites for malignant germ-cell tumours. Two cases, pure yolk-sac tumour and yolk sac-sac tumour/embryonal carcinoma are described in young males who presented with rapid progression of respiratory symptoms. The malignant mixed germ cell tumour occurred in the right lung, while the yolk-sac tumour had a pseudomesotheliomatous growth pattern suggesting a pleural origin. Alpha-foetoprotein was immunohistochemically demonstrated in both.

  7. Electron microscopic observation of 137Cs-irradiated rat testis. Production of basal laminae for germ cells, despite their absence

    International Nuclear Information System (INIS)

    Sawada, Hajime; Esaki, Michiyo

    2003-01-01

    Whole body γ-ray irradiation of rats with caesium-137 ( 137 Cs) at embryonic day 20 induced marked reduction of the weight of the testis. Body weight and other tissues, however, seemed to remain normal. By light microscopy, complete loss of germ cells was observed in the testis. Other components, such as Sertoli cells and interstitial cells, seemed to be normal. The testes from day 8 postpartum rats contained very few spermatogonia compared with newborn rats, indicating loss of germ cells between days 0 and 8. In the adult, 137 Cs-irradiated testes showed two conspicuous features other than the loss of germ cells: empty vacuolar spaces between Sertoli cells and multilayered seminiferous tubule basal laminae (lamina densa). The junctional structures (ectoplasmic specializations) between Sertoli cells, however, seemed normal. The thickness of each layer of multilayered basal laminae was the same as that of normal rats and electron-lucent layers similar to lamina lucida were interposed between them. Of the empty vacuolar spaces between Sertoli cells, basal laminae bridge the gap. The basal laminae contained laminin, type IV collagen and heparan sulphate proteoglycan evenly distributed among layers, suggesting a normal composition. Rough estimation of the amount of basal laminae deposited in 137 Cs-irradiated rats indicates that it is within a range similar to that in normal testis. These features imply that Sertoli cells are, in part, determined perinatally to produce basal laminae for germ-line cells. (author)

  8. Development and evaluation of a meter for measuring return line fluid flow rates during drilling

    Energy Technology Data Exchange (ETDEWEB)

    Loeppke, G.E.; Schafer, D.M.; Glowka, D.A.; Scott, D.D.; Wernig, M.D. (Sandia National Labs., Albuquerque, NM (United States)); Wright, E.K. (Ktech Corp., Albuquerque, NM (United States))

    1992-06-01

    The most costly problem routinely encountered in geothermal drilling is lost circulation, which occurs when drilling fluid is lost to the formation rather than circulating back to the surface. The successful and economical treatment of lost circulation requires the accurate measurement of drilling fluid flow rate both into and out of the well. This report documents the development of a meter for measuring drilling fluid outflow rates in the return line of a drilling rig. The meter employs a rolling counterbalanced float that rides on the surface of the fluid in the return line. The angle of the float pivot arm is sensed with a pendulum potentiometer, and the height of the float is calculated from this measurement. The float height is closely related to the fluid height and, therefore, the flow rate in the line. The prototype rolling float meter was extensively tested under laboratory conditions in the Wellbore Hydraulics Flow Facility; results from these tests were used in the design of the field prototype rolling float meter. The field prototype meter was tested under actual drilling conditions in August and September 1991 at the Long Valley Exploratory Well near Mammoth Lakes, Ca. In addition, the performance of several other commercially available inflow and outflow meters was evaluated in the field. The tested inflow meters included conventional pump stroke counters, rotary pump speed counters, magnetic flowmeters, and an ultrasonic Doppler flowmeter. On the return flow line, a standard paddlemeter, an acoustic level meter, and the prototype rolling float meter were evaluated for measuring drilling fluid outflow rates.

  9. Developing an EEG based On-line Closed-loop Lapse Detection and Mitigation System

    Directory of Open Access Journals (Sweden)

    Yu-Te eWang

    2014-10-01

    Full Text Available In America, sixty percent of adults reported that they have driven a motor vehicle while feeling drowsy, and at least 15-20% of fatal car accidents are fatigue-related. This study translates previous laboratory-oriented neurophysiological research to design, develop, and test an On-line Closed-loop Lapse Detection and Mitigation (OCLDM System featuring a mobile wireless dry-sensor EEG headgear and a cell-phone based real-time EEG processing platform. Eleven subjects participated in an event-related lane-keeping task, in which they were instructed to manipulate a randomly deviated, fixed-speed cruising car on a 4-lane highway. This was simulated in a 1st person view with an 8-screen and 8-projector immersive virtual-realty environment. When the subjects experienced lapses or failed to respond to events during the experiment, auditory feedback was delivered to rectify the performance decrements. However, the arousing auditory signals were not always effective. The EEG spectra exhibited statistically significant differences between effective and ineffective arousing signals, suggesting that EEG spectra could be used as a countermeasure of the efficacy of arousing signals. In this on-line pilot study, the proposed OCLDM System was able to continuously detect EEG signatures of fatigue, deliver arousing feedback to subjects suffering momentary cognitive lapses, and assess the efficacy of the feedback in near real-time to rectify cognitive lapses. The on-line testing results of the OCLDM System validated the efficacy of the arousing signals in improving subjects' response times to the subsequent lane-departure events. This study may lead to a practical on-line lapse detection and mitigation system in real-world environments.

  10. Development and Identification of Introgression Lines from Cross of Oryza sativa and Oryza minuta

    Institute of Scientific and Technical Information of China (English)

    GUO Si-bin; WEI Yu; LI Xiao-qiong; LIU Kai-qiang; HUANG Feng-kuan; CHEN Cai-hong; GAO Guo-qing

    2013-01-01

    Introgression line population is effectively used in mapping quantitative trait loci (QTLs),identifying favorable genes,discovering hidden genetic variation,evaluating the action or interaction of QTLs in multiple conditions and providing the favorable experimental materials for plant breeding and genetic research.In this study,an advanced backcross and consecutive selfing strategy was used to develop introgression lines (ILs),which derived from an accession of Oryza minuta (accession No.101133) with BBCC genome,as the donor,and an elite indica cultivar IR24 (O.sativa),as the recipient.Introgression segments from O.minuta were screened using 164 polymorphic simple sequence repeat (SSR) markers in the genome of each IL.Introgressed segments carried by 131 ILs covered the whole O.sativa genome.The average number of homozygous O.minuta segments per introgression line was about 9.99.The average length of introgressed segments was approximate 14.78 cM,and about 79.64%of these segments had sizes less than 20 cM.In the genome of each introgression line,the O.minuta chromosomal segments harbored chromosomal fragments of O.sativa ranging from 1.15% to 27.6%,with an overall average of 8.57%.At each locus,the ratio of substitution of O.minuta alleles had a range of 1.5%-25.2%,with an average of 8.3% Based on the evaluation of the phenotype of these ILs,a wide range of alterations in morphological and yield-related traits were found.After inoculation,ILs 41,11 and 7 showed high resistance to bacterial blight,brown planthopper and whitebacked planthopper,respectively.These O.minuta-O.sativa ILs will serve as genetic materials for identifying and using favorable genes from O.minuta.

  11. Developing an EEG-based on-line closed-loop lapse detection and mitigation system.

    Science.gov (United States)

    Wang, Yu-Te; Huang, Kuan-Chih; Wei, Chun-Shu; Huang, Teng-Yi; Ko, Li-Wei; Lin, Chin-Teng; Cheng, Chung-Kuan; Jung, Tzyy-Ping

    2014-01-01

    In America, 60% of adults reported that they have driven a motor vehicle while feeling drowsy, and at least 15-20% of fatal car accidents are fatigue-related. This study translates previous laboratory-oriented neurophysiological research to design, develop, and test an On-line Closed-loop Lapse Detection and Mitigation (OCLDM) System featuring a mobile wireless dry-sensor EEG headgear and a cell-phone based real-time EEG processing platform. Eleven subjects participated in an event-related lane-keeping task, in which they were instructed to manipulate a randomly deviated, fixed-speed cruising car on a 4-lane highway. This was simulated in a 1st person view with an 8-screen and 8-projector immersive virtual-reality environment. When the subjects experienced lapses or failed to respond to events during the experiment, auditory warning was delivered to rectify the performance decrements. However, the arousing auditory signals were not always effective. The EEG spectra exhibited statistically significant differences between effective and ineffective arousing signals, suggesting that EEG spectra could be used as a countermeasure of the efficacy of arousing signals. In this on-line pilot study, the proposed OCLDM System was able to continuously detect EEG signatures of fatigue, deliver arousing warning to subjects suffering momentary cognitive lapses, and assess the efficacy of the warning in near real-time to rectify cognitive lapses. The on-line testing results of the OCLDM System validated the efficacy of the arousing signals in improving subjects' response times to the subsequent lane-departure events. This study may lead to a practical on-line lapse detection and mitigation system in real-world environments.

  12. Line facilities outline

    International Nuclear Information System (INIS)

    1998-08-01

    This book deals with line facilities. The contents of this book are outline line of wire telecommunication ; development of line, classification of section of line and theory of transmission of line, cable line ; structure of line, line of cable in town, line out of town, domestic cable and other lines, Optical communication ; line of optical cable, transmission method, measurement of optical communication and cable of the sea bottom, Equipment of telecommunication line ; telecommunication line facilities and telecommunication of public works, construction of cable line and maintenance and Regulation of line equipment ; regulation on technique, construction and maintenance.

  13. Preconception exposures to potential germ-cell mutagens

    International Nuclear Information System (INIS)

    Draper, G.

    2008-01-01

    Radiation and other agents can cause germ-cell mutations in animal systems. No human germ-cell mutagen has been identified, but this does not mean that human germ-cells are not vulnerable to mutagenesis. There has been particular concern about the possible health effects on offspring following parental preconception exposure to ionizing radiation - both occupational and therapeutic. A strong association with preconception radiation exposure in the fathers of the cases was found in a case-control study of young people with leukaemia living near the Sellafield nuclear plant in the UK. Subsequent studies of workers occupationally exposed to ionizing radiation have failed to confirm these findings. No statistically significant effects have been reported from studies of possible indicators of germ-cell mutagenesis in the A-bomb survivors. Studies of offspring of cancer survivors who receive radiotherapy and mutagenic chemotherapy have found no evidence of germ-cell mutagenesis. Failure to detect human germ-cell mutagenic agents may be a consequence of inadequate study sizes or insufficiently sensitive laboratory techniques. (authors)

  14. Development of piping evaluation diagram for LBB application to KNGR surge line

    International Nuclear Information System (INIS)

    Yoon, K. S.; Park, W. B.; Kim, J. M.; Choi, T. S.; Yang, J. S.; Park, C. Y.

    1998-01-01

    Plant specific data, such as pipe geometry, material properties and pipe loads, are required in order to evaluate Leak-Before-Break (LBB) applicability to piping systems in nuclear power plant under the construction. However, the existing method of LBB evaluation for KSNP's can not be used for newly developed nuclear plants such as Korean Next Generation Reactor (KNGR) which material properties is not available and LBB evaluation is required during design process. In order to solve this problem during developing process for KNGR surge line LBB Piping Evaluation Diagram (PED), which is independent of piping geometry and has a function of the loads applied in piping system, is developed in this paper. Also, in order to evaluate LBB applicability during construction process with only the comparative evaluation of material properties between actually used and expected, the expected changes of material properties are considered in the PED. The PED, therefore, can be used for quick LBB evaluation of KNGR surge line in the process of both design and construction. The benefit obtained by using the PED is : 1) to be able to very quickly confirm LBB applicability without calculating any leakage crack length for all concerned piping locations in the process of both iterative design for optimal routing and construction and 2) to save significantly a lot of computing times required for the corresponding LBB analyses

  15. Development of real-time on-line vibration testing system for seismic experiments

    International Nuclear Information System (INIS)

    Horiuchi, T.; Nakagawa, M.; Kametani, M.

    1993-01-01

    An on-line vibration testing method is being developed for seismic experiments. This method combines computer simulation and an actuator for vibration testing of structures. A real-time, on-line testing system was developed to improve the method. In the system, the timing of the vibration testing and the computer simulation are the same. This allows time-dependent reaction forces, such as damping force, to be immediately considered in the computer simulation. The real-time system has many requirements, such as complicated matrix calculations within a small time step, and communication with outer devices like sensors and actuators through A/D and D/A converters. These functions arc accomplished by using a newly-developed, real-time controller that employs a parallel processing technique. A small structural model is used to demonstrate the system. The reliability and applicability of the system for seismic experiments can be demonstrated by comparing the results of the system and a shaking table, which are in almost agreement. (author)

  16. MRI of intracranial germ-cell tumours

    International Nuclear Information System (INIS)

    Liang, L.; Korogi, Y.; Sugahara, T.; Ikushima, I.; Shigematsu, Y.; Okuda, T.; Takahashi, M.; Kochi, M.; Ushio, Y.

    2002-01-01

    Abstract. Our aim was to review the MRI appearances of primary intracranial germ-cell tumours (GCT). We reviewed the MRI studies of 32 patients: 19 with germinomas, five with teratomas, one with an embryonal carcinoma, five with mixed and two with malignant nongerminomatous GCT. Eleven were in the pineal region, 12 suprasellar, five in the both sites, two in the basal ganglia and two in the corpus callosum. Contrast-enhanced images were available for 27 patients. The solid parts of GCT were nearly isointense with grey matter on both T1- and T2-weighted images. In seven patients with nongerminomatous GCT high-signal components were found on T1-weighted images, representing haemorrhage, high-protein fluid or fat. Cystic components were detected in 17 of 27 patients; eight germinomas and all nine nongerminomatous GCT had cysts. The solid components of germinomas enhanced homogeneously in eight cases and heterogeneously in 10, while all nongerminomatous GCT showed heterogeneous enhancement. MRI features tumours can facilitate correct diagnosis of GCT, including histological subtypes. (orig.)

  17. Development of a polarized neutron beam line at Algerian research reactors using McStas software

    Science.gov (United States)

    Makhloufi, M.; Salah, H.

    2017-02-01

    Unpolarized instrumentation has long been studied and designed using McStas simulation tool. But, only recently new models were developed for McStas to simulate polarized neutron scattering instruments. In the present contribution, we used McStas software to design a polarized neutron beam line, taking advantage of the available spectrometers reflectometer and diffractometer in Algeria. Both thermal and cold neutron was considered. The polarization was made by two types of supermirrors polarizers FeSi and CoCu provided by the HZB institute. For sake of performance and comparison, the polarizers were characterized and their characteristics reproduced. The simulated instruments are reported. Flipper and electromagnets for guide field are developed. Further developments including analyzers and upgrading of the existing spectrometers are underway.

  18. Polymorphic variation in the androgen receptor gene: association with risk of testicular germ cell cancer and metastatic disease

    DEFF Research Database (Denmark)

    Västermark, Åke; Giwercman, Yvonne Lundberg; Hagströmer, Oskar

    2011-01-01

    Increasing incidence of testicular germ cell cancer (TGCC) is most probably related to environment and lifestyle. However, an underlying genetic predisposition may play a role and since sex steroids are assumed to be important for the rise and progression of TGCC, a study of androgen receptor (AR...... of endocrine disruptors. From a biological point of view, our findings strengthen the hypothesis of the importance of androgen action in the aetiology and pathogenesis of testicular malignancy. Future studies should focus on the impact of sex hormones on foetal germ cell development and the interaction between...

  19. Genome-wide assessment of the association of rare and common copy number variations to testicular germ cell cancer

    DEFF Research Database (Denmark)

    Edsgard, Stefan Daniel; Dalgaard, Marlene Danner; Weinhold, Nils

    2013-01-01

    Testicular germ cell cancer (TGCC) is one of the most heritable forms of cancer. Previous genome-wide association studies have focused on single nucleotide polymorphisms, largely ignoring the influence of copy number variants (CNVs). Here we present a genome-wide study of CNV on a cohort of 212...... of rare CNVs related to cell migration (false-discovery rate = 0.021, 1.8% of cases and 1.1% of controls). Dysregulation during migration of primordial germ cells has previously been suspected to be a part of TGCC development and this set of multiple rare variants may thereby have a minor contribution...

  20. SOX4 regulates gonad morphogenesis and promotes male germ cell differentiation in mice.

    Science.gov (United States)

    Zhao, Liang; Arsenault, Michel; Ng, Ee Ting; Longmuss, Enya; Chau, Tevin Chui-Ying; Hartwig, Sunny; Koopman, Peter

    2017-03-01

    The group C SOX transcription factors SOX4, -11 and -12 play important and mutually overlapping roles in development of a number of organs. Here, we examined the role of SoxC genes during gonadal development in mice. All three genes were expressed in developing gonads of both sexes, predominantly in somatic cells, with Sox4 being most strongly expressed. Sox4 deficiency resulted in elongation of both ovaries and testes, and an increased number of testis cords. While female germ cells entered meiosis normally, male germ cells showed reduced levels of differentiation markers Nanos2 and Dnmt3l and increased levels of pluripotency genes Cripto and Nanog, suggesting that SOX4 may normally act to restrict the pluripotency period of male germ cells and ensure their proper differentiation. Finally, our data reveal that SOX4 (and, to a lesser extent, SOX11 and -12) repressed transcription of the sex-determining gene Sox9 via an upstream testis-specific enhancer core (TESCO) element in fetal gonads, raising the possibility that SOXC proteins may function as transcriptional repressors in a context-dependent manner. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Development of new on-line statistical program for the Korean Society for Radiation Oncology.

    Science.gov (United States)

    Song, Si Yeol; Ahn, Seung Do; Chung, Weon Kuu; Shin, Kyung Hwan; Choi, Eun Kyung; Cho, Kwan Ho

    2015-06-01

    To develop new on-line statistical program for the Korean Society for Radiation Oncology (KOSRO) to collect and extract medical data in radiation oncology more efficiently. The statistical program is a web-based program. The directory was placed in a sub-folder of the homepage of KOSRO and its web address is http://www.kosro.or.kr/asda. The operating systems server is Linux and the webserver is the Apache HTTP server. For database (DB) server, MySQL is adopted and dedicated scripting language is the PHP. Each ID and password are controlled independently and all screen pages for data input or analysis are made to be friendly to users. Scroll-down menu is actively used for the convenience of user and the consistence of data analysis. Year of data is one of top categories and main topics include human resource, equipment, clinical statistics, specialized treatment and research achievement. Each topic or category has several subcategorized topics. Real-time on-line report of analysis is produced immediately after entering each data and the administrator is able to monitor status of data input of each hospital. Backup of data as spread sheets can be accessed by the administrator and be used for academic works by any members of the KOSRO. The new on-line statistical program was developed to collect data from nationwide departments of radiation oncology. Intuitive screen and consistent input structure are expected to promote entering data of member hospitals and annual statistics should be a cornerstone of advance in radiation oncology.

  2. Development of new on line statistical program for the Korean society for radiation oncology

    International Nuclear Information System (INIS)

    Song, Si Yeol; Ahn, Seung Do; Choi, Eun Kyung; Chung, Weon Kuu; Shin, Kyung Hwan; Cho, Kwan Ho

    2015-01-01

    To develop new on-line statistical program for the Korean Society for Radiation Oncology (KOSRO) to collect and extract medical data in radiation oncology more efficiently. The statistical program is a web-based program. The directory was placed in a sub-folder of the homepage of KOSRO and its web address is http://www.kosro.or.kr/asda. The operating systems server is Linux and the webserver is the Apache HTTP server. For database (DB) server, MySQL is adopted and dedicated scripting language is the PHP. Each ID and password are controlled independently and all screen pages for data input or analysis are made to be friendly to users. Scroll-down menu is actively used for the convenience of user and the consistence of data analysis. Year of data is one of top categories and main topics include human resource, equipment, clinical statistics, specialized treatment and research achievement. Each topic or category has several subcategorized topics. Real-time on-line report of analysis is produced immediately after entering each data and the administrator is able to monitor status of data input of each hospital. Backup of data as spread sheets can be accessed by the administrator and be used for academic works by any members of the KOSRO. The new on-line statistical program was developed to collect data from nationwide departments of radiation oncology. Intuitive screen and consistent input structure are expected to promote entering data of member hospitals and annual statistics should be a cornerstone of advance in radiation oncology

  3. Material development for waste to energy plants. Overlay welding and refractory linings. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Noergaard Hansson, A.

    2011-02-15

    Waste is an extremely corrosive fuel. In order to recover a higher percentage of the energy in waste, waste incineration plants have developed from purely heat producing units to heat and power producing units. The change in concept results in higher material temperatures and thereby faster material degradation. As a result material failures have been observed in many waste incineration plants. The purpose of this project was to develop materials with higher resistance to the corrosive elements, in order to reduce the cost of maintenance, increase the availability, and increase the efficiency. The focus is on overlay welding and refractory linings. Inconel 625, alloy 50, alloy 686, and Super 625 offer equivalent corrosion protection at panel walls. 100% overlay performs better than 50% overlay. The corrosion morphology changes with increasing temperature from pitting and general corrosion to pitting and selective corrosion (dendritic core or grain boundaries). The previously observed detrimental effect of Fe on the corrosion resistance was not confirmed. It probably depends on factors such as microstructure of the alloy and local metal temperature. Ni-overlay also reduces the corrosion rates on superheater tubes. However, the superheater environment is less aggressive than the water wall environment. Failure of refractory linings is linked to excess porosity, detrimental reactions between raw materials and other mix constituents, volume growth reactions between base material and salt depositions, and thermal stress induced crack formation. Free water and not decomposition of hydrates causes spalling and cracking during the initial heating of refractory linings. Finite Element analysis confirms the stress levels between steel and refractory with the higher stress level at the top of the panel wall tube. A number of LCC mixes were formulated, adjusted and tested. Mixes with low open porosities ({approx} 10%) and state of the art resistance to KCl were achieved. (LN)

  4. Development of new on line statistical program for the Korean society for radiation oncology

    Energy Technology Data Exchange (ETDEWEB)

    Song, Si Yeol; Ahn, Seung Do; Choi, Eun Kyung [Dept. of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Chung, Weon Kuu [Dept. of Radiation Oncology, Kyung Hee University Hospital at Kangdong, Kyung Hee University School of Medicine, Seoul (Korea, Republic of); Shin, Kyung Hwan [Dept. of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cho, Kwan Ho [Dept. of Radiation Oncology, Proton Therapy Center, National Cancer Center Hospital, Goyang (Korea, Republic of)

    2015-06-15

    To develop new on-line statistical program for the Korean Society for Radiation Oncology (KOSRO) to collect and extract medical data in radiation oncology more efficiently. The statistical program is a web-based program. The directory was placed in a sub-folder of the homepage of KOSRO and its web address is http://www.kosro.or.kr/asda. The operating systems server is Linux and the webserver is the Apache HTTP server. For database (DB) server, MySQL is adopted and dedicated scripting language is the PHP. Each ID and password are controlled independently and all screen pages for data input or analysis are made to be friendly to users. Scroll-down menu is actively used for the convenience of user and the consistence of data analysis. Year of data is one of top categories and main topics include human resource, equipment, clinical statistics, specialized treatment and research achievement. Each topic or category has several subcategorized topics. Real-time on-line report of analysis is produced immediately after entering each data and the administrator is able to monitor status of data input of each hospital. Backup of data as spread sheets can be accessed by the administrator and be used for academic works by any members of the KOSRO. The new on-line statistical program was developed to collect data from nationwide departments of radiation oncology. Intuitive screen and consistent input structure are expected to promote entering data of member hospitals and annual statistics should be a cornerstone of advance in radiation oncology.

  5. Development of transgenic Brassica juncea lines for reduced seed sinapine content by perturbing phenylpropanoid pathway genes.

    Directory of Open Access Journals (Sweden)

    Sachin Kajla

    Full Text Available Sinapine is a major anti-nutritive compound that accumulates in the seeds of Brassica species. When ingested, sinapine imparts gritty flavuor in meat and milk of animals and fishy odor to eggs of brown egg layers, thereby compromising the potential use of the valuable protein rich seed meal. Sinapine content in Brassica juncea germplasm ranges from 6.7 to 15.1 mg/g of dry seed weight (DSW which is significantly higher than the prescribed permissible level of 3.0 mg/g of DSW. Due to limited natural genetic variability, conventional plant breeding approach for reducing the sinapine content has largely been unsuccessful. Hence, transgenic approach for gene silencing was adopted by targeting two genes-SGT and SCT, encoding enzymes UDP- glucose: sinapate glucosyltransferase and sinapoylglucose: choline sinapoyltransferase, respectively, involved in the final two steps of sinapine biosynthetic pathway. These two genes were isolated from B. juncea and eight silencing constructs were developed using three different RNA silencing approaches viz. antisense RNA, RNAi and artificial microRNA. Transgenics in B. juncea were developed following Agrobacterium-mediated transformation. From a total of 1232 independent T0 transgenic events obtained using eight silencing constructs, 25 homozygous lines showing single gene inheritance were identified in the T2 generation. Reduction of seed sinapine content in these lines ranged from 15.8% to 67.2%; the line with maximum reduction had sinapine content of 3.79 mg/g of DSW. The study also revealed that RNAi method was more efficient than the other two methods used in this study.

  6. Effect of selection for productive traits in broiler maternal lines on embryo development

    Directory of Open Access Journals (Sweden)

    Schmidt GS

    2003-01-01

    Full Text Available This study used 300 females and 30 males with 36 weeks of age from the selected PP and control PPc maternal broiler lines. PP has been selected for heavy body weight (PC and high egg production for eight generations. Fertile eggs were collected and weighed individually for 4 periods of 5 consecutive days at two-week intervals. In each period, a total of 960 eggs/line were identified and separated in groups of 240 eggs, and stored for later incubation. Embryo weight (PE was evaluated at 9 (P9, 11 (P11, 13 (P13, 15 (P15, 17 (P17 and 21 (P21 days of incubation. The objective was to estimate the effect of selection on embryo development. Egg weight (PO was similar between the two lines. The differences in PE were significant from P15 on, resulting in 1.9g of difference in the chick weight, indicating correlated genetic changes in the embryo development, which can be credited to the selection for PC. Changes in PE while PO was kept unaltered modified the correlations between these two traits. Differences were significant from P13 on and estimated correlations for P21 were 0.72 and 0.70 for PP and PPc, respectively. Chick weight corresponded to 70.91% (PP and 68.48% (PPc of egg weight. The estimated increase in P21 that resulted from the increase of 1.0g in PO was 0.71 in PP and 0.68g in PPc.

  7. BAX-mediated cell death affects early germ cell loss and incidence of testicular teratomas in Dnd1(Ter/Ter) mice.

    Science.gov (United States)

    Cook, Matthew S; Coveney, Douglas; Batchvarov, Iordan; Nadeau, Joseph H; Capel, Blanche

    2009-04-15

    A homozygous nonsense mutation (Ter) in murine Dnd1 (Dnd1(Ter/Ter)) results in a significant early loss of primordial germ cells (PGCs) prior to colonization of the gonad in both sexes and all genetic backgrounds tested. The same mutation also leads to testicular teratomas only on the 129Sv/J background. Male mutants on other genetic backgrounds ultimately lose all PGCs with no incidence of teratoma formation. It is not clear how these PGCs are lost or what factors directly control the strain-specific phenotype variation. To determine the mechanism underlying early PGC loss we crossed Dnd1(Ter/Ter) embryos to a Bax-null background and found that germ cells were partially rescued. Surprisingly, on a mixed genetic background, rescued male germ cells also generated fully developed teratomas at a high rate. Double-mutant females on a mixed background did not develop teratomas, but were fertile and produced viable off-spring. However, when Dnd1(Ter/Ter) XX germ cells developed in a testicular environment they gave rise to the same neoplastic clusters as mutant XY germ cells in a testis. We conclude that BAX-mediated apoptosis plays a role in early germ cell loss and protects from testicular teratoma formation on a mixed genetic background.

  8. THE INFLUENCE OF PROCESSED PRODUCTS OF WHEAT GERM ON GRAIN BREAD QUALITY

    Directory of Open Access Journals (Sweden)

    E. I. Ponomareva

    2014-01-01

    Full Text Available Development and introduction of new types of bakery products with increased nutritional value is one of the basic and urgent problems in the bakery industry. The solution of it is the use of whole grains, as well as secondary products of their processing. The use of by-products of wheat germ (oil, oilcake, oilcake flour, which are rich in proteins and enhances the nutritional value of products is considered to be a promising area in the bakery industry. At the same time the program objectives products, developed in the framework of the "Strategy of development of the food processing industry of the Russian Federation for the period up to 2020"products, are expanding the production of cereal-based foods , and involving of secondary resources in the economy. These technologies are re-source efficient. They allow efficient use of by-products raw materials of the milling industry. The process for the preparation of grain bread on the basis of a thick sourdough from bioactivated wheat grain is known. However, despite all the advantages of grain breads with high amounts of dietary fiber, minerals and vitamins, they exhibit low levels of protein and lysine deficiency. At present larger preference is given to the raw materials of natural origin (millet, buckwheat and oatmeal flours, fruit puree, whole grains, oil, flour and wheat germ flakes, and etc. for foods enrichment in modern food science. Products of processing of wheat germ: oil, flakes, oilcake and oil-cake flour are widely used in bakery technology. To improve the nutritional value flour from wheat germ oilcake was used in the work. In the course of the research its positive effect on the quality of semi-finished and finished products was found. They differed from the control sample in a high content of antioxidants and better digestibility of proteins bread crumb.

  9. BMP signaling in the human fetal ovary is developmentally regulated and promotes primordial germ cell apoptosis.

    Science.gov (United States)

    Childs, Andrew J; Kinnell, Hazel L; Collins, Craig S; Hogg, Kirsten; Bayne, Rosemary A L; Green, Samira J; McNeilly, Alan S; Anderson, Richard A

    2010-08-01

    Primordial germ cells (PGCs) are the embryonic precursors of gametes in the adult organism, and their development, differentiation, and survival are regulated by a combination of growth factors collectively known as the germ cell niche. Although many candidate niche components have been identified through studies on mouse PGCs, the growth factor composition of the human PGC niche has not been studied extensively. Here we report a detailed analysis of the expression of components of the bone morphogenetic protein (BMP) signaling apparatus in the human fetal ovary, from postmigratory PGC proliferation to the onset of primordial follicle formation. We find developmentally regulated and reciprocal patterns of expression of BMP2 and BMP4 and identify germ cells to be the exclusive targets of ovarian BMP signaling. By establishing long-term cultures of human fetal ovaries in which PGCs are retained within their physiological niche, we find that BMP4 negatively regulates postmigratory PGC numbers in the human fetal ovary by promoting PGC apoptosis. Finally, we report expression of both muscle segment homeobox (MSX)1 and MSX2 in the human fetal ovary and reveal a selective upregulation of MSX2 expression in human fetal ovary in response to BMP4, suggesting this gene may act as a downstream effector of BMP-induced apoptosis in the ovary, as in other systems. These data reveal for the first time growth factor regulation of human PGC development in a physiologically relevant context and have significant implications for the development of cultures systems for the in vitro maturation of germ cells, and their derivation from pluripotent stem cells.

  10. Sex reversal in zebrafish fancl mutants is caused by Tp53-mediated germ cell apoptosis.

    Directory of Open Access Journals (Sweden)

    Adriana Rodríguez-Marí

    2010-07-01

    Full Text Available The molecular genetic mechanisms of sex determination are not known for most vertebrates, including zebrafish. We identified a mutation in the zebrafish fancl gene that causes homozygous mutants to develop as fertile males due to female-to-male sex reversal. Fancl is a member of the Fanconi Anemia/BRCA DNA repair pathway. Experiments showed that zebrafish fancl was expressed in developing germ cells in bipotential gonads at the critical time of sexual fate determination. Caspase-3 immunoassays revealed increased germ cell apoptosis in fancl mutants that compromised oocyte survival. In the absence of oocytes surviving through meiosis, somatic cells of mutant gonads did not maintain expression of the ovary gene cyp19a1a and did not down-regulate expression of the early testis gene amh; consequently, gonads masculinized and became testes. Remarkably, results showed that the introduction of a tp53 (p53 mutation into fancl mutants rescued the sex-reversal phenotype by reducing germ cell apoptosis and, thus, allowed fancl mutants to become fertile females. Our results show that Fancl function is not essential for spermatogonia and oogonia to become sperm or mature oocytes, but instead suggest that Fancl function is involved in the survival of developing oocytes through meiosis. This work reveals that Tp53-mediated germ cell apoptosis induces sex reversal after the mutation of a DNA-repair pathway gene by compromising the survival of oocytes and suggests the existence of an oocyte-derived signal that biases gonad fate towards the female developmental pathway and thereby controls zebrafish sex determination.

  11. Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 4: intercellular bridges, mitochondria, nuclear envelope, apoptosis, ubiquitination, membrane/voltage-gated channels, methylation/acetylation, and transcription factors.

    Science.gov (United States)

    Hermo, Louis; Pelletier, R-Marc; Cyr, Daniel G; Smith, Charles E

    2010-04-01

    As germ cells divide and differentiate from spermatogonia to spermatozoa, they share a number of structural and functional features that are common to all generations of germ cells and these features are discussed herein. Germ cells are linked to one another by large intercellular bridges which serve to move molecules and even large organelles from the cytoplasm of one cell to another. Mitochondria take on different shapes and features and topographical arrangements to accommodate their specific needs during spermatogenesis. The nuclear envelope and pore complex also undergo extensive modifications concomitant with the development of germ cell generations. Apoptosis is an event that is normally triggered by germ cells and involves many proteins. It occurs to limit the germ cell pool and acts as a quality control mechanism. The ubiquitin pathway comprises enzymes that ubiquitinate as well as deubiquitinate target proteins and this pathway is present and functional in germ cells. Germ cells express many proteins involved in water balance and pH control as well as voltage-gated ion channel movement. In the nucleus, proteins undergo epigenetic modifications which include methylation, acetylation, and phosphorylation, with each of these modifications signaling changes in chromatin structure. Germ cells contain specialized transcription complexes that coordinate the differentiation program of spermatogenesis, and there are many male germ cell-specific differences in the components of this machinery. All of the above features of germ cells will be discussed along with the specific proteins/genes and abnormalities to fertility related to each topic. Copyright 2009 Wiley-Liss, Inc.

  12. Critical role of CCDC6 in the neoplastic growth of testicular germ cell tumors

    International Nuclear Information System (INIS)

    Staibano, Stefania; Fusco, Alfredo; Chieffi, Paolo; Celetti, Angela; Ilardi, Gennaro; Leone, Vincenza; Luise, Chiara; Merolla, Francesco; Esposito, Francesco; Morra, Francesco; Siano, Maria; Franco, Renato

    2013-01-01

    DNA damage response has been clearly described as an anti-cancer barrier in early human tumorigenesis. Moreover, interestingly, testicular germ cell tumors (TGCTs) have been reported to lack the DNA Damage Response (DDR) pathway activation. CCDC6 is a pro-apoptotic phosphoprotein substrate of the kinase ataxia telangectasia mutated (ATM) able to sustain DNA damage checkpoint in response to genotoxic stress and is commonly rearranged in malignancies upon fusion with different partners. In our study we sought to determine whether CCDC6 could have a role in the patho-genesis of testicular germ cell tumors. To achieve this aim, analysis for CCDC6 expression has been evaluated on serial sections of the mouse testis by immunohistochemistry and on separate populations of murine testicular cells by western blot. Next, the resistance to DNA damage-induced apoptosis and the production of reactive oxygen species has been investigated in GC1 cells, derived from immortalized type B murine germ cells, following CCDC6 silencing. Finally, the CCDC6 expression in normal human testicular cells, in Intratubular Germ Cell Neoplasia Unclassified (IGCNU), in a large series of male germ cell tumours and in the unique human seminoma TCam2 cell line has been evaluated by immunohistochemistry and by Western Blot analyses. The analysis of the CCDC6 expression revealed its presence in Sertoli cells and in spermatogonial cells. CCDC6 loss was the most consistent feature among the primary tumours and TCam2 cells. Interestingly, following treatment with low doses of H 2 O 2 , the silencing of CCDC6 in GC1 cells caused a decrease in the oxidized form of cytochrome c and low detection of Bad, PARP-1 and Caspase 3 proteins. Moreover, in the silenced cells, upon oxidative damage, the cell viability was protected, the γH2AX activation was impaired and the Reactive Oxygen Species (ROS) release was decreased. Therefore, our results suggest that the loss of CCDC6 could aid the spermatogonial cells to

  13. Clinical and genetic aspects of testicular germ cell tumours

    Directory of Open Access Journals (Sweden)

    Holzik Martijn

    2008-02-01

    Full Text Available Abstract In this paper we review clinical and genetic aspects of testicular germ cell tumours (TGCTs. TGCT is the most common type of malignant disorder in men aged 15-40 years. Its incidence has increased sharply in recent years. Fortunately, survival of patients with TGCT has improved enormously, which can chiefly be attributed to the cisplatin-based polychemotherapy that was introduced in the nineteen eighties to treat patients with metastasized TGCT. In addition, new strategies have been developed in the surgical approach to metastasized/non-metastasized TGCT and alterations have been made to the radiotherapy technique and radiation dose for seminoma. Family history of TGCT is among the strongest risk factors for this tumour type. Although this fact and others suggest the existence of genetic predisposition to develop TGCT, no germline mutations conferring high risk of developing TGCT have been identified so far. A small deletion, referred to as gr/gr, identified on the Y chromosome is probably associated with only a modest increase in TGCT risk, and linkage of familial TGCT to the Xq27 region has not been confirmed yet. Whether highly penetrant TGCT-predisposing mutations truly exist or familial clustering of TGCT can be explained by combinations of weak predispositions, shared in utero or postnatal risks factors and coincidental somatic mutations is an intriguing puzzle, still waiting to be solved.

  14. Clinical and genetic aspects of testicular germ cell tumours.

    Science.gov (United States)

    Lutke Holzik, Martijn F; Sijmons, Rolf H; Hoekstra-Weebers, Josette Ehm; Sleijfer, Dirk T; Hoekstra, Harald J

    2008-02-15

    In this paper we review clinical and genetic aspects of testicular germ cell tumours (TGCTs). TGCT is the most common type of malignant disorder in men aged 1540 years. Its incidence has increased sharply in recent years. Fortunately, survival of patients with TGCT has improved enormously, which can chiefly be attributed to the cisplatin-based polychemotherapy that was introduced in the nineteen eighties to treat patients with metastasized TGCT. In addition, new strategies have been developed in the surgical approach to metastasized/non-metastasized TGCT and alterations have been made to the radiotherapy technique and radiation dose for seminoma. Family history of TGCT is among the strongest risk factors for this tumour type. Although this fact and others suggest the existence of genetic predisposition to develop TGCT, no germline mutations conferring high risk of developing TGCT have been identified so far. A small deletion, referred to as gr/gr, identified on the Y chromosome is probably associated with only a modest increase in TGCT risk, and linkage of familial TGCT to the Xq27 region has not been confirmed yet. Whether highly penetrant TGCT-predisposing mutations truly exist or familial clustering of TGCT can be explained by combinations of weak predispositions, shared in utero or postnatal risks factors and coincidental somatic mutations is an intriguing puzzle, still waiting to be solved.

  15. The origin and migration of primordial germ cells in sturgeons.

    Directory of Open Access Journals (Sweden)

    Taiju Saito

    Full Text Available Primordial germ cells (PGCs arise elsewhere in the embryo and migrate into developing gonadal ridges during embryonic development. In several model animals, formation and migration patterns of PGCs have been studied, and it is known that these patterns vary. Sturgeons (genus Acipenser have great potential for comparative and evolutionary studies of development. Sturgeons belong to the super class Actinoptergii, and their developmental pattern is similar to that of amphibians, although their phylogenetic position is an out-group to teleost fishes. Here, we reveal an injection technique for sturgeon eggs allowing visualization of germplasm and PGCs. Using this technique, we demonstrate that the PGCs are generated at the vegetal pole of the egg and they migrate on the yolky cell mass toward the gonadal ridge. We also provide evidence showing that PGCs are specified by inheritance of maternally supplied germplasm. Furthermore, we demonstrate that the migratory mechanism is well-conserved between sturgeon and other remotely related teleosts, such as goldfish, by a single PGCs transplantation (SPT assay. The mode of PGCs specification in sturgeon is similar to that of anurans, but the migration pattern resembles that of teleosts.

  16. Development of an induction motor abnormality monitoring system(IMAMS) using power line signal analysis

    International Nuclear Information System (INIS)

    Jung, Jae Cheon

    1997-02-01

    An induction motor abnormality monitoring system using power line signal analysis is developed in this work. Various studies have focused their attention on the detection of particular harmonic frequencies produced from each defect mode of motors. However, these harmonic frequencies are valuable only when the motor has a continuous slip frequency and operate in constant torque/load condition. The basic concept of the system developed in this work is to detect the characteristic harmonic frequencies occurred when the motor is in abnormal state and to compare it with a predetermined setpoint. Based on these analyses, the place and degree of defect can be easily identified. The experimental results under test bench simulation are also introduced. To find out an alternative way to obtain a threshold level independent of slip/torque, with the rotating field theory, the ratio between harmonic current and total current was calculated with the simplified circuit that is equivalent to two abnormal cases, such as the spatial rotor resistance variation and the symmetrical components changes with field. Also, the threshold level calculation was done with performed the rotating field theory. The results show that they are in good agreement with a experimental results. Further studies are undertaken to extend this work to the on-line monitoring and diagnostic system with a likelihood ratio test method for field application

  17. Equipment line-up developed for structuring programmed digital systems important to safety

    International Nuclear Information System (INIS)

    Remus, L.; Colling, J.M.; Buisson, J.

    1986-01-01

    The use of the programmed digital techniques in systems important to safety led to developing equipment line-ups which allow to procedure, through using a restricted number of sub-assemblies, a variety of facilities capable of performing diversified functions. Upon remembering the requirements that such equipment are required to meet (quality assurance both at the design and production stages, qualification, testing opportunities, etc.) the equipments produced by MERLIN GERIN are described in this paper. Such equipments include a whole set of printed circuit boards, plug-in units with self-engaging connectors and the related cabinets to accomodate them. The following systems are made up of such equipments: Digital integrated protection system; Rod control and monitoring system; Reactor power distribution monitoring equipment. This equipment line-up has been gradually complemented and is still further expanding both as a result of the component further development or for the purpose of meeting new requirements or applications (new digital neutron instrumentation, local area networks). Experience gained thus far provides us with the capability of working out in a short time programmed systems for further applications in the nuclear power field

  18. Development of the On-line Acoustic Leak Detection Tool for the SFR Steam Generator Protection

    International Nuclear Information System (INIS)

    Kim, Tae-Joon; Jeong, Ji-Young; Kim, Jong-Man; Kim, Byung-Ho; Kim, Seong-O

    2007-01-01

    The successful detection of a water/steam into a sodium leak in the SFR SG (steam generator) at an early phase of a leak origin depends on the fast response and sensitivity of a leak detection system. This intention of an acoustic leak detection system is stipulated by a key impossibility of a fast detecting of an intermediate leak by the present nominal systems such as the hydrogen meter. Subject of this study is to introduce the detection performance of an on-line acoustic leak detection tool discriminated by a back-propagation neural network with a preprocessing of the 1/m Octave band analysis, and to introduce the status of an on-line development being developed with the acoustic leak detection tool(S/W) in KAERI. For a performance test, it was used with the acoustic signals for a sodium-water reaction from the injected steam into water experiments in KAERI, the acoustic signals injected from the water into the sodium obtained in IPPE, and the background noise of the PFR superheater

  19. Development Ground Fault Detecting System for D.C Voltage Line

    Energy Technology Data Exchange (ETDEWEB)

    Kim Taek Soo; Song Ung Il; Gwon, Young Dong; Lee Hyoung Kee [Korea Electric Power Research Institute, Taejon (Korea, Republic of)

    1996-12-31

    It is necessary to keep the security of reliability and to maximize the efficiency of maintenance by prompt detection of a D.C feeder ground fault point at the built ed or a building power plants. At present, the most of the power plants are set up the ground fault indicator lamp in the monitor room. If a ground fault occurs on DC voltage feeder, a current through the ground fault relay is adjusted and the lamps have brightened while the current flows the relay coil. In order to develop such a system, it is analyzed a D.C feeder ground circuit theoretically and studied a principles which can determine ground fault point or a polarity discrimination and a phase discrimination of the line. So, the developed system through this principles can compute a resistance ground fault current and a capacitive ground fault current. It shows that the system can defect a ground fault point or a bad insulated line by measuring a power plant D.C feeder insulation resistance at the un interruptible power status, and therefore the power plant could protect an unexpected service interruption . (author). 18 refs., figs.

  20. Is the FSHR 2039A>G variant associated with susceptibility to testicular germ cell cancer?

    DEFF Research Database (Denmark)

    Bang, A K; Busch, A S; Almstrup, K

    2018-01-01

    Testicular germ cell cancer (TGCC) is derived from germ cell neoplasia in situ (GCNIS), which arises due to niche disturbances affecting the Sertoli cells. It is believed that exogenous endocrine factors have a crucial role in governing neoplastic transformation but on a strong hereditary...... background. Follicle-stimulating hormone (FSH) is the major regulatory hormone of the Sertoli cells. FSH signalling-related single-nucleotide polymorphisms (SNPs) have previously been shown to affect FSH action in men at different levels. We aimed to investigate whether three FSH-related SNPs (FSHR 2039A......>G, FSHR -29G>A and FSHB -211G>T) are associated with development of TGCC. A total of 752 Danish and German patients with TGCC from two tertiary andrological referral centres were included. Three control groups comprising 2020 men from the general population, 679 fertile men and 417 infertile men, were...

  1. Male germ cell-specific expression of a novel Patched-domain containing gene Ptchd3

    International Nuclear Information System (INIS)

    Fan Jun; Akabane, Hiroto; Zheng Xuehai; Zhou Xuan; Zhang Li; Liu Qiang; Zhang Yonglian; Yang Jing; Zhu Guozhang

    2007-01-01

    The Hedgehog (Hh) signaling pathway plays an important role in various biological processes, including pattern formation, cell fate determination, proliferation, and differentiation. Hh function is mediated through its membrane receptor Patched. Herein, we have characterized a novel Patched-domain containing gene Ptchd3 in mouse. Messenger RNA of Ptchd3 was exclusively detected in the testis, and existed in two isoforms Ptchd3a and Ptchd3b. The expression of these two mRNA isoforms was shown to be developmentally regulated in testes, and specifically found in male germ cells. Further analysis revealed that the Ptchd3 protein was located on the midpiece of mouse, rat and human sperm. Collectively, these results indicate that Ptchd3 is a novel male germ cell-specific gene and may be involved in the Hh signaling to regulate sperm development and/or sperm function

  2. A transplant recipient with a mixed germ-cell ovarian tumor

    Directory of Open Access Journals (Sweden)

    Ketata Hafed

    2008-01-01

    Full Text Available Immunosuppressed renal transplant recipients seem to be at significantly increased risk of developing neoplasms comparatively to nonimmunosuppressed individuals. A history of malignancy exposes the patient to a high risk for relapse after transplantation. We present a trans-plant recipient with a history of an ovarian mixed germ-cell tumor, with choriocarcinoma com-ponent, which was treated seven years prior to transplantation. After three years of follow-up, there was no evidence of tumor relapse. To our knowledge, there is no report of such case in the English literature. Regarding our case report and patients with a history of ovarian germ-cell neoplasm, waiting time before transplantation must take into consideration the stage of the tumor, its prognosis, the proportion of different tumor components, and the overall prognosis of the patient if transplantation is withheld.

  3. New milk medium for germ tube and chlamydoconidia production by Candida albicans.

    Science.gov (United States)

    Jitsurong, S; Kiamsiri, S; Pattararangrong, N

    1993-08-01

    A new medium consisting of UHT milk, tween 80 and agar is described for the development of both germ tube and chlamydoconidia by Candida albicans. In total 172 isolates from clinical specimens, including C. albicans (112), C. guilliermondii (4), C. krusei (3), C. parasilopsis (16). C. tropicalis (28), Torulopsis glabrata (6) and Trichosporon beigellii (3), were examined in this medium by using the standard method. A higher percentage (98.2%) of germ tube production by C. albicans was found in this medium than in undiluted serum (90.2%). In addition, only C. albicans was found to be able to produce a high percentage of chlamydoconidia (95.5%) after 48 hours' incubation. In comparison with the conventional medium, corn meal tween 80 agar (21.4%), this new medium gives a significantly higher percentage and abundance of chlamydoconidia production. Being simple, cheap and easy to prepare, the new milk medium is proposed as very practical in the clinical mycology laboratory.

  4. Development of 700 pps high-duty-cycle line-type pulse modulator

    Energy Technology Data Exchange (ETDEWEB)

    Baba, H.; Satoh, K.; Miura, A. [NIHON KOSHUHA Co., LTD., Yokohama, Kanagawa (Japan)] [and others

    1997-04-01

    The high-duty-cycle line-type pulse modulator has been developed to drive the 5.5 MW S-band klystron at the 700 pps maximum repetition-rate and the 14 {mu}sec flat-top pulse-width. To keep an enough recovery time to the thyratron-tube, the command charging scheme was adopted. To do this, a charging SCR-bank has been developed, which is capable of handling the peak charging current of 50 A. The system achieved the world wide highest average output-power of 205 kW. Two modulators have been installed in a new high-duty-cycle electron linear accelerator, which has been started its business operation in March 1996 as an electron-beam-sterilization facility. (J.P.N)

  5. Development of On-line Monitoring System for Shape Memory Alloy Composite

    International Nuclear Information System (INIS)

    Lee, Jin Kyung; Park, Young Chul; Lee, Min Rae; Lee, Dong Hwa; Lee, Kyu Chang

    2003-01-01

    A hot press method was use for the optimal manufacturing condition for a shape memory alloy(SMA) composite. The bonding between the matrix and the reinforcement within the SMA composite by the hot press method was strengthened by cold rolling. In this study, the objective was to develop an on-line monitoring system for the prevention of the crack initiation and propagation by shape memory effort of SMA composite. Shape memory effect was used to prevent the SMA composite from cracking. For the system to be developed, an optimal hE parameter should be determined based on the degree of damage and crack initiation. When the SHA composite was heated by the plate heater attached at the composite, the propagating cracks appeared to be controlled by the compressive force of SMA

  6. A development of an automated ultrasonic TOFD inspection system using an welding line tracing robot

    International Nuclear Information System (INIS)

    Cho, Hyun; Song, Sung Jin; Lee, Kang Won; Kim, Young Jin; Woo, Jong Sik

    2006-01-01

    Large scaled ships, manufactured inside of the country, should be passed welding inspection and painting film inspection. Normally, these kind of inspections are conducted by human inspectors manually, although it cause industrial disasters such as falling accidents and diving accidents frequently. In addition, Ship makers are not to give a full trust to shipowners because manual inspections cannot be conducted all over the welding parts. So, in this study we developed an automated ultrasonic TOFD inspection system using an welding line tracing robot. This system, controlled by an inspector at a remote field, can inspect welding parts of ship outer panel both under water and in air. In this paper we present the developed robot and ultrasonic TOFD inspection system and the inspection result.

  7. A development of an automated ultrasonic TOFD inspection system using an welding line tracing robot

    International Nuclear Information System (INIS)

    Cho, Hyun; Song, Sung Jin; Lee, Kang Won; Kim, Young Jin; Woo, Jong Sik

    2006-01-01

    Large scaled ships, manufactured inside of the country, should be passed welding inspection and painting film inspection. Normally, these kind of inspections are conducted by human inspectors manually, although it cause industrial disasters such as falling accidents and diving accidents frequently. In addition, Ship makers are not to give a full trust to ship owners because manual inspections cannot be conducted all over the welding parts. So, in this study we developed an automated ultrasonic TOFD inspection system using an welding line tracing robot. This system, controlled by an inspector at a remote field, can inspect welding parts of ship outer panel both under water and in air. In this paper we present the developed robot and ultrasonic TOFD inspection system and the inspection result.

  8. Development and design of a line imaging spectrometer sampler (LISS) - A user manual

    DEFF Research Database (Denmark)

    Jørgensen, R.N.; Rasmussen, P.

    2002-01-01

    The objective of this report is to develop and describe the software for a Line Imaging Spectrometer Sampler (LISS) to perform measurements of spectra combined with a digital RGB photo of a measurant. Secondly this report should enable users to performmeasurements with the system. The measuring...... are developed as a Graphical User Interfaced (GUI) hosted by Matlab Release 12 from Mathworks. This GUI enables the operator to perform measurements from alldevices simultaneously together with notes specific for the measurant and store all the data in one Matlab data structure. The software includes dynamic...... exposure of the two CCD cameras ensuring optimal use of 16 bit range under unstable illuminationconditions. A routine, handling dark frame subtraction in a robust manner minimising the effect of hot pixels is also included. This report enables a novice user to perform measurements with LISS relatively easy...

  9. Distinct and Cooperative Roles of amh and dmrt1 in Self-Renewal and Differentiation of Male Germ Cells in Zebrafish.

    Science.gov (United States)

    Lin, Qiaohong; Mei, Jie; Li, Zhi; Zhang, Xuemei; Zhou, Li; Gui, Jian-Fang

    2017-11-01

    Spermatogenesis is a fundamental process in male reproductive biology and depends on precise balance between self-renewal and differentiation of male germ cells. However, the regulative factors for controlling the balance are poorly understood. In this study, we examined the roles of amh and dmrt1 in male germ cell development by generating their mutants with Crispr/Cas9 technology in zebrafish. Amh mutant zebrafish displayed a female-biased sex ratio, and both male and female amh mutants developed hypertrophic gonads due to uncontrolled proliferation and impaired differentiation of germ cells. A large number of proliferating spermatogonium-like cells were observed within testicular lobules of the amh -mutated testes, and they were demonstrated to be both Vasa- and PH3-positive. Moreover, the average number of Sycp3- and Vasa-positive cells in the amh mutants was significantly lower than in wild-type testes, suggesting a severely impaired differentiation of male germ cells. Conversely, all the dmrt1 -mutated testes displayed severe testicular developmental defects and gradual loss of all Vasa-positive germ cells by inhibiting their self-renewal and inducing apoptosis. In addition, several germ cell and Sertoli cell marker genes were significantly downregulated, whereas a prominent increase of Insl3-positive Leydig cells was revealed by immunohistochemical analysis in the disorganized dmrt1 -mutated testes. Our data suggest that amh might act as a guardian to control the balance between proliferation and differentiation of male germ cells, whereas dmrt1 might be required for the maintenance, self-renewal, and differentiation of male germ cells. Significantly, this study unravels novel functions of amh gene in fish. Copyright © 2017 by the Genetics Society of America.

  10. Exposure to Brefeldin A promotes initiation of meiosis in murine female germ cells.

    Science.gov (United States)

    Zhang, Lian-Jun; Chen, Bo; Feng, Xin-Lei; Ma, Hua-Gang; Sun, Li-Lan; Feng, Yan-Min; Liang, Gui-Jin; Cheng, Shun-Feng; Li, Lan; Shen, Wei

    2015-01-01

    In mammals, ontogenesis starts from a fusion of spermatozoon and oocyte, which are produced by reductive nuclear division of a diploid germ cell in a specialised but complex biological process known as meiosis. However, little is known about the mechanism of meiotic initiation in germ cells, although many factors may be responsible for meiosis both in male and female gonads. In this study, 11.5 days post coitum (dpc) female fetal mouse genital ridges were cultured in vitro with exposure to Brefeldin A (BFA) for 6h, and the changes in meiosis were detected. Synaptonemal-complex analysis implied that BFA played a positive role in meiosis initiation and this hypothesis was confirmed by quantitative PCR of meiosis-specific genes: stimulated by retinoic acid gene 8 (Stra8) and deleted in a zoospermia-like (DAZL). At the same time, mRNA expression of retinoic acid synthetase (Raldh2) and retinoic acid (RA) receptors increased in female gonads with in vitro exposure to BFA. Transplanting genital ridges treated with BFA into the kidney capsule of immunodeficient mice demonstrated that the development capacity of female germ cells was normal, while formation of primordial follicles was seen to be a result of accelerated meiosis after exposure to BFA. In conclusion, the study indicated that BFA stimulated meiosis initiation partly by RA signalling and then promoted the development of follicles.

  11. Development Approach of the Advanced Life Support On-line Project Information System

    Science.gov (United States)

    Levri, Julie A.; Hogan, John A.; Morrow, Rich; Ho, Michael C.; Kaehms, Bob; Cavazzoni, Jim; Brodbeck, Christina A.; Whitaker, Dawn R.

    2005-01-01

    The Advanced Life Support (ALS) Program has recently accelerated an effort to develop an On-line Project Information System (OPIS) for research project and technology development data centralization and sharing. There has been significant advancement in the On-line Project Information System (OPIS) over the past year (Hogan et al, 2004). This paper presents the resultant OPIS development approach. OPIS is being built as an application framework consisting of an uderlying Linux/Apache/MySQL/PHP (LAMP) stack, and supporting class libraries that provides database abstraction and automatic code generation, simplifying the ongoing development and maintenance process. Such a development approach allows for quick adaptation to serve multiple Programs, although initial deployment is for an ALS module. OPIS core functionality will involve a Web-based annual solicitation of project and technology data directly from ALS Principal Investigators (PIs) through customized data collection forms. Data provided by PIs will be reviewed by a Technical Task Monitor (TTM) before posting the information to OPIS for ALS Community viewing via the Web. Such Annual Reports will be permanent, citable references within OPIS. OPlS core functionality will also include Project Home Sites, which will allow PIS to provide updated technology information to the Community in between Annual Report updates. All data will be stored in an object-oriented relational database, created in MySQL(Reistered Trademark) and located on a secure server at NASA Ames Research Center (ARC). Upon launch, OPlS can be utilized by Managers to identify research and technology development (R&TD) gaps and to assess task performance. Analysts can employ OPlS to obtain the current, comprehensive, accurate information about advanced technologies that is required to perform trade studies of various life support system options. ALS researchers and technology developers can use OPlS to achieve an improved understanding of the NASA

  12. Maternal smoking and testicular germ cell tumors.

    Science.gov (United States)

    McGlynn, Katherine A; Zhang, Yawei; Sakoda, Lori C; Rubertone, Mark V; Erickson, Ralph L; Graubard, Barry I

    2006-10-01

    Testicular germ cell tumors (TGCT) are the most common cancer among men ages 15 to 35 years in the United States. The well-established TGCT risk factors cryptorchism, prior diagnosis of TGCT, and family history of testicular cancer indicate that exposures in early life and/or in the familial setting may be critical to determining risk. Previous reports of familial clustering of lung cancer in mothers and testicular cancers in sons suggest that passive smoking in childhood may be such an exposure. To clarify the relationship of passive smoking exposure to TGCT risk, data from 754 cases and 928 controls enrolled in the Servicemen's Testicular Tumor Environmental and Endocrine Determinants study were analyzed. Data from 1,086 mothers of the cases and controls were also examined. Overall, there was no relationship between maternal [odds ratio (OR), 1.1; 95% confidence interval (95% CI), 0.9-1.3] or paternal smoking (OR, 1.0; 95% CI, 0.8-1.3) and TGCT risk. Although living with a non-parent smoker was marginally related to risk (OR, 1.4; 95% CI, 1.0-2.1), there was no relationship with number of smokers, amount smoked, or duration of smoking. Responses from both case-control participants and mothers also revealed no relationship between either maternal smoking while pregnant or while breast-feeding. Results did not differ by TGCT histology (seminoma, non-seminoma). These results do not support the hypothesis that passive smoking, either in utero or in childhood, is related to risk of TGCT. Other early life exposures, however, may explain the familial clustering of lung cancer in mothers and TGCT in sons.

  13. A pilgrim's progress: Seeking meaning in primordial germ cell migration.

    Science.gov (United States)

    Cantú, Andrea V; Laird, Diana J

    2017-10-01

    Comparative studies of primordial germ cell (PGC) development across organisms in many phyla reveal surprising diversity in the route of migration, timing and underlying molecular mechanisms, suggesting that the process of migration itself is conserved. However, beyond the perfunctory transport of cellular precursors to their later arising home of the gonads, does PGC migration serve a function? Here we propose that the process of migration plays an additional role in quality control, by eliminating PGCs incapable of completing migration as well as through mechanisms that favor PGCs capable of responding appropriately to migration cues. Focusing on PGCs in mice, we explore evidence for a selective capacity of migration, considering the tandem regulation of proliferation and migration, cell-intrinsic and extrinsic control, the potential for tumors derived from failed PGC migrants, the potential mechanisms by which migratory PGCs vary in their cellular behaviors, and corresponding effects on development. We discuss the implications of a selective role of PGC migration for in vitro gametogenesis. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Functions of huntingtin in germ layer specification and organogenesis.

    Directory of Open Access Journals (Sweden)

    Giang D Nguyen

    Full Text Available Huntington's disease (HD is a neurodegenerative disease caused by abnormal polyglutamine expansion in the huntingtin protein (Htt. Although both Htt and the HD pathogenic mutation (mHtt are implicated in early developmental events, their individual involvement has not been adequately explored. In order to better define the developmental functions and pathological consequences of the normal and mutant proteins, respectively, we employed embryonic stem cell (ESC expansion, differentiation and induction experiments using huntingtin knock-out (KO and mutant huntingtin knock-in (Q111 mouse ESC lines. In KO ESCs, we observed impairments in the spontaneous specification and survival of ectodermal and mesodermal lineages during embryoid body formation and under inductive conditions using retinoic acid and Wnt3A, respectively. Ablation of BAX improves cell survival, but failed to correct defects in germ layer specification. In addition, we observed ensuing impairments in the specification and maturation of neural, hepatic, pancreatic and cardiomyocyte lineages. These developmental deficits occurred in concert with alterations in Notch, Hes1 and STAT3 signaling pathways. Moreover, in Q111 ESCs, we observed differential developmental stage-specific alterations in lineage specification and maturation. We also observed changes in Notch/STAT3 expression and activation. Our observations underscore essential roles of Htt in the specification of ectoderm, endoderm and mesoderm, in the specification of neural and non-neural organ-specific lineages, as well as cell survival during early embryogenesis. Remarkably, these developmental events are differentially deregulated by mHtt, raising the possibility that HD-associated early developmental impairments may contribute not only to region-specific neurodegeneration, but also to non-neural co-morbidities.

  15. Design and development of an in-line sputtering system and process development of thin film multilayer neutron supermirrors

    Energy Technology Data Exchange (ETDEWEB)

    Biswas, A.; Sampathkumar, R.; Kumar, Ajaya; Bhattacharyya, D.; Sahoo, N. K. [Atomic and Molecular Physics Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Lagoo, K. D.; Veerapur, R. D.; Padmanabhan, M.; Puri, R. K. [Division of Remote Handling and Robotics, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Bhattacharya, Debarati; Singh, Surendra; Basu, S. [Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)

    2014-12-15

    Neutron supermirrors and supermirror polarizers are thin film multilayer based devices which are used for reflecting and polarizing neutrons in various neutron based experiments. In the present communication, the in-house development of a 9 m long in-line dc sputtering system has been described which is suitable for deposition of neutron supermirrors on large size (1500 mm × 150 mm) substrates and in large numbers. The optimisation process of deposition of Co and Ti thin film, Co/Ti periodic multilayers, and a-periodic supermirrors have also been described. The system has been used to deposit thin film multilayer supermirror polarizers which show high reflectivity up to a reasonably large critical wavevector transfer of ∼0.06 Å{sup −1} (corresponding to m = 2.5, i.e., 2.5 times critical wavevector transfer of natural Ni). The computer code for designing these supermirrors has also been developed in-house.

  16. Development of data acquisition and control system for ICH & CD transmission line components test facility

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Manoj, E-mail: manoj.patel@iter-india.org [ITER-India, Institute for Plasma Research, Bhat, Gandhinagar 382428, Gujarat (India); Jha, Akhil [ITER-India, Institute for Plasma Research, Bhat, Gandhinagar 382428, Gujarat (India); Patel, Nidhi [Department of Instrumentation & Control Engineering, Dharmsinh Desai University, Nadiad 387001, Gujarat (India); Krishna, J.V.S. Hari; Rajnish, Kumar; Soni, Dipal; Verma, Sriprakash; Patel, Hriday; Trivedi, Rajesh; Mukherjee, Aparajita [ITER-India, Institute for Plasma Research, Bhat, Gandhinagar 382428, Gujarat (India)

    2016-11-15

    Highlights: • Traveling Wave Resonator (TWR) gain achieved is 13.58 dB using 10 dB coupler. • Software module for Automatic calibration for power detector is developed and integrated. • Application module is developed using LabVIEW™ for high power RF operation of TWR. - Abstarct: India is developing a very high power test bed (∼MW level) based on concept of Travelling Wave Resonator (TWR) for testing of passive transmission line components [3]. Data acquisition and control system is required for safe and reliable operation of TWR. It includes online monitoring of input power and circulating ring power. Acquired RF signal provides information about forward and reflected RF power. For MW power level testing, system is protected against arc and thermal effect during CW operation. National Instrument make hardware and software have been used to acquire signals from RF detector, Arc detectors, IR camera and thermocouples etc. LabVIEW™ based software has been developed for calculation of RF parameters. Graphical user interface is developed for better visualization. Initial testing of the TWR setup with 10 dB coupler provides a power gain of 13.58 dB (22X). For future 3 MW TWR test bed the required power gain is ∼20 dB (100X) since the available source is ∼40 kW. This paper describes the detail design and integrated test results for data acquisition and control system for TWR test bed.

  17. Sexual dimorphism in parental imprint ontogeny and contribution to embryonic development.

    Science.gov (United States)

    Bourc'his, Déborah; Proudhon, Charlotte

    2008-01-30

    Genomic imprinting refers to the functional non-equivalence of parental genomes in mammals that results from the parent-of-origin allelic expression of a subset of genes. Parent-specific expression is dependent on the germ line acquisition of DNA methylation marks at imprinting control regions (ICRs), coordinated by the DNA-methyltransferase homolog DNMT3L. We discuss here how the gender-specific stages of DNMT3L expression may have influenced the various sexually dimorphic aspects of genomic imprinting: (1) the differential developmental timing of methylation establishment at paternally and maternally imprinted genes in each parental germ line, (2) the differential dependence on DNMT3L of parental methylation imprint establishment, (3) the unequal duration of paternal versus maternal methylation imprints during germ cell development, (4) the biased distribution of methylation-dependent ICRs towards the maternal genome, (5) the different genomic organization of paternal versus maternal ICRs, and finally (6) the overwhelming contribution of maternal germ line imprints to development compared to their paternal counterparts.

  18. Intracranial germ cell tumors in adults. A retrospective study of 19 cases

    International Nuclear Information System (INIS)

    Agranat, P.; Jedynak, P.; Epardeau, B.; Mignot, L.; Extra, J.M.

    1995-01-01

    The authors report on the retrospective analysis of 19 patients with primary cerebral germ cell tumors which were treated between 1965 and 1993. Median age is 18 years (extremes: 16-55 years). There were 16 men and three women. The location of the primary tumor was the pineal area in six patients, suprasellar and hypothalamic area in five patients and other areas in eight patients. The histological pattern was non seminoma in six patients, dysgerminoma in eight; however no histological sample was obtained in five patients who did not have any particular characteristics (either cytological abnormalities or elevated tumor marker level). Three patients were treated by surgery only, eight patients received exclusive radiotherapy and eight patients had first line chemotherapy and further cranial irradiation. One was lost to follow up. Six of eight assessable patients with dysgerminoma are alive with non evolutive disease (NED) after 15 to 176 month of follow-up. One out of five assessable patients with non seminomatous tumor in NED (163 month of follow-up). Finally all five patients who have no histological subtyping are alive with NED at 24 to 138 months. The standard treatment of dysgerminoma is currently first line chemotherapy followed by relatively low-dose and limited irradiation; the standard treatment of non-seminomatous cerebral germ cell tumor is chemotherapy, the study of which is warranted with the aim to decrease the toxicity and to increase the efficacy. (authors). 36 refs., 7 tabs

  19. Development of highly polished, grazing incidence mirrors for synchrotron radiation beam lines at SSRL

    Energy Technology Data Exchange (ETDEWEB)

    Tirsell, K.G.; Berglin, E.J.; Fuchs, B.A.; Holdener, F.R.; Humpal, H.H.; Karpenko, V.P.; Kulkarni, S.; Fantone, S.D.

    1987-08-01

    New platinum-coated grazing incidence mirrors with low surface roughnesses have been developed to focus bending magnet radiation from the SSRL/SLAC SPEAR storage ring on the entrance slits of two Beam Line VIII grating monochromators. The first mirror in the toroidal grating monochromator (TGM) branch is a cooled SiC cylinder capable of absorbing synchrotron radiation power levels of up to 260 watts without excessive distortion. This mirror deflects the beam vertically through a 12/degree/ angle and focuses it sagitally on the TGM entrance slit plane. The second TGM optical element is a fused-silica spherical mirror with a large radius of curvature that deflects the beam vertically through an additional 12/degree/ and focuses it tangentially with 3/1 demagnification. The first mirror in our spherical grating branch is a 5/degree/-vertically deflecting, cooled SiC toroid designed to focus tangentially on the monochromator entrance slits and sagitally in the exit slits. A 4/degree/-deflecting fused silica mirror is used after the exit sites in each beam line to refocus on to the sample. For this application a thin cylinder is bent to approximate an ellipsoid. The mirrors are now installed at SSRL and performance measurements are planned. Qualitatively the focus of the TGM optics at the entrance slit plane appears very good. In this paper we discuss considerations leading to the choice of SiC for each of the two first mirrors. We present highlights of the development of these mirrors with some emphasis on SiC polishing techniques. In addition, the specialized metrology developed to produce the more difficult figure of the toroid will be described. Measured surface roughness and figure results will be presented. 19 refs., 11 figs.

  20. Development of highly polished, grazing incidence mirrors for synchrotron radiation beam lines at SSRL

    International Nuclear Information System (INIS)

    Tirsell, K.G.; Berglin, E.J.; Fuchs, B.A.; Holdener, F.R.; Humpal, H.H.; Karpenko, V.P.; Kulkarni, S.; Fantone, S.D.

    1987-08-01

    New platinum-coated grazing incidence mirrors with low surface roughnesses have been developed to focus bending magnet radiation from the SSRL/SLAC SPEAR storage ring on the entrance slits of two Beam Line VIII grating monochromators. The first mirror in the toroidal grating monochromator (TGM) branch is a cooled SiC cylinder capable of absorbing synchrotron radiation power levels of up to 260 watts without excessive distortion. This mirror deflects the beam vertically through a 12/degree/ angle and focuses it sagitally on the TGM entrance slit plane. The second TGM optical element is a fused-silica spherical mirror with a large radius of curvature that deflects the beam vertically through an additional 12/degree/ and focuses it tangentially with 3/1 demagnification. The first mirror in our spherical grating branch is a 5/degree/-vertically deflecting, cooled SiC toroid designed to focus tangentially on the monochromator entrance slits and sagitally in the exit slits. A 4/degree/-deflecting fused silica mirror is used after the exit sites in each beam line to refocus on to the sample. For this application a thin cylinder is bent to approximate an ellipsoid. The mirrors are now installed at SSRL and performance measurements are planned. Qualitatively the focus of the TGM optics at the entrance slit plane appears very good. In this paper we discuss considerations leading to the choice of SiC for each of the two first mirrors. We present highlights of the development of these mirrors with some emphasis on SiC polishing techniques. In addition, the specialized metrology developed to produce the more difficult figure of the toroid will be described. Measured surface roughness and figure results will be presented. 19 refs., 11 figs

  1. Development of phenomena identification and ranking table for APR1400 main steam line break

    International Nuclear Information System (INIS)

    Song, J. H.; Chung, B. D.; Jeong, J. J.

    2003-01-01

    A Phenomena Identification and Ranking Table (PIRT) was developed for the Main Steam Line Break (MSLB) event of an APR-1400 (Advanced Power Reactor-1400). A team of experts from research institutes, industries, and regulatory bodies participated in the development. The selected event was a double-ended steam line break at full power with the reactor coolant pump running. The panel selected the fuel performance as the primary safety criterion for ranking. The plant design data, the results of APR-1400 safety analysis, and the results of additional best estimate analysis by MARS2.1 were utilized. Three phases of pre-trip, rapid cool-down, and safety injection phase were identified. Then, the ranking of a system, components, phenomenon/process based on the relative importance to the primary evaluation criterion were followed for each time phase. Finally, the knowledge-level for each important process in the component was ranked in terms of the existing knowledge. The highly ranked phenomena identified for APR-1400 MSLB are tube wall heat transfer at the steam generator shell, void distribution at the steam generator shell, liquid entrainment in the separators, mixture level in the separators, boron mixing in the upper down comer, boron transport and thermal mixing in the lower plenum, stored energy release in the upper head, and flow to and/from the upper head. The PIRT will be used as a guide in planning cost effective experimental programs and code development efforts, especially for the quantification of the process and/or phenomena, which have a high importance but low knowledge level

  2. Presumed pluripotency markers UTF-1 and REX-1 are expressed in human adult testes and germ cell neoplasms

    DEFF Research Database (Denmark)

    Kristensen, David M; Nielsen, John E; Skakkebaek, Niels E

    2008-01-01

    UTF-1 and REX-1/ZFP42 are transcription factors involved in pluripotency. Because of phenotypic similarities between pluripotent embryonic stem cells and testicular germ cell tumours (TGCT) and the derivation of pluripotent cells from testes, we investigated the expression of UTF-1 and REX-1 during...... human gonadal development and in TGCT....

  3. Development of a see-through hollow cathode discharge lamp for (Li/Ne) optogalvanic studies

    Science.gov (United States)

    Saini, V. K.; Kumar, P.; Sarangpani, K. K.; Dixit, S. K.; Nakhe, S. V.

    2017-09-01

    Development of a demountable and see-through hollow cathode (HC) discharge lamp suitable for optogalvanic (OG) spectroscopy is described. The design of the HC lamp is simple, compact, and inexpensive. Lithium, investigated rarely by the OG method, is selected for cathode material as its isotopes are important for nuclear industry. The HC lamp is characterized electrically and optically for discharge oscillations free OG effect. Strong OG signals of lithium as well as neon (as buffer gas) are produced precisely upon copper vapor laser pumped tunable dye laser irradiation. The HC lamp is capable of generating a clean OG resonance spectrum in the available dye laser wavelength scanning range (627.5-676 nm) obtained with 4-(Dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran dye. About 28 resonant OG lines are explicitly observed. Majority of them have been identified using j-l coupling scheme and assigned to the well-known neon transitions. One line that corresponds to wavelength near about 670.80 nm is assigned to lithium and resolved for its fine (2S1/2 → 2P1/2, 3/2) transitions. These OG transitions allow 0.33 cm-1 accuracy and can be used to supplement the OG transition data available from other sources to calibrate the wavelength of a scanning dye laser with precision at atomic levels.

  4. Plant biology: From on-campus to on-line development and implementation

    Science.gov (United States)

    Bradley, Lucy K.

    The lecture content of the Plant Biology class for non-majors was transformed from a traditional on-campus lecture to an asynchronous website that could be used both as a stand-alone course and as an adjunct to the on campus course sections. In addition, an interactive, on-line website with home laboratory experiments was developed and implemented by the Plant Biology Department in collaboration with design specialists from the Information Technology and Instructional Support Department of the Arizona State University. The 259-page lecture website included 134 interactive animations, as well as 11 videos. The lab website included 176 pages, with 187 graphics and 36 separate animations. Convenience was identified by most students as the key benefit of taking the course on-line. Website construction was rated highly by all of the students; however, website audio was problematic for 50% of them; video, for 71%. Students, staff, and faculty all agreed that to benefit fully from the website, adequate hardware, software, and internet connection speed were vital. Challenges with the web-based lab were either technological (inadequate equipment or skills), logistical (dissatisfaction with having to pick up home lab kits from campus), or motivational (student survey responses added to the growing literature that suggests that mature, focused, self-motivated students benefit more from distance learning).

  5. Radiological study on newly developed composite corn advance lines in Malaysia

    Science.gov (United States)

    Adekunle Olatunji, Michael; Bemigho Uwatse, Onosohwo; Uddin Khandaker, Mayeen; Amin, Y. M.; Faruq, G.

    2014-12-01

    Owing to population growth, there has been high demand for food across the world, and hence, different agricultural activities such as use of phosphate fertilizers, recycling of organic matters, etc, have been deployed to increase crop yields. In Malaysia, a total of nine composite corn advance lines have been developed at the Institute of Biological Sciences, University of Malaya and are being grown under different conditions with a bid to meet the average daily human need for energy and fiber intake. To this end, the knowledge of radioactivity levels in these corn advance lines are of paramount importance for the estimation of possible radiological hazards due to its consumption. Hence, the radioactivity concentrations of 226Ra, 228Ra and 40K in the corn have been determined using HPGe γ-ray spectrometry. The activity concentrations in the corn ranged from 0.05 to 19.18 Bq kg-1 for 226Ra, from 0.10 to 3.22 Bq kg-1 for 228Ra and from 26.4 to 129 Bq kg-1 for 40K. In order to ascertain the radiological safety of the population regarding maize consumption, the daily intakes of these radionuclides as well as the annual effective dose were estimated. The total effective dose obtained due to the ingestion of radionuclides via maize consumption is 15.39 μSv y-1, which is less than the international recommendations.

  6. Radiological study on newly developed composite corn advance lines in Malaysia

    International Nuclear Information System (INIS)

    Olatunji, Michael Adekunle; Uwatse, Onosohwo Bemigho; Khandaker, Mayeen Uddin; Amin, Y M; Faruq, G

    2014-01-01

    Owing to population growth, there has been high demand for food across the world, and hence, different agricultural activities such as use of phosphate fertilizers, recycling of organic matters, etc, have been deployed to increase crop yields. In Malaysia, a total of nine composite corn advance lines have been developed at the Institute of Biological Sciences, University of Malaya and are being grown under different conditions with a bid to meet the average daily human need for energy and fiber intake. To this end, the knowledge of radioactivity levels in these corn advance lines are of paramount importance for the estimation of possible radiological hazards due to its consumption. Hence, the radioactivity concentrations of 226 Ra, 228 Ra and 40 K in the corn have been determined using HPGe γ-ray spectrometry. The activity concentrations in the corn ranged from 0.05 to 19.18 Bq kg −1 for 226 Ra, from 0.10 to 3.22 Bq kg −1 for 228 Ra and from 26.4 to 129 Bq kg −1 for 40 K. In order to ascertain the radiological safety of the population regarding maize consumption, the daily intakes of these radionuclides as well as the annual effective dose were estimated. The total effective dose obtained due to the ingestion of radionuclides via maize consumption is 15.39 μSv y −1 , which is less than the international recommendations. (paper)

  7. The development of on-line thermal performance monitors in Nuclear Electric Company's stations

    International Nuclear Information System (INIS)

    Conner, A.S.

    1992-01-01

    The paper examines the economic benefits of using on-line monitoring techniques in assisting Station Staff with the task of optimising the efficient use of reactor fuel. The role of thermal performance monitoring for detecting changes in plant condition is also examined and the way in which the data can be used by engineers to assist with the preparation of operating and maintenance programmes. To enable genuine gradual changes in plant performance to be detected when operating against a background of changing plant signal accuracy conditions, plant transducers have to be calibrated on a regular basis. This can be both costly and labour intensive. To reduce this requirement for regular calibrations, an automatic software signal verification program has been developed for use in on-line monitoring schemes. It forms part of the total unit performance calculation package and uses a whole plant model to verify plant signals. All plant signals used to calculate unit heat rate are verified typically every 15 minutes with signals going outside predetermined limits being automatically reported to the user. The program is interactive allowing the user to interrogate the condition of the signal, with respect to both its error magnitude and rate of drift outside signal limits. The program runs in real time mode on a Workstation connected directly to the plant

  8. Field validation of protocols developed to evaluate in-line mastitis detection systems.

    Science.gov (United States)

    Kamphuis, C; Dela Rue, B T; Eastwood, C R

    2016-02-01

    This paper reports on a field validation of previously developed protocols for evaluating the performance of in-line mastitis-detection systems. The protocols outlined 2 requirements of these systems: (1) to detect cows with clinical mastitis (CM) promptly and accurately to enable timely and appropriate treatment and (2) to identify cows with high somatic cell count (SCC) to manage bulk milk SCC levels. Gold standard measures, evaluation tests, performance measures, and performance targets were proposed. The current study validated the protocols on commercial dairy farms with automated in-line mastitis-detection systems using both electrical conductivity (EC) and SCC sensor systems that both monitor at whole-udder level. The protocol for requirement 1 was applied on 3 commercial farms. For requirement 2, the protocol was applied on 6 farms; 3 of them had low bulk milk SCC (128×10(3) cells/mL) and were the same farms as used for field evaluation of requirement 1. Three farms with high bulk milk SCC (270×10(3) cells/mL) were additionally enrolled. The field evaluation methodology and results were presented at a workshop including representation from 7 international suppliers of in-line mastitis-detection systems. Feedback was sought on the acceptance of standardized performance evaluation protocols and recommended refinements to the protocols. Although the methodology for requirement 1 was relatively labor intensive and required organizational skills over an extended period, no major issues were encountered during the field validation of both protocols. The validation, thus, proved the protocols to be practical. Also, no changes to the data collection process were recommended by the technology supplier representatives. However, 4 recommendations were made to refine the protocols: inclusion of an additional analysis that ignores small (low-density) clot observations in the definition of CM, extension of the time window from 4 to 5 milkings for timely alerts for CM

  9. Temporally and spatially dynamic germ cell niches in Botryllus schlosseri revealed by expression of a TGF-beta family ligand and vasa

    Directory of Open Access Journals (Sweden)

    Adam D. Langenbacher

    2016-04-01

    Full Text Available Abstract Background Germ cells are specified during early development and are responsible for generating gametes in the adult. After germ cells are specified, they typically migrate to a particular niche in the organism where they reside for the remainder of its lifetime. For some model organisms, the specification and migration of germ cells have been extensively studied, but how these events occur in animals that reproduce both sexually and asexually is not well understood. Results We have identified a novel TGF-β family member in Botryllus schlosseri, tgfβ-f, and found that it is expressed by follicle cell progenitors and the differentiated follicle and support cells surrounding the maturing gametes. Using the expression of tgfβ-f and the germ cell marker vasa, we have found that nearly all germ cells in Botryllus are associated with tgfβ-f-expressing follicle progenitors in clusters consisting solely of those two cell types. These clusters were mostly small, consisting of ten or fewer cells, and generally contained between a 2:1 and 1:1 ratio of follicle progenitors to germ cells. Clusters of germ and follicle progenitor cells were primarily localized to niches in the primary and secondary buds, but could also be found in other locations including the vasculature. We analyzed the location of germ cell clusters throughout the asexual life cycle of Botryllus and found that at the stage when germ cells are first detected in the secondary bud niche, a dramatic change in the size and location of germ/follicle cell clusters also occurred. Conclusions Our findings suggest that germ/follicle cell clusters have predictable migratory patterns during the weekly asexual developmental cycle in Botryllus. An increased number of small clusters and the presence of clusters in the vasculature coinciding with the appearance of clusters in the secondary bud suggest that fragmentation of clusters and the migration of smaller clusters through the vasculature

  10. Early imaging findings in germ cell tumors arising from the basal ganglia

    Energy Technology Data Exchange (ETDEWEB)

    Lee, So Mi [Seoul National University College of Medicine, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Kyungpook National University Medical Center, Department of Radiology, Daegu (Korea, Republic of); Kim, In-One; Choi, Young Hun; Cheon, Jung-Eun; Kim, Woo Sun [Seoul National University College of Medicine, Department of Radiology and Institute of Radiation Medicine, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Cho, Hyun-Hae [Seoul National University College of Medicine, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Ewha Woman' s University Mokdong Hospital, Department of Radiology, Seoul (Korea, Republic of); You, Sun Kyoung [Seoul National University College of Medicine, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Chungnam National University Hospital, Department of Radiology, Daejeon (Korea, Republic of)

    2016-05-15

    It is difficult to diagnosis early stage germ cell tumors originating in the basal ganglia, but early recognition is important for better outcome. To evaluate serial MR images of basal ganglia germ cell tumors, with emphasis on the features of early stage tumors. We retrospectively reviewed serial MR images of 15 tumors in 14 children and young adults. We categorized MR images of the tumors as follows: type I, ill-defined patchy lesions (<3 cm) without cyst; type II, small mass lesions (<3 cm) with cyst; and type III, large lesions (≥3 cm) with cyst. We also assessed temporal changes of the MR images. On the initial images, 8 of 11 (73%) type I tumors progressed to types II or III, and 3 of 4 (75%) type II tumors progressed to type III. The remaining 4 tumors did not change in type. All type II tumors (5/5, 100%) that changed from type I had a few tiny cysts. Intratumoral hemorrhage was observed even in the type I tumor. Ipsilateral hemiatrophy was observed in most of the tumors (13/15, 87%) on initial MR images. As tumors grew, cystic changes, intratumoral hemorrhage, and ipsilateral hemiatrophy became more apparent. Early stage basal ganglia germ cell tumors appear as ill-defined small patchy hyperintense lesions without cysts on T2-weighted images, are frequently associated with ipsilateral hemiatrophy, and sometimes show microhemorrhage. Tumors develop tiny cysts at a relatively early stage. (orig.)

  11. Early imaging findings in germ cell tumors arising from the basal ganglia

    International Nuclear Information System (INIS)

    Lee, So Mi; Kim, In-One; Choi, Young Hun; Cheon, Jung-Eun; Kim, Woo Sun; Cho, Hyun-Hae; You, Sun Kyoung

    2016-01-01

    It is difficult to diagnosis early stage germ cell tumors originating in the basal ganglia, but early recognition is important for better outcome. To evaluate serial MR images of basal ganglia germ cell tumors, with emphasis on the features of early stage tumors. We retrospectively reviewed serial MR images of 15 tumors in 14 children and young adults. We categorized MR images of the tumors as follows: type I, ill-defined patchy lesions (<3 cm) without cyst; type II, small mass lesions (<3 cm) with cyst; and type III, large lesions (≥3 cm) with cyst. We also assessed temporal changes of the MR images. On the initial images, 8 of 11 (73%) type I tumors progressed to types II or III, and 3 of 4 (75%) type II tumors progressed to type III. The remaining 4 tumors did not change in type. All type II tumors (5/5, 100%) that changed from type I had a few tiny cysts. Intratumoral hemorrhage was observed even in the type I tumor. Ipsilateral hemiatrophy was observed in most of the tumors (13/15, 87%) on initial MR images. As tumors grew, cystic changes, intratumoral hemorrhage, and ipsilateral hemiatrophy became more apparent. Early stage basal ganglia germ cell tumors appear as ill-defined small patchy hyperintense lesions without cysts on T2-weighted images, are frequently associated with ipsilateral hemiatrophy, and sometimes show microhemorrhage. Tumors develop tiny cysts at a relatively early stage. (orig.)

  12. Extremely Low Frequency Magnetic Fields Induce Spermatogenic Germ Cell Apoptosis: Possible Mechanism

    Directory of Open Access Journals (Sweden)

    Sang-Kon Lee

    2014-01-01

    Full Text Available The energy generated by an extremely low frequency electromagnetic field (ELF-EMF is too weak to directly induce genotoxicity. However, it is reported that an extremely low frequency magnetic field (ELF-MF is related to DNA strand breakage and apoptosis. The testes that conduct spermatogenesis through a dynamic cellular process involving meiosis and mitosis seem vulnerable to external stress such as heat, MF exposure, and chemical or physical agents. Nevertheless the results regarding adverse effects of ELF-EMF on human or animal reproductive functions are inconclusive. According to the guideline of the International Commission on Non-Ionizing Radiation Protection (ICNIRP; 2010 for limiting exposure to time-varying MF (1 Hz to 100 kHz, overall conclusion of epidemiologic studies has not consistently shown an association between human adverse reproductive outcomes and maternal or paternal exposure to low frequency fields. In animal studies there is no compelling evidence of causal relationship between prenatal development and ELF-MF exposure. However there is increasing evidence that EL-EMF exposure is involved with germ cell apoptosis in testes. Biophysical mechanism by which ELF-MF induces germ cell apoptosis has not been established. This review proposes the possible mechanism of germ cell apoptosis in testes induced by ELF-MF.

  13. ATTEMPT TO APPLY STABILIZED WHEAT GERM FOR BREAD SUPPLEMENTATION

    Directory of Open Access Journals (Sweden)

    Halina Gambuś

    2015-02-01

    Full Text Available The increased interest in rational nutrition causes, that from many years is observed a growing consumption of bread, and novel food supplemented with health promoting components. For the bread production in Poland mainly wheat and rye cake flours are used, depleted of a many valuable nutrients such as protein, dietary fibre, minerals and vitamins. Because of their unique chemical composition wheat germs are a particularly valuable resource, both for direct consumption and to enhance the nutritional value of food products. The aim of the study was to prepare wheat bread with a 10% addition of commercial stabilized wheat germs. Based on the obtained results, it was found that wheat germs, due to their unique chemical composition, were a particularly valuable resource to supplement the nutritional value of bread. However, germs had detrimental effect on mechanical properties of dough, and on bread quality. Texture of bread crumb and its chemical composition were analysed. It was shown, that germs subjected to fermentation process could be used in wheat bread production as dietary fibre and mineral compound supplement.

  14. Development of an on-line analyzer for organic phase uranium concentration in extraction process

    International Nuclear Information System (INIS)

    Dong Yanwu; Song Yufen; Zhu Yaokun; Cong Peiyuan; Cui Songru

    1998-10-01

    The working principle, constitution, performance of an on-line analyzer and the development characteristic of immersion sonde, data processing system and examination standard are reported. The performance of this instrument is reliable. For identical sample, the signal fluctuation in continuous monitoring for four months is less than +-1%. According to required measurement range by choosing appropriate length of sample cell the precision of measurement is better than 1% at uranium concentration 100 g/L. The detection limit is (50 +- 10) mg/L. The uranium concentration in process stream can be automatically displayed and printed out in real time and 4∼20 mA current signal being proportional to the uranium concentration can be presented. So the continuous control and computer management for the extraction process can be achieved

  15. Development of on line automatic separation device for apple and sleeve

    Science.gov (United States)

    Xin, Dengke; Ning, Duo; Wang, Kangle; Han, Yuhang

    2018-04-01

    Based on STM32F407 single chip microcomputer as control core, automatic separation device of fruit sleeve is designed. This design consists of hardware and software. In hardware, it includes mechanical tooth separator and three degree of freedom manipulator, as well as industrial control computer, image data acquisition card, end effector and other structures. The software system is based on Visual C++ development environment, to achieve localization and recognition of fruit sleeve with the technology of image processing and machine vision, drive manipulator of foam net sets of capture, transfer, the designated position task. Test shows: The automatic separation device of the fruit sleeve has the advantages of quick response speed and high separation success rate, and can realize separation of the apple and plastic foam sleeve, and lays the foundation for further studying and realizing the application of the enterprise production line.

  16. Development of uniform hazard response spectra for rock sites considering line and point sources of earthquakes

    International Nuclear Information System (INIS)

    Ghosh, A.K.; Kushwaha, H.S.

    2001-12-01

    Traditionally, the seismic design basis ground motion has been specified by normalised response spectral shapes and peak ground acceleration (PGA). The mean recurrence interval (MRI) used to computed for PGA only. It is shown that the MRI associated with such response spectra are not the same at all frequencies. The present work develops uniform hazard response spectra i.e. spectra having the same MRI at all frequencies for line and point sources of earthquakes by using a large number of strong motion accelerograms recorded on rock sites. Sensitivity of the number of the results to the changes in various parameters has also been presented. This work is an extension of an earlier work for aerial sources of earthquakes. These results will help to determine the seismic hazard at a given site and the associated uncertainities. (author)

  17. Expert System Development on On-line Measurement of Sewage Treatment Based Process

    Directory of Open Access Journals (Sweden)

    Jianjun QIN

    2014-02-01

    Full Text Available This article puts forward a solution in which an instrument on-line automatic measurement and expert system process are optimized according to the complexity and great process dynamics of sewage treatment process. Firstly modeling has been set up with configuration sewage treatment process in which the process has been integrated into the computer software environment. Secondly certain number of water quality automatic monitoring instruments and sensor probes are set in the reaction tanks according to the needs of process changes and management. The data information acquired can be displayed and recorded at the real time. A human-machine integration expert system featuring computer automation management is developed for the base by one-off method thus to realize the intelligent and unmanned management. The advantages brought about from it can fill up the inexperience of the on-site management personnel and solve the contradiction between the water quality dynamics and difficulty in the process adjustment.

  18. Glass fiber -reinforced plastic tapered poles for transmission and distribution lines: development and experimental study

    International Nuclear Information System (INIS)

    Ibrahim, S.; Burachysnsky, V.; Polyzois, D.

    1999-01-01

    A research project to develop lightweight poles for use in power transmission and distribution lines and involving the use of glass fiber-reinforced plastic using the filament winding process is described. Twelve full scale specimen poles were designed, fabricated and subjected to cantilever bending to test failure modes. The test parameters included fiber orientation, ratio of longitudinal-to-circumferential fiber, and the number of layers. Results showed that local buckling was the most dominant failure mode, attributable to the high radius-to-thickness ratio of the specimen poles. Overall, however, these fiber-reinforced plastic poles compared favourably to wooden poles in carrying capacity with significant weight reduction. Lateral displacement at ultimate loads did not exceed the acceptable limit of 10 per cent of the specimen free length. 7 refs., 3 tabs., 2 figs

  19. Development of on-line uranium enrichment monitor of gaseous UF6 for uranium enrichment plant

    International Nuclear Information System (INIS)

    Lu Xuesheng; Liu Guorong; Jin Huimin; Zhao Yonggang; Li Jinghuai; Hao Xueyuan; Ying Bin; Yu Zhaofei

    2013-01-01

    An on-line enrichment monitor was developed to measure the enrichment of UF 6 , flowing through the processing pipes in uranium enrichment plant. A Nal (Tl) detector was used to measure the count rates of the 185.7 keV γ-ray emitted from 235 U, and the total quantity of uranium was determined from thermodynamic characteristics of gaseous uranium hexafluoride. The results show that the maximum relative standard deviation is less than 1% when the measurement time is 120 s or more and the pressure is more than 2 kPa in the measurement chamber. Uranium enrichment of gaseous uranium hexafluoride in the output end of cascade can be monitored continuously by using the device. It should be effective for nuclear materials accountability verifications and materials balance verification at uranium enrichment plant. (authors)

  20. Development of a plug-in for Variability Modeling in Software Product Lines

    Directory of Open Access Journals (Sweden)

    María Lucía López-Araujo

    2012-03-01

    Full Text Available Las Líneas de Productos de Software (LPS toman ventaja económica de las similitudes y variación entre un conjunto de sistemas de software dentro de un dominio específico. La Ingeniería de Líneas de Productos de Software por lo tanto, define una serie de procesos para el desarrollo de LPS que consideran las similitudes y variación a lo largo del ciclo devida. El modelado de variabilidad, en consecuencia, es una actividad esencial en un enfoque de Ingeniería de Líneas de Productos de Software. Existen varias técnicas para modelado de variabilidad. Entre ellas resalta COVAMOF que permite modelar los puntos de variación, variantes y dependencias como entidades de primera clase, proporcionando una manera uniforme de representarlos en los diversos niveles de abstracción de una LPS. Para poder aprovechar los beneficios de COVAMOF es necesario contar con una herramienta, de otra manera el modelado y la administración de la variabilidad pueden resultar una labor ardua para el ingeniero de software. Este trabajo presenta el desarrollo de un plug-in de COVAMOF para Eclipse.Software Product Lines (SPL take economic advantage of commonality and variability among a set of software systems that exist within a specific domain. Therefore, Software Product Line Engineering defines a series of processes for the development of a SPL that consider commonality and variability during the software life cycle. Variability modeling is therefore an essential activity in a Software Product Line Engineering approach. There are several techniques for variability modeling nowadays. COVAMOF stands out among them since it allows the modeling of variation points, variants and dependencies as first class elements. COVAMOF, therefore, provides an uniform manner for representing such concepts in different levels of abstraction within a SPL. In order to take advantage of COVAMOF benefits, it is necessary to have a computer aided tool, otherwise variability modeling and

  1. The Development of Quality Control Genotyping Approaches: A Case Study Using Elite Maize Lines.

    Directory of Open Access Journals (Sweden)

    Jiafa Chen

    Full Text Available Quality control (QC of germplasm identity and purity is a critical component of breeding and conservation activities. SNP genotyping technologies and increased availability of markers provide the opportunity to employ genotyping as a low-cost and robust component of this QC. In the public sector available low-cost SNP QC genotyping methods have been developed from a very limited panel of markers of 1,000 to 1,500 markers without broad selection of the most informative SNPs. Selection of optimal SNPs and definition of appropriate germplasm sampling in addition to platform section impact on logistical and resource-use considerations for breeding and conservation applications when mainstreaming QC. In order to address these issues, we evaluated the selection and use of SNPs for QC applications from large DArTSeq data sets generated from CIMMYT maize inbred lines (CMLs. Two QC genotyping strategies were developed, the first is a "rapid QC", employing a small number of SNPs to identify potential mislabeling of seed packages or plots, the second is a "broad QC", employing a larger number of SNP, used to identify each germplasm entry and to measure heterogeneity. The optimal marker selection strategies combined the selection of markers with high minor allele frequency, sampling of clustered SNP in proportion to marker cluster distance and selecting markers that maintain a uniform genomic distribution. The rapid and broad QC SNP panels selected using this approach were further validated using blind test assessments of related re-generation samples. The influence of sampling within each line was evaluated. Sampling 192 individuals would result in close to 100% possibility of detecting a 5% contamination in the entry, and approximately a 98% probability to detect a 2% contamination of the line. These results provide a framework for the establishment of QC genotyping. A comparison of financial and time costs for use of these approaches across different

  2. Development of a polarized neutron beam line at Algerian research reactors using McStas software

    Energy Technology Data Exchange (ETDEWEB)

    Makhloufi, M., E-mail: makhloufi_8m@yahoo.fr [Centre de Recherche Nucléaire de Birine (Algeria); Salah, H. [Centre de Recherche Nucléaire d' Alger (Algeria)

    2017-02-01

    Unpolarized instrumentation has long been studied and designed using McStas simulation tool. But, only recently new models were developed for McStas to simulate polarized neutron scattering instruments. In the present contribution, we used McStas software to design a polarized neutron beam line, taking advantage of the available spectrometers reflectometer and diffractometer in Algeria. Both thermal and cold neutron was considered. The polarization was made by two types of supermirrors polarizers FeSi and CoCu provided by the HZB institute. For sake of performance and comparison, the polarizers were characterized and their characteristics reproduced. The simulated instruments are reported. Flipper and electromagnets for guide field are developed. Further developments including analyzers and upgrading of the existing spectrometers are underway. - Highlights: • Permit to evaluate the feasibility of a polarized neutron scattering instrument prior to its implementation. • Help to understand the origin of instrumental imperfections and offer an optimized set up configuration. • Provide the possibility to use the FeSi and CoCu supermirrors, designed to polarize spin up cold neutron, to polarize thermal neutron.

  3. A Software Product Line Process to Develop Agents for the IoT.

    Science.gov (United States)

    Ayala, Inmaculada; Amor, Mercedes; Fuentes, Lidia; Troya, José M

    2015-07-01

    One of the most important challenges of this decade is the Internet of Things (IoT), which aims to enable things to be connected anytime, anyplace, with anything and anyone, ideally using any path/network and any service. IoT systems are usually composed of heterogeneous and interconnected lightweight devices that support applications that are subject to change in their external environment and in the functioning of these devices. The management of the variability of these changes, autonomously, is a challenge in the development of these systems. Agents are a good option for developing self-managed IoT systems due to their distributed nature, context-awareness and self-adaptation. Our goal is to enhance the development of IoT applications using agents and software product lines (SPL). Specifically, we propose to use Self-StarMASMAS, multi-agent system) agents and to define an SPL process using the Common Variability Language. In this contribution, we propose an SPL process for Self-StarMAS, paying particular attention to agents embedded in sensor motes.

  4. A Software Product Line Process to Develop Agents for the IoT

    Directory of Open Access Journals (Sweden)

    Inmaculada Ayala

    2015-07-01

    Full Text Available One of the most important challenges of this decade is the Internet of Things (IoT, which aims to enable things to be connected anytime, anyplace, with anything and anyone, ideally using any path/network and any service. IoT systems are usually composed of heterogeneous and interconnected lightweight devices that support applications that are subject to change in their external environment and in the functioning of these devices. The management of the variability of these changes, autonomously, is a challenge in the development of these systems. Agents are a good option for developing self-managed IoT systems due to their distributed nature, context-awareness and self-adaptation. Our goal is to enhance the development of IoT applications using agents and software product lines (SPL. Specifically, we propose to use Self-StarMASMAS, multi-agent system agents and to define an SPL process using the Common Variability Language. In this contribution, we propose an SPL process for Self-StarMAS, paying particular attention to agents embedded in sensor motes.

  5. On-line monitoring system development for single-phase flow accelerated corrosion

    International Nuclear Information System (INIS)

    Lee, Na Young; Lee, Seung Gi; Ryu, Kyung Ha; Hwang, Il Soon

    2007-01-01

    Aged nuclear piping has been reported to undergo corrosion-induced accelerated failures, often without giving signatures to current inspection campaigns. Therefore, we need diverse sensors which can cover a wide area in an on-line application. We suggest an integrated approach to monitor the flow accelerated corrosion (FAC) susceptible piping. Since FAC is a combined phenomenon, we need to monitor as many parameters as possible and that cover wide area, since we do not know where the FAC occurs. For this purpose, we introduce the wearing rate model which focuses on the electrochemical parameters. Using this model, we can predict the wearing rate and then compare testing results. Through analysis we identified feasibility and then developed electrochemical sensors for high temperature application; we also introduced a mechanical monitoring system which is still under development. To support the validation of the monitored results, we adopted high temperature ultrasonic transducer (UT), which shows good resolution in the testing environment. As such, all the monitored results can be compared in terms of thickness. Our validation tests demonstrated the feasibility of sensors. To support direct thickness measurement for a wide-area, the direct current potential drop (DCPD) method will be researched to integrate into the developed framework

  6. Development of on-line monitoring system for flow accelerated corrosion

    International Nuclear Information System (INIS)

    Lee, N.Y.; Lee, S.G.; Hwang, I.S.; Kim, J.T.; Luk, V.K.

    2005-01-01

    Aged nuclear piping has been reported to undergo corrosion-induced accelerated failures, often without giving signatures to current inspection campaigns. Therefore, we need diverse sensors which can cover wide area in the on-line application. We suggested integrated approach to monitor the FAC-susceptible piping. Since FAC is a combined phenomenon, we need to monitor as many parameters as possible, and that cover wide area, since we don't know where the FAC occurs. For this purpose, we introduced wearing rate model, which concentrates on the electrochemical parameters. By the model, we can predict the wearing rate and then can compare the testing result. After we identified feasibility by analytical way, we developed electrochemical sensors for high temperature application, and introduced mechanical monitoring system, which is still under development. To support the validation of the monitored results, we adopted high temperature UT, which shows good resolution in the testing environment. By this way, all the monitored results can be compared in terms of thickness. Validation test shows the feasibility of sensors. To support direct thickness measurement for wide-area, Direct Current Potential Drop method will be researched to integrate to the developed framework. (authors)

  7. Development of a polarized neutron beam line at Algerian research reactors using McStas software

    International Nuclear Information System (INIS)

    Makhloufi, M.; Salah, H.

    2017-01-01

    Unpolarized instrumentation has long been studied and designed using McStas simulation tool. But, only recently new models were developed for McStas to simulate polarized neutron scattering instruments. In the present contribution, we used McStas software to design a polarized neutron beam line, taking advantage of the available spectrometers reflectometer and diffractometer in Algeria. Both thermal and cold neutron was considered. The polarization was made by two types of supermirrors polarizers FeSi and CoCu provided by the HZB institute. For sake of performance and comparison, the polarizers were characterized and their characteristics reproduced. The simulated instruments are reported. Flipper and electromagnets for guide field are developed. Further developments including analyzers and upgrading of the existing spectrometers are underway. - Highlights: • Permit to evaluate the feasibility of a polarized neutron scattering instrument prior to its implementation. • Help to understand the origin of instrumental imperfections and offer an optimized set up configuration. • Provide the possibility to use the FeSi and CoCu supermirrors, designed to polarize spin up cold neutron, to polarize thermal neutron.

  8. Germ cell neoplasia in situ (GCNIS)

    DEFF Research Database (Denmark)

    Berney, Daniel M; Looijenga, Leendert H J; Idrees, Muhammad

    2016-01-01

    The pre-invasive lesion associated with post-pubertal malignant germ cell tumours of the testis was first recognized in the early 1970s and confirmed by a number of observational and follow-up studies. Until this year, this scientific story has been confused by resistance to the entity and disagr......The pre-invasive lesion associated with post-pubertal malignant germ cell tumours of the testis was first recognized in the early 1970s and confirmed by a number of observational and follow-up studies. Until this year, this scientific story has been confused by resistance to the entity...... and disagreement on its name. Initially termed 'carcinoma in situ' (CIS), it has also been known as 'intratubular germ cell neoplasia, unclassified' (IGCNU) and 'testicular intraepithelial neoplasia' (TIN). In this paper, we review the history of discovery and controversy concerning these names and introduce...

  9. Material development for waste-to-energy plants. Refractory linings. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Hede Larsen, O.

    2010-10-15

    Evaluation and SEM analysis of plant exposed, failed linings confirm over and again that failure in broad lines is linked to excess porosity, inferior quality on raw materials, detrimental reactions between raw materials and other mix constituents, volume growth reactions between base material and salt depositions, thermal stress induced crack formation, and uncontrolled craftsmanship. Extensive evaluations, calculations and considerations revealed numerous ways to execute the formulation of experimental castable mixes, of which some formed a broad base for phase I trials. Three mixes of the experimental castable phase II batches reached apparent porosities of {approx} 10% measured with alcohol, estimated to less than 8%-9% if measured in water. These results compare favourably to the open porosities measure with water of generally applied LCCs in the Danish marketplace of 15.5-16.0%. Converted to bonding phase porosities the low levels realised in experiments look rather good: 28% vs 55-57%. Salt cup tests confirm state of the art resistance. Experiments and assessment of surface oxidation of Silicon Carbide grains of three levels of purity confirm that it is impossible to stabilise SiC by pre-oxydation for the purpose of creating a thicker, protective surface layer of SiO{sub 2}. It is evident from the literature and qualified assessment that free Si, as a remnant surplus from SiC manufacture, does indeed hydrolyse in the castable basic environment under development of H{sub 2} gas bubbles adding on to unwanted porosity. Heat conductivity measurements of six different, representative products conducted by the Danish Technological Institute from 300 dec. C to 750 dec. C according to their credited calorimetric method confirm that the pre-firing to excess temperatures and subsequent measurement according to the DIN/EUN norm does indeed give misleading data of up to 45% for a castable containing {approx} 55% Silicon Carbide. Finite Element analysis confirms the

  10. Expression of arf tumor suppressor in spermatogonia facilitates meiotic progression in male germ cells.

    Directory of Open Access Journals (Sweden)

    Michelle L Churchman

    2011-07-01

    Full Text Available The mammalian Cdkn2a (Ink4a-Arf locus encodes two tumor suppressor proteins (p16(Ink4a and p19(Arf that respectively enforce the anti-proliferative functions of the retinoblastoma protein (Rb and the p53 transcription factor in response to oncogenic stress. Although p19(Arf is not normally detected in tissues of young adult mice, a notable exception occurs in the male germ line, where Arf is expressed in spermatogonia, but not in meiotic spermatocytes arising from them. Unlike other contexts in which the induction of Arf potently inhibits cell proliferation, expression of p19(Arf in spermatogonia does not interfere with mitotic cell division. Instead, inactivation of Arf triggers germ cell-autonomous, p53-dependent apoptosis of primary spermatocytes in late meiotic prophase, resulting in reduced sperm production. Arf deficiency also causes premature, elevated, and persistent accumulation of the phosphorylated histone variant H2AX, reduces numbers of chromosome-associated complexes of Rad51 and Dmc1 recombinases during meiotic prophase, and yields incompletely synapsed autosomes during pachynema. Inactivation of Ink4a increases the fraction of spermatogonia in S-phase and restores sperm numbers in Ink4a-Arf doubly deficient mice but does not abrogate γ-H2AX accumulation in spermatocytes or p53-dependent apoptosis resulting from Arf inactivation. Thus, as opposed to its canonical role as a tumor suppressor in inducing p53-dependent senescence or apoptosis, Arf expression in spermatogonia instead initiates a salutary feed-forward program that prevents p53-dependent apoptosis, contributing to the survival of meiotic male germ cells.

  11. Effects of chemical-induced DNA damage on male germ cells

    Energy Technology Data Exchange (ETDEWEB)

    Holme, J.A.; Bjoerge, C.; Trbojevic, M.; Olsen, A.K.; Brunborg, G.; Soederlund, E.J. [National Inst. of Public Health, Oslo (Norway). Dept. of Environmental Medicine; Bjoeras, M.; Seeberg, E. [National Hospital, Oslo (Norway). Dept. of Microbiology; Scholz, T.; Dybing, E.; Wiger, R. [National Hospital, Oslo (Norway). Inst. for Surgical Research and Surgical Dept. B

    1998-12-31

    Several recent studies indicate declines in sperm production, as well as increases in the incidence of genitourinary abnormalities such as testicular cancer, cryptorchidism and hypospadias. It is not known if these effects are due to exposure to chemical pollutants or if other ethiological factors are involved. Animal studies indicate that chemicals will induce such effects by various genetic, epigenetic or non-genetic mechanisms. Recently, much attention has been focused on embryonic/fetal exposure to oestrogen-mimicking chemicals (Toppari et al., 1996). However, the possibility that chemicals may cause reproductive toxicity by other mechanisms such as interactions with DNA, should not be ignored. DNA damage in germ cells may lead to the production of mutated spermatozoa, which in turn may result in spontaneous abortions, malformations and/or genetic defects in the offspring. Regarding the consequences of DNA alterations for carcinogenesis it is possible that genetic damage may occur germ cells, but the consequences are not expressed until certain genetic events occur in postnatal life. Transmission of genetic risk is best demonstrated by cancer-prone disorders such as hereditary retinoblastoma and the Li-Fraumeni syndrome. A number of experiments indicate that germ cells and proliferating cells may be particularly sensitive to DNA damaging agents compared to other cells. Furthermore, several lines of evidence have indicated that one of the best documented male reproductive toxicants, 1,2-dibrome-3-chloropropane (DBCP), causes testicular toxicity through DNA damage. It is possible that testicular cells at certain maturational stages are more subject to DNA damage, have less efficient DNA repair, or have different thresholds for initiating apoptosis following DNA damage than other cell types. (orig.)

  12. Development of Brassica oleracea-nigra monosomic alien addition lines: genotypic, cytological and morphological analyses.

    Science.gov (United States)

    Tan, Chen; Cui, Cheng; Xiang, Yi; Ge, Xianhong; Li, Zaiyun

    2017-12-01

    We report the development and characterization of Brassica oleracea - nigra monosomic alien addition lines (MAALs) to dissect the Brassica B genome. Brassica nigra (2n = 16, BB) represents the diploid Brassica B genome which carries many useful genes and traits for breeding but received limited studies. To dissect the B genome from B. nigra, the triploid F 1 hybrid (2n = 26, CCB) obtained previously from the cross B. oleracea var. alboglabra (2n = 18, CC) × B. nigra was used as the maternal parent and backcrossed successively to parental B. oleracea. The progenies in BC 1 to BC 3 generations were analyzed by the methods of FISH and SSR markers to screen the monosomic alien addition lines (MAALs) with each of eight different B-genome chromosomes added to C genome (2n = 19, CC + 1B 1-8 ), and seven different MAALs were established, except for the one with chromosome B2 which existed in one triple addition. Most of these MAALs were distinguishable morphologically from each other, as they expressed the characters from B. nigra differently and at variable extents. The alien chromosome remained unpaired as a univalent in 86.24% pollen mother cells at diakinesis or metaphase I, and formed a trivalent with two C-genome chromosomes in 13.76% cells. Transmission frequency of all the added chromosomes was far higher through the ovules (averagely 14.40%) than the pollen (2.64%). The B1, B4 and B5 chromosomes were transmitted by female at much higher rates (22.38-30.00%) than the other four (B3, B6, B7, B8) (5.04-8.42%). The MAALs should be valuable for exploiting the genome structure and evolution of B. nigra.

  13. Development of an on-line radon monitoring apparatus and design of the on-line radon monitoring platform based on CAN bus

    International Nuclear Information System (INIS)

    Guo Huiping; Lu Ning; Shang Aiguo; Zhou Chunlin; Chen Yingfen; Yu Hongwei

    2004-12-01

    For actual demand, an idea of 'on-line monitoring' is put forward as a way of radon monitoring, instead of traditional so called 'off-line monitoring'. In this way, the apparatus has some automatic functions such as continuous monitoring, real-time alarm; thereby, there is no need for operators' intervention in each monitoring process. With technique of hardware and software design in automation's field, the authors have successfully developed the prototype and finished the scale of it in a standard radon-chamber. This apparatus is composed of detector part and secondary-instrument. The detector part is made up of a passive diffusion collecting chamber, high voltage static electricity, semiconductor detector, charge-sensitive preamplifier and forming circuit. The secondary-instrument is actually a micro-controller system, which consists of a single-chip micro-controller cored measure-controlling unit, display unit, printing unit and alarming unit. Taking this apparatus as a cell, a 'on-line Radon Monitoring Platform' based on CAN bus has been put forward, which can realize multi-points environmental radioactivity real-time monitoring radioactivity and data process. (authors)

  14. Nanotopography induced contact guidance of the F11 cell line during neuronal differentiation: a neuronal model cell line for tissue scaffold development

    International Nuclear Information System (INIS)

    Wieringa, Paul; Micera, Silvestro; Tonazzini, Ilaria; Cecchini, Marco

    2012-01-01

    The F11 hybridoma, a dorsal root ganglion-derived cell line, was used to investigate the response of nociceptive sensory neurons to nanotopographical guidance cues. This established this cell line as a model of peripheral sensory neuron growth for tissue scaffold design. Cells were seeded on substrates of cyclic olefin copolymer (COC) films imprinted via nanoimprint lithography (NIL) with a grating pattern of nano-scale grooves and ridges. Different ridge widths were employed to alter the focal adhesion formation, thereby changing the cell/substrate interaction. Differentiation was stimulated with forskolin in culture medium consisting of either 1 or 10% fetal bovine serum (FBS). Per medium condition, similar neurite alignment was achieved over the four day period, with the 1% serum condition exhibiting longer, more aligned neurites. Immunostaining for focal adhesions found the 1% FBS condition to also have fewer, less developed focal adhesions. The robust response of the F11 to guidance cues further builds on the utility of this cell line as a sensory neuron model, representing a useful tool to explore the design of regenerative guidance tissue scaffolds. (paper)

  15. Systems, methods and apparatus for developing and maintaining evolving systems with software product lines

    Science.gov (United States)

    Hinchey, Michael G. (Inventor); Rash, James L. (Inventor); Pena, Joaquin (Inventor)

    2011-01-01

    Systems, methods and apparatus are provided through which an evolutionary system is managed and viewed as a software product line. In some embodiments, the core architecture is a relatively unchanging part of the system, and each version of the system is viewed as a product from the product line. Each software product is generated from the core architecture with some agent-based additions. The result may be a multi-agent system software product line.

  16. Reduction of the number of germs in spices by radappertization

    International Nuclear Information System (INIS)

    Beczner, Laszlone; Kiss, Istvan

    1983-01-01

    The sterilization by fumigation with ethylene oxide and propylene oxide of ground paprika and spice mixtures used in preserves and meat industry was compared with the radappertization of the same spices. The number of germs including that of spores and moulds was determined. It can be established that irradiation with ionizing radiation (5 kGy) has the same effect on the reduction of the number of germs as sterilization by ethylene oxide. In addition, the side effects of sterilization can be avoided. (V.N.)

  17. Radiation-induced genetic effects in germ cells of mammals

    International Nuclear Information System (INIS)

    Van der Schans, G.P.

    1993-01-01

    The objectives of the project are a better understanding of the fundamental principles that determine the radiation sensitivity in humans, with specific attention for the role of DNA repair in germ cells. The induction and repair of damage in DNA of germ cells of the Syrian golden hamster exposed to ionizing radiation is studied at biologically relevant doses. It has also been investigated which aspects of DNA sequence or chromosomal organisation are important with respect to their influence on the repairability of DNA damage. (R.P.) 10 refs

  18. New developments in cognitive behavioral therapy as the first-line treatment of insomnia

    Directory of Open Access Journals (Sweden)

    Allison T Siebern

    2011-02-01

    Full Text Available Allison T Siebern, Rachel ManberSleep Medicine Center, Stanford University School of Medicine, Redwood City, California, USAAbstract: Insomnia is the most common sleep disorder. Psychological, behavioral, and biological factors are implicated in the development and maintenance of insomnia as a disorder, although the etiology of insomnia remains under investigation, as it is still not fully understood. Cognitive behavioral therapy for insomnia (CBTI is a treatment for insomnia that is grounded in the science of behavior change, psychological theories, and the science of sleep. There is strong empirical evidence that CBTI is effective. Recognition of CBTI as the first-line treatment for chronic insomnia (National Institutes of Health consensus, British Medical Association was based largely on evidence of its efficacy in primary insomnia. The aim of this article is to provide background information and review recent developments in CBTI, focusing on three domains: promising data on the use of CBTI when insomnia is experienced in the presence of comorbid conditions, new data on the use of CBTI as maintenance therapy, and emerging data on the delivery of CBTI through the use of technology and in primary care settings.Keywords: insomnia, CBTI, nonpharmacological treatment

  19. Development of on-line operator aid system (OASYSTM) for nuclear power plants

    International Nuclear Information System (INIS)

    Kang, Ki Sig; Choi, Seong Soo; Kim, Han Gon; Chang, Soon Heung; Jeong, Hee Kyo; Yi, Chul Un

    1994-01-01

    In this paper, the development of On - line operator Aid SYStem (OASYS TM ) are discussed by focusing attention on the importance of the operator's role for nuclear power plants. The OASYS TM is under development to support the operator's decision making process and to enhance the safety of a nuclear power plant by providing the plant operators with timely and proper guideline during abnormal and emergency conditions. The OASYS TM has capabilities for the signal validation/management, the alarm processing, the failure diagnosis using abnormal operating procedures, and the dynamic tracking of emergency operating procedures using function restoration guidelines and optimal recovery guidelines with a series of complex logic steps covering a broad spectrum of event sequences. The proposed system is being implemented on a SUN-4/75 Workstation using C and Quintus TM prolog language. For verification studies a full-scope real-time simulator is being used. Test results show that the OASYS TM is capable of diagnosing a plant failure quickly and providing an operator guideline with fast response time. After verification the OASYS TM will be installed in the simulator II of Kori nuclear training center

  20. Graded Approach to the Development of a Contingency Plan for On-Line Maintenance

    International Nuclear Information System (INIS)

    Chang, Hee Seung; Kim, Jung Wun; Song, Tae Young

    2012-01-01

    Many utilities perform preventive maintenance for safety systems during power operation to improve equipment reliability so as to focus on the work activities more easily and improve the quality of maintenance. Such a strategy can also reduce outage work activities, thus allowing resources to be utilized effectively. Preventive maintenance during power operation, known as on-line maintenance (OLM), requires an assessment and mitigation of risk, which can increase owing to out-of-service safety systems. One of the mitigation action plans is a contingency plan. EPRI recommends the development of a contingency plan for all planned system outages which include factors that strongly affect safety. The Korea Hydro and Nuclear Power Company (KHNP) undertook the preventive maintenance of the Essential Chilled Water System (ECWS) of a Westinghouse plant as a pilot OLM implementation. During the preparation of the work activities, a contingency plan was a pertinent issue during the discussions with regulators, especially regarding the scope and depth of the plan. This paper discusses the purpose of a contingency plan, including as examples some cases of US utilities, and proposes a graded approach to develop a contingency plan for OLM in consideration of the risks

  1. The Development of On-Line Statistics Program for Radiation Oncology

    International Nuclear Information System (INIS)

    Kim, Yoon Jong; Lee, Dong Hoon; Ji, Young Hoon; Lee, Dong Han; Jo, Chul Ku; Kim, Mi Sook; Ru, Sung Rul; Hong, Seung Hong

    2001-01-01

    Purpose : By developing on-line statistics program to record the information of radiation oncology to share the information with internet. It is possible to supply basic reference data for administrative plans to improve radiation oncology. Materials and methods : The information of radiation oncology statistics had been collected by paper forms about 52 hospitals in the past. Now, we can input the data by internet web browsers. The statistics program used windows NT 4.0 operation system, Internet Information Server 4.0 (IIS4.0) as a web server and the Microsoft Access MDB. We used Structured Query Language (SQL), Visual Basic, VBScript and JAVAScript to display the statistics according to years and hospitals. Results : This program shows present conditions about man power, research, therapy machines, technic, brachytherapy, clinic statistics, radiation safety management, institution, quality assurance and radioisotopes in radiation oncology department. The database consists of 38 inputs and 6 outputs windows. Statistical output windows can be increased continuously according to user need. Conclusion : We have developed statistics program to process all of the data in department of radiation oncology for reference information. Users easily could input the data by internet web browsers and share the information

  2. Mechanical design and development of analyzing magnet for the RIB charge breeder beam line

    International Nuclear Information System (INIS)

    Bhattacharyya, Pranab; Ghosh, Sundeep; Bhattacharya, Mahuwa; Gupta, Anjan Dutta; Pal, Gautam; Naik, Vaishali

    2015-01-01

    An iron dominated analyzing magnet of uniform peak field 0.6 T has been developed for Radioactive Ion Beam (RIB) charge breeder beam line at VECC, Kolkata. It has two room temperature coils made of copper having channels for passage of cooling water. The other important parts of the magnet includes two yokes, two poles, vacuum chamber, view port, iron plates and the support structures. The most important properties of magnets designed and fabricated for this application is the need for high field quality. The magnet assembly has got overall dimensions of 1.1 metres x 0.91 metres x 0.63 metres and the required field uniformity is 6 x 10 -4 over pole width of ± 2.5 cm. The most critical parameter that has to be maintained to achieve the desired magnetic field is the pole gap of 80 ± 0.25 rom.This paper describes in detail about the mechanical design, coil cooling analysis, development and assembly of this magnet. (author)

  3. On-Line GIS Analysis and Image Processing for Geoportal Kielce/poland Development

    Science.gov (United States)

    Hejmanowska, B.; Głowienka, E.; Florek-Paszkowski, R.

    2016-06-01

    GIS databases are widely available on the Internet, but mainly for visualization with limited functionality; very simple queries are possible i.e. attribute query, coordinate readout, line and area measurements or pathfinder. A little more complex analysis (i.e. buffering or intersection) are rare offered. Paper aims at the concept of Geoportal functionality development in the field of GIS analysis. Multi-Criteria Evaluation (MCE) is planned to be implemented in web application. OGC Service is used for data acquisition from the server and results visualization. Advanced GIS analysis is planned in PostGIS and Python programming. In the paper an example of MCE analysis basing on Geoportal Kielce is presented. Other field where Geoportal can be developed is implementation of processing new available satellite images free of charge (Sentinel-2, Landsat 8, ASTER, WV-2). Now we are witnessing a revolution in access to the satellite imagery without charge. This should result in an increase of interest in the use of these data in various fields by a larger number of users, not necessarily specialists in remote sensing. Therefore, it seems reasonable to expand the functionality of Internet's tools for data processing by non-specialists, by automating data collection and prepared predefined analysis.

  4. Overcoming inter-subspecific hybrid sterility in rice by developing indica-compatible japonica lines.

    Science.gov (United States)

    Guo, Jie; Xu, Xiaomei; Li, Wentao; Zhu, Wenyin; Zhu, Haitao; Liu, Ziqiang; Luan, Xin; Dai, Ziju; Liu, Guifu; Zhang, Zemin; Zeng, Ruizhen; Tang, Guang; Fu, Xuelin; Wang, Shaokui; Zhang, Guiquan

    2016-06-01

    Rice (Oryza sativa L.) is an important staple crop. The exploitation of the great heterosis that exists in the inter-subspecific crosses between the indica and japonica rice has long been considered as a promising way to increase the yield potential. However, the male and female sterility frequently occurred in the inter-subspecific hybrids hampered the utilization of the heterosis. Here we report that the inter-subspecific hybrid sterility in rice is mainly affected by the genes at Sb, Sc, Sd and Se loci for F1 male sterility and the gene at S5 locus for F1 female sterility. The indica-compatible japonica lines (ICJLs) developed by pyramiding the indica allele (S-i) at Sb, Sc, Sd and Se loci and the neutral allele (S-n) at S5 locus in japonica genetic background through marker-assisted selection are compatible with indica rice in pollen fertility and in spikelet fertility. These results showed a great promise of overcoming the inter-subspecific hybrid sterility and exploiting the heterosis by developing ICJLs.

  5. ON-LINE GIS ANALYSIS AND IMAGE PROCESSING FOR GEOPORTAL KIELCE/POLAND DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    B. Hejmanowska

    2016-06-01

    Full Text Available GIS databases are widely available on the Internet, but mainly for visualization with limited functionality; very simple queries are possible i.e. attribute query, coordinate readout, line and area measurements or pathfinder. A little more complex analysis (i.e. buffering or intersection are rare offered. Paper aims at the concept of Geoportal functionality development in the field of GIS analysis. Multi-Criteria Evaluation (MCE is planned to be implemented in web application. OGC Service is used for data acquisition from the server and results visualization. Advanced GIS analysis is planned in PostGIS and Python programming. In the paper an example of MCE analysis basing on Geoportal Kielce is presented. Other field where Geoportal can be developed is implementation of processing new available satellite images free of charge (Sentinel-2, Landsat 8, ASTER, WV-2. Now we are witnessing a revolution in access to the satellite imagery without charge. This should result in an increase of interest in the use of these data in various fields by a larger number of users, not necessarily specialists in remote sensing. Therefore, it seems reasonable to expand the functionality of Internet's tools for data processing by non-specialists, by automating data collection and prepared predefined analysis.

  6. Bringing home sustainability and climate change research and developments via on-line virtual reality

    Science.gov (United States)

    Granshaw, F. D.

    2016-12-01

    One of the key challenges of sustainability and climate education is one of accessibility. For example many of the sites where significant climate research is taking place in National Parks are largely inaccessible to the average park visitor. Likewise, taking students to visit exemplary efforts in environmentally sustainable design or habitat restoration projects may be logistically difficult or impossible for the average class. Yet despite these difficulties, finding ways to give students, park visitors, and the general public a chance to explore these areas is critical to their developing sustainability and climate literacy. To address this issue, the author has been working with National Park staff and community groups to develop desktop virtual reality environments that showcase glacier-climate research sites, developments designed with environmental sustainability in mind, and urban watersheds being rehabilitated by volunteer groups and public agencies. These environments provide the user with a chance to take a virtual walk through a site of interest, access data collected at the site, and even listen to researchers and site stewards talk about key activities taking place there. Though they are used as proxies for actual visits via independent on-line exploration, media for public talks, or the framework for student lab exercises, they these virtual environments have also been used to encourage and guide actual sites visits. A focus of this talk will be a recently launched project involving the construction of a library showcasing environmental sustainability projects in the Portland Metropolitan area. In addition to being a resource for local sustainability educators, the library will be a contribution to international sustainability education efforts as it is being developed under the umbrella of a UN affiliate (Greater Portland Sustainability Education Network).

  7. Establishment of cell lines with rat spermatogonial stem cell characteristics

    NARCIS (Netherlands)

    van Pelt, Ans M. M.; Roepers-Gajadien, Hermien L.; Gademan, Iris S.; Creemers, Laura B.; de Rooij, Dirk G.; van Dissel-Emiliani, Federica M. F.

    2002-01-01

    Spermatogonial cell lines were established by transfecting a mixed population of purified rat A(s) (stem cells), A(pr) and A(al) spermatogonia with SV40 large T antigen. Two cell lines were characterized and found to express Hsp90alpha and oct-4, specific markers for germ cells and A spermatogonia,

  8. Derivation of the human embryonic stem cell line RCM1

    Directory of Open Access Journals (Sweden)

    P.A. De Sousa

    2016-03-01

    Full Text Available The human embryonic stem cell line RCM-1 was derived from a failed to fertilise egg undergoing parthenogenetic stimulation. The cell line shows normal pluripotency marker expression and differentiation to three germ layers in vitro and in vivo. It has a normal 46XX female karyotype and microsatellite PCR identity, HLA and blood group typing data is available.

  9. Radiation induced mutation to develop dwarf and precocious lines of papaya

    International Nuclear Information System (INIS)

    Singh, K.; Prakash, Jai; Goswami, A.K.

    2014-01-01

    Papaya (Carica papaya L.) is one of the most important fruit cultivated throughout the tropical and subtropical regions of the country. Almost all the varieties of papaya developed either through selection or hybridization. As regards mutation breeding, very little work has been done in India. Only one variety PusaNanha has been developed through mutation breeding by treating the seed of papaya strain Pusa 1-15 with 15 Kr gamma rays. Mutation breeding is the most appropriate for improving one or two easily identifiable traits in an otherwise well accepted breeding lines or commercial variety. Dwarfness and earliness in flowering are important traits in high density planting as breeding objective for improving papaya varieties for high yield with medium size fruits and good fruit quality. With these objectives, seeds of the papaya P 7-2 were treated with gamma rays 0.1, 0.15, 0.2, 0.25 and 0.3 kGy. The control recorded maximum germination (68%). Among the other treatments maximum germination (64.25%) was recorded at 0.1 kGy. The germination percentage was observed to be least (45%) at 0.3 kGy. Minimum length of seedlings (8.5 cm) and diameter (3.92 mm) was recorded in treatment 0.1 kGy while maximum length (19.2 cm) and diameter (6.26 mm) was recorded in treatment 0.3 kGy after 30 days of sowing. Minimum height of the plant (79.24 cm) was recorded in treatment 0.1 kGy while maximum (112.20) in control. Minimum plant girth (33.40 cm) was measured in 0.3 kGy while maximum (44.34 cm) in 0.15 kGy treatment. Minimum height at first flower initiation (55.28 cm), days to flower initiation (78.28) and length of petiole (60.45 cm) was noted in treatment 0.1 kGy while maximum height at first flower initiation (78.2 cm), days to flower initiation (87.46) and length of petiole (68.24 cm) was found in control. Among treatments, maximum number (18) of fruit was counted in 0.3 kGy treatment while maximum weight of fruit (750 g) was recorded in control. Maximum TSS (10.6 °Brix) in

  10. Formation of the hindgut cuticular lining during embryonic development of Porcellio scaber (Crustacea, Isopoda

    Directory of Open Access Journals (Sweden)

    Polona Mrak

    2015-07-01

    Full Text Available The hindgut and foregut in terrestrial isopod crustaceans are ectodermal parts of the digestive system and are lined by cuticle, an apical extracellular matrix secreted by epithelial cells. Morphogenesis of the digestive system was reported in previous studies, but differentiation of the gut cuticle was not followed in detail. This study is focused on ultrastructural analyses of hindgut apical matrices and cuticle in selected intramarsupial developmental stages of the terrestrial isopod Porcellio scaber in comparison to adult animals to obtain data on the hindgut cuticular lining differentiation. Our results show that in late embryos of stages 16 and 18 the apical matrix in the hindgut consists of loose material overlaid by a thin intensely ruffled electron dense lamina facing the lumen. The ultrastructural resemblance to the embryonic epidermal matrices described in several arthropods suggests a common principle in chitinous matrix differentiation. The hindgut matrix in the prehatching embryo of stage 19 shows characteristics of the hindgut cuticle, specifically alignment to the apical epithelial surface and a prominent electron dense layer of epicuticle. In the preceding embryonic stage – stage 18 – an electron dense lamina, closely apposed to the apical cell membrane, is evident and is considered as the first epicuticle formation. In marsupial mancae the advanced features of the hindgut cuticle and epithelium are evident: a more prominent epicuticular layer, formation of cuticular spines and an extensive apical labyrinth. In comparison to the hindgut cuticle of adults, the hindgut cuticle of marsupial manca and in particular the electron dense epicuticular layer are much thinner and the difference between cuticle architecture in the anterior chamber and in the papillate region is not yet distinguishable. Differences from the hindgut cuticle in adults imply not fully developed structure and function of the hindgut cuticle in marsupial

  11. Development of Fibroblast Cell Lines From the Cow Used to Sequence the Bovine Genome

    Science.gov (United States)

    Two cell lines, designated MARC.BGCF.2 and MARC.BGCF.1-3, were initiated from skin biopsies obtained from the Hereford cow whose DNA was used in sequencing the bovine genome. These cell lines were submitted to American Type Culture Collection (ATCC, Manassas, VA, USA) and will be made publicly avai...

  12. Development of a non-delay-line constant-fraction discriminator

    International Nuclear Information System (INIS)

    Yang Tao; Zhao Bo; Zhang Chi

    2002-01-01

    A Non-Delay-Line Constant-Fraction Discriminator (CFD) timing circuit is introduced. The delay line in the CFD is replaced with a low pass filter in this simplified circuit. The timing resolution of the CFD is better than 150 ps

  13. Recent Developments in On-Line Assessment of Steel Strip Properties

    International Nuclear Information System (INIS)

    Meilland, P.; Kroos, J.; Buchholtz, O. W.; Hartmann, H.-J.

    2006-01-01

    On-line non-destructive assessment of steel strip properties is a subject of growing interest amongst European manufacturers, as it provides information all along the products length, without slowing down the production. Arcelor, Salzgitter and TKS recently undertook a collective effort to assess the performance of 3 systems for flat carbon steel strips mechanical properties at the exit of galvanizing lines

  14. PERSPECTIVES OF UKRAINIAN RAILWAY TOURISM DEVELOPMENT ON NARROW-GAUGE LINES OF ZAKARPATTIA

    Directory of Open Access Journals (Sweden)

    V. G. Kuznetsov

    2015-07-01

    Full Text Available Purpose.The purpose of the paper is: (1 the definition of perspectives development of Ukrainian railway tourism on the narrow gauge lines of Zakarpattia; 2 technical condition analysis of Borzhava narrow gauge railway for the project to restore the effective functioning of mountain railways track, width 750 mm in the Carpathian region, with the possibility of their accession to the distributed travel network; 3 the study of the modern state and tendencies of development of tourist industry of Ukraine and the passenger economy of national railways; 4 clarification of the role and place of the railway tourism in the transportation system. Methodology. The expert group has carried out field inspections and field investigations of facilities track facilities and passenger infrastructure, rolling stock and ancillary industries involved in the functioning narrow-gauge railway. It was estimated the overall technical condition of the railway track and engineering structures section of narrow-gauge Railways in the Carpathian region. Findings. In the framework of on-site examinations of the expert group found that the objects of tracks, passenger and freight infrastructure, rolling stock and ancillary industries involved in the operation of narrow-gauge Railways are in poor condition and require significant updates and major repairs. But the routes of passenger trains remain fit for participation in the project of development of railway tourism of Ukraine Originality. For the first time the state of the narrow-gauge railway for further implementation of the project on the development of rail tourism in Ukraine was realized. The analysis of foreign experience of organization of railway tourism has been carried out. The modern state and tendencies of development of tourist industry of Ukraine was studied, the factors of competitiveness of rail transport for providing tourist transport in Ukraine were identified and systematized.Practical value. The recovery

  15. Developmental plasticity of bacterial colonies and consortia in germ-free and gnotobiotic settings

    Directory of Open Access Journals (Sweden)

    Pátková Irena

    2012-08-01

    Full Text Available Abstract Background Bacteria grown on semi-solid media can build two types of multicellular structures, depending on the circumstances. Bodies (colonies arise when a single clone is grown axenically (germ-free, whereas multispecies chimeric consortia contain monoclonal microcolonies of participants. Growth of an axenic colony, mutual interactions of colonies, and negotiation of the morphospace in consortial ecosystems are results of intricate regulatory and metabolic networks. Multicellular structures developed by Serratia sp. are characteristically shaped and colored, forming patterns that reflect their growth conditions (in particular medium composition and the presence of other bacteria. Results Building on our previous work, we developed a model system for studying ontogeny of multicellular bacterial structures formed by five Serratia sp. morphotypes of two species grown in either "germ-free" or "gnotobiotic" settings (i.e. in the presence of bacteria of other conspecific morphotype, other Serratia species, or E. coli. Monoclonal bodies show regular and reproducible macroscopic appearance of the colony, as well as microscopic pattern of its growing margin. Standard development can be modified in a characteristic and reproducible manner in close vicinity of other bacterial structures (or in the presence of their products. Encounters of colonies with neighbors of a different morphotype or species reveal relationships of dominance, cooperation, or submission; multiple interactions can be summarized in "rock – paper – scissors" network of interrelationships. Chimerical (mixed plantings consisting of two morphotypes usually produced a “consortium” whose structure is consistent with the model derived from interaction patterns observed in colonies. Conclusions Our results suggest that development of a bacterial colony can be considered analogous to embryogenesis in animals, plants, or fungi: to proceed, early stages require thorough

  16. A Small RNA-Based Immune System Defends Germ Cells against Mobile Genetic Elements

    Directory of Open Access Journals (Sweden)

    Astrid D. Haase

    2016-01-01

    Full Text Available Transposons are mobile genetic elements that threaten the survival of species by destabilizing the germline genomes. Limiting the spread of these selfish elements is imperative. Germ cells employ specialized small regulatory RNA pathways to restrain transposon activity. PIWI proteins and Piwi-interacting RNAs (piRNAs silence transposons at the transcriptional and posttranscriptional level with loss-of-function mutant animals universally exhibiting sterility often associated with germ cell defects. This short review aims to illustrate basic strategies of piRNA-guided defense against transposons. Mechanisms of piRNA silencing are most readily studied in Drosophila melanogaster, which serves as a model to delineate molecular concepts and as a reference for mammalian piRNA systems. PiRNA pathways utilize two major strategies to handle the challenges of transposon control: (1 the hard-wired molecular memory of prior transpositions enables recognition of mobile genetic elements and discriminates transposons from host genes; (2 a feed-forward adaptation mechanism shapes piRNA populations to selectively combat the immediate threat of transposon transcripts. In flies, maternally contributed PIWI-piRNA complexes bolster both of these lines of defense and ensure transgenerational immunity. While recent studies have provided a conceptual framework of what could be viewed as an ancient immune system, we are just beginning to appreciate its many molecular innovations.

  17. File list: Oth.Gon.20.AllAg.Testicular_germ_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Gon.20.AllAg.Testicular_germ_cells mm9 TFs and others Gonad Testicular germ cel...ls http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Gon.20.AllAg.Testicular_germ_cells.bed ...

  18. File list: Oth.Gon.10.AllAg.Testicular_germ_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Gon.10.AllAg.Testicular_germ_cells mm9 TFs and others Gonad Testicular germ cel...ls http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Gon.10.AllAg.Testicular_germ_cells.bed ...

  19. File list: Pol.Gon.05.AllAg.Testicular_germ_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Gon.05.AllAg.Testicular_germ_cells mm9 RNA polymerase Gonad Testicular germ cel...ls http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Gon.05.AllAg.Testicular_germ_cells.bed ...

  20. File list: DNS.Gon.05.AllAg.Testicular_germ_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Gon.05.AllAg.Testicular_germ_cells mm9 DNase-seq Gonad Testicular germ cells ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Gon.05.AllAg.Testicular_germ_cells.bed ...

  1. Adult Immunohistochemical Markers Fail to Detect Intratubular Germ Cell Neoplasia in Prepubertal Boys with Cryptorchidism

    DEFF Research Database (Denmark)

    Kvist, Kolja; Clasen-Linde, Erik; Cortes, Dina

    2013-01-01

    Intratubular germ cell neoplasia (ITGCN) is a precursor to testicular germ cell cancer. It is characterized by large germ cells with large nuclei with a hyperchromatic, coarse chromatin pattern, large prominent nucleoli and abundant pale cytoplasm. In prepubertal boys these cells are located both...

  2. ALTERATIONS IN THE DEVELOPING TESTIS TRANSCRIPTOME FOLLOWING EMBRYONIC VINCLOZOLIN EXPOSURE

    OpenAIRE

    Clement, Tracy M.; Savenkova, Marina I.; Settles, Matthew; Anway, Matthew D.; Skinner, Michael K.

    2010-01-01

    The current study investigates the direct effects of in utero vinclozolin exposure on the developing F1 generation rat testis transcriptome. Previous studies have demonstrated that exposure to vinclozolin during embryonic gonadal sex determination induces epigenetic modifications of the germ line and transgenerational adult onset disease states. Microarray analyses were performed to compare control and vinclozolin treated testis transcriptomes at embryonic day 13, 14 and 16. A total of 576 di...

  3. Development and calibration of an on-line aerosol monitor for PHEBUS test FPT1

    International Nuclear Information System (INIS)

    O'Brien, J.E.; Carmack, W.J.; Sprenger, M.H.; Thurston, G.C.; Hunt, J.L.

    1994-10-01

    An on-line aerosol monitor (OLAM2) has been developed and tested for PHEBUS test FPT1. OLAM2 utilizes new detachable fiber optic cables and sapphire light pipes for light transmission between the OLAM and the electronics. This light transmission system was tested and found to provide better signal-to-noise performance than was achieved with the continuous fibers used for test FPT0. An additional advantage of the detachable fiber/light pipe system is ease of installation. Aerosol testing (OLAM calibration) was performed in order to verify adequate signal-to-noise performance of the new fiber optic system over the specified operating conditions and to check the quantitative light attenuation measurements against theoretical predictions. Results of the testing indicated that light extinction measurements obtained during Phebus tests could be used to estimate aerosol volume concentrations, if diamond window fouling can be avoided. OLAM2 was also subjected to a proof pressure test and a long-term thermal stability test. These tests verified the mechanical and thermal integrity of the OLAM within design specifications. Long-term output signal stability was also verified with the system maintained at design temperature and half-design pressure

  4. Development of an Evaluation Methodology for Triple Bottom Line Reports Using International Standards on Reporting

    Science.gov (United States)

    Skouloudis, Antonis; Evangelinos, Konstantinos; Kourmousis, Fotis

    2009-08-01

    The purpose of this article is twofold. First, evaluation scoring systems for triple bottom line (TBL) reports to date are examined and potential methodological weaknesses and problems are highlighted. In this context, a new assessment methodology is presented based explicitly on the most widely acknowledged standard on non-financial reporting worldwide, the Global Reporting Initiative (GRI) guidelines. The set of GRI topics and performance indicators was converted into scoring criteria while the generic scoring devise was set from 0 to 4 points. Secondly, the proposed benchmark tool was applied to the TBL reports published by Greek companies. Results reveal major gaps in reporting practices, stressing the need for the further development of internal systems and processes in order to collect essential non-financial performance data. A critical overview of the structure and rationale of the evaluation tool in conjunction with the Greek case study is discussed while recommendations for future research on the field of this relatively new form of reporting are suggested.

  5. New developments in velocity profile measurement and pipe wall wear monitoring for hydrotransport lines

    Energy Technology Data Exchange (ETDEWEB)

    O' Keefe, C.; Maron, R.J. [CiDRA Minerals Processing Inc., Wallingford, CT (United States); Fernald, M.; Bailey, T. [CiDRA Corporate Services, Wallingford, CT (United States); Van der Spek, A. [ZDOOR, Rotterdam (Netherlands)

    2009-07-01

    Sonar array flow measurement technology was initially developed a decade ago with the goal of non-invasively measuring multi-phase flows in the petroleum industry. The same technology was later adapted to the mineral processing industry where it has been rapidly adopted. The specific sensor technology, based on piezoelectric film sensors, provides unique measurement capabilities, including the ability to non-invasively measure localized strains in the walls of pipes. Combined with sonar array processing algorithms, an axial array of such sensors can measure flow velocities within a pipe. The sensors are useful for monitoring and managing slurry flow in horizontal pipes since they provide real-time velocity profiles measurement. The information is useful in determining the approach and onset of solid deposition on the bottom of the pipe. The sensors also provide a non-invasive measurement of pipe wear on slurry lines. Such measurements are currently made by hand-held portable ultrasonic thickness gages. The shortfalls associated with this manual method are overcome with a set of permanently or semi-permanently installed transducers clamped onto the outside of the pipe, where sensors measure the thickness of the pipe. This system and approach results in better repeatability and accuracy compared to manual methods. It also decreases inspection labor costs and pipe access requirements. It was concluded that the potential impact on personnel safety and environmental savings will be significant. 3 refs., 20 figs.

  6. Development of on-line core performance evaluation system for 'FUGEN'

    International Nuclear Information System (INIS)

    Natori, Hisahide; Kaneto, Kunikazu; Oteru, Shigeru.

    1982-01-01

    An on-line core performance evaluation system ATROPOS has been developed in order to carry out safe and efficient reactor operation of ''FUGEN''(a heavy water moderated, boiling light water cooled, pressure tube type reactor). This system offers detailed and useful information on such items of core performance as core thermal power, power distribution and thermal operation limits. The power distribution is calculated first by using a three-dimensional nodal coupling model, employing such process data as control rod position and 10 B concentration in the D 2 O moderator. Then the calculated power distribution is corrected by local power monitor readings. An axial one-dimensional nodal coupling model, which considers radial power distribution, and a localized three-dimensional nodal coupling model are used to predict the core thermal power and the power distribution for the region surrounding the control rods respectively, within a short time in advance of control rod operation. The methods employed in this system are verified by comparison with start-up test data from the FUGEN initial core. The estimated power distribution and channel flow agree with values measured by the power calibration monitor and with channel flow converted from measured values of pressure drop, within 3 and 5% respectively, in their root mean square values. The difference in core thermal power between the predicted value and the value measured by the total power monitor is about 1% for control rod operation. (author)

  7. Development of an evaluation methodology for triple bottom line reports using international standards on reporting.

    Science.gov (United States)

    Skouloudis, Antonis; Evangelinos, Konstantinos; Kourmousis, Fotis

    2009-08-01

    The purpose of this article is twofold. First, evaluation scoring systems for triple bottom line (TBL) reports to date are examined and potential methodological weaknesses and problems are highlighted. In this context, a new assessment methodology is presented based explicitly on the most widely acknowledged standard on non-financial reporting worldwide, the Global Reporting Initiative (GRI) guidelines. The set of GRI topics and performance indicators was converted into scoring criteria while the generic scoring devise was set from 0 to 4 points. Secondly, the proposed benchmark tool was applied to the TBL reports published by Greek companies. Results reveal major gaps in reporting practices, stressing the need for the further development of internal systems and processes in order to collect essential non-financial performance data. A critical overview of the structure and rationale of the evaluation tool in conjunction with the Greek case study is discussed while recommendations for future research on the field of this relatively new form of reporting are suggested.

  8. Effect of mulching systems on fruit quality and phytochemical composition of newly developed strawberry lines

    Directory of Open Access Journals (Sweden)

    Li Fan

    2012-06-01

    Full Text Available The effects of three mulching systems on total yield, average yield per plant, average fruit weight, soluble solids content (SSC, titratable acidity (TA, firmness and oxygen radical absorbance capacity (ORAC of two newly developed lines (‘Orléans’ and ‘Saint Pierre’, one advanced selection (‘SJ8976-1’ and two commonly used cultivars (‘Jewel’ and ‘Kent’ were evaluated. The studied mulching systems were: plastic mulch (PM, mulch with row cover (PMRC, and matted-row system (MRS. Results showed that plastic mulch with row cover (PMRC generally increased yield per plant, average fruit weight, SSC, firmness and ORAC, but differences varied within harvest times. No significant differences in total yield and TA were observed under the selected mulching systems. Both PMRC and PM accelerated the harvest periods compared to MRS. ‘Kent’ and ‘Jewel’ had the highest total yield while ‘SJ8976-1’ and ‘St-Pierre’ had the highest average fruit weight. The highest SSC, TA and ORAC were found in ‘Jewel’. There was no interaction between the mulching systems and genotypes, indicating that the effect of production system is independent of cultivars. PMRC seems to be a better growing system, improving fruit quality and increasing the nutritional value of all genotypes. By allowing off-season fruit production in cool climates, PMRC can be an alternative method to the costly high tunnels.

  9. Stability of wheat germ oil obtained by supercritical carbon dioxide ...

    African Journals Online (AJOL)

    심정은

    For determination of stability, wheat germ oil obtained by ethanolysis reactants was characterized by ... extract non polar lipids with lipid soluble bioactive com- pounds from different sources (Esquivel et al., 1997; ... thin layer of cotton was placed at the bottom of the extraction vessel. Before plugging with cap another layer of ...

  10. Genetic analysis of neonatal and infantile germ cell tumours.

    NARCIS (Netherlands)

    Veltman, I.M.

    2006-01-01

    Human germ cell tumours (GCTs) can be classified into five distinct types, based on differences in anatomical location, histology, clinical outcome, age and genotype. The first type, the type I GCTs primarily occur in neonates and infants under the age of five years and include teratomas and yolk

  11. Germ cell tumours in neonates and infants: a distinct subgroup?

    NARCIS (Netherlands)

    Veltman, I.M.; Schepens, M.T.M.; Looijenga, L.H.J.; Strong, L.C.; Geurts van Kessel, A.H.M.

    2003-01-01

    Human germ cell tumours (GCTs) constitute a heterogeneous group of tumours that can be classified into four major subgroups. One of these subgroups encompasses (immature) teratomas and yolk sac tumours of patients under the age of 5 years. In this paper we review the various clinical, histological

  12. Mutability of germ cells of descedants of irradiated drosophila males

    International Nuclear Information System (INIS)

    Fokina, T.L.; Vorobtsova, I.E.

    1987-01-01

    The increased frequency of random and radiation-induced mutation was registered in germ cells of drosophila irradiated male descendants of the first generation. The effect observed depended on of radiation dose delivered to parent males, test dose to posterity, type of mutation registered, and sex of the descendants under study

  13. Treatment Options for Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... tumors: Yolk sac tumors make a hormone called alpha-fetoprotein (AFP). They can form in the ovary, testicle, ... are used to detect extracranial germ cell tumors: Alpha-fetoprotein (AFP). Beta-human chorionic gonadotropin (β-hCG). For ...

  14. General Information about Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... tumors: Yolk sac tumors make a hormone called alpha-fetoprotein (AFP). They can form in the ovary, testicle, ... are used to detect extracranial germ cell tumors: Alpha-fetoprotein (AFP). Beta-human chorionic gonadotropin (β-hCG). For ...

  15. Dynamics of germs responsible for acute bacterial meningitis in ...

    African Journals Online (AJOL)

    The aim of this study was to analyze ten (10) years of epidemiological surveillance data of meningitis in Burkina Faso for high risk germs patterns identification in order to contribute to the strengthening of prevention strategies. A retrospective study of the past decade (2005- 2014) of cases of acute bacterial meningitis ...

  16. 10 original article dynamics of germs responsible for acute bacterial ...

    African Journals Online (AJOL)

    boaz

    The aim of this study was to analyze ten (10) years of epidemiological surveillance data of meningitis in Burkina Faso for high risk germs patterns identification in order to contribute to the strengthening of prevention strategies. A retrospective study of the past decade (2005- 2014) of cases of acute bacterial meningitis ...

  17. Wheat Germ Oil Attenuates Gamma Radiation-Induced Skeletal ...

    African Journals Online (AJOL)

    Muscular strength is important in sport as well as in daily activities. Exposure to ionizing radiation is thought to increase oxidative stress and damage muscle tissue. Wheat germ oil is a natural unrefined vegetable oil. It is an excellent source of vitamin E, octacosanol, linoleic and linolenic essential fatty acids, which may be ...

  18. Towards Optimal Diagnosis of Type II Germ Cell Tumors

    NARCIS (Netherlands)

    J.A. Stoop (Hans)

    2011-01-01

    textabstractThe aim of the work described in this thesis is to improve the understanding of the pathobiology of testicular cancer (type II Germ Cell Tumors) to create possibilities for optimalization of diagnosis for this type of malignancy in routine pathology laboratories. The different studies

  19. Clinical and genetic aspects of testicular germ cell tumours

    NARCIS (Netherlands)

    Holzik, Martijn F. Lutke; Sijmons, Rolf H.; Hoekstra-Weebers, Josette E. H. M.; Sleijfer, Dirk Th.; Hoekstra, Harald J.

    2008-01-01

    In this paper we review clinical and genetic aspects of testicular germ cell tumours (TGCTs). TGCT is the most common type of malignant disorder in men aged 15-40 years. Its incidence has increased sharply in recent years. Fortunately, survival of patients with TGCT has improved enormously, which

  20. A comparison between hominy chop and defatted maize germ meal ...

    African Journals Online (AJOL)

    Defatted maize germ meal (DMG) is arbitrarily rated at a lower economic value than maize meal or hominy chop (HC). Five treatments with 15 steers each were fed different inclusion levels of DMG (0%, 25%, 50%, 75% and 100%), replacing hominy chop during the fattening period. Slaughter data were collected for carcass ...