Sample records for factor lin28 marks

  1. Lin28 sustains early renal progenitors and induces Wilms tumor

    PubMed Central

    Urbach, Achia; Yermalovich, Alena; Zhang, Jin; Spina, Catherine S.; Zhu, Hao; Perez-Atayde, Antonio R.; Shukrun, Rachel; Charlton, Jocelyn; Sebire, Neil; Mifsud, William; Dekel, Benjamin; Pritchard-Jones, Kathy; Daley, George Q.

    2014-01-01

    Wilms Tumor, the most common pediatric kidney cancer, evolves from the failure of terminal differentiation of the embryonic kidney. Here we show that overexpression of the heterochronic regulator Lin28 during kidney development in mice markedly expands nephrogenic progenitors by blocking their final wave of differentiation, ultimately resulting in a pathology highly reminiscent of Wilms tumor. Using lineage-specific promoters to target Lin28 to specific cell types, we observed Wilms tumor only when Lin28 is aberrantly expressed in multiple derivatives of the intermediate mesoderm, implicating the cell of origin as a multipotential renal progenitor. We show that withdrawal of Lin28 expression reverts tumorigenesis and markedly expands the numbers of glomerulus-like structures and that tumor formation is suppressed by enforced expression of Let-7 microRNA. Finally, we demonstrate overexpression of the LIN28B paralog in a significant percentage of human Wilms tumor. Our data thus implicate the Lin28/Let-7 pathway in kidney development and tumorigenesis. PMID:24732380

  2. Importance of the pluripotency factor LIN28 in the mammalian nucleolus during early embryonic development.

    PubMed

    Vogt, Edgar J; Meglicki, Maciej; Hartung, Kristina Ilka; Borsuk, Ewa; Behr, Rüdiger

    2012-12-01

    The maternal nucleolus is required for proper activation of the embryonic genome (EGA) and early embryonic development. Nucleologenesis is characterized by the transformation of a nucleolar precursor body (NPB) to a mature nucleolus during preimplantation development. However, the function of NPBs and the involved molecular factors are unknown. We uncover a novel role for the pluripotency factor LIN28, the biological significance of which was previously demonstrated in the reprogramming of human somatic cells to induced pluripotent stem (iPS) cells. Here, we show that LIN28 accumulates at the NPB and the mature nucleolus in mouse preimplantation embryos and embryonic stem cells (ESCs), where it colocalizes with the nucleolar marker B23 (nucleophosmin 1). LIN28 has nucleolar localization in non-human primate (NHP) preimplantation embryos, but is cytoplasmic in NHP ESCs. Lin28 transcripts show a striking decline before mouse EGA, whereas LIN28 protein localizes to NPBs at the time of EGA. Following knockdown with a Lin28 morpholino, the majority of embryos arrest between the 2- and 4-cell stages and never develop to morula or blastocyst. Lin28 morpholino-injected embryos arrested at the 2-cell stage were not enriched with nucleophosmin at presumptive NPB sites, indicating that functional NPBs were not assembled. Based on these results, we propose that LIN28 is an essential factor of nucleologenesis during early embryonic development.

  3. MYCN-driven regulatory mechanisms controlling LIN28B in neuroblastoma

    PubMed Central

    Beckers, Anneleen; Van Peer, Gert; Carter, Daniel R.; Gartlgruber, Moritz; Herrmann, Carl; Agarwal, Saurabh; Helsmoortel, Hetty H.; Althoff, Kristina; Molenaar, Jan J.; Cheung, Belamy B.; Schulte, Johannes H.; Benoit, Yves; Shohet, Jason M.; Westermann, Frank; Marshall, Glenn M.; Vandesompele, Jo; De Preter, Katleen; Speleman, Frank

    2016-01-01

    LIN28B has been identified as an oncogene in various tumor entities, including neuroblastoma, a childhood cancer that originates from neural crest-derived cells, and is characterized by amplification of the MYCN oncogene. Recently, elevated LIN28B expression levels were shown to contribute to neuroblastoma tumorigenesis via let-7 dependent de-repression of MYCN. However, additional insight in the regulation of LIN28B in neuroblastoma is lacking. Therefore, we have performed a comprehensive analysis of the regulation of LIN28B in neuroblastoma, with a specific focus on the contribution of miRNAs. We show that MYCN regulates LIN28B expression in neuroblastoma tumors via two distinct parallel mechanisms. First, through an unbiased LIN28B-3′UTR reporter screen, we found that miR-26a-5p and miR-26b-5p regulate LIN28B expression. Next, we demonstrated that MYCN indirectly affects the expression of miR-26a-5p, and hence regulates LIN28B, therefor establishing a MYCN-miR-26a-5p-LIN28B regulatory axis. Second, we provide evidence that MYCN regulates LIN28B expression via interaction with the LIN28B promotor, establishing a direct MYCN-LIN28B regulatory axis. We believe that these findings mark LIN28B as an important effector of the MYCN oncogenic phenotype and underlines the importance of MYCN-regulated miRNAs in establishing the MYCN-driven oncogenic process. PMID:26123663

  4. The Lin28 Expression in Stallion Testes.

    PubMed

    Lee, Geumhui; Jung, Heejun; Yoon, Minjung

    2016-01-01

    The molecular markers for specific germ cell stages can be utilized for identifying, monitoring, and separating a particular stage of germ cells. The RNA-binding protein Lin28 is expressed in gonocytes of human fetal testes. The Lin28 expression is restricted to a very small population of spermatogonial cells in human, mice, and monkey. The main objective of this study was to investigate the expression pattern of Lin28 in stallion testes at different reproductive stages. Based on the presence or absence of full spermatogenesis and lumina in seminiferous tubules, the testicular samples were categorized into two reproductive stages pre-pubertal and post-pubertal. We performed a reverse transcription polymerase chain reaction to confirm the presence of Lin28 mRNA in the testicular tissues and a western blot analysis to verify the cross-reactivity of rabbit Lin28 antibody with horse testicular tissue. For immunohistochemistry, Lin28 (rabbit anti-human), GATA4 (goat anti-human) or DAZL (goat anti-human) antibodies were used. The results of RT-PCR confirmed the expression of Lin28 mRNA in the stallion testes. The western blot analysis showed that the expression of 28 kDa Lin28 protein was localized in the cytoplasm of spermatogonia at both reproductive stages. The numbers of Lin28-positive germ cells per 1000 Sertoli cells in pre- and post-pubertal stages were 253 ± 8.66 and 29.67 ± 2.18, respectively. At both reproductive stages, all Lin28 positive cells showed no co-stained with GATA4 antibody, whereas only some of the Lin28-positive germ cells showed co-staining with DAZL antibody. The results from whole-mount staining showed that the Lin28 expression was limited to Asingle (As) and Apaired (Apr) spermatogonia. In conclusion, Lin28 might be utilized as a molecular marker for undifferentiated spermatogonial stem cells when used with DAZL antibody.

  5. The Lin28 Expression in Stallion Testes

    PubMed Central

    Yoon, Minjung

    2016-01-01

    The molecular markers for specific germ cell stages can be utilized for identifying, monitoring, and separating a particular stage of germ cells. The RNA-binding protein Lin28 is expressed in gonocytes of human fetal testes. The Lin28 expression is restricted to a very small population of spermatogonial cells in human, mice, and monkey. The main objective of this study was to investigate the expression pattern of Lin28 in stallion testes at different reproductive stages. Based on the presence or absence of full spermatogenesis and lumina in seminiferous tubules, the testicular samples were categorized into two reproductive stages pre-pubertal and post-pubertal. We performed a reverse transcription polymerase chain reaction to confirm the presence of Lin28 mRNA in the testicular tissues and a western blot analysis to verify the cross-reactivity of rabbit Lin28 antibody with horse testicular tissue. For immunohistochemistry, Lin28 (rabbit anti-human), GATA4 (goat anti-human) or DAZL (goat anti-human) antibodies were used. The results of RT-PCR confirmed the expression of Lin28 mRNA in the stallion testes. The western blot analysis showed that the expression of 28 kDa Lin28 protein was localized in the cytoplasm of spermatogonia at both reproductive stages. The numbers of Lin28-positive germ cells per 1000 Sertoli cells in pre- and post-pubertal stages were 253 ± 8.66 and 29.67 ± 2.18, respectively. At both reproductive stages, all Lin28 positive cells showed no co-stained with GATA4 antibody, whereas only some of the Lin28-positive germ cells showed co-staining with DAZL antibody. The results from whole-mount staining showed that the Lin28 expression was limited to Asingle (As) and Apaired (Apr) spermatogonia. In conclusion, Lin28 might be utilized as a molecular marker for undifferentiated spermatogonial stem cells when used with DAZL antibody. PMID:27798668

  6. H19/let-7/LIN28 reciprocal negative regulatory circuit promotes breast cancer stem cell maintenance

    PubMed Central

    Peng, Fei; Li, Ting-Ting; Wang, Kai-Li; Xiao, Guo-Qing; Wang, Ju-Hong; Zhao, Hai-Dong; Kang, Zhi-Jie; Fan, Wen-Jun; Zhu, Li-Li; Li, Mei; Cui, Bai; Zheng, Fei-Meng; Wang, Hong-Jiang; Lam, Eric W-F; Wang, Bo; Xu, Jie; Liu, Quentin

    2017-01-01

    Long noncoding RNA-H19 (H19), an imprinted oncofetal gene, has a central role in carcinogenesis. Hitherto, the mechanism by which H19 regulates cancer stem cells, remains elusive. Here we show that breast cancer stem cells (BCSCs) express high levels of H19, and ectopic overexpression of H19 significantly promotes breast cancer cell clonogenicity, migration and mammosphere-forming ability. Conversely, silencing of H19 represses these BCSC properties. In concordance, knockdown of H19 markedly inhibits tumor growth and suppresses tumorigenesis in nude mice. Mechanistically, we found that H19 functions as a competing endogenous RNA to sponge miRNA let-7, leading to an increase in expression of a let-7 target, the core pluripotency factor LIN28, which is enriched in BCSC populations and breast patient samples. Intriguingly, this gain of LIN28 expression can also feedback to reverse the H19 loss-mediated suppression of BCSC properties. Our data also reveal that LIN28 blocks mature let-7 production and, thereby, de-represses H19 expression in breast cancer cells. Appropriately, H19 and LIN28 expression exhibits strong correlations in primary breast carcinomas. Collectively, these findings reveal that lncRNA H19, miRNA let-7 and transcriptional factor LIN28 form a double-negative feedback loop, which has a critical role in the maintenance of BCSCs. Consequently, disrupting this pathway provides a novel therapeutic strategy for breast cancer. PMID:28102845

  7. Lin28a regulates germ cell pool size and fertility

    PubMed Central

    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. The Lin28/let-7 axis regulates glucose metabolism

    PubMed Central

    Zhu, Hao; Shyh-Chang, Ng; Segrè, Ayellet V.; Shinoda, Gen; Shah, Samar P.; Einhorn, William S.; Takeuchi, Ayumu; Engreitz, Jesse M.; Hagan, John P.; Kharas, Michael G; Urbach, Achia; Thornton, James E.; Triboulet, Robinson; Gregory, Richard I.; Altshuler, David; Daley, George Q.

    2012-01-01

    SUMMARY The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by blocking let-7 biogenesis. In studies of the Lin28/let-7 pathway, we discovered unexpected roles in regulating metabolism. When overexpressed in mice, both Lin28a and LIN28B promoted an insulin-sensitized state that resisted high fat diet-induced diabetes, whereas muscle-specific loss of Lin28a and overexpression of let-7 resulted in insulin resistance and impaired glucose tolerance. These phenomena occurred in part through let-7-mediated repression of multiple components of the insulin-PI3K-mTOR pathway, including IGF1R, INSR, and IRS2. The mTOR inhibitor rapamycin abrogated the enhanced glucose uptake and insulin-sensitivity conferred by Lin28a in vitro and in vivo. In addition, we found that let-7 targets were enriched for genes that contain SNPs associated with type 2 diabetes and fasting glucose in human genome-wide association studies. These data establish the Lin28/let-7 pathway as a central regulator of mammalian glucose metabolism. PMID:21962509

  9. Lin28 induces resistance to anti-androgens via promotion of AR splice variant generation.

    PubMed

    Tummala, Ramakumar; Nadiminty, Nagalakshmi; Lou, Wei; Evans, Christopher P; Gao, Allen C

    2016-04-01

    Prostate cancer (PCa) is androgen-dependent initially and progresses to a castration-resistant state after androgen deprivation therapy. Treatment options for castration-resistant PCa include the potent second-generation anti-androgen enzalutamide or CYP17A1 inhibitor abiraterone. Recent clinical observations point to the development of resistance to these therapies which may be mediated by constitutively active alternative splice variants of the androgen receptor (AR). Sensitivity of LNCaP cells overexpressing Lin28 (LN-Lin28) to enzalutamide, abiraterone, or bicalutamide was compared to that of control LN-neo cells using cell growth assays, proliferation assays using MTT, anchorage-dependent clonogenic ability assays and soft agar assays. Ability of LN-Lin28 cells to maintain AR activation after treatment with enzalutamide, abiraterone, or bicalutamide was tested using immunofluorescence, Western blotting, ChIP assays, and qRT-PCR. Importance of Lin28 in enzalutamide resistance was assessed by the downregulation of Lin28 expression in C4-2B and 22Rv1 cells chronically treated with enzalutamide. Requirement for sustained AR signaling in LN-Lin28 cells was examined by the downregulation of either full length AR or AR-V7 using siRNA. We show that Lin28 promotes the development of resistance to currently used targeted therapeutics by enhancing the expression of AR splice variants such as AR-V7. PCa cells overexpressing Lin28 exhibit resistance to treatment with enzalutamide, abiraterone, or bicalutamide. Downregulation of Lin28 resensitizes enzalutamide-resistant PCa cells to enzalutamide treatment. We also show that the upregulation of splicing factors such as hnRNPA1 by Lin28 may mediate the enhanced generation of AR splice variants in Lin28-expressing cells. Our findings suggest that Lin28 plays a key role in the acquisition of resistance to AR-targeted therapies by PCa cells and establish the importance of Lin28 in PCa progression. © 2015 Wiley Periodicals, Inc.

  10. Lin-28 binds IGF-2 mRNA and participates in skeletal myogenesis by increasing translation efficiency.

    PubMed

    Polesskaya, Anna; Cuvellier, Sylvain; Naguibneva, Irina; Duquet, Arnaud; Moss, Eric G; Harel-Bellan, Annick

    2007-05-01

    Lin-28 is a highly conserved, RNA-binding, microRNA-regulated protein that is involved in regulation of developmental timing in Caenorhabditis elegans. In mammals, Lin-28 is stage-specifically expressed in embryonic muscle, neurons, and epithelia, as well as in embryonic carcinoma cells, but is suppressed in most adult tissues, with the notable exception of skeletal and cardiac muscle. The specific function and mechanism of action of Lin-28 are not well understood. Here we used loss-of-function and gain-of-function assays in cultured myoblasts to show that expression of Lin-28 is essential for skeletal muscle differentiation in mice. In order to elucidate the specific function of Lin-28, we used a combination of biochemical and functional assays, which revealed that, in differentiating myoblasts, Lin-28 binds to the polysomes and increases the efficiency of protein synthesis. An important target of Lin-28 is IGF-2, a crucial growth and differentiation factor for muscle tissue. Interaction of Lin-28 with translation initiation complexes in skeletal myoblasts and in the embryonic carcinoma cell line P19 was confirmed by localization of Lin-28 to the stress granules, temporary structures that contain stalled mRNA-protein translation complexes. Our results unravel novel mechanisms of translational regulation in skeletal muscle and suggest that Lin-28 performs the role of "translational enhancer" in embryonic and adult cells and tissues.

  11. Clinicopathological Characteristics of Patients with Gastric Cancer according to the Expression of LIN28A.

    PubMed

    Park, Chan Hyuk; Lee, Jung Hwa; Lee, Na Keum; Lee, Yong Chan; Lee, Sang Kil

    2016-09-15

    Although LIN28A is known to potentially play a role in the oncogenesis of various cancers, whether LIN28A expression is a predictor of poor prognosis in patients with gastric cancer has not been fully explored. We sought to evaluate clinicopathological characteristics according to the expression of LIN28A in numerous gastric cancer tissue samples. LIN28A expression was evaluated by immunohistochemical (IHC) analysis of a tissue microarray comprising 288 gastric cancer tissues and 288 adjacent normal tissues. Clinicopathological characteristics, including overall survival, were compared according to LIN28A expression. The IHC staining score was lower for the cancer tissues than the normal tissues (p<0.001). However, no significant differences were observed in the clinicopathological characteristics between the low and high LIN28A expression groups. In addition, the 5-year overall survival rate did not differ between the two groups: 75.3% (95% confidence interval [CI], 69.3% to 81.7%) versus 71.6% (95% CI, 63.3% to 80.9%) for low versus high expression, respectively. The expression of LIN28A did not appear to play a distinct role in predicting the clinicopathological characteristics of patients with gastric cancer. In addition, LIN28A expression was not an independently associated factor for overall survival in patients with gastric cancer.

  12. Selective blockade of microRNA processing by Lin-28

    PubMed Central

    Viswanathan, Srinivas R.; Daley, George Q.; Gregory, Richard I.

    2012-01-01

    MicroRNAs (miRNAs) play critical roles in development, and dysregulation of miRNA expression has been observed in human malignancies. Recent evidence suggests that the processing of several primary miRNA transcripts (pri-miRNAs) is blocked post-transcriptionally in embryonic stem (ES) cells, embryonal carcinoma (EC) cells, and primary tumors. Here we show that Lin-28, a developmentally regulated RNA-binding protein, selectively blocks the processing of pri-let-7 miRNAs in embryonic cells. Using in vitro and in vivo studies, we demonstrate that Lin-28 is necessary and sufficient for blocking Microprocessor-mediated cleavage of pri-let-7 miRNAs. Our results identify Lin-28 as a negative regulator of miRNA biogenesis and suggest that Lin-28 may play a central role in blocking miRNA-mediated differentiation in stem cells and certain cancers. PMID:18292307

  13. Stepwise assembly of multiple Lin28 proteins on the terminal loop of let-7 miRNA precursors

    PubMed Central

    Desjardins, Alexandre; Bouvette, Jonathan; Legault, Pascale

    2014-01-01

    Lin28 inhibits the biogenesis of let-7 miRNAs through direct interactions with let-7 precursors. Previous studies have described seemingly inconsistent Lin28 binding sites on pre-let-7 RNAs. Here, we reconcile these data by examining the binding mechanism of Lin28 to the terminal loop of pre-let-7g (TL-let-7g) using biochemical and biophysical methods. First, we investigate Lin28 binding to TL-let-7g variants and short RNA fragments and identify three independent binding sites for Lin28 on TL-let-7g. We then determine that Lin28 assembles in a stepwise manner on TL-let-7g to form a stable 1:3 complex. We show that the cold-shock domain (CSD) of Lin28 is responsible for remodelling the terminal loop of TL-let-7g, whereas the NCp7-like domain facilitates the initial binding of Lin28 to TL-let-7g. This stable binding of multiple Lin28 molecules to the terminal loop of pre-let-7g extends to other precursors of the let-7 family, but not to other pre-miRNAs tested. We propose a model for stepwise assembly of the 1:1, 1:2 and 1:3 pre-let-7g/Lin28 complexes. Stepwise multimerization of Lin28 on pre-let-7 is required for maximum inhibition of Dicer cleavage for a least one member of the let-7 family and may be important for orchestrating the activity of the several factors that regulate let-7 biogenesis. PMID:24452802

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

    PubMed Central

    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

  15. Dynamic gene expression of Lin-28 during embryonic development in mouse and chicken.

    PubMed

    Yokoyama, Shigetoshi; Hashimoto, Megumi; Shimizu, Hirohito; Ueno-Kudoh, Hiroe; Uchibe, Kenta; Kimura, Ichiro; Asahara, Hiroshi

    2008-02-01

    The Caenorhabditis elegans heterochronic gene lin-28 regulates developmental timing in the nematode trunk. We report the dynamic expression patterns of Lin-28 homologues in mouse and chick embryos. Whole mount in situ hybridization revealed specific and intriguing expression patterns of Lin-28 in the developing mouse and chick limb bud. Mouse Lin-28 expression was detected in both the forelimb and hindlimb at E9.5, but disappeared from the forelimb at E10.5, and finally from the forelimb and hindlimb at E11.5. Chicken Lin-28, which was first detected in the limb primordium at stage 15/16, was also downregulated as the stage proceeded. The amino acid sequences of mouse and chicken Lin-28 genes are highly conserved and the similar expression patterns of Lin-28 during limb development in mouse and chicken suggest that this heterochronic gene is also conserved during vertebrate limb development.

  16. Overexpression of Lin28 inhibits the proliferation, migration and cell cycle progression and induces apoptosis of BGC-823 gastric cancer cells.

    PubMed

    Song, Hu; Xu, Wei; Song, Jun; Liang, Yong; Fu, Wei; Zhu, Xiao-Cheng; Li, Chao; Peng, Jun-Sheng; Zheng, Jun-Nian

    2015-02-01

    Lin28 plays important roles in the development, maintenance of pluripotency and progression of various types of cancers. Lin28 represses the biogenesis of let-7 microRNAs and is implicated in both development and tumorigenesis. Oncogenic regulation of let-7 microRNAs has been demonstrated in several human malignancies, yet their correlation with Lin28 has not yet been studied in gastric cancer. Therefore, in the present study, we explored the possible mechanisms involved in the effects by Lin28 on the proliferation, migration, cell cycle arrest and apoptosis in gastric cancer cells via alteration of let-7 miRNA. The expression levels of Lin28 and let-7 were detected by real-time PCR in gastric cancer cell lines in vitro. Lin28 was overexpressed in the BGC-823 cells via lentiviral transfection, and let-7 expression was assessed. Cell proliferation and migration capabilities were investigated by MTT and Transwell assays, while cell cycle distribution and the apoptosis rate were detected using flow cytometry. The expression of Lin28 was moderately expressed in the GES cells while underexpressed in the BGC-823, SGC-7901 and HGC-27 cells. Let-7a miRNA was highly expressed in the GES, BGC-823, SGC-7901 and HGC-27 cells. Overexpression of Lin28 was inversely correlated with the downregulated expression of let-7a, and markedly suppressed the proliferation, migration, cell cycle progression and induced apoptosis in the BGC-823 cells. These findings demonstrated that overexpression of Lin28 can suppress the biological behavior of gastric cancer in vitro, and let-7 miRNA may play an important role in the process. We suggest that Lin28 may be a candidate predictor or an anticancer therapeutic target for gastric cancer patients.

  17. Fetal deficiency of Lin28 programs life-long aberrations in growth and glucose metabolism

    PubMed Central

    Shinoda, Gen; Shyh-Chang, Ng; de Soysa, T. Yvanka; Zhu, Hao; Seligson, Marc T.; Shah, Samar P.; Abo-Sido, Nora; Yabuuchi, Akiko; Hagan, John P.; Gregory, Richard I.; Asara, John M.; Cantley, Lewis C.; Moss, Eric G.; Daley, George Q.

    2013-01-01

    LIN28A/B are RNA binding proteins implicated by genetic association studies in human growth and glucose metabolism. Mice with ectopic over-expression of Lin28a have shown related phenotypes. Here we describe the first comprehensive analysis of the physiologic consequences of Lin28a and Lin28b deficiency in knockout (KO) mice. Lin28a/b-deficiency led to dwarfism starting at different ages, and compound gene deletions showed a cumulative dosage effect on organismal growth. Conditional gene deletion at specific developmental stages revealed that fetal but neither neonatal nor adult deficiency resulted in growth defects and aberrations in glucose metabolism. Tissue-specific KO mice implicated skeletal muscle-deficiency in the abnormal programming of adult growth and metabolism. The effects of Lin28b KO can be rescued by Tsc1 haplo-insufficiency in skeletal muscles. Our data implicate fetal expression of Lin28a/b in the regulation of life-long effects on metabolism and growth, and demonstrate that fetal Lin28b acts at least in part via mTORC1 signaling. PMID:23666760

  18. A role for Lin-28 in growth and metamorphosis in Drosophila melanogaster.

    PubMed

    González-Itier, Sergio; Contreras, Esteban G; Larraín, Juan; Glavic, Álvaro; Faunes, Fernando

    2018-06-13

    Insect metamorphosis has been a classic model to understand the role of hormones in growth and timing of developmental transitions. In addition to hormones, transitions in some species are regulated by genetic programs, such as the heterochronic gene network discovered in C. elegans. However, the functional link between hormones and heterochronic genes is not clear. The heterochronic gene lin-28 is involved in the maintenance of stem cells, growth and developmental timing in vertebrates. In this work, we used gain-of-function and loss-of-function experiments to study the role of Lin-28 in larval growth and the timing of metamorphosis of Drosophila melanogaster. During the late third instar stage, Lin-28 is mainly expressed in neurons of the central nervous system and in the intestine. Loss-of-function lin-28 mutant larvae are smaller and the larval-to-pupal transition is accelerated. This faster transition correlates with increased levels of ecdysone direct target genes such as Broad-Complex (BR-C) and Ecdysone Receptor (EcR). Overexpression of Lin-28 does not affect the timing of pupariation but most animals are not able to eclose, suggesting defects in metamorphosis. Overexpression of human Lin-28 results in delayed pupariation and the death of animals during metamorphosis. Altogether, these results suggest that Lin-28 is involved in the control of growth during larval development and in the timing and progression of metamorphosis. Copyright © 2017. Published by Elsevier B.V.

  19. LIN28 cooperates with WNT signaling to drive invasive intestinal and colorectal adenocarcinoma in mice and humans

    PubMed Central

    Tu, Ho-Chou; Schwitalla, Sarah; Qian, Zhirong; LaPier, Grace S.; Yermalovich, Alena; Ku, Yuan-Chieh; Chen, Shann-Ching; Viswanathan, Srinivas R.; Zhu, Hao; Nishihara, Reiko; Inamura, Kentaro; Kim, Sun A.; Morikawa, Teppei; Mima, Kosuke; Sukawa, Yasutaka; Yang, Juhong; Meredith, Gavin; Fuchs, Charles S.; Ogino, Shuji

    2015-01-01

    Colorectal cancer (CRC) remains a major contributor to cancer-related mortality. LIN28A and LIN28B are highly related RNA-binding protein paralogs that regulate biogenesis of let-7 microRNAs and influence development, metabolism, tissue regeneration, and oncogenesis. Here we demonstrate that overexpression of either LIN28 paralog cooperates with the Wnt pathway to promote invasive intestinal adenocarcinoma in murine models. When LIN28 alone is induced genetically, half of the resulting tumors harbor Ctnnb1 (β-catenin) mutation. When overexpressed in ApcMin/+ mice, LIN28 accelerates tumor formation and enhances proliferation and invasiveness. In conditional genetic models, enforced expression of a LIN28-resistant form of the let-7 microRNA reduces LIN28-induced tumor burden, while silencing of LIN28 expression reduces tumor volume and increases tumor differentiation, indicating that LIN28 contributes to tumor maintenance. We detected aberrant expression of LIN28A and/or LIN28B in 38% of a large series of human CRC samples (n = 595), where LIN28 expression levels were associated with invasive tumor growth. Our late-stage CRC murine models and analysis of primary human tumors demonstrate prominent roles for both LIN28 paralogs in promoting CRC growth and progression and implicate the LIN28/let-7 pathway as a therapeutic target. PMID:25956904

  20. Let-7 miRNA Precursors Co-express with LIN28B in Cervical Cells.

    PubMed

    Zamora-Contreras, Aida Margarita; Alvarez-Salas, Luis Marat

    2018-01-01

    The let-7 microRNAs (miRNAs) are frequently dysregulated in carcinogenic processes, including cervical cancer. LIN28 proteins regulate let-7 biogenesis by binding to conserved sequences within the pre-miRNA structure. Nevertheless, recent research has shown that some let-7 miRNAs may escape LIN28 regulation. Correlate pre-let-7 miRNAs and LIN28B levels in cervical cell lines with different malignancy and HPV content. Pre-let-7 levels were determined by RTqPCR. LIN28B and other let-7 targets were analyzed by immunoblot. In silico tools were used to correlate let-7 and LIN28B expression and to analyze prelet- 7 sequences and structures. Lin28B protein was detected in all tested cell lines although it was more expressed in tumor cell lines. High levels of pre-let-7c/f-1 and pre-miR-98 were present in almost all cell lines regardless malignancy and LIN28B expression. Pre-let-7g/i were mainly expressed in tumor cell lines, pre-let-7e and pre-let-7-a3 were absent in all cell lines and pre-let-7a-2 showed indistinct expression. LIN28B showed positive correlation with pre-let-7i/g/f-1 and pre-miR-98 in tumor cell lines, suggesting escape from regulation. Sequence alignment and analysis of pre-let-7 miRNAs showed distinctive structural features within the preE region that may influence the ideal pre-let-7 structuring for LIN28B interaction. Short preE-stems were present in pre-let-7 that may escape LIN28B regulation, but long preEstems were mostly associated with high-level pre-let-7 miRNAs. The observed differences of pre-let-7 levels in cervical cell lines may be the result of alternative preE structuring affecting interaction with LIN28B thus resulting in differential let-7 regulation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Lin28b is sufficient to drive liver cancer and necessary for its maintenance in murine models

    PubMed Central

    Nguyen, Liem H.; Robinton, Daisy A.; Seligson, Marc; Wu, Linwei; Li, Lin; Rakheja, Dinesh; Comerford, Sarah; Ramezani, Saleh; Sun, Xiankai; Parikh, Monisha; Yang, Erin; Powers, John T.; Shinoda, Gen; Shah, Samar; Hammer, Robert; Daley, George Q.; Zhu, Hao

    2014-01-01

    SUMMARY Lin28a/b are RNA-binding proteins that influence stem cell maintenance, metabolism, and oncogenesis. Poorly differentiated, aggressive cancers often overexpress Lin28, but its role in tumor initiation or maintenance has not been definitively addressed. We report that LIN28B overexpression is sufficient to initiate hepatoblastoma and hepatocellular carcinoma in murine models. We also detected Lin28b overexpression in MYC-driven hepatoblastomas, and liver-specific deletion of Lin28a/b reduced tumor burden, extended latency, and prolonged survival. Both intravenous siRNA against Lin28b and conditional Lin28b deletion reduced tumor burden and prolonged survival. Igf2bp proteins are upregulated and Igf2bp3 is required in the context of LIN28B overexpression to promote growth. Thus, multiple murine models demonstrate that Lin28b is both sufficient to initiate liver cancer and necessary for its maintenance. PMID:25117712

  2. The heterochronic gene Lin28 regulates amphibian metamorphosis through disturbance of thyroid hormone function.

    PubMed

    Faunes, Fernando; Gundermann, Daniel G; Muñoz, Rosana; Bruno, Renzo; Larraín, Juan

    2017-05-15

    Metamorphosis is a classic example of developmental transition, which involves important morphological and physiological changes that prepare the organism for the adult life. It has been very well established that amphibian metamorphosis is mainly controlled by Thyroid Hormone (TH). Here, we show that the heterochronic gene Lin28 is downregulated during Xenopus laevis metamorphosis. Lin28 overexpression before activation of TH signaling delays metamorphosis and inhibits the expression of TH target genes. The delay in metamorphosis is rescued by incubation with exogenous TH, indicating that Lin28 works upstream or parallel to TH. High-throughput analyses performed before any delay on metamorphosis or change in TH signaling showed that overexpression of Lin28 reduces transcript levels of several hormones secreted by the pituitary, including the Thyroid-Stimulating Hormone (TSH), and regulates the expression of proteins involved in TH transport, metabolism and signaling, showing that Lin28 disrupts TH function at different levels. Our data demonstrates that the role of Lin28 in controlling developmental transitions is evolutionary conserved and establishes a functional interaction between Lin28 and thyroid hormone function introducing a new regulatory step in perinatal development with implications for our understanding of endocrine disorders. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Lin28 Mediates Cancer Chemotherapy Resistance via Regulation of miRNA Signaling.

    PubMed

    Xu, Chaoyang; Xie, Shuduo; Song, Chunjiao; Huang, Liming; Jiang, Zhinong

    2014-06-01

    Chemotherapy resistance is one of the major obstacles limiting the success of cancer drug treatment. Among the mechanisms of resistance to chemotherapy treatment, there are those closely related to P-Glycoprotein, multidrug resistance-related protein, glutathione S-transferase pi and topoisomerase-II. Lin28 is a highly conserved RNA-binding protein, it consists of a cold shock domain and retroviral-type (CCHC) zinc finger motifs. In previous preclinical and clinical studies, positive Lin28 expression in cancer cells was correlated with decreased sensitivity to chemotherapy. And Lin28 could mediate cancer chemotherapy resistance via regulation of miR107 and Let-7 MiRNA. This article reviews current knowledge on predictive value of Lin28 in response to chemotherapy. Better understanding of its role may facilitate patient's selection of therapeutic regimen and lead to optimal clinical outcome.

  4. Lin28a is a putative factor in regulating cancer stem cell-like properties in side population cells of oral squamous cell carcinoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hayashi, S.; Tanaka, J.; Okada, S.

    Cancer stem cells (CSCs) are among the target cells of cancer therapy because they are uniquely involved in both cancer progression and sensitivity to chemotherapeutic agents. We identified side population (SP) cells, which are known to be an enriched population of CSC, in five oral squamous cell carcinoma (OSCC) cells (SCC9, SCC25, TOSCC7, TOSCC17, and TOSCC23). The percentages of SP cells ranged from 0% to 3.3%, with TOSCC23 cells showing the highest percentages of SP cells (3.3% of the total cell population). The SP cells isolated from TOSCC23 cells also showed greater cell proliferation and invasion compared to non-SP (MP)more » cells. Therefore, our initial findings suggested that SP cells were enriched for CSC-like cells. Furthermore, DNA microarray analysis revealed that the expression of cell proliferation-related and anti-apoptotic genes was greater in SP cells compared to MP cells. We focused on Lin28a, which showed the highest expression (approximately 22-fold) among the upregulated genes. The overexpression of Lin28a in TOSCC23 cells increased their proliferation, colony formation, and invasion. These findings suggest that Lin28a is an appropriate CSC target molecule for OSCC treatment - Highlights: ► Lin28a is a SP cell-specific factor in oral squamous cell carcinoma (OSCC) cells. ► SP cells in OSCC cells show cancer stem cell-like properties. ► Lin28a regulates OSCC proliferative and invasive activities.« less

  5. LIN28 phosphorylation by MAPK/ERK couples signaling to the post-transcriptional control of pluripotency

    PubMed Central

    Tsanov, Kaloyan M.; Pearson, Daniel S.; Wu, Zhaoting; Han, Areum; Triboulet, Robinson; Seligson, Marc T.; Powers, John T.; Osborne, Jihan K.; Kane, Susan; Gygi, Steven P.; Gregory, Richard I.; Daley, George Q.

    2016-01-01

    Signaling and post-transcriptional gene control are both critical for the regulation of pluripotency1,2, yet how they are integrated to influence cell identity remains poorly understood. LIN28 (also known as LIN28A), a highly conserved RNA-binding protein (RBP), has emerged as a central post-transcriptional regulator of cell fate through blockade of let-7 microRNA (miRNA) biogenesis and direct modulation of mRNA translation3. Here we show that LIN28 is phosphorylated by MAPK/ERK in pluripotent stem cells (PSCs), which increases its levels via post-translational stabilization. LIN28 phosphorylation had little impact on let-7 but enhanced LIN28’s effect on its direct mRNA targets, revealing a mechanism that uncouples LIN28’s let-7-dependent and independent activities. We have linked this mechanism to the induction of pluripotency by somatic cell reprogramming and the transition from naïve to primed pluripotency. Collectively, our findings indicate that MAPK/ERK directly impacts LIN28, defining an axis that connects signaling, post-transcriptional gene control, and cell fate regulation. PMID:27992407

  6. Developmental regulation of myeloerythroid progenitor function by the Lin28b–let-7–Hmga2 axis

    PubMed Central

    Rowe, R. Grant; Wang, Leo D.; Coma, Silvia; Pearson, Daniel S.; Nguyen, Phi T.; Wagers, Amy J.

    2016-01-01

    For appropriate development, tissue and organ system morphogenesis and maturation must occur in synchrony with the overall developmental requirements of the host. Mistiming of such developmental events often results in disease. The hematopoietic system matures from the fetal state, characterized by robust erythrocytic output that supports prenatal growth in the hypoxic intrauterine environment, to the postnatal state wherein granulocytes predominate to provide innate immunity. Regulation of the developmental timing of these myeloerythroid states is not well understood. In this study, we find that expression of the heterochronic factor Lin28b decreases in common myeloid progenitors during hematopoietic maturation to adulthood in mice. This decrease in Lin28b coincides with accumulation of mature let-7 microRNAs, whose biogenesis is regulated by Lin28 proteins. We find that inhibition of let-7 in the adult hematopoietic system recapitulates fetal erythroid-dominant hematopoiesis. Conversely, deletion of Lin28b or ectopic activation of let-7 microRNAs in the fetal state induces a shift toward adult-like myeloid-dominant output. Furthermore, we identify Hmga2 as an effector of this genetic switch. These studies provide the first detailed analysis of the roles of endogenous Lin28b and let-7 in the timing of hematopoietic states during development. PMID:27401346

  7. Bistable switch in let-7 miRNA biogenesis pathway involving Lin28.

    PubMed

    Shi, Fei; Yu, Wenbao; Wang, Xia

    2014-10-21

    miRNAs are small noncoding RNAs capable of regulating gene expression at the post-transcriptional level. A growing body of evidence demonstrated that let-7 family of miRNAs, as one of the highly conserved miRNAs, plays an important role in cell differentiation and development, as well as tumor suppressor function depending on their levels of expression. To explore the physiological significance of let-7 in regulating cell fate decisions, we present a coarse grained model of let-7 biogenesis network, in which let-7 and its regulator Lin28 inhibit mutually. The dynamics of this minimal network architecture indicates that, as the concentration of Lin28 increases, the system undergoes a transition from monostability to a bistability and then to a one-way switch with increasing strength of positive feedback of let-7, while in the absence of Lin28 inhibition, the system loses bistability. Moreover, the ratio of degradation rates of let-7 and Lin28 is critical for the switching sensitivity and resistance to stimulus fluctuations. These findings may highlight why let-7 is required for normal gene expression in the context of embryonic development and oncogenesis, which will facilitate the development of approaches to exploit this regulatory pathway by manipulating Lin28/let-7 axis for novel treatments of human diseases.

  8. Lin28a protects against postinfarction myocardial remodeling and dysfunction through Sirt1 activation and autophagy enhancement.

    PubMed

    Hao, Yuanyuan; Lu, Qun; Yang, Guodong; Ma, Aiqun

    2016-10-28

    Myocardial remodeling and cardiac dysfunction prevention may represent a therapeutic approach to reduce mortality in patients with myocardial infarction (MI). We investigated the effects of Lin28a in experimental MI models, as well as the mechanisms underlying these effects. Left anterior descending (LAD) coronary artery ligation was used to construct an MI-induced injury model. Neonatal cardiomyocytes were isolated and cultured to investigate the mechanisms underlying the protective effects of Lin28a against MI-induced injury. Lin28a significantly inhibited left ventricular remodeling and cardiac dysfunction after MI, as demonstrated via echocardiography and hemodynamic measurements. Lin28a reduced cardiac enzyme and inflammatory marker release in mice subjected to MI-induced injury. The mechanisms underlying the protective effects of Lin28a against MI-induced injury were associated with autophagy enhancements and apoptosis inhibition. Consistent with these findings, Lin28a knockdown aggravated cardiac remodeling and dysfunction after MI-induced injury. Lin28a knockdown also inhibited cardiomyocyte autophagy and increased cardiomyocyte apoptosis in mice subjected to MI-induced injury. Interestingly, Sirt1 knockdown abolished the protective effects of Lin28a against cardiac remodeling and dysfunction after MI, and Lin28a failed to increase the numbers of GFP-LC3-positive punctae and decrease aggresome and p62 accumulation in Sirt1-knockdown neonatal cardiomyocytes subjected to hypoxia-induced injury. Lin28a inhibits cardiac remodeling, improves cardiac function, and reduces cardiac enzyme and inflammatory marker release after MI. Lin28a also up-regulates cardiomyocyte autophagy and inhibits cardiomyocyte apoptosis through Sirt1 activation. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Lin28B promotes Müller glial cell de-differentiation and proliferation in the regenerative rat retinas

    PubMed Central

    Tao, Zui; Zhao, Chen; Jian, Qian; Gillies, Mark; Xu, Haiwei; Yin, Zheng Qin

    2016-01-01

    Retinal regeneration and repair are severely impeded in higher mammalian animals. Although Müller cells can be activated and show some characteristics of progenitor cells when injured or under pathological conditions, they quickly form gliosis scars. Unfortunately, the basic mechanisms that impede retinal regeneration remain unknown. We studied retinas from Royal College of Surgeon (RCS) rats and found that let-7 family molecules, let-7e and let-7i, were significantly overexpressed in Müller cells of degenerative retinas. It demonstrated that down-regulation of the RNA binding protein Lin28B was one of the key factors leading to the overexpression of let-7e and let-7i. Lin28B ectopic expression in the Müller cells suppressed overexpression of let-7e and let-7i, stimulated and mobilized Müller glia de-differentiation, proliferation, promoted neuronal commitment, and inhibited glial fate acquisition of de-differentiated Müller cells. ERG recordings revealed that the amplitudes of a-wave and b-wave were improved significantly after Lin28B was delivered into the subretinal space of RCS rats. In summary, down-regulation of Lin28B as well as up-regulation of let-7e and let-7i may be the main factors that impede Müller cell de-differentiation and proliferation in the retina of RCS rats. PMID:27384999

  10. Primordial dwarfism gene maintains Lin28 expression to safeguard embryonic stem cells from premature differentiation.

    PubMed

    Dai, Qian; Luan, Guangxin; Deng, Li; Lei, Tingjun; Kang, Han; Song, Xu; Zhang, Yujun; Xiao, Zhi-Xiong; Li, Qintong

    2014-05-08

    Primordial dwarfism (PD) is characterized by global growth failure, both during embryogenesis and postnatally. Loss-of-function germline mutations in La ribonucleoprotein domain family, member 7 (LAPR7) have recently been linked to PD. Paradoxically, LARP7 deficiency was previously assumed to be associated with increased cell growth and proliferation via activation of positive transcription elongation factor b (P-TEFb). Here, we show that Larp7 deficiency likely does not significantly increase P-TEFb activity. We further discover that Larp7 knockdown does not affect pluripotency but instead primes embryonic stem cells (ESCs) for differentiation via downregulation of Lin28, a positive regulator of organismal growth. Mechanistically, we show that Larp7 interacts with a poly(A) polymerase Star-PAP to maintain Lin28 mRNA stability. We propose that proper regulation of Lin28 and PTEFb is essential for embryonic cells to achieve a sufficient number of cell divisions prior to differentiation and ultimately to maintain proper organismal size. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  11. The let-7/Lin28 axis regulates activation of hepatic stellate cells in alcoholic liver injury.

    PubMed

    McDaniel, Kelly; Huang, Li; Sato, Keisaku; Wu, Nan; Annable, Tami; Zhou, Tianhao; Ramos-Lorenzo, Sugeily; Wan, Ying; Huang, Qiaobing; Francis, Heather; Glaser, Shannon; Tsukamoto, Hidekazu; Alpini, Gianfranco; Meng, Fanyin

    2017-07-07

    The let-7/Lin28 axis is associated with the regulation of key cellular regulatory genes known as microRNAs in various human disorders and cancer development. This study evaluated the role of the let-7/Lin28 axis in regulating a mesenchymal phenotype of hepatic stellate cells in alcoholic liver injury. We identified that ethanol feeding significantly down-regulated several members of the let-7 family in mouse liver, including let-7a and let-7b. Similarly, the treatment of human hepatic stellate cells (HSCs) with lipopolysaccharide (LPS) and transforming growth factor-β (TGF-β) significantly decreased the expressions of let-7a and let-7b. Conversely, overexpression of let-7a and let-7b suppressed the myofibroblastic activation of cultured human HSCs induced by LPS and TGF-β, as evidenced by repressed ACTA2 (α-actin 2), COL1A1 (collagen 1A1), TIMP1 (TIMP metallopeptidase inhibitor 1), and FN1 (fibronectin 1); this supports the notion that HSC activation is controlled by let-7. A combination of bioinformatics, dual-luciferase reporter assay, and Western blot analysis revealed that Lin28B and high-mobility group AT-hook (HMGA2) were the direct targets of let-7a and let-7b. Furthermore, Lin28B deficiency increased the expression of let-7a/let-7b as well as reduced HSC activation and liver fibrosis in mice with alcoholic liver injury. This feedback regulation of let-7 by Lin28B is verified in hepatic stellate cells isolated by laser capture microdissection from the model. The identification of the let-7/Lin28 axis as an important regulator of HSC activation as well as its upstream modulators and down-stream targets will provide insights into the involvement of altered microRNA expression in contributing to the pathogenesis of alcoholic liver fibrosis and novel therapeutic approaches for human alcoholic liver diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Germline Genetic Variants Disturbing the Let-7/LIN28 Double-Negative Feedback Loop Alter Breast Cancer Susceptibility

    PubMed Central

    Fan, Lei; Li, Ji-Yu; Yang, Chen; Huang, A-Ji; Shao, Zhi-Ming

    2011-01-01

    Previous studies have shown that let-7 can repress the post-transcriptional translation of LIN28, and LIN28 in turn could block the maturation of let-7, forming a double-negative feedback loop. In this study, we investigated the effect of germline genetic variants on regulation of the homeostasis of the let-7/LIN28 loop and breast cancer risk. We initially demonstrated that the T/C variants of rs3811463, a single nucleotide polymorphism (SNP) located near the let-7 binding site in LIN28, could lead to differential regulation of LIN28 by let-7. Specifically, the C allele of rs3811463 weakened let-7–induced repression of LIN28 mRNA, resulting in increased production of LIN28 protein, which could in turn down-regulate the level of mature let-7. This effect was then validated at the tissue level in that the normal breast tissue of individuals with the rs3811463-TC genotype expressed significantly lower levels of let-7 and higher levels of LIN28 protein than those individuals with the rs3811463-TT genotype. Because previous in vitro and ex vivo experiments have consistently suggested that LIN28 could promote cellular transformation, we then systematically evaluated the relationship between rs3811463 as well as other common LIN28 SNPs and the risk of breast cancer in a stepwise manner. The first hospital-based association study (n = 2,300) demonstrated that two SNPs were significantly associated with breast cancer risk, one of which was rs3811463, while the other was rs6697410. The C allele of the rs3811463 SNP corresponded to an increased risk of breast cancer with an odds ratio (OR) of 1.25 (P = 0.0091), which was successfully replicated in a second independent study (n = 1,156) with community-based controls. The combined P-value of the two studies was 8.0×10−5. Taken together, our study demonstrates that host genetic variants could disturb the regulation of the let-7/LIN28 double-negative feedback loop and alter breast cancer risk. PMID:21912531

  13. RNA binding protein Lin28B confers gastric cancer cells stemness via directly binding to NRP-1.

    PubMed

    Wang, Xiaocong; Hu, Huihua; Liu, Hebo

    2018-05-19

    This work aims to explore the roles and related mechanisms of RNA binding protein Lin28B in gastric cancer cells stemness. We found that Lin28B expression was negatively correlated with the overall survival (OS) of gastric cancer patients, and significantly increased in gastric cancer cells compared with that in gastric epithelial cells. Lin28B overexpression increased spheroid formation, expression of gastric cancer stemness-related markers, and decreased cisplatin sensitivity in gastric cancer cells. Mechanistically, Lin28B could directly bind to NRP-1 3'UTR, thus increasing NRP-1 mRNA stability and expression, and activate the downstream Wnt/β-catenin signaling. Knockdown of NRP-1 or treatment with Wnt/β-catenin antagonist could rescue the promotive effects of Lin28B on gastric cancer stemness. Thus, thes results indicate that Lin28B could facilitate gastric cancer stemness via directly binding to NRP-1 3'UTR and activating the downstream Wnt/β-catenin signaling. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  14. Mechanisms of Lin28-Mediated miRNA and mRNA Regulation—A Structural and Functional Perspective

    PubMed Central

    Mayr, Florian; Heinemann, Udo

    2013-01-01

    Lin28 is an essential RNA-binding protein that is ubiquitously expressed in embryonic stem cells. Its physiological function has been linked to the regulation of differentiation, development, and oncogenesis as well as glucose metabolism. Lin28 mediates these pleiotropic functions by inhibiting let-7 miRNA biogenesis and by modulating the translation of target mRNAs. Both activities strongly depend on Lin28’s RNA-binding domains (RBDs), an N-terminal cold-shock domain (CSD) and a C-terminal Zn-knuckle domain (ZKD). Recent biochemical and structural studies revealed the mechanisms of how Lin28 controls let-7 biogenesis. Lin28 binds to the terminal loop of pri- and pre-let-7 miRNA and represses their processing by Drosha and Dicer. Several biochemical and structural studies showed that the specificity of this interaction is mainly mediated by the ZKD with a conserved GGAGA or GGAGA-like motif. Further RNA crosslinking and immunoprecipitation coupled to high-throughput sequencing (CLIP-seq) studies confirmed this binding motif and uncovered a large number of new mRNA binding sites. Here we review exciting recent progress in our understanding of how Lin28 binds structurally diverse RNAs and fulfills its pleiotropic functions. PMID:23939427

  15. Lin28-let7 Modulates Radiosensitivity of Human Cancer Cells With Activation of K-Ras

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Oh, Jee-Sun.; Kim, Jae-Jin; Byun, Ju-Yeon

    2010-01-15

    Purpose: To evaluate the potential of targeting Lin28-let7 microRNA regulatory network for overcoming the radioresistance of cancer cells having activated K-Ras signaling. Methods and Materials: A549 lung carcinoma cells and ASPC1 pancreatic cancer cells possessing K-RAS mutation were transfected with pre-let7a microRNA or Lin28 siRNA, respectively. Clonogenic assay, quantitative reverse transcription polymerase chain reaction, and Western analysis were performed. The effects of Lin28 on SQ20B cells having wild-type K-RAS, and a normal fibroblast were also assessed. Results: The overexpression of let-7a decreased expression of K-Ras and radiosensitized A549 cells. Inhibition of Lin28, a repressor of let-7, attenuated K-Ras expression andmore » radiosensitized A549 and ASPC1 cells. Neither SQ20B cells expressing wild-type K-RAS nor HDF, the normal human fibroblasts, were radiosensitized by this approach. Conclusions: The Lin28-let7 regulatory network may be a potentially useful therapeutic target for overcoming the radioresistance of human cancers having activated K-Ras signaling.« less

  16. The Lin28/Let-7 System in Early Human Embryonic Tissue and Ectopic Pregnancy

    PubMed Central

    Steffani, Liliana; Martínez, Sebastián; Monterde, Mercedes; Ferri, Blanca; Núñez, Maria Jose; AinhoaRomero-Espinós; Zamora, Omar; Gurrea, Marta; Sangiao-Alvarellos, Susana; Vega, Olivia; Simón, Carlos; Pellicer, Antonio; Tena-Sempere, Manuel

    2014-01-01

    Our objective was to determine the expression of the elements of the Lin28/Let-7 system, and related microRNAs (miRNAs), in early stages of human placentation and ectopic pregnancy, as a means to assess the potential role of this molecular hub in the pathogenesis of ectopic gestation. Seventeen patients suffering from tubal ectopic pregnancy (cases) and forty-three women with normal on-going gestation that desired voluntary termination of pregnancy (VTOP; controls) were recruited for the study. Embryonic tissues were subjected to RNA extraction and quantitative PCR analyses for LIN28B, Let-7a, miR-132, miR-145 and mir-323-3p were performed. Our results demonstrate that the expression of LIN28B mRNA was barely detectable in embryonic tissue from early stages of gestation and sharply increased thereafter to plateau between gestational weeks 7–9. In contrast, expression levels of Let-7, mir-132 and mir-145 were high in embryonic tissue from early gestations (≤6-weeks) and abruptly declined thereafter, especially for Let-7. Opposite trends were detected for mir-323-3p. Embryonic expression of LIN28B mRNA was higher in early stages (≤6-weeks) of ectopic pregnancy than in normal gestation. In contrast, Let-7a expression was significantly lower in early ectopic pregnancies, while miR-132 and miR-145 levels were not altered. Expression of mir-323-3p was also suppressed in ectopic embryonic tissue. We are the first to document reciprocal changes in the expression profiles of the gene encoding the RNA-binding protein, LIN28B, and the related miRNAs, Let-7a, mir-132 and mir-145, in early stages of human placentation. This finding suggests the potential involvement of LIN28B/Let-7 (de)regulated pathways in the pathophysiology of ectopic pregnancy in humans. PMID:24498170

  17. The oncogenic triangle of HMGA2, LIN28B and IGF2BP1 antagonizes tumor-suppressive actions of the let-7 family

    PubMed Central

    Busch, Bianca; Bley, Nadine; Müller, Simon; Glaß, Markus; Misiak, Danny; Lederer, Marcell; Vetter, Martina; Strauß, Hans-Georg; Thomssen, Christoph; Hüttelmaier, Stefan

    2016-01-01

    The tumor-suppressive let-7 microRNA family targets various oncogene-encoding mRNAs. We identify the let-7 targets HMGA2, LIN28B and IGF2BP1 to form a let-7 antagonizing self-promoting oncogenic triangle. Surprisingly, 3′-end processing of IGF2BP1 mRNAs is unaltered in aggressive cancers and tumor-derived cells although IGF2BP1 synthesis was proposed to escape let-7 attack by APA-dependent (alternative polyadenylation) 3′ UTR shortening. However, the expression of the triangle factors is inversely correlated with let-7 levels and promoted by LIN28B impairing let-7 biogenesis. Moreover, IGF2BP1 enhances the expression of all triangle factors by recruiting the respective mRNAs in mRNPs lacking AGO proteins and let-7 miRNAs. This indicates that the downregulation of let-7, largely facilitated by LIN28B upregulation, and the protection of let-7 target mRNAs by IGF2BP1-directed shielding in mRNPs synergize in enhancing the expression of triangle factors. The oncogenic potential of this triangle was confirmed in ovarian cancer (OC)-derived ES-2 cells transduced with let-7 targeting decoys. In these, the depletion of HMGA2 only diminishes tumor cell growth under permissive conditions. The depletion of LIN28B and more prominently IGF2BP1 severely impairs tumor cell viability, self-renewal and 2D as well as 3D migration. In conclusion, this suggests the targeting of the HMGA2-LIN28B-IGF2BP1 triangle as a promising strategy in cancer treatment. PMID:26917013

  18. Lin28a uses distinct mechanisms of binding to RNA and affects miRNA levels positively and negatively.

    PubMed

    Nowak, Jakub Stanislaw; Hobor, Fruzsina; Downie Ruiz Velasco, Angela; Choudhury, Nila Roy; Heikel, Gregory; Kerr, Alastair; Ramos, Andres; Michlewski, Gracjan

    2017-03-01

    Lin28a inhibits the biogenesis of let-7 miRNAs by triggering the polyuridylation and degradation of their precursors by terminal uridylyltransferases TUT4/7 and 3'-5' exoribonuclease Dis3l2, respectively. Previously, we showed that Lin28a also controls the production of neuro-specific miRNA-9 via a polyuridylation-independent mechanism. Here we reveal that the sequences and structural characteristics of pre-let-7 and pre-miRNA-9 are eliciting two distinct modes of binding to Lin28a. We present evidence that Dis3l2 controls miRNA-9 production. Finally, we show that the constitutive expression of untagged Lin28a during neuronal differentiation in vitro positively and negatively affects numerous other miRNAs. Our findings shed light on the role of Lin28a in differentiating cells and on the ways in which one RNA-binding protein can perform multiple roles in the regulation of RNA processing. © 2017 Nowak et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  19. LIN28 expression in malignant germ cell tumors down-regulates let-7 and increases oncogene levels

    PubMed Central

    Murray, Matthew J.; Saini, Harpreet K.; Siegler, Charlotte A.; Hanning, Jennifer E.; Barker, Emily M.; van Dongen, Stijn; Ward, Dawn M.; Raby, Katie L.; Groves, Ian J.; Scarpini, Cinzia G.; Pett, Mark R.; Thornton, Claire M.; Enright, Anton J.; Nicholson, James C.; Coleman, Nicholas

    2013-01-01

    Despite their clinico-pathologic heterogeneity, malignant germ-cell-tumors (GCTs) share molecular abnormalities that are likely to be functionally important. In this study, we investigated the potential significance of down-regulation of the let-7 family of tumor-suppressor microRNAs in malignant-GCTs. Microarray results from pediatric and adult samples (n=45) showed that LIN28, the negative-regulator of let-7 biogenesis, was abundant in malignant-GCTs, regardless of patient age, tumor site or histologic subtype. Indeed, a strong negative-correlation existed between LIN28 and let-7 levels in specimens with matched datasets. Low let-7 levels were biologically significant, since the sequence complementary to the 2-7nt common let-7 seed ‘GAGGUA’ was enriched in the 3′untranslated regions of mRNAs up-regulated in pediatric and adult malignant-GCTs, compared with normal gonads (a mixture of germ cells and somatic cells). We identified 27 mRNA targets of let-7 that were up-regulated in malignant-GCT cells, confirming significant negative-correlations with let-7 levels. Among 16 mRNAs examined in a largely independent set of specimens by qRT-PCR, we defined negative-associations with let-7e levels for six oncogenes, including MYCN, AURKB, CCNF, RRM2, MKI67 and C12orf5 (when including normal control tissues). Importantly, LIN28 depletion in malignant-GCT cells restored let-7 levels and repressed all of these oncogenic let-7 mRNA targets, with LIN28 levels correlating with cell proliferation and MYCN levels. Conversely, ectopic expression of let-7e was sufficient to reduce proliferation and down-regulate MYCN, AURKB and LIN28, the latter via a double-negative feedback loop. We concluded that the LIN28/let-7 pathway has a critical pathobiological role in malignant-GCTs and therefore offers a promising target for therapeutic intervention. PMID:23774216

  20. The oncogenic triangle of HMGA2, LIN28B and IGF2BP1 antagonizes tumor-suppressive actions of the let-7 family.

    PubMed

    Busch, Bianca; Bley, Nadine; Müller, Simon; Glaß, Markus; Misiak, Danny; Lederer, Marcell; Vetter, Martina; Strauß, Hans-Georg; Thomssen, Christoph; Hüttelmaier, Stefan

    2016-05-05

    The tumor-suppressive let-7 microRNA family targets various oncogene-encoding mRNAs. We identify the let-7 targets HMGA2, LIN28B and IGF2BP1 to form a let-7 antagonizing self-promoting oncogenic triangle. Surprisingly, 3'-end processing of IGF2BP1 mRNAs is unaltered in aggressive cancers and tumor-derived cells although IGF2BP1 synthesis was proposed to escape let-7 attack by APA-dependent (alternative polyadenylation) 3' UTR shortening. However, the expression of the triangle factors is inversely correlated with let-7 levels and promoted by LIN28B impairing let-7 biogenesis. Moreover, IGF2BP1 enhances the expression of all triangle factors by recruiting the respective mRNAs in mRNPs lacking AGO proteins and let-7 miRNAs. This indicates that the downregulation of let-7, largely facilitated by LIN28B upregulation, and the protection of let-7 target mRNAs by IGF2BP1-directed shielding in mRNPs synergize in enhancing the expression of triangle factors. The oncogenic potential of this triangle was confirmed in ovarian cancer (OC)-derived ES-2 cells transduced with let-7 targeting decoys. In these, the depletion of HMGA2 only diminishes tumor cell growth under permissive conditions. The depletion of LIN28B and more prominently IGF2BP1 severely impairs tumor cell viability, self-renewal and 2D as well as 3D migration. In conclusion, this suggests the targeting of the HMGA2-LIN28B-IGF2BP1 triangle as a promising strategy in cancer treatment. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  1. Efficient method to create integration-free, virus-free, Myc and Lin28-free human induced pluripotent stem cells from adherent cells.

    PubMed

    Kamath, Anant; Ternes, Sara; McGowan, Stephen; English, Anthony; Mallampalli, Rama; Moy, Alan B

    2017-08-01

    Nonviral induced pluripotent stem cell (IPSC) reprogramming is not efficient without the oncogenes, Myc and Lin28 . We describe a robust Myc and Lin28 -free IPSC reprogramming approach using reprogramming molecules. IPSC colony formation was compared in the presence and absence of Myc and Lin28 by the mixture of reprogramming molecules and episomal vectors. While more colonies were observed in cultures transfected with the aforementioned oncogenes, the Myc and Lin28 -free method achieved the same reprogramming efficiency as reports that used these oncogenes. Further, all colonies were fully reprogrammed based on expression of SSEA4, even in the absence of Myc and Lin28 . This approach satisfies an important regulatory pathway for developing IPSC cell therapies with lower clinical risk.

  2. Trim25 Is an RNA-Specific Activator of Lin28a/TuT4-Mediated Uridylation.

    PubMed

    Choudhury, Nila Roy; Nowak, Jakub S; Zuo, Juan; Rappsilber, Juri; Spoel, Steven H; Michlewski, Gracjan

    2014-11-20

    RNA binding proteins have thousands of cellular RNA targets and often exhibit opposite or passive molecular functions. Lin28a is a conserved RNA binding protein involved in pluripotency and tumorigenesis that was previously shown to trigger TuT4-mediated pre-let-7 uridylation, inhibiting its processing and targeting it for degradation. Surprisingly, despite binding to other pre-microRNAs (pre-miRNAs), only pre-let-7 is efficiently uridylated by TuT4. Thus, we hypothesized the existence of substrate-specific cofactors that stimulate Lin28a-mediated pre-let-7 uridylation or restrict its functionality on non-let-7 pre-miRNAs. Through RNA pull-downs coupled with quantitative mass spectrometry, we identified the E3 ligase Trim25 as an RNA-specific cofactor for Lin28a/TuT4-mediated uridylation. We show that Trim25 binds to the conserved terminal loop (CTL) of pre-let-7 and activates TuT4, allowing for more efficient Lin28a-mediated uridylation. These findings reveal that protein-modifying enzymes, only recently shown to bind RNA, can guide the function of canonical ribonucleoprotein (RNP) complexes in cis, thereby providing an additional level of specificity.

  3. Trim25 Is an RNA-Specific Activator of Lin28a/TuT4-Mediated Uridylation

    PubMed Central

    Choudhury, Nila Roy; Nowak, Jakub S.; Zuo, Juan; Rappsilber, Juri; Spoel, Steven H.; Michlewski, Gracjan

    2014-01-01

    Summary RNA binding proteins have thousands of cellular RNA targets and often exhibit opposite or passive molecular functions. Lin28a is a conserved RNA binding protein involved in pluripotency and tumorigenesis that was previously shown to trigger TuT4-mediated pre-let-7 uridylation, inhibiting its processing and targeting it for degradation. Surprisingly, despite binding to other pre-microRNAs (pre-miRNAs), only pre-let-7 is efficiently uridylated by TuT4. Thus, we hypothesized the existence of substrate-specific cofactors that stimulate Lin28a-mediated pre-let-7 uridylation or restrict its functionality on non-let-7 pre-miRNAs. Through RNA pull-downs coupled with quantitative mass spectrometry, we identified the E3 ligase Trim25 as an RNA-specific cofactor for Lin28a/TuT4-mediated uridylation. We show that Trim25 binds to the conserved terminal loop (CTL) of pre-let-7 and activates TuT4, allowing for more efficient Lin28a-mediated uridylation. These findings reveal that protein-modifying enzymes, only recently shown to bind RNA, can guide the function of canonical ribonucleoprotein (RNP) complexes in cis, thereby providing an additional level of specificity. PMID:25457611

  4. Knockdown of miR-128a induces Lin28a expression and reverts myeloid differentiation blockage in acute myeloid leukemia

    PubMed Central

    De Luca, Luciana; Trino, Stefania; Laurenzana, Ilaria; Tagliaferri, Daniela; Falco, Geppino; Grieco, Vitina; Bianchino, Gabriella; Nozza, Filomena; Campia, Valentina; D'Alessio, Francesca; La Rocca, Francesco; Caivano, Antonella; Villani, Oreste; Cilloni, Daniela; Musto, Pellegrino; Del Vecchio, Luigi

    2017-01-01

    Lin28A is a highly conserved RNA-binding protein that concurs to control the balance between stemness and differentiation in several tissue lineages. Here, we report the role of miR-128a/Lin28A axis in blocking cell differentiation in acute myeloid leukemia (AML), a genetically heterogeneous disease characterized by abnormally controlled proliferation of myeloid progenitor cells accompanied by partial or total inability to undergo terminal differentiation. First, we found Lin28A underexpressed in blast cells from AML patients and AML cell lines as compared with CD34+ normal precursors. In vitro transfection of Lin28A in NPM1-mutated OCI-AML3 cell line significantly triggered cell-cycle arrest and myeloid differentiation, with increased expression of macrophage associate genes (EGR2, ZFP36 and ANXA1). Furthermore, miR-128a, a negative regulator of Lin28A, was found overexpressed in AML cells compared with normal precursors, especially in acute promyelocytic leukemia (APL) and in ‘AML with maturation’ (according to 2016 WHO classification of myeloid neoplasms and acute leukemia). Its forced overexpression by lentiviral infection in OCI-AML3 downregulated Lin28A with ensuing repression of macrophage-oriented differentiation. Finally, knockdown of miR-128a in OCI-AML3 and in APL/AML leukemic cells (by transfection and lentiviral infection, respectively) induced myeloid cell differentiation and increased expression of Lin28A, EGR2, ZFP36 and ANXA1, reverting myeloid differentiation blockage. In conclusion, our findings revealed a new mechanism for AML differentiation blockage, suggesting new strategies for AML therapy based upon miR-128a inhibition. PMID:28569789

  5. Overexpression of Lin28b in Neural Stem Cells is Insufficient for Brain Tumor Formation, but Induces Pathological Lobulation of the Developing Cerebellum.

    PubMed

    Wefers, Annika K; Lindner, Sven; Schulte, Johannes H; Schüller, Ulrich

    2017-02-01

    LIN28B is a homologue of the RNA-binding protein LIN28A and regulates gene expression during development and carcinogenesis. It is strongly upregulated in a variety of brain tumors, such as medulloblastoma, embryonal tumor with multilayered rosettes (ETMR), atypical teratoid/rhabdoid tumor (AT/RT), or glioblastoma, but the effect of an in vivo overexpression of LIN28B on the developing central nervous system is unknown. We generated transgenic mice that either overexpressed Lin28b in Math1-positive cerebellar granule neuron precursors or in a broad range of Nestin-positive neural precursors. Sections of the cerebellar vermis from adult Math1-Cre::lsl-Lin28b mice had an additional subfissure in lobule IV. Vermes from p0 and p7 Nestin-Cre::lsl-Lin28b mice appeared normal, but we found a pronounced vermal hypersublobulation at p15 and p21 in these mice. Also, the external granule cell layer (EGL) was thicker at p15 than in controls, contained more proliferating cells, and persisted up to p21. Consistently, some Pax6- and NeuN-positive cells were present in the EGL of Nestin-Cre::lsl-Lin28b mice even at p21, and we detected more NeuN-positive granule neuron precursors in the molecular layer (ML) as compared to control. Finally, we found some residual Pax2-positive precursors of inhibitory interneurons in the ML of Nestin-Cre::lsl-Lin28b mice at p21, which have already disappeared in controls. We conclude that while overexpression of LIN28B in Nestin-positive cells does not lead to tumor formation, it results in a protracted development of granule cells and inhibitory interneurons and leads to a hypersublobulation of the cerebellar vermis.

  6. Expression and associations of TRAF1, BMI-1, ALDH1, and Lin28B in oral squamous cell carcinoma.

    PubMed

    Wu, Tian-Fu; Li, Yi-Cun; Ma, Si-Rui; Bing-Liu; Zhang, Wen-Feng; Sun, Zhi-Jun

    2017-04-01

    Tumor necrosis factor receptor-associated factor 1, an adaptor protein of tumor necrosis factor 2, is involved in classical nuclear factor (NF)-κB activation and lymphocyte recruitment. However, less is known about the expression and association of tumor necrosis factor receptor-associated factor 1 with cancer stem cell markers in oral squamous cell carcinoma. This study aimed to investigate the expression of tumor necrosis factor receptor-associated factor 1 and stem cell characteristic markers (lin28 homolog B, B cell-specific Moloney murine leukemia virus integration site 1, and aldehyde dehydrogenase 1) in oral squamous cell carcinoma and analyze their relations. Paraffin-embedded tissues of 78 oral squamous cell carcinomas, 39 normal oral mucosa, and 12 oral dysplasia tissues were employed in tissue microarrays, and the expression of tumor necrosis factor receptor-associated factor 1, B cell-specific Moloney murine leukemia virus integration site 1, aldehyde dehydrogenase 1, and lin28 homolog B was measured by immunohistostaining and digital pathological analysis. The expression of tumor necrosis factor receptor-associated factor 1 was higher in the oral squamous cell carcinoma group as compared with the expression in the oral mucosa (p < 0.01) and oral dysplasia (p < 0.001) groups. In addition, the expression of tumor necrosis factor receptor-associated factor 1 was associated with those of B cell-specific Moloney murine leukemia virus integration site 1, aldehyde dehydrogenase 1, and lin28 homolog B (p = 0.032, r 2  = 0.109; p < 0.0001, r 2  = 0.64; and p < 0.001, r 2  = 0.16) in oral squamous cell carcinoma. The patient survival rate was lower in the highly expressed tumor necrosis factor receptor-associated factor 1 group, although the difference was not significant. The clustering analysis showed that tumor necrosis factor receptor-associated factor 1 was most related to aldehyde dehydrogenase 1. These findings suggest

  7. LIN28A enhances the therapeutic potential of cultured neural stem cells in a Parkinson's disease model.

    PubMed

    Rhee, Yong-Hee; Kim, Tae-Ho; Jo, A-Young; Chang, Mi-Yoon; Park, Chang-Hwan; Kim, Sang-Mi; Song, Jae-Jin; Oh, Sang-Min; Yi, Sang-Hoon; Kim, Hyeon Ho; You, Bo-Hyun; Nam, Jin-Wu; Lee, Sang-Hun

    2016-10-01

    The original properties of tissue-specific stem cells, regardless of their tissue origins, are inevitably altered during in vitro culturing, lessening the clinical and research utility of stem cell cultures. Specifically, neural stem cells derived from the ventral midbrain lose their dopamine neurogenic potential, ventral midbrain-specific phenotypes, and repair capacity during in vitro cell expansion, all of which are critical concerns in using the cultured neural stem cells in therapeutic approaches for Parkinson's disease. In this study, we observed that the culture-dependent changes of neural stem cells derived from the ventral midbrain coincided with loss of RNA-binding protein LIN28A expression. When LIN28A expression was forced and sustained during neural stem cell expansion using an inducible expression-vector system, loss of dopamine neurogenic potential and midbrain phenotypes after long-term culturing was blocked. Furthermore, dopamine neurons that differentiated from neural stem cells exhibited remarkable survival and resistance against toxic insults. The observed effects were not due to a direct action of LIN28A on the differentiated dopamine neurons, but rather its action on precursor neural stem cells as exogene expression was switched off in the differentiating/differentiated cultures. Remarkable and reproducible behavioural recovery was shown in all Parkinson's disease rats grafted with neural stem cells expanded with LIN28A expression, along with extensive engraftment of dopamine neurons expressing mature neuronal and midbrain-specific markers. These findings suggest that LIN28A expression during stem cell expansion could be used to prepare therapeutically competent donor cells. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Functional study of risk loci of stem cell-associated gene lin-28B and associations with disease survival outcomes in epithelial ovarian cancer.

    PubMed

    Lu, Lingeng; Katsaros, Dionyssios; Mayne, Susan T; Risch, Harvey A; Benedetto, Chiara; Canuto, Emilie Marion; Yu, Herbert

    2012-11-01

    Several single-nucleotide polymorphisms (SNPs) of the stem cell-associated gene lin-28B have been identified in association with ovarian cancer and ovarian cancer-related risk factors. However, whether these SNPs are functional or might be potential biomarkers for ovarian cancer prognosis remains unknown. The purposes of this study were to investigate the functional relevance of the identified lin-28B SNPs, as well as the associations of genotype and phenotype with epithelial ovarian cancer (EOC) survival. We analyzed five SNPs and mRNA levels of lin-28B in 211 primary EOC tissues using Taqman(®) SNP genotyping assays and SYBR green-based real-time PCR, respectively. The RNA secondary structures at the region of a genome-wide association-identified intronic rs314276 were analyzed theoretically with mfold and experimentally with circular dichroism spectroscopy. We found that rs314276 was a cis-acting expression quantitative trait locus (eQTL) in both additive and dominant models, while rs7759938 and rs314277 were significant or of borderline significance in dominant models only. The rs314276 variant significantly affects RNA secondary structure. No SNPs alone were associated with patient survival. However, we found that among patients initially responding to chemotherapy, those with higher lin-28B expression had higher mortality risk (hazard ratio =3.27, 95% confidence interval: 1.63-6.56) and relapse risk (hazard ratio = 2.53, 95% confidence interval: 1.41-4.54) than those with lower expression, and these associations remained in multivariate analyses. These results suggest that rs314276 alters RNA secondary structure and thereby influences gene expression, and that lin-28B is a cancer stem cell-associated marker, which may be a pharmaceutical target in the management of EOC.

  9. The gga-let-7 family post-transcriptionally regulates TGFBR1 and LIN28B during the differentiation process in early chick development.

    PubMed

    Lee, Sang In; Jeon, Mi-Hyang; Kim, Jeom Sun; Jeon, Ik-Soo; Byun, Sung June

    2015-12-01

    Early chick embryogenesis is governed by a complex mechanism involving transcriptional and post-transcriptional regulation, although how post-transcriptional processes influence the balance between pluripotency and differentiation during early chick development have not been previously investigated. Here, we characterized the microRNA (miRNA) signature associated with differentiation in the chick embryo, and found that as expression of the gga-let-7 family increases through early development, expression of their direct targets, TGFBR1 and LIN28B, decreases; indeed, gga-let-7a-5p and gga-let-7b miRNAs directly bind to TGFBR1 and LIN28B transcripts. Our data further indicate that TGFBR1 and LIN28B maintain pluripotency by regulating POUV, NANOG, and CRIPTO. Therefore, gga-let-7 miRNAs act as post-transcriptional regulators of differentiation in blastodermal cells by repressing the expression of the TGFBR1 and LIN28B, which intrinsically controls blastodermal cell differentiation in early chick development. © 2015 Wiley Periodicals, Inc.

  10. Therapeutic Inhibitors of LIN28/let-7 Pathway in Ovarian Cancer

    DTIC Science & Technology

    2015-09-01

    generate loss of function lines (siRNA and the CrispR /Cas9 system). Task 4. Determine oncogenic properties associated with TUTase and LIN28B loss in...of-function cell lines to complement our already generated shRNA lines, we are developing handson experience with CrispR /Cas9 technology to...generate stable cell lines where our genes of interest will be inactivated. The advantage of the CrispR /Cas9 method is that stable lines can be

  11. 27 CFR 28.144 - Export marks.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.144... § 28.144 Export marks. (a) General Requirement. In addition to the marks and brands required to be... brewer shall mark the word “Export” on each container or case of beer, or the words “Beer concentrate for...

  12. 27 CFR 28.103 - Export marks.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.103... Manufacturing Bonded Warehouse § 28.103 Export marks. (a) General. In addition to the marks and brands required... provisions of part 19 of this chapter, the proprietor shall mark the word “Export” on the Government side of...

  13. 27 CFR 28.193 - Export marks.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.193... Drawback Filing of Notice and Removal § 28.193 Export marks. In addition to the marks and brands required... chapter, the exporter shall mark the word “Export” on the Government side of each case or Government head...

  14. 27 CFR 28.154 - Export marks.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.154..., for Exportation or Transfer to a Foreign-Trade Zone § 28.154 Export marks. In addition to the marks... provisions of part 19 of this chapter, the proprietor shall mark the word “Export” on the Government side of...

  15. Multiple transcription factors directly regulate Hox gene lin-39 expression in ventral hypodermal cells of the C. elegans embryo and larva, including the hypodermal fate regulators LIN-26 and ELT-6.

    PubMed

    Liu, Wan-Ju; Reece-Hoyes, John S; Walhout, Albertha J M; Eisenmann, David M

    2014-05-13

    Hox genes encode master regulators of regional fate specification during early metazoan development. Much is known about the initiation and regulation of Hox gene expression in Drosophila and vertebrates, but less is known in the non-arthropod invertebrate model system, C. elegans. The C. elegans Hox gene lin-39 is required for correct fate specification in the midbody region, including the Vulval Precursor Cells (VPCs). To better understand lin-39 regulation and function, we aimed to identify transcription factors necessary for lin-39 expression in the VPCs, and in particular sought factors that initiate lin-39 expression in the embryo. We used the yeast one-hybrid (Y1H) method to screen for factors that bound to 13 fragments from the lin-39 region: twelve fragments contained sequences conserved between C. elegans and two other nematode species, while one fragment was known to drive reporter gene expression in the early embryo in cells that generate the VPCs. Sixteen transcription factors that bind to eight lin-39 genomic fragments were identified in yeast, and we characterized several factors by verifying their physical interactions in vitro, and showing that reduction of their function leads to alterations in lin-39 levels and lin-39::GFP reporter expression in vivo. Three factors, the orphan nuclear hormone receptor NHR-43, the hypodermal fate regulator LIN-26, and the GATA factor ELT-6 positively regulate lin-39 expression in the embryonic precursors to the VPCs. In particular, ELT-6 interacts with an enhancer that drives GFP expression in the early embryo, and the ELT-6 site we identified is necessary for proper embryonic expression. These three factors, along with the factors ZTF-17, BED-3 and TBX-9, also positively regulate lin-39 expression in the larval VPCs. These results significantly expand the number of factors known to directly bind and regulate lin-39 expression, identify the first factors required for lin-39 expression in the embryo, and hint at a

  16. 27 CFR 28.123 - Export marks.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.123..., or Transportation to a Manufacturing Bonded Warehouse § 28.123 Export marks. (a) General. In addition... filled under the provisions of part 24 of this chapter, the proprietor shall mark the word “Export” on...

  17. lin-4 and the NRDE pathway are required to activate a transgenic lin-4 reporter but not the endogenous lin-4 locus in C. elegans.

    PubMed

    Jiao, Alan L; Foster, Daniel J; Dixon, Julia; Slack, Frank J

    2018-01-01

    As the founding member of the microRNA (miRNA) gene family, insights into lin-4 regulation and function have laid a conceptual foundation for countless miRNA-related studies that followed. We previously showed that a transcriptional lin-4 reporter in C. elegans was positively regulated by a lin-4-complementary element (LCE), and by lin-4 itself. In this study, we sought to (1) identify additional factors required for lin-4 reporter expression, and (2) validate the endogenous relevance of a potential positive autoregulatory mechanism of lin-4 expression. We report that all four core nuclear RNAi factors (nrde-1, nrde-2, nrde-3 and nrde-4), positively regulate lin-4 reporter expression. In contrast, endogenous lin-4 levels were largely unaffected in nrde-2;nrde-3 mutants. Further, an endogenous LCE deletion generated by CRISPR-Cas9 revealed that the LCE was also not necessary for the activity of the endogenous lin-4 promoter. Finally, mutations in mature lin-4 did not reduce primary lin-4 transcript levels. Taken together, these data indicate that under growth conditions that reveal effects at the transgenic locus, a direct, positive autoregulatory mechanism of lin-4 expression does not occur in the context of the endogenous lin-4 locus.

  18. In vitro expansion of Lin+ and Lin- mononuclear cells from human peripheral blood

    NASA Astrophysics Data System (ADS)

    Norhaiza, H. Siti; Rohaya, M. A. W.; Zarina, Z. A. Intan; Hisham, Z. A. Shahrul

    2013-11-01

    Haematopoietic stem cells (HSCs) are used in the therapy of blood disorders due to the ability of these cells to reconstitute haematopoietic lineage cells when transplanted into myeloablative recipients. However, substantial number of cells is required in order for the reconstitution to take place. Since HSCs present in low frequency, larger number of donor is required to accommodate the demand of transplantable HSCs. Therefore, in vitro expansion of HSCs will have profound impact on clinical purposes. The aim of this study was to expand lineage negative (Lin-) stem cells from human peripheral blood. Total peripheral blood mononuclear cells (PBMNCs) were fractionated from human blood by density gradient centrifugation. Subsequently, PBMNCs were subjected to magnetic assisted cell sorter (MACS) which depletes lineage positive (Lin+) mononuclear cells expressing lineage positive markers such as CD2, CD3, CD11b, CD14, CD15, CD16, CD19, CD56, CD123, and CD235a to obtained Lin- cell population. The ability of Lin+ and Lin- to survive in vitro was explored by culturing both cell populations in complete medium consisting of Alpha-Minimal Essential Medium (AMEM) +10% (v/v) Newborn Calf Serum (NBCS)+ 2% (v/v) pen/strep. In another experiment, Lin+ and Lin- were cultured with complete medium supplemented with 10ng/mL of the following growth factors: stem cell factor (SCF), interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF), 2IU/mL of Erythropoietin (Epo) and 20ng/mL of IL-6. Three samples were monitored in static culture for 22 days. The expansion potential was assessed by the number of total viable cells, counted by trypan blue exclusion assay. It was found that Lin+ mononuclear cells were not able to survive either in normal proliferation medium or proliferation medium supplemented with cytokines. Similarly, Lin- stem cells were not able to survive in proliferation medium however, addition of cytokines into the proliferation medium support Lin

  19. 27 CFR 28.223 - Export marks.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.223... Export marks. In addition to the marks and brands required to be placed on kegs, barrels, cases, crates... “Export” on each container or case before removal for export, for use on vessels or aircraft, or for...

  20. 27 CFR 28.216 - Export marks.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.216 Section 28.216 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS EXPORTATION OF ALCOHOL Exportation of Wine With Benefit of Drawback § 28.216...

  1. In vitro expansion of Lin{sup +} and Lin{sup −} mononuclear cells from human peripheral blood

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Norhaiza, H. Siti; Zarina, Z. A. Intan; Hisham, Z. A. Shahrul

    2013-11-27

    Haematopoietic stem cells (HSCs) are used in the therapy of blood disorders due to the ability of these cells to reconstitute haematopoietic lineage cells when transplanted into myeloablative recipients. However, substantial number of cells is required in order for the reconstitution to take place. Since HSCs present in low frequency, larger number of donor is required to accommodate the demand of transplantable HSCs. Therefore, in vitro expansion of HSCs will have profound impact on clinical purposes. The aim of this study was to expand lineage negative (Lin{sup −}) stem cells from human peripheral blood. Total peripheral blood mononuclear cells (PBMNCs)more » were fractionated from human blood by density gradient centrifugation. Subsequently, PBMNCs were subjected to magnetic assisted cell sorter (MACS) which depletes lineage positive (Lin{sup +}) mononuclear cells expressing lineage positive markers such as CD2, CD3, CD11b, CD14, CD15, CD16, CD19, CD56, CD123, and CD235a to obtained Lin{sup −} cell population. The ability of Lin{sup +} and Lin{sup −} to survive in vitro was explored by culturing both cell populations in complete medium consisting of Alpha-Minimal Essential Medium (AMEM) +10% (v/v) Newborn Calf Serum (NBCS)+ 2% (v/v) pen/strep. In another experiment, Lin{sup +} and Lin{sup −} were cultured with complete medium supplemented with 10ng/mL of the following growth factors: stem cell factor (SCF), interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF), 2IU/mL of Erythropoietin (Epo) and 20ng/mL of IL-6. Three samples were monitored in static culture for 22 days. The expansion potential was assessed by the number of total viable cells, counted by trypan blue exclusion assay. It was found that Lin{sup +} mononuclear cells were not able to survive either in normal proliferation medium or proliferation medium supplemented with cytokines. Similarly, Lin{sup −} stem cells were not able to survive in proliferation medium

  2. The NCU Lu-Lin Observatory Survived the Taiwan 921 Earthquake

    NASA Astrophysics Data System (ADS)

    Tsay, W. S.; Chang, K. H.; Li, H. H.

    1999-12-01

    The NCU (National Central University) Lu-Lin Observatory is located at Mt. Front Lu-Lin, 120o 52' 25" E and 23o 28' 07" N, a 2862-m peak in the Yu-Shan National Park. The construction of Lu-Lin Observatory was finished in January 1999. Fortunately the Lu-Lin Observatory survived the Taiwan 921 Earthquake that was 7.3 on the Ritcher scale. We are proud of the design of Lu-Lin Observatory adopted H-beam and steel wall even the center of earthquake was only 40 km away. The initial study of Lu-Lin site was started since late 1989. Later on, a three-year project was founded by the National Science Council , which supported the development of a modern seeing monitor for this site survey study from 1990 through 1993. The average seeing of Lu-Lin site is about 1.39 arc-second with average 200 clear nights annually. The sky background of this site is 20.72 mag/arcsec2 in V band and 21.22 mag/arcsec2 in B band. The Lu-Lin observatory is developed for both research and education activity. A homemade 76-cm Super Light Telescope (SLT) and three TAOS's 50-cm robotic telescopes will be the two major research facilities. This work is supported by the National Science Council of Taiwan.

  3. RNA-Binding Protein L1TD1 Interacts with LIN28 via RNA and is Required for Human Embryonic Stem Cell Self-Renewal and Cancer Cell Proliferation

    PubMed Central

    Närvä, Elisa; Rahkonen, Nelly; Emani, Maheswara Reddy; Lund, Riikka; Pursiheimo, Huha-Pekka; Nästi, Juuso; Autio, Reija; Rasool, Omid; Denessiouk, Konstantin; Lähdesmäki, Harri; Rao, Anjana; Lahesmaa, Ritta

    2012-01-01

    Human embryonic stem cells (hESC) have a unique capacity to self-renew and differentiate into all the cell types found in human body. Although the transcriptional regulators of pluripotency are well studied, the role of cytoplasmic regulators is still poorly characterized. Here, we report a new stem cell-specific RNA-binding protein L1TD1 (ECAT11, FLJ10884) required for hESC self-renewal and cancer cell proliferation. Depletion of L1TD1 results in immediate downregulation of OCT4 and NANOG. Furthermore, we demonstrate that OCT4, SOX2, and NANOG all bind to the promoter of L1TD1. Moreover, L1TD1 is highly expressed in seminomas, and depletion of L1TD1 in these cancer cells influences self-renewal and proliferation. We show that L1TD1 colocalizes and interacts with LIN28 via RNA and directly with RNA helicase A (RHA). LIN28 has been reported to regulate translation of OCT4 in complex with RHA. Thus, we hypothesize that L1TD1 is part of the L1TD1-RHA-LIN28 complex that could influence levels of OCT4. Our results strongly suggest that L1TD1 has an important role in the regulation of stemness. PMID:22162396

  4. A lncRNA fine tunes the dynamics of a cell state transition involving Lin28, let-7 and de novo DNA methylation

    PubMed Central

    Li, Meng Amy; Amaral, Paulo P; Cheung, Priscilla; Bergmann, Jan H; Kinoshita, Masaki; Kalkan, Tüzer; Ralser, Meryem; Robson, Sam; von Meyenn, Ferdinand; Paramor, Maike; Yang, Fengtang; Chen, Caifu; Nichols, Jennifer; Spector, David L; Kouzarides, Tony; He, Lin; Smith, Austin

    2017-01-01

    Execution of pluripotency requires progression from the naïve status represented by mouse embryonic stem cells (ESCs) to a state capacitated for lineage specification. This transition is coordinated at multiple levels. Non-coding RNAs may contribute to this regulatory orchestra. We identified a rodent-specific long non-coding RNA (lncRNA) linc1281, hereafter Ephemeron (Eprn), that modulates the dynamics of exit from naïve pluripotency. Eprn deletion delays the extinction of ESC identity, an effect associated with perduring Nanog expression. In the absence of Eprn, Lin28a expression is reduced which results in persistence of let-7 microRNAs, and the up-regulation of de novo methyltransferases Dnmt3a/b is delayed. Dnmt3a/b deletion retards ES cell transition, correlating with delayed Nanog promoter methylation and phenocopying loss of Eprn or Lin28a. The connection from lncRNA to miRNA and DNA methylation facilitates the acute extinction of naïve pluripotency, a pre-requisite for rapid progression from preimplantation epiblast to gastrulation in rodents. Eprn illustrates how lncRNAs may introduce species-specific network modulations. DOI: http://dx.doi.org/10.7554/eLife.23468.001 PMID:28820723

  5. Safety and Feasibility of Lin- Cells Administration to ALS Patients: A Novel View on Humoral Factors and miRNA Profiles.

    PubMed

    Sobuś, Anna; Baumert, Bartłomiej; Litwińska, Zofia; Gołąb-Janowska, Monika; Stępniewski, Jacek; Kotowski, Maciej; Pius-Sadowska, Ewa; Kawa, Miłosz P; Gródecka-Szwajkiewicz, Dorota; Peregud-Pogorzelski, Jarosław; Dulak, Józef; Nowacki, Przemysław; Machaliński, Bogusław

    2018-04-27

    Therapeutic options for amyotrophic lateral sclerosis (ALS) are still limited. Great hopes, however, are placed in growth factors that show neuroprotective abilities (e.g., nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF)) and in the immune modulating features, in particular, the anti-inflammatory effects. In our study we aimed to investigate whether a bone marrow-derived lineage-negative (Lin-) cells population, after autologous application into cerebrospinal fluid (CSF), is able to produce noticeable concentrations of trophic factors and inflammatory-related proteins and thus influence the clinical course of ALS. To our knowledge, the evaluation of Lin- cells transplantation for ALS treatment has not been previously reported. Early hematopoietic Lin- cells were isolated from twelve ALS patients’ bone marrow, and later, the suspension of cells was administered into the subarachnoid space by lumbar puncture. Concentrations of selected proteins in the CSF and plasma were quantified by multiplex fluorescent bead-based immunoassays at different timepoints post-transplantation. We also chose microRNAs (miRNAs) related to muscle biology (miRNA-1, miRNA-133a, and miRNA-206) and angiogenesis and inflammation (miRNA-155 and miRNA-378) and tested, for the first time, their expression profiles in the CSF and plasma of ALS patients after Lin- cells transplantation. The injection of bone marrow cells resulted in decreased concentration of selected inflammatory proteins (C3) after Lin- cells injection, particularly in patients who had a better clinical outcome. Moreover, several analyzed miRNAs have changed expression levels in the CSF and plasma of ALS patients subsequent to Lin- cells administration. Interestingly, the expression of miR-206 increased in ALS patients, while miR-378 decreased both in the CSF and plasma one month after the cells’ injection. We propose that autologous lineage

  6. Antagonism of LIN-17/Frizzled and LIN-18/Ryk in nematode vulva induction reveals evolutionary alterations in core developmental pathways.

    PubMed

    Wang, Xiaoyue; Sommer, Ralf J

    2011-07-01

    Most diversity in animals and plants results from the modification of already existing structures. Many organ systems, for example, are permanently modified during evolution to create developmental and morphological diversity, but little is known about the evolution of the underlying developmental mechanisms. The theory of developmental systems drift proposes that the development of conserved morphological structures can involve large-scale modifications in their regulatory mechanisms. We test this hypothesis by comparing vulva induction in two genetically tractable nematodes, Caenorhabditis elegans and Pristionchus pacificus. Previous work indicated that the vulva is induced by epidermal growth factor (EGF)/RAS and WNT signaling in Caenorhabditis and Pristionchus, respectively. Here, we show that the evolution of vulva induction involves major molecular alterations and that this shift of signaling pathways involves a novel wiring of WNT signaling and the acquisition of novel domains in otherwise conserved receptors in Pristionchus vulva induction. First, Ppa-LIN-17/Frizzled acts as an antagonist of WNT signaling and suppresses the ligand Ppa-EGL-20 by ligand sequestration. Second, Ppa-LIN-18/Ryk transmits WNT signaling and requires inhibitory SH3 domain binding motifs, unknown from Cel-LIN-18/Ryk. Third, Ppa-LIN-18/Ryk signaling involves Axin and β-catenin and Ppa-axl-1/Axin is epistatic to Ppa-lin-18/Ryk. These results confirm developmental system drift as an important theory for the evolution of organ systems and they highlight the significance of protein modularity in signal transduction and the dynamics of signaling networks.

  7. Antagonism of LIN-17/Frizzled and LIN-18/Ryk in Nematode Vulva Induction Reveals Evolutionary Alterations in Core Developmental Pathways

    PubMed Central

    Wang, Xiaoyue; Sommer, Ralf J.

    2011-01-01

    Most diversity in animals and plants results from the modification of already existing structures. Many organ systems, for example, are permanently modified during evolution to create developmental and morphological diversity, but little is known about the evolution of the underlying developmental mechanisms. The theory of developmental systems drift proposes that the development of conserved morphological structures can involve large-scale modifications in their regulatory mechanisms. We test this hypothesis by comparing vulva induction in two genetically tractable nematodes, Caenorhabditis elegans and Pristionchus pacificus. Previous work indicated that the vulva is induced by epidermal growth factor (EGF)/RAS and WNT signaling in Caenorhabditis and Pristionchus, respectively. Here, we show that the evolution of vulva induction involves major molecular alterations and that this shift of signaling pathways involves a novel wiring of WNT signaling and the acquisition of novel domains in otherwise conserved receptors in Pristionchus vulva induction. First, Ppa-LIN-17/Frizzled acts as an antagonist of WNT signaling and suppresses the ligand Ppa-EGL-20 by ligand sequestration. Second, Ppa-LIN-18/Ryk transmits WNT signaling and requires inhibitory SH3 domain binding motifs, unknown from Cel-LIN-18/Ryk. Third, Ppa-LIN-18/Ryk signaling involves Axin and β-catenin and Ppa-axl-1/Axin is epistatic to Ppa-lin-18/Ryk. These results confirm developmental system drift as an important theory for the evolution of organ systems and they highlight the significance of protein modularity in signal transduction and the dynamics of signaling networks. PMID:21814488

  8. Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B

    PubMed Central

    Lee, Chih-Yung Sean; Lu, Tu

    2017-01-01

    Nanos RNA-binding proteins are required for germline development in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of primordial germ cells (PGCs) lacking the nanos homologs nos-1 and nos-2 in C. elegans. nos-1nos-2 PGCs fail to silence hundreds of transcripts normally expressed in oocytes. We find that this misregulation is due to both delayed turnover of maternal transcripts and inappropriate transcriptional activation. The latter appears to be an indirect consequence of delayed turnover of the maternally-inherited transcription factor LIN-15B, a synMuvB class transcription factor known to antagonize PRC2 activity. PRC2 is required for chromatin reprogramming in the germline, and the transcriptome of PGCs lacking PRC2 resembles that of nos-1nos-2 PGCs. Loss of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These findings suggest that Nanos promotes germ cell fate by downregulating maternal RNAs and proteins that would otherwise interfere with PRC2-dependent reprogramming of PGC chromatin. PMID:29111977

  9. Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B.

    PubMed

    Lee, Chih-Yung Sean; Lu, Tu; Seydoux, Geraldine

    2017-11-07

    Nanos RNA-binding proteins are required for germline development in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of primordial germ cells (PGCs) lacking the nanos homologs nos-1 and nos-2 in C. elegans. nos-1nos-2 PGCs fail to silence hundreds of transcripts normally expressed in oocytes. We find that this misregulation is due to both delayed turnover of maternal transcripts and inappropriate transcriptional activation. The latter appears to be an indirect consequence of delayed turnover of the maternally-inherited transcription factor LIN-15B, a synMuvB class transcription factor known to antagonize PRC2 activity. PRC2 is required for chromatin reprogramming in the germline, and the transcriptome of PGCs lacking PRC2 resembles that of nos-1nos-2 PGCs. Loss of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These findings suggest that Nanos promotes germ cell fate by downregulating maternal RNAs and proteins that would otherwise interfere with PRC2-dependent reprogramming of PGC chromatin.

  10. The DREAM complex through its subunit Lin37 cooperates with Rb to initiate quiescence

    PubMed Central

    Mages, Christina FS; Wintsche, Axel; Bernhart, Stephan H

    2017-01-01

    The retinoblastoma Rb protein is an important factor controlling the cell cycle. Yet, mammalian cells carrying Rb deletions are still able to arrest under growth-limiting conditions. The Rb-related proteins p107 and p130, which are components of the DREAM complex, had been suggested to be responsible for a continued ability to arrest by inhibiting E2f activity and by recruiting chromatin-modifying enzymes. Here, we show that p130 and p107 are not sufficient for DREAM-dependent repression. We identify the MuvB protein Lin37 as an essential factor for DREAM function. Cells not expressing Lin37 proliferate normally, but DREAM completely loses its ability to repress genes in G0/G1 while all remaining subunits, including p130/p107, still bind to target gene promoters. Furthermore, cells lacking both Rb and Lin37 are incapable of exiting the cell cycle. Thus, Lin37 is an essential component of DREAM that cooperates with Rb to induce quiescence. PMID:28920576

  11. Ground-state geometries and stability of impurity doped clusters: LinBe and LinMg (n=1-12)

    NASA Astrophysics Data System (ADS)

    Deshpande, M.; Dhavale, A.; Zope, R. R.; Chacko, S.; Kanhere, D. G.

    2000-12-01

    We have investigated the ground-state geometries of LinBe and LinMg (n=1-12) clusters using ab initio molecular dynamics. These divalent impurities Be and Mg induce different geometries and follow a different growth path for n>5. LinMg clusters are significantly different from the host geometries while LinBe clusters can be approximately viewed as Be occupying an interstitial site in the host. Our results indicate that Be gets trapped inside the Li cage, while Mg remains on the surface of the cluster. Mg-induced geometries become three-dimensional earlier at n=4 as compared to the Be system. In spite of a distinct arrangement of atoms in both cases the character of the wave functions in the d manifold is remarkably similar. In both cases an eight valence electron system has been found to be the most stable, in conformity with the spherical jellium model.

  12. Weighted Lin-Wang Tests for Crossing Hazards

    PubMed Central

    Koziol, James A.; Jia, Zhenyu

    2014-01-01

    Lin and Wang have introduced a quadratic version of the logrank test, appropriate for situations in which the underlying survival distributions may cross. In this note, we generalize the Lin-Wang procedure to incorporate weights and investigate the performance of Lin and Wang's test and weighted versions in various scenarios. We find that weighting does increase statistical power in certain situations; however, none of the procedures was dominant under every scenario. PMID:24795776

  13. Bacterial diversity and real-time PCR based assessment of linA and linB gene distribution at hexachlorocyclohexane contaminated sites.

    PubMed

    Lal, Devi; Jindal, Swati; Kumari, Hansi; Jit, Simran; Nigam, Aeshna; Sharma, Pooja; Kumari, Kirti; Lal, Rup

    2015-03-01

    The disposal of hexachlorocyclohexane (HCH) muck has created large number of HCH dumpsites all over the world from where the harmful HCH isomers are leaking into the environment. Bacteria have evolved at such contaminated sites that have the ability to degrade HCH. Degradation of various HCH isomers in bacterial strains is mediated primarily by two genes: linA and linB which encode dehydrochlorinase and haloalkane dehalogenase respectively. In this study we explored one such highly contaminated HCH dumpsite located in Lucknow, Uttar Pradesh, India. To assess the biostimulation potential of the contaminated site, microbial diversity study and real-time PCR based quantification of lin genes was carried out. The soil samples from dumpsite and surrounding areas were found to be highly contaminated with HCH residue levels as high as 1.8 × 10(5)  mg kg(-1). The residues were detected in areas upto 13 km from the dumpsite. Sphingomonads, Chromohalobacter, and Marinobacter were the dominant genera present at the dump-site. Role of Sphingomonads in HCH degradation has been well documented. The highest copy numbers of linA and linB genes as determined using real-time PCR were 6.2 × 10(4) and 5.3 × 10(5), respectively, were found in sample from the dump site. The presence of Sphingomonads, linA, and linB genes from HCH contaminated soil indicates the presence of indigenous bacterial communities capable of HCH degradation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. 76 FR 50111 - Airworthiness Directives; Fokker Services B.V. Model F.28 Mark 1000, 2000, 3000, and 4000 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-12

    ... Directives; Fokker Services B.V. Model F.28 Mark 1000, 2000, 3000, and 4000 Airplanes AGENCY: Federal... Services B.V. Model F.28 Mark 1000, 2000, 3000, and 4000 airplanes, certificated in any category, all...

  15. The mutational landscape of MYCN, Lin28b and ALK F1174L driven murine neuroblastoma mimics human disease.

    PubMed

    De Wilde, Bram; Beckers, Anneleen; Lindner, Sven; Kristina, Althoff; De Preter, Katleen; Depuydt, Pauline; Mestdagh, Pieter; Sante, Tom; Lefever, Steve; Hertwig, Falk; Peng, Zhiyu; Shi, Le-Ming; Lee, Sangkyun; Vandermarliere, Elien; Martens, Lennart; Menten, Björn; Schramm, Alexander; Fischer, Matthias; Schulte, Johannes; Vandesompele, Jo; Speleman, Frank

    2018-02-02

    Genetically engineered mouse models have proven to be essential tools for unraveling fundamental aspects of cancer biology and for testing novel therapeutic strategies. To optimally serve these goals, it is essential that the mouse model faithfully recapitulates the human disease. Recently, novel mouse models for neuroblastoma have been developed. Here, we report on the further genomic characterization through exome sequencing and DNA copy number analysis of four of the currently available murine neuroblastoma model systems ( ALK, Th- MYCN, Dbh- MYCN and Lin28b ). The murine tumors revealed a low number of genomic alterations - in keeping with human neuroblastoma - and a positive correlation of the number of genetic lesions with the time to onset of tumor formation was observed. Gene copy number alterations are the hallmark of both murine and human disease and frequently affect syntenic genomic regions. Despite low mutational load, the genes mutated in murine disease were found to be enriched for genes mutated in human disease. Taken together, our study further supports the validity of the tested mouse models for mechanistic and preclinical studies of human neuroblastoma.

  16. A Dynamic Attitude Measurement System Based on LINS

    PubMed Central

    Li, Hanzhou; Pan, Quan; Wang, Xiaoxu; Zhang, Juanni; Li, Jiang; Jiang, Xiangjun

    2014-01-01

    A dynamic attitude measurement system (DAMS) is developed based on a laser inertial navigation system (LINS). Three factors of the dynamic attitude measurement error using LINS are analyzed: dynamic error, time synchronization and phase lag. An optimal coning errors compensation algorithm is used to reduce coning errors, and two-axis wobbling verification experiments are presented in the paper. The tests indicate that the attitude accuracy is improved 2-fold by the algorithm. In order to decrease coning errors further, the attitude updating frequency is improved from 200 Hz to 2000 Hz. At the same time, a novel finite impulse response (FIR) filter with three notches is designed to filter the dither frequency of the ring laser gyro (RLG). The comparison tests suggest that the new filter is five times more effective than the old one. The paper indicates that phase-frequency characteristics of FIR filter and first-order holder of navigation computer constitute the main sources of phase lag in LINS. A formula to calculate the LINS attitude phase lag is introduced in the paper. The expressions of dynamic attitude errors induced by phase lag are derived. The paper proposes a novel synchronization mechanism that is able to simultaneously solve the problems of dynamic test synchronization and phase compensation. A single-axis turntable and a laser interferometer are applied to verify the synchronization mechanism. The experiments results show that the theoretically calculated values of phase lag and attitude error induced by phase lag can both match perfectly with testing data. The block diagram of DAMS and physical photos are presented in the paper. The final experiments demonstrate that the real-time attitude measurement accuracy of DAMS can reach up to 20″ (1σ) and the synchronization error is less than 0.2 ms on the condition of three axes wobbling for 10 min. PMID:25177802

  17. Regulation of C. elegans L4 cuticle collagen genes by the heterochronic protein LIN-29.

    PubMed

    Abete-Luzi, Patricia; Eisenmann, David M

    2018-05-01

    The cuticle, the outer covering of the nematode C. elegans, is synthesized five times during the worm's life by the underlying hypodermis. Cuticle collagens, the major cuticle component, are encoded by a large family of col genes and, interestingly, many of these genes express predominantly at a single developmental stage. This temporal preference motivated us to investigate the mechanisms underlying col gene expression and here we focus on a subset of col genes expressed in the L4 stage. We identified minimal promoter regions of <300 bp for col-38, col-49, and col-63. In these regions, we predicted cis-regulatory sequences and evaluated their function in vivo via mutagenesis of a col-38p::yfp reporter. We used RNAi to study the requirement for candidate transcription regulators ELT-1 and ELT-3, LIN-29, and the LIN-29 co-factor MAB-10, and found LIN-29 to be necessary for the expression of four L4-specific genes (col-38, col-49, col-63, and col-138). Temporal misexpression of LIN-29 was also sufficient to activate these genes at a different developmental stage. The LIN-29 DNA-binding domain bound the col-38, col-49, and col-63 minimal promoters in vitro. For col-38 we showed that the LIN-29 sites necessary for reporter expression in vivo are also bound in vitro: this is the first identification of specific binding sites for LIN-29 necessary for in vivo target gene expression. © 2018 Wiley Periodicals, Inc.

  18. Differential Processing of let-7a Precursors Influences RRM2 Expression and Chemosensitivity in Pancreatic Cancer: Role of LIN-28 and SET Oncoprotein

    PubMed Central

    Bhutia, Yangzom Doma; Hung, Sau Wai; Krentz, Madeline; Patel, Dimal; Lovin, Dylan; Manoharan, Radhika; Thomson, J. Michael; Govindarajan, Rajgopal

    2013-01-01

    Overexpression of ribonucleotide reductase subunit M2 (RRM2), involved in deoxyribonucleotide synthesis, drives the chemoresistance of pancreatic cancer to nucleoside analogs (e.g., gemcitabine). While silencing RRM2 by synthetic means has shown promise in reducing chemoresistance, targeting endogenous molecules, especially microRNAs (miRNAs), to advance chemotherapeutic outcomes has been poorly explored. Based on computational predictions, we hypothesized that the let-7 tumor suppressor miRNAs will inhibit RRM2-mediated gemcitabine chemoresistance in pancreatic cancer. Reduced expression of the majority of let-7 miRNAs with an inverse relationship to RRM2 expression was identified in innately gemcitabine-resistant pancreatic cancer cell lines. Direct binding of let-7 miRNAs to the 3′ UTR of RRM2 transcripts identified post-transcriptional regulation of RRM2 influencing gemcitabine chemosensitivity. Intriguingly, overexpression of human precursor-let-7 miRNAs led to differential RRM2 expression and chemosensitivity responses in a poorly differentiated pancreatic cancer cell line, MIA PaCa-2. Defective processing of let-7a precursors to mature forms, in part, explained the discrepancies observed with let-7a expressional outcomes. Consistently, the ratios of mature to precursor let-7a were progressively reduced in gemcitabine-sensitive L3.6pl and Capan-1 cell lines induced to acquire gemcitabine resistance. Besides known regulators of let-7 biogenesis (e.g., LIN-28), short hairpin RNA library screening identified several novel RNA binding proteins, including the SET oncoprotein, to differentially impact let-7 biogenesis and chemosensitivity in gemcitabine-sensitive versus -resistant pancreatic cancer cells. Further, LIN-28 and SET knockdown in the cells led to profound reductions in cellular proliferation and colony-formation capacities. Finally, defective processing of let-7a precursors with a positive correlation to RRM2 overexpression was identified in patient

  19. 46 CFR 28.135 - Lifesaving equipment markings.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY UNINSPECTED VESSELS REQUIREMENTS FOR COMMERCIAL... Resolution A.658(16). (d) A wearable personal flotation device must be marked with the name of either the... Equipment Markings Item Markings Required Name of vessel Retroflective material Wearable personal flotation...

  20. 46 CFR 28.135 - Lifesaving equipment markings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY UNINSPECTED VESSELS REQUIREMENTS FOR COMMERCIAL... Resolution A.658(16). (d) A wearable personal flotation device must be marked with the name of either the... Equipment Markings Item Markings Required Name of vessel Retroflective material Wearable personal flotation...

  1. Integrative genomic analyses identify LIN28 and OLIG2 as markers of survival and metastatic potential in childhood central nervous system primitive neuro-ectodermal brain tumours

    PubMed Central

    Picard, Daniel; Miller, Suzanne; Hawkins, Cynthia E; Bouffet, Eric; Rogers, Hazel A; Chan, Tiffany SY; Kim, Seung-Ki; Ra, Young-Shin; Fangusaro, Jason; Korshunov, Andrey; Toledano, Helen; Nakamura, Hideo; Hayden, James T; Chan, Jennifer; Lafay-Cousin, Lucie; Hu, Ping X; Fan, Xing; Muraszko, Karin M; Pomeroy, Scott L; Lau, Ching C; Ng, Ho-Keung; Jones, Chris; Meter, Timothy Van; Clifford, Steven C; Eberhart, Charles; Gajjar, Amar; Pfister, Stefan M; Grundy, Richard G; Huang, Annie

    2013-01-01

    Background Childhood Central Nervous System Primitive Neuro-Ectodermal brain Tumours (CNS-PNETs) are highly aggressive brain tumours for which molecular features and best therapeutic strategy remains unknown. We interrogated a large cohort of these rare tumours in order to identify molecular markers that will enhance clinical management of CNS-PNET. Methods Transcriptional and copy number profiles from primary hemispheric CNS-PNETs were examined using clustering, gene and pathways enrichment analyses to discover tumour sub-groups and group-specific molecular markers. Immuno-histochemical and/or gene expression analyses were used to validate and examine the clinical significance of novel sub-group markers in 123 primary CNS-PNETs. Findings Three molecular sub-groups of CNS-PNETs distinguished by primitive neural (Group 1), oligo-neural (Group 2) and mesenchymal lineage (Group 3) gene expression signature were identified. Tumour sub-groups exhibited differential expression of cell lineage markers, LIN28 and OLIG2, and correlated with distinct demographics, survival and metastatic incidence. Group 1 tumours affected primarily younger females; male: female ratios were respectively 0.61 (median age 2.9 years; 95% CI: 2.4–5.2; p≤ 0.005), 1.25 (median age 7.9 years; 95% CI: 6–9.7) and 1.63 (median age 5.9 years; 95% CI: 4.9–7.8) for group 1, 2 and 3 patients. Overall outcome was poorest in group 1 patients which had a median survival of 0.8 years (95% CI: 0.47–1.2; p=0.019) as compared to 1.8 years (95% CI: 1.4–2.3) and 4.3 years; (95% CI: 0.82–7.8) respectively for group 2 and 3 patients. Group 3 tumours had the highest incidence of metastases at diagnosis; M0: M+ ratio were respectively 0.9 and 3.9 for group 3, versus group 1 and 2 tumours combined (p=0.037). Interpretation LIN28 and OLIG2 represent highly promising, novel diagnostic and prognostic molecular markers for CNS PNET that warrants further evaluation in prospective clinical trials. PMID:22691720

  2. A Network of Genes Antagonistic to the LIN-35 Retinoblastoma Protein of Caenorhabditis elegans

    PubMed Central

    Polley, Stanley R. G.; Fay, David S.

    2012-01-01

    The Caenorhabditis elegans pRb ortholog, LIN-35, functions in a wide range of cellular and developmental processes. This includes a role of LIN-35 in nutrient utilization by the intestine, which it carries out redundantly with SLR-2, a zinc-finger protein. This and other redundant functions of LIN-35 were identified in genetic screens for mutations that display synthetic phenotypes in conjunction with loss of lin-35. To explore the intestinal role of LIN-35, we conducted a genome-wide RNA-interference-feeding screen for suppressors of lin-35; slr-2 early larval arrest. Of the 26 suppressors identified, 17 fall into three functional classes: (1) ribosome biogenesis genes, (2) mitochondrial prohibitins, and (3) chromatin regulators. Further characterization indicates that different categories of suppressors act through distinct molecular mechanisms. We also tested lin-35; slr-2 suppressors, as well as suppressors of the synthetic multivulval phenotype, to determine the spectrum of lin-35-synthetic phenotypes that could be suppressed following inhibition of these genes. We identified 19 genes, most of which are evolutionarily conserved, that can suppress multiple unrelated lin-35-synthetic phenotypes. Our study reveals a network of genes broadly antagonistic to LIN-35 as well as genes specific to the role of LIN-35 in intestinal and vulval development. Suppressors of multiple lin-35 phenotypes may be candidate targets for anticancer therapies. Moreover, screening for suppressors of phenotypically distinct synthetic interactions, which share a common altered gene, may prove to be a novel and effective approach for identifying genes whose activities are most directly relevant to the core functions of the shared gene. PMID:22542970

  3. Who Should Mark What? A Study of Factors Affecting Marking Accuracy in a Biology Examination

    ERIC Educational Resources Information Center

    Suto, Irenka; Nadas, Rita; Bell, John

    2011-01-01

    Accurate marking is crucial to the reliability and validity of public examinations, in England and internationally. Factors contributing to accuracy have been conceptualised as affecting either marking task demands or markers' personal expertise. The aim of this empirical study was to develop this conceptualisation through investigating the…

  4. Dynamics of Multiple lin Gene Expression in Sphingomonas paucimobilis B90A in Response to Different Hexachlorocyclohexane Isomers

    PubMed Central

    Suar, Mrutyunjay; van der Meer, Jan Roelof; Lawlor, Kirsten; Holliger, Christof; Lal, Rup

    2004-01-01

    Sphingomonas paucimobilis B90A is able to degrade the α-, β-, γ-, and δ-isomers of hexachlorocyclohexane (HCH). It contains the genes linA, linB, linC, linD, linE, and linR, which have been implicated in HCH degradation. In this study, dynamic expression of the lin genes was measured in chemostat-grown S. paucimobilis B90A by RNA dot blot hybridization and real-time reverse transcriptase PCR upon exposure to a pulse of different HCH isomers. Irrespective of the addition of HCH, linA, linB, and linC were all expressed constitutively. In contrast, linD and linE were induced with α-HCH (2 mg/liter) and γ-HCH (7 mg/liter). A sharp increase in mRNA levels for linD and linE was observed from 10 to 45 min after the addition of α- or γ-HCH. Induction of linD and linE was not detectable upon the addition of 0.7 mg of γ-HCH per liter, although the compound was degraded by the cells. The addition of β-HCH (5 mg/liter) or δ-HCH (20 mg/liter) did not lead to linE and linD induction, despite the fact that 50% of the compounds were degraded. This suggests that degradation of β- and δ-HCH proceeds by a different pathway than that of α- and γ-HCH. PMID:15528530

  5. 42 CFR 414.28 - Conversion factors.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Conversion factors. 414.28 Section 414.28 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... § 414.28 Conversion factors. CMS establishes CFs in accordance with section 1848(d) of the Act. (a) Base...

  6. 42 CFR 414.28 - Conversion factors.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Conversion factors. 414.28 Section 414.28 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... § 414.28 Conversion factors. CMS establishes CFs in accordance with section 1848(d) of the Act. (a) Base...

  7. Lin Receives 2010 Natural Hazards Focus Group Award for Graduate Research

    NASA Astrophysics Data System (ADS)

    2010-11-01

    Ning Lin has been awarded the Natural Hazards Focus Group Award for Graduate Research, given annually to a recent Ph.D. recipient for outstanding contributions to natural hazards research. Lin's thesis is entitled “Multi-hazard risk analysis related to hurricanes.” She is scheduled to present an invited talk in the Extreme Natural Events: Modeling, Prediction, and Mitigation session (NH20) during the 2010 AGU Fall Meeting, held 13-17 December in San Francisco, Calif. Lin will be formally presented with the award at the Natural Hazards focus group reception on 14 December 2010.

  8. Lin4Neuro: a customized Linux distribution ready for neuroimaging analysis

    PubMed Central

    2011-01-01

    Background A variety of neuroimaging software packages have been released from various laboratories worldwide, and many researchers use these packages in combination. Though most of these software packages are freely available, some people find them difficult to install and configure because they are mostly based on UNIX-like operating systems. We developed a live USB-bootable Linux package named "Lin4Neuro." This system includes popular neuroimaging analysis tools. The user interface is customized so that even Windows users can use it intuitively. Results The boot time of this system was only around 40 seconds. We performed a benchmark test of inhomogeneity correction on 10 subjects of three-dimensional T1-weighted MRI scans. The processing speed of USB-booted Lin4Neuro was as fast as that of the package installed on the hard disk drive. We also installed Lin4Neuro on a virtualization software package that emulates the Linux environment on a Windows-based operation system. Although the processing speed was slower than that under other conditions, it remained comparable. Conclusions With Lin4Neuro in one's hand, one can access neuroimaging software packages easily, and immediately focus on analyzing data. Lin4Neuro can be a good primer for beginners of neuroimaging analysis or students who are interested in neuroimaging analysis. It also provides a practical means of sharing analysis environments across sites. PMID:21266047

  9. Lin4Neuro: a customized Linux distribution ready for neuroimaging analysis.

    PubMed

    Nemoto, Kiyotaka; Dan, Ippeita; Rorden, Christopher; Ohnishi, Takashi; Tsuzuki, Daisuke; Okamoto, Masako; Yamashita, Fumio; Asada, Takashi

    2011-01-25

    A variety of neuroimaging software packages have been released from various laboratories worldwide, and many researchers use these packages in combination. Though most of these software packages are freely available, some people find them difficult to install and configure because they are mostly based on UNIX-like operating systems. We developed a live USB-bootable Linux package named "Lin4Neuro." This system includes popular neuroimaging analysis tools. The user interface is customized so that even Windows users can use it intuitively. The boot time of this system was only around 40 seconds. We performed a benchmark test of inhomogeneity correction on 10 subjects of three-dimensional T1-weighted MRI scans. The processing speed of USB-booted Lin4Neuro was as fast as that of the package installed on the hard disk drive. We also installed Lin4Neuro on a virtualization software package that emulates the Linux environment on a Windows-based operation system. Although the processing speed was slower than that under other conditions, it remained comparable. With Lin4Neuro in one's hand, one can access neuroimaging software packages easily, and immediately focus on analyzing data. Lin4Neuro can be a good primer for beginners of neuroimaging analysis or students who are interested in neuroimaging analysis. It also provides a practical means of sharing analysis environments across sites.

  10. The POU transcription factor UNC-86 controls the timing and ventral guidance of C. elegans axon growth

    PubMed Central

    Olsson-Carter, Katherine; Slack, Frank J.

    2012-01-01

    The in vivo mechanisms that coordinate the timing of axon growth and guidance are not well understood. In the C. elegans hermaphrodite specific neurons, the lin-4 microRNA controls the stage of axon initiation independent of the UNC-40 and SAX-3 ventral guidance receptors. lin-4 loss-of-function mutants exhibit marked delays in axon outgrowth, while lin-4 overexpression, leads to precocious growth in the L3. Here we show that loss of the POU transcription factor UNC-86 not only results in penetrant ventral axon growth defects in the HSNs, but also causes processes to extend in the L1, three stages earlier than wild-type. This temporal shift is not dependent on UNC-40 or SAX-3, and does not require the presence of lin-4. We propose that unc-86(lf) HSN axons are misguided due to the temporal decoupling of axon initiation and ventral guidance responses. PMID:21656875

  11. Reciprocal Expression of lin-41 and the microRNAs let-7 and mir-125 During Mouse Embryogenesis

    PubMed Central

    Schulman, Betsy R. Maller; Esquela-Kerscher, Aurora; Slack, Frank J.

    2008-01-01

    In C. elegans, heterochronic genes control the timing of cell fate determination during development. Two heterochronic genes, let-7 and lin-4, encode microRNAs (miRNAs) that down-regulate a third heterochronic gene lin-41 by binding to complementary sites in its 3’UTR. let-7 and lin-4 are conserved in mammals. Here we report the cloning and sequencing of mammalian lin-41 orthologs. We find that mouse and human lin-41 genes contain predicted conserved complementary sites for let-7 and the lin-4 ortholog, mir-125, in their 3’UTRs. Mouse lin-41 (Mlin-41) is temporally expressed in developing mouse embryos, most dramatically in the limb buds. Mlin-41 is down-regulated during mid-embryogenesis at the time when mouse let-7c and mir-125 RNA levels are up-regulated. Our results suggest that mammalian lin-41 is temporally regulated by miRNAs in order to direct key developmental events such as limb formation. PMID:16247770

  12. LinAir: A multi-element discrete vortex Weissinger aerodynamic prediction method

    NASA Technical Reports Server (NTRS)

    Durston, Donald A.

    1993-01-01

    LinAir is a vortex lattice aerodynamic prediction method similar to Weissinger's extended lifting-line theory, except that the circulation around a wing is represented by discrete horseshoe vortices, not a continuous distribution of vorticity. The program calculates subsonic longitudinal and lateral/directional aerodynamic forces and moments for arbitrary aircraft geometries. It was originally written by Dr. Ilan Kroo of Stanford University, and subsequently modified by the author to simplify modeling of complex configurations. The Polhamus leading-edge suction analogy was added by the author to extend the range of applicability of LinAir to low aspect ratio (i.e., fighter-type) configurations. A brief discussion of the theory of LinAir is presented, and details on how to run the program are given along with some comparisons with experimental data to validate the code. Example input and output files are given in the appendices to aid in understanding the program and its use. This version of LinAir runs in the VAX/VMS, Cray UNICOS, and Silicon Graphics Iris workstation environments at the time of this writing.

  13. Identification and Characterization of Genes That Interact with Lin-12 in Caenorhabditis Elegans

    PubMed Central

    Tax, F. E.; Thomas, J. H.; Ferguson, E. L.; Horvitz, H. R.

    1997-01-01

    We identified and characterized 14 extragenic mutations that suppressed the dominant egg-laying defect of certain lin-12 gain-of-function mutations. These suppressors defined seven genes: sup-17, lag-2, sel-4, sel-5, sel-6, sel-7 and sel-8. Mutations in six of the genes are recessive suppressors, whereas the two mutations that define the seventh gene, lag-2, are semi-dominant suppressors. These suppressor mutations were able to suppress other lin-12 gain-of-function mutations. The suppressor mutations arose at a very low frequency per gene, 10-50 times below the typical loss-of-function mutation frequency. The suppressor mutations in sup-17 and lag-2 were shown to be rare non-null alleles, and we present evidence that null mutations in these two genes cause lethality. Temperature-shift studies for two suppressor genes, sup-17 and lag-2, suggest that both genes act at approximately the same time as lin-12 in specifying a cell fate. Suppressor alleles of six of these genes enhanced a temperature-sensitive loss-of-function allele of glp-1, a gene related to lin-12 in structure and function. Our analysis of these suppressors suggests that the majority of these genes are part of a shared lin-12/glp-1 signal transduction pathway, or act to regulate the expression or stability of lin-12 and glp-1. PMID:9409830

  14. From lin-benzoguanines to lin-benzohypoxanthines as ligands for Zymomonas mobilis tRNA-guanine transglycosylase: replacement of protein-ligand hydrogen bonding by importing water clusters.

    PubMed

    Barandun, Luzi Jakob; Immekus, Florian; Kohler, Philipp C; Tonazzi, Sandro; Wagner, Björn; Wendelspiess, Severin; Ritschel, Tina; Heine, Andreas; Kansy, Manfred; Klebe, Gerhard; Diederich, François

    2012-07-23

    The foodborne illness shigellosis is caused by Shigella bacteria that secrete the highly cytotoxic Shiga toxin, which is also formed by the closely related enterohemorrhagic Escherichia coli (EHEC). It has been shown that tRNA-guanine transglycosylase (TGT) is essential for the pathogenicity of Shigella flexneri. Herein, the molecular recognition properties of a guanine binding pocket in Zymomonas mobilis TGT are investigated with a series of lin-benzohypoxanthine- and lin-benzoguanine-based inhibitors that bear substituents to occupy either the ribose-33 or the ribose-34 pocket. The three inhibitor scaffolds differ by the substituent at C(6) being H, NH(2), or NH-alkyl. These differences lead to major changes in the inhibition constants, pK(a) values, and binding modes. Compared to the lin-benzoguanines, with an exocyclic NH(2) at C(6), the lin-benzohypoxanthines without an exocyclic NH(2) group have a weaker affinity as several ionic protein-ligand hydrogen bonds are lost. X-ray cocrystal structure analysis reveals that a new water cluster is imported into the space vacated by the lacking NH(2) group and by a conformational shift of the side chain of catalytic Asp102. In the presence of an N-alkyl group at C(6) in lin-benzoguanine ligands, this water cluster is largely maintained but replacement of one of the water molecules in the cluster leads to a substantial loss in binding affinity. This study provides new insight into the role of water clusters at enzyme active sites and their challenging substitution by ligand parts, a topic of general interest in contemporary structure-based drug design. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. [Analysis of acid rain characteristics of Lin'an Regional Background Station using long-term observation data].

    PubMed

    Li, Zheng-Quan; Ma, Hao; Mao, Yu-Ding; Feng, Tao

    2014-02-01

    Using long-term observation data of acid rain at Lin'an Regional Background Station (Lin'an RBS), this paper studied the interannual and monthly variations of acid rain, the reasons for the variations, and the relationships between acid rain and meteorological factors. The results showed that interannual variation of acid rain at Lin'an RBS had a general increasing trend in which there were two obvious intensifying processes and two distinct weakening processes, during the period ranging from 1985 to 2012. In last two decades, the monthly variation of acid rain at Lin'an RBS indicated that rain acidity and frequency of severe acid rain were increasing but the frequency of weak acid rain was decreasing when moving towards bilateral side months of July. Acid rain occurrence was affected by rainfall intensity, wind speed and wind direction. High frequency of severe acid rain and low frequency of weak acid rain were on days with drizzle, but high frequency of weak acid rain and low frequency of severe acid rain occurred on rainstorm days. With wind speed upgrading, the frequency of acid rain and the proportion of severe acid rain were declining, the pH value of precipitation was reducing too. Another character is that daily dominant wind direction of weak acid rain majorly converged in S-W section ,however that of severe acid rain was more likely distributed in N-E section. The monthly variation of acid rain at Lin'an RBS was mainly attributed to precipitation variation, the increasing and decreasing of monthly incoming wind from SSE-WSW and NWN-ENE sections of wind direction. The interannual variation of acid rain could be due to the effects of energy consumption raising and significant green policies conducted in Zhejiang, Jiangsu and Shanghai.

  16. Using Lin's method to solve Bykov's problems

    NASA Astrophysics Data System (ADS)

    Knobloch, Jürgen; Lamb, Jeroen S. W.; Webster, Kevin N.

    2014-10-01

    We consider nonwandering dynamics near heteroclinic cycles between two hyperbolic equilibria. The constituting heteroclinic connections are assumed to be such that one of them is transverse and isolated. Such heteroclinic cycles are associated with the termination of a branch of homoclinic solutions, and called T-points in this context. We study codimension-two T-points and their unfoldings in Rn. In our consideration we distinguish between cases with real and complex leading eigenvalues of the equilibria. In doing so we establish Lin's method as a unified approach to (re)gain and extend results of Bykov's seminal studies and related works. To a large extent our approach reduces the study to the discussion of intersections of lines and spirals in the plane. Case (RR): Under open conditions on the eigenvalues, there exist open sets in parameter space for which there exist periodic orbits close to the heteroclinic cycle. In addition, there exist two one-parameter families of homoclinic orbits to each of the saddle points p1 and p2.See Theorem 2.1 and Proposition 2.2 for precise statements and Fig. 2 for bifurcation diagrams. Cases (RC) and (CC): At the bifurcation point μ=0 and for each N≥2, there exists an invariant set S0N close to the heteroclinic cycle on which the first return map is topologically conjugated to a full shift on N symbols. For any fixed N≥2, the invariant set SμN persists for |μ| sufficiently small.In addition, there exist infinitely many transversal and non-transversal heteroclinic orbits connecting the saddle points p1 and p2 in a neighbourhood of μ=0, as well as infinitely many one-parameter families of homoclinic orbits to each of the saddle points.For full statements of the results see Theorem 2.3 and Propositions 2.4, 2.5 and Fig. 3 for bifurcation diagrams. The dynamics near T-points has been studied previously by Bykov [6-10], Glendinning and Sparrow [20], Kokubu [27,28] and Labouriau and Rodrigues [30,31,38]. See also the surveys

  17. LIN9, a Subunit of the DREAM Complex, Regulates Mitotic Gene Expression and Proliferation of Embryonic Stem Cells

    PubMed Central

    Esterlechner, Jasmina; Reichert, Nina; Iltzsche, Fabian; Krause, Michael; Finkernagel, Florian; Gaubatz, Stefan

    2013-01-01

    The DREAM complex plays an important role in regulation of gene expression during the cell cycle. We have previously shown that the DREAM subunit LIN9 is required for early embryonic development and for the maintenance of the inner cell mass in vitro. In this study we examined the effect of knocking down LIN9 on ESCs. We demonstrate that depletion of LIN9 alters the cell cycle distribution of ESCs and results in an accumulation of cells in G2 and M and in an increase of polyploid cells. Genome-wide expression studies showed that the depletion of LIN9 results in downregulation of mitotic genes and in upregulation of differentiation-specific genes. ChIP-on chip experiments showed that mitotic genes are direct targets of LIN9 while lineage specific markers are regulated indirectly. Importantly, depletion of LIN9 does not alter the expression of pluripotency markers SOX2, OCT4 and Nanog and LIN9 depleted ESCs retain alkaline phosphatase activity. We conclude that LIN9 is essential for proliferation and genome stability of ESCs by activating genes with important functions in mitosis and cytokinesis. PMID:23667535

  18. LIN-39/Hox triggers cell division and represses EFF-1/fusogen-dependent vulval cell fusion

    PubMed Central

    Shemer, Gidi; Podbilewicz, Benjamin

    2002-01-01

    General mechanisms by which Hox genes establish cell fates are known. However, a few Hox effectors mediating cell behaviors have been identified. Here we found the first effector of LIN-39/HoxD4/Dfd in Caenorhabditis elegans. In specific vulval precursor cells (VPCs), LIN-39 represses early and late expression of EFF-1, a membrane protein essential for cell fusion. Repression of eff-1 is also achieved by the activity of CEH-20/Exd/Pbx, a known cofactor of Hox proteins. Unfused VPCs in lin-39(−);eff-1(−) double mutants fail to divide but migrate, executing vulval fates. Thus, lin-39 is essential for inhibition of EFF-1-dependent cell fusion and stimulation of cell proliferation during vulva formation. Supplemental material is available at http://www.genesdev.org. PMID:12502736

  19. H3K9me2/3 Binding of the MBT Domain Protein LIN-61 Is Essential for Caenorhabditis elegans Vulva Development

    PubMed Central

    Koester-Eiserfunke, Nora; Fischle, Wolfgang

    2011-01-01

    MBT domain proteins are involved in developmental processes and tumorigenesis. In vitro binding and mutagenesis studies have shown that individual MBT domains within clustered MBT repeat regions bind mono- and dimethylated histone lysine residues with little to no sequence specificity but discriminate against the tri- and unmethylated states. However, the exact function of promiscuous histone methyl-lysine binding in the biology of MBT domain proteins has not been elucidated. Here, we show that the Caenorhabditis elegans four MBT domain protein LIN-61, in contrast to other MBT repeat factors, specifically interacts with histone H3 when methylated on lysine 9, displaying a strong preference for di- and trimethylated states (H3K9me2/3). Although the fourth MBT repeat is implicated in this interaction, H3K9me2/3 binding minimally requires MBT repeats two to four. Further, mutagenesis of residues conserved with other methyl-lysine binding MBT regions in the fourth MBT repeat does not abolish interaction, implicating a distinct binding mode. In vivo, H3K9me2/3 interaction of LIN-61 is required for C. elegans vulva development within the synMuvB pathway. Mutant LIN-61 proteins deficient in H3K9me2/3 binding fail to rescue lin-61 synMuvB function. Also, previously identified point mutant synMuvB alleles are deficient in H3K9me2/3 interaction although these target residues that are outside of the fourth MBT repeat. Interestingly, lin-61 genetically interacts with two other synMuvB genes, hpl-2, an HP1 homologous H3K9me2/3 binding factor, and met-2, a SETDB1 homologous H3K9 methyl transferase (H3K9MT), in determining C. elegans vulva development and fertility. Besides identifying the first sequence specific and di-/trimethylation binding MBT domain protein, our studies imply complex multi-domain regulation of ligand interaction of MBT domains. Our results also introduce a mechanistic link between LIN-61 function and biology, and they establish interplay of the H3K9me2

  20. 28 CFR 17.25 - Identification and markings.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... classified at a level equivalent to that level of classification assigned by the originating foreign government. (c) Information assigned a level of classification under predecessor Executive Orders shall be... ACCESS TO CLASSIFIED INFORMATION Classified Information § 17.25 Identification and markings. (a...

  1. Clinical application of Lin's biopsy grasper for intrauterine targeted biopsy and polypectomy during office hysteroscopy.

    PubMed

    Cheng, Hsin-Yi; Lin, Bao-Liang; Tseng, Jen-Yu; Ueno, Kazunori; Nakada, Sakura

    2018-06-01

    Hysteroscopy has widely been used for diagnosis of the uterine cavity; however, target biopsy has often been difficult in part to the inherent limitations of ancillary instruments. Lin's biopsy grasper was specifically designed to work in conjunction with a flexible hysteroscope to obtain intrauterine biopsy under transabdominal sonography. Herein, we share our clinical experience in the management of endometrial abnormalities with the use of Lin's biopsy grasper during office-based hysteroscopy. From February 2006 to November 2016, the use of Lin's biopsy grasper for tissue biopsy was attempted on 126 cases. We retrospectively recorded and analyzed the patients' preoperative characteristics and biopsy outcomes to demonstrate the feasibility and efficacy of Lin's biopsy grasper. Out of the one hundred and twenty-six enrolled patients, satisfactory targeted biopsies were achieved; including high diagnostic rate (92.1%, with 116 cases confirmed histologically) and adequate tissue retrieval (77.8%, with 98 cases obtaining optimal specimen volume). All patients tolerated the procedure without analgesics or anesthesia. Diagnostic flexible hysteroscopy combined with the use of Lin's biopsy grasper has proven to be an effective tool for intrauterine evaluation and obtaining tissue sample. Copyright © 2018. Published by Elsevier B.V.

  2. Metabolomics of hexachlorocyclohexane (HCH) transformation: ratio of LinA to LinB determines metabolic fate of HCH isomers.

    PubMed

    Geueke, Birgit; Garg, Nidhi; Ghosh, Sneha; Fleischmann, Thomas; Holliger, Christof; Lal, Rup; Kohler, Hans-Peter E

    2013-04-01

    Although the production and use of technical hexachlorocyclohexane (HCH) and lindane (the purified insecticidal isomer γ-HCH) are prohibited in most countries, residual concentrations still constitute an immense environmental burden. Many studies describe the mineralization of γ-HCH by bacterial strains under aerobic conditions. However, the metabolic fate of the other HCH isomers is not well known. In this study, we investigated the transformation of α-, β-, γ-, δ-, ε-HCH, and a heptachlorocyclohexane isomer in the presence of varying ratios of the two enzymes that initiate γ-HCH degradation, a dehydrochlorinase (LinA) and a haloalkane dehalogenase (LinB). Each substrate yielded a unique metabolic profile that was strongly dependent on the enzyme ratio. Comparison of these results to those of in vivo experiments with different bacterial isolates showed that HCH transformation in the tested strains was highly optimized towards productive metabolism of γ-HCH and that under these conditions other HCH-isomers were metabolized to mixtures of dehydrochlorinated and hydroxylated side-products. In view of these results, bioremediation efforts need very careful planning and toxicities of accumulating metabolites need to be evaluated. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

  3. Biodegradation of γ-hexachlorocyclohexane by transgenic hairy root cultures of Cucurbita moschata that accumulate recombinant bacterial LinA.

    PubMed

    Nanasato, Yoshihiko; Namiki, Sayuri; Oshima, Masao; Moriuchi, Ryota; Konagaya, Ken-Ichi; Seike, Nobuyasu; Otani, Takashi; Nagata, Yuji; Tsuda, Masataka; Tabei, Yutaka

    2016-09-01

    γ-HCH was successfully degraded using LinA-expressed transgenic hairy root cultures of Cucurbita moschata . Fusing an endoplasmic reticulum-targeting signal peptide to LinA was essential for stable accumulation in the hairy roots. The pesticide γ-hexachlorocyclohexane (γ-HCH) is a persistent organic pollutant (POP) that raises public health and environmental pollution concerns worldwide. Although several isolates of γ-HCH-degrading bacteria are available, inoculating them directly into γ-HCH-contaminated soil is ineffective because of the bacterial survival rate. Cucurbita species incorporate significant amounts of POPs from soils compared with other plant species. Here, we describe a novel bioremediation strategy that combines the bacterial degradation of γ-HCH and the efficient uptake of γ-HCH by Cucurbita species. We produced transgenic hairy root cultures of Cucurbita moschata that expressed recombinant bacterial linA, isolated from the bacterium Sphingobium japonicum UT26. The LinA protein was accumulated stably in the hairy root cultures by fusing an endoplasmic reticulum (ER)-targeting signal peptide to LinA. Then, we demonstrated that the cultures degraded more than 90 % of γ-HCH (1 ppm) overnight and produced the γ-HCH metabolite 1,2,4-trichlorobenzene, indicating that LinA degraded γ-HCH. These results indicate that the gene linA has high potential for phytoremediation of environmental γ-HCH.

  4. 75 FR 70861 - Airworthiness Directives; Fokker Services B.V. Model F.28 Mark 0100, 1000, 2000, 3000, and 4000...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-19

    ... source can develop in the wing tank vapour space during fuel transfer from bag tank CWT [center wing tank... vapour space during fuel transfer from bag tank CWT [center wing tank], if the electrical power for... with a center wing tank (CWT); and Model F28 Mark 0100 airplanes, serial numbers 11244 through 11441...

  5. ChiLin: a comprehensive ChIP-seq and DNase-seq quality control and analysis pipeline.

    PubMed

    Qin, Qian; Mei, Shenglin; Wu, Qiu; Sun, Hanfei; Li, Lewyn; Taing, Len; Chen, Sujun; Li, Fugen; Liu, Tao; Zang, Chongzhi; Xu, Han; Chen, Yiwen; Meyer, Clifford A; Zhang, Yong; Brown, Myles; Long, Henry W; Liu, X Shirley

    2016-10-03

    Transcription factor binding, histone modification, and chromatin accessibility studies are important approaches to understanding the biology of gene regulation. ChIP-seq and DNase-seq have become the standard techniques for studying protein-DNA interactions and chromatin accessibility respectively, and comprehensive quality control (QC) and analysis tools are critical to extracting the most value from these assay types. Although many analysis and QC tools have been reported, few combine ChIP-seq and DNase-seq data analysis and quality control in a unified framework with a comprehensive and unbiased reference of data quality metrics. ChiLin is a computational pipeline that automates the quality control and data analyses of ChIP-seq and DNase-seq data. It is developed using a flexible and modular software framework that can be easily extended and modified. ChiLin is ideal for batch processing of many datasets and is well suited for large collaborative projects involving ChIP-seq and DNase-seq from different designs. ChiLin generates comprehensive quality control reports that include comparisons with historical data derived from over 23,677 public ChIP-seq and DNase-seq samples (11,265 datasets) from eight literature-based classified categories. To the best of our knowledge, this atlas represents the most comprehensive ChIP-seq and DNase-seq related quality metric resource currently available. These historical metrics provide useful heuristic quality references for experiment across all commonly used assay types. Using representative datasets, we demonstrate the versatility of the pipeline by applying it to different assay types of ChIP-seq data. The pipeline software is available open source at https://github.com/cfce/chilin . ChiLin is a scalable and powerful tool to process large batches of ChIP-seq and DNase-seq datasets. The analysis output and quality metrics have been structured into user-friendly directories and reports. We have successfully compiled 23

  6. The role of lin-22, a hairy/enhancer of split homolog, in patterning the peripheral nervous system of C. elegans.

    PubMed

    Wrischnik, L A; Kenyon, C J

    1997-08-01

    In C. elegans, six lateral epidermal stem cells, the seam cells V1-V6, are located in a row along the anterior-posterior (A/P) body axis. Anterior seam cells (V1-V4) undergo a fairly simple sequence of stem cell divisions and generate only epidermal cells. Posterior seam cells (V5 and V6) undergo a more complicated sequence of cell divisions that include additional rounds of stem cell proliferation and the production of neural as well as epidermal cells. In the wild type, activity of the gene lin-22 allows V1-V4 to generate their normal epidermal lineages rather than V5-like lineages. lin-22 activity is also required to prevent additional neurons from being produced by one branch of the V5 lineage. We find that the lin-22 gene exhibits homology to the Drosophila gene hairy, and that lin-22 activity represses neural development within the V5 lineage by blocking expression of the posterior-specific Hox gene mab-5 in specific cells. In addition, in order to prevent anterior V cells from generating V5-like lineages, wild-type lin-22 gene activity must inhibit (directly or indirectly) at least five downstream regulatory gene activities. In anterior body regions, lin-22(+) inhibits expression of the Hox gene mab-5. It also inhibits the activity of the achaete-scute homolog lin-32 and an unidentified gene that we postulate regulates stem cell division. Each of these three genes is required for the expression of a different piece of the ectopic V5-like lineages generated in lin-22 mutants. In addition, lin-22 activity prevents two other Hox genes, lin-39 and egl-5, from acquiring new activities within their normal domains of function along the A/P body axis. Some, but not all, of the patterning activities of lin-22 in C. elegans resemble those of hairy in Drosophila.

  7. Coordinated Regulation of Intestinal Functions in C. elegans by LIN-35/Rb and SLR-2

    PubMed Central

    Kirienko, Natalia V.; McEnerney, John D. K.; Fay, David S.

    2008-01-01

    LIN-35 is the sole C. elegans representative of the pocket protein family, which includes the mammalian Retinoblastoma protein pRb and its paralogs p107 and p130. In addition to having a well-established and central role in cell cycle regulation, pocket proteins have been increasingly implicated in the control of critical and diverse developmental and cellular processes. To gain a greater understanding of the roles of pocket proteins during development, we have characterized a synthetic genetic interaction between lin-35 and slr-2, which we show encodes a C2H2-type Zn-finger protein. Whereas animals harboring single mutations in lin-35 or slr-2 are viable and fertile, lin-35; slr-2 double mutants arrest uniformly in early larval development without obvious morphological defects. Using a combination of approaches including transcriptome profiling, mosaic analysis, starvation assays, and expression analysis, we demonstrate that both LIN-35 and SLR-2 act in the intestine to regulate the expression of many genes required for normal nutrient utilization. These findings represent a novel role for pRb family members in the maintenance of organ function. Our studies also shed light on the mechanistic basis of genetic redundancy among transcriptional regulators and suggest that synthetic interactions may result from the synergistic misregulation of one or more common targets. PMID:18437219

  8. [Professor LIN Guohua's experience of gold implantation at acupoint for rheumatoid arthritis].

    PubMed

    Li, Jingjing; Pei, Wenya

    2015-12-01

    Based on the pathogenesis and symptom of rheumatoid arthritis (RA), professor LIN Guohua's unique opinion and method for RA in clinical treatment are summarized and analyzed. In the opinion of Professor Lin, RA is considered as "Jinbi" and "Gubi" in TCM, which is caused by deficient root with superficial excess. Based on the symptoms of RA, attention should be focused on lung-kidney diagnosis and treatment, and gold and catgut implantation at acupoint can be mutually combined, which is aimed to provide a special and effective method for clinical treatment of RA.

  9. Initial results on computational performance of Intel Many Integrated Core (MIC) architecture: implementation of the Weather and Research Forecasting (WRF) Purdue-Lin microphysics scheme

    NASA Astrophysics Data System (ADS)

    Mielikainen, Jarno; Huang, Bormin; Huang, Allen H.

    2014-10-01

    Purdue-Lin scheme is a relatively sophisticated microphysics scheme in the Weather Research and Forecasting (WRF) model. The scheme includes six classes of hydro meteors: water vapor, cloud water, raid, cloud ice, snow and graupel. The scheme is very suitable for massively parallel computation as there are no interactions among horizontal grid points. In this paper, we accelerate the Purdue Lin scheme using Intel Many Integrated Core Architecture (MIC) hardware. The Intel Xeon Phi is a high performance coprocessor consists of up to 61 cores. The Xeon Phi is connected to a CPU via the PCI Express (PICe) bus. In this paper, we will discuss in detail the code optimization issues encountered while tuning the Purdue-Lin microphysics Fortran code for Xeon Phi. In particularly, getting a good performance required utilizing multiple cores, the wide vector operations and make efficient use of memory. The results show that the optimizations improved performance of the original code on Xeon Phi 5110P by a factor of 4.2x. Furthermore, the same optimizations improved performance on Intel Xeon E5-2603 CPU by a factor of 1.2x compared to the original code.

  10. Drosophila Lin-52 Acts in Opposition to Repressive Components of the Myb-MuvB/dREAM Complex

    PubMed Central

    Lewis, Peter W.; Sahoo, Debashis; Geng, Cuiyun; Bell, Maren

    2012-01-01

    The Drosophila melanogaster Myb-MuvB/dREAM complex (MMB/dREAM) participates in both the activation and repression of developmentally regulated genes and origins of DNA replication. Mutants in MMB subunits exhibit diverse phenotypes, including lethality, eye defects, reduced fecundity, and sterility. Here, we used P-element excision to generate mutations in lin-52, which encodes the smallest subunit of the MMB/dREAM complex. lin-52 is required for viability, as null mutants die prior to pupariation. The generation of somatic and germ line mutant clones indicates that lin-52 is required for adult eye development and for early embryogenesis via maternal effects. Interestingly, the maternal-effect embryonic lethality, larval lethality, and adult eye defects could be suppressed by mutations in other subunits of the MMB/dREAM complex. These results suggest that a partial MMB/dREAM complex is responsible for the lethality and eye defects of lin-52 mutants. Furthermore, these findings support a model in which the Lin-52 and Myb proteins counteract the repressive activities of the other members of the MMB/dREAM complex at specific genomic loci in a developmentally controlled manner. PMID:22688510

  11. The ubiquitin ligase LIN41/TRIM71 targets p53 to antagonize cell death and differentiation pathways during stem cell differentiation

    PubMed Central

    Nguyen, Duong Thi Thuy; Richter, Daniel; Michel, Geert; Mitschka, Sibylle; Kolanus, Waldemar; Cuevas, Elisa; Gregory Wulczyn, F

    2017-01-01

    Rapidity and specificity are characteristic features of proteolysis mediated by the ubiquitin-proteasome system. Therefore, the UPS is ideally suited for the remodeling of the embryonic stem cell proteome during the transition from pluripotent to differentiated states and its inverse, the generation of inducible pluripotent stem cells. The Trim-NHL family member LIN41 is among the first E3 ubiquitin ligases to be linked to stem cell pluripotency and reprogramming. Initially discovered in C. elegans as a downstream target of the let-7 miRNA, LIN41 is now recognized as a critical regulator of stem cell fates as well as the timing of neurogenesis. Despite being indispensable for embryonic development and neural tube closure in mice, the underlying mechanisms for LIN41 function in these processes are poorly understood. To better understand the specific contributions of the E3 ligase activity for the stem cell functions of LIN41, we characterized global changes in ubiquitin or ubiquitin-like modifications using Lin41-inducible mouse embryonic stem cells. The tumor suppressor protein p53 was among the five most strongly affected proteins in cells undergoing neural differentiation in response to LIN41 induction. We show that LIN41 interacts with p53, controls its abundance by ubiquitination and antagonizes p53-dependent pro-apoptotic and pro-differentiation responses. In vivo, the lack of LIN41 is associated with upregulation of Grhl3 and widespread caspase-3 activation, two downstream effectors of p53 with essential roles in neural tube closure. As Lin41-deficient mice display neural tube closure defects, we conclude that LIN41 is critical for the regulation of p53 functions in cell fate specification and survival during early brain development. PMID:28430184

  12. Genome packaging in EL and Lin68, two giant phiKZ-like bacteriophages of P. aeruginosa

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sokolova, O.S., E-mail: sokolova@mail.bio.msu.ru; A.V. Shoubnikov Institute of Crystallography RAS, Moscow; Shaburova, O.V.

    A unique feature of the Pseudomonas aeruginosa giant phage phiKZ is its way of genome packaging onto a spool-like protein structure, the inner body. Until recently, no similar structures have been detected in other phages. We have studied DNA packaging in P. aeruginosa phages EL and Lin68 using cryo-electron microscopy and revealed the presence of inner bodies. The shape and positioning of the inner body and the density of the DNA packaging in EL are different from those found in phiKZ and Lin68. This internal organization explains how the shorter EL genome is packed into a large EL capsid, whichmore » has the same external dimensions as the capsids of phiKZ and Lin68. The similarity in the structural organization in EL and other phiKZ-like phages indicates that EL is phylogenetically related to other phiKZ-like phages, and, despite the lack of detectable DNA homology, EL, phiKZ, and Lin68 descend from a common ancestor. - Highlights: • We performed a comparative structural study of giant P. aeruginosa phages: EL, Lin68 and phiKZ. • We revealed that the inner body is a common feature in giant phages. • The phage genome size correlates with the overall dimensions of the inner body.« less

  13. 75 FR 842 - Action Affecting Export Privileges: Hailin Lin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-06

    ... DEPARTMENT OF COMMERCE Bureau of Industry and Security Action Affecting Export Privileges: Hailin... Regulations. Charges 112-12415: CFR 764.2(h)--Taking Action With Intent To Evade the Regulations In connection... through on or about September 30, 2004, Lin took actions with intent to evade the provisions of the...

  14. Genome packaging in EL and Lin68, two giant phiKZ-like bacteriophages of P. aeruginosa.

    PubMed

    Sokolova, O S; Shaburova, O V; Pechnikova, E V; Shaytan, A K; Krylov, S V; Kiselev, N A; Krylov, V N

    2014-11-01

    A unique feature of the Pseudomonas aeruginosa giant phage phiKZ is its way of genome packaging onto a spool-like protein structure, the inner body. Until recently, no similar structures have been detected in other phages. We have studied DNA packaging in P. aeruginosa phages EL and Lin68 using cryo-electron microscopy and revealed the presence of inner bodies. The shape and positioning of the inner body and the density of the DNA packaging in EL are different from those found in phiKZ and Lin68. This internal organization explains how the shorter EL genome is packed into a large EL capsid, which has the same external dimensions as the capsids of phiKZ and Lin68. The similarity in the structural organization in EL and other phiKZ-like phages indicates that EL is phylogenetically related to other phiKZ-like phages, and, despite the lack of detectable DNA homology, EL, phiKZ, and Lin68 descend from a common ancestor. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Analyzing Lie symmetry and constructing conservation laws for time-fractional Benny-Lin equation

    NASA Astrophysics Data System (ADS)

    Rashidi, Saeede; Hejazi, S. Reza

    This paper investigates the invariance properties of the time fractional Benny-Lin equation with Riemann-Liouville and Caputo derivatives. This equation can be reduced to the Kawahara equation, fifth-order Kdv equation, the Kuramoto-Sivashinsky equation and Navier-Stokes equation. By using the Lie group analysis method of fractional differential equations (FDEs), we derive Lie symmetries for the Benny-Lin equation. Conservation laws for this equation are obtained with the aid of the concept of nonlinear self-adjointness and the fractional generalization of the Noether’s operators. Furthermore, by means of the invariant subspace method, exact solutions of the equation are also constructed.

  16. Transcription factors, coregulators, and epigenetic marks are linearly correlated and highly redundant

    PubMed Central

    Ahsendorf, Tobias; Müller, Franz-Josef; Topkar, Ved; Gunawardena, Jeremy; Eils, Roland

    2017-01-01

    The DNA microstates that regulate transcription include sequence-specific transcription factors (TFs), coregulatory complexes, nucleosomes, histone modifications, DNA methylation, and parts of the three-dimensional architecture of genomes, which could create an enormous combinatorial complexity across the genome. However, many proteins and epigenetic marks are known to colocalize, suggesting that the information content encoded in these marks can be compressed. It has so far proved difficult to understand this compression in a systematic and quantitative manner. Here, we show that simple linear models can reliably predict the data generated by the ENCODE and Roadmap Epigenomics consortia. Further, we demonstrate that a small number of marks can predict all other marks with high average correlation across the genome, systematically revealing the substantial information compression that is present in different cell lines. We find that the linear models for activating marks are typically cell line-independent, while those for silencing marks are predominantly cell line-specific. Of particular note, a nuclear receptor corepressor, transducin beta-like 1 X-linked receptor 1 (TBLR1), was highly predictive of other marks in two hematopoietic cell lines. The methodology presented here shows how the potentially vast complexity of TFs, coregulators, and epigenetic marks at eukaryotic genes is highly redundant and that the information present can be compressed onto a much smaller subset of marks. These findings could be used to efficiently characterize cell lines and tissues based on a small number of diagnostic marks and suggest how the DNA microstates, which regulate the expression of individual genes, can be specified. PMID:29216191

  17. 77 FR 18862 - Zhiwei Lin, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-28

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 10-54] Zhiwei Lin, M.D.; Decision and Order On September 19, 2011, Administrative Law Judge (ALJ) Timothy D. Wing issued the....C. 824, of the CSA. Calvin Ramsey, 76 FR 20034, 20036 (2011) (other citations omitted); Brenton D...

  18. The ceilometer inter-comparison campaign CeiLinEx2015

    NASA Astrophysics Data System (ADS)

    Mattis, Ina; Begbie, Robert; Boyouk, Neda; Bravo-Aranda, Juan Antonio; Brettle, Mike; Cermak, Jan; Drouin, Marc-Antoine; Geiß, Alexander; Görsdorf, Ulrich; Haefele, Alexander; Haeffelin, Martial; Hervo, Maxime; Komínková, Kateřina; Leinweber, Ronny; Müller, Gerhard; Münkel, Christoph; Pattantyús-Ábrahám, Margit; Pönitz, Kornelia; Wagner, Frank; Wiegner, Matthias

    2016-04-01

    Ceilometers are well established instruments for the detection of cloud base heights. Since about 2000, modern ceilometer types (mainly CHM15k, CL51, and CL31) are used also for investigations of the top height of the planetary boundary layer and for quantitative retrievals of vertical profiles of backscatter coefficients. In the framework of the European projects E-PROFILE and TOPROF, tools for the exchange of ceilometer data among European meteorological services, as well as calibration and visualization procedures are developed and established. Unfortunately, the national networks are equipped with instruments of different generations and different manufacturers. In order to quantify and reduce those inhomogeneities, the ceilometer inter-comparison experiment CeiLinEx2015 was performed between June and September 2015 at the Meteorological Observatory Lindenberg, Germany. We tested six different instrument types: LD40, CL31, CL51, CHM15k, CHM15kx, and CS135. Each instrument type was represented by two instruments to estimate the instrument-to-instrument variability and the influence of different firmware versions. Two Raman lidars (RAMSES and RALPH), operated by German Meteorological Service (DWD) are used as reference instruments. Further ancillary data are available, e.g., hourly eye observations, four radio soundings per day, and AERONET sun photometer observations. Beside the typical vertically pointing measurement scheme, we performed special measurements with horizontal pointing direction or blocked receiver telescope. During the experiment, we could collect measurements under very different meteorological situations: Several clear nights allow for Rayleigh-Calibration (see Hervo and CeiLinEx2015 team [EGU2016-4785]), a strong event of Sahara dust intrusion can be used to study the behaviour of the instruments in presence of large, non-spherical particles (like volcanic ash). Further investigations focus, e.g., on the detection of very low cloud base

  19. 28 CFR 51.57 - Relevant factors.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Relevant factors. 51.57 Section 51.57 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR THE ADMINISTRATION OF SECTION 5 OF... from the normal procedural sequence; (5) Whether there are substantive departures from the normal...

  20. 28 CFR 51.57 - Relevant factors.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Relevant factors. 51.57 Section 51.57 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR THE ADMINISTRATION OF SECTION 5 OF... from the normal procedural sequence; (5) Whether there are substantive departures from the normal...

  1. 28 CFR 51.57 - Relevant factors.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Relevant factors. 51.57 Section 51.57 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR THE ADMINISTRATION OF SECTION 5 OF... from the normal procedural sequence; (5) Whether there are substantive departures from the normal...

  2. [Heavy metal pollution characteristics and ecological risk analysis for soil in Phyllostachys praecox stands of Lin'an].

    PubMed

    Fang, Xiao-bo; Shi, Han; Liao, Xin-feng; Lou, Zhong; Zhou, Lyu-yan; Yu, Hai-xia; Yao, Lin; Sun, Li-ping

    2015-06-01

    An investigation was carried out in an attempt to reveal the characteristics of heavy metals contamination in the soils of Phyllostachys praecox forest in Lin' an. Based on the concentrations of Hg, As, Cu, Pb, Zn, Cd, Cr, Ni, Co and Mn in 160 topsoil samples, the pollution status and ecological risks of heavy metals in the soils were assessed by single factor pollution index, Nemerow integrated pollution index and Hankanson potential ecological risk index. The spatial variability of heavy metal concentrations in the soils closely related to the distribution of traffic, industrial and livestock pollution sources. The average concentrations of Hg, As, Cu, Pb, Zn, Cd, Cr, Ni, Co and Mn in the soils were 0.16, 7.41, 34.36, 87.98, 103.98, 0.26, 59.12, 29.56, 11.44 and 350.26 mg · kg(-1), respectively. Pb, Cd, Zn and Cu concentrations were as 2.89, 1.70, 1.12 and 1.12 times as the background values of soil in Zhejiang Province, respectively. But their concentrations were all lower than the threshold values of the National Environmental Quality Standard for Soil (GB 15618-1995). The average single factor pollution index revealed that the level of heavy metal pollution in the soils was in order of Pb>Cd>Cu= Zn>Hg>As>Ni>Co>Cr>Mn. Pb pollution was of moderate level while Cd, Cu and Zn pollutions were slight. There was no soil pollution caused by the other heavy metals. However, the Nemerow integrated pollution index showed that all the 160 soil samples were contaminated by heavy metals to a certain extent. Among total 160 soil samples, slight pollution level, moderate pollution level and heavy pollution level accounted for 55.6%, 29.4% and 15.0%, respectively. The average single factor potential ecological risk index (Er(i)) implied that the potential ecological risk related to Cd reached moderate level, while the others were of slight level. Furthermore, Cd and Hg showed higher potential ecological risk indices which reached up to 256.82 and 187.33 respectively

  3. 42 CFR 414.28 - Conversion factors.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Practitioners § 414.28 Conversion factors. CMS establishes CFs in accordance with section 1848(d) of the Act. (a) Base-year CFs. CMS established the CF for 1992 so that had section 1848 of the Act applied during 1991... in § 414.30. (b) Subsequent CFs. For calendar years 1993 through 1995, the CF for each year is equal...

  4. The influence of social and endocrine factors on urine-marking by captive wolves (Canis lupus)

    USGS Publications Warehouse

    Asa, C.S.; Mech, L.D.; Seal, U.S.; Plotka, E.D.

    1990-01-01

    Although serum hormones varied seasonally in all adult animals, only dominant male and female wolves urine-marked. Serum testosterone and urine-marking rates, which increased during the fall/winter breeding season, were positively correlated in both male and female dominant wolves. Estradiol, which increased in conjunction with proestrus and estrus, was not correlated with female urine-marking. These findings suggest that hormonal influence on urine-marking in the wolf is modulated by social factors and contrast with those for both domestic dogs and coyotes, two other members of the genus Canis.

  5. A Synthetic Lethal Screen Identifies a Role for Lin-44/Wnt in C. elegans Embryogenesis.

    PubMed

    Hartin, Samantha N; Hudson, Martin L; Yingling, Curtis; Ackley, Brian D

    2015-01-01

    The C. elegans proteins PTP-3/LAR-RPTP and SDN-1/Syndecan are conserved cell adhesion molecules. Loss-of-function (LOF) mutations in either ptp-3 or sdn-1 result in low penetrance embryonic developmental defects. Work from other systems has shown that syndecans can function as ligands for LAR receptors in vivo. We used double mutant analysis to test whether ptp-3 and sdn-1 function in a linear genetic pathway during C. elegans embryogenesis. We found animals with LOF in both sdn-1 and ptp-3 exhibited a highly penetrant synthetic lethality (SynLet), with only a small percentage of animals surviving to adulthood. Analysis of the survivors demonstrated that these animals had a synergistic increase in the penetrance of embryonic developmental defects. Together, these data strongly suggested PTP-3 and SDN-1 function in parallel during embryogenesis. We subsequently used RNAi to knockdown ~3,600 genes predicted to encode secreted and/or transmembrane molecules to identify genes that interacted with ptp-3 or sdn-1. We found that the Wnt ligand, lin-44, was SynLet with sdn-1, but not ptp-3. We used 4-dimensional time-lapse analysis to characterize the interaction between lin-44 and sdn-1. We found evidence that loss of lin-44 caused defects in the polarization and migration of endodermal precursors during gastrulation, a previously undescribed role for lin-44 that is strongly enhanced by the loss of sdn-1. PTP-3 and SDN-1 function in compensatory pathways during C. elegans embryonic and larval development, as simultaneous loss of both genes has dire consequences for organismal survival. The Wnt ligand lin-44 contributes to the early stages of gastrulation in parallel to sdn-1, but in a genetic pathway with ptp-3. Overall, the SynLet phenotype provides a robust platform to identify ptp-3 and sdn-1 interacting genes, as well as other genes that function in development, yet might be missed in traditional forward genetic screens.

  6. A Synthetic Lethal Screen Identifies a Role for Lin-44/Wnt in C. elegans Embryogenesis

    PubMed Central

    Hartin, Samantha N.; Hudson, Martin L.; Yingling, Curtis; Ackley, Brian D.

    2015-01-01

    Background The C. elegans proteins PTP-3/LAR-RPTP and SDN-1/Syndecan are conserved cell adhesion molecules. Loss-of-function (LOF) mutations in either ptp-3 or sdn-1 result in low penetrance embryonic developmental defects. Work from other systems has shown that syndecans can function as ligands for LAR receptors in vivo. We used double mutant analysis to test whether ptp-3 and sdn-1 function in a linear genetic pathway during C. elegans embryogenesis. Results We found animals with LOF in both sdn-1 and ptp-3 exhibited a highly penetrant synthetic lethality (SynLet), with only a small percentage of animals surviving to adulthood. Analysis of the survivors demonstrated that these animals had a synergistic increase in the penetrance of embryonic developmental defects. Together, these data strongly suggested PTP-3 and SDN-1 function in parallel during embryogenesis. We subsequently used RNAi to knockdown ~3,600 genes predicted to encode secreted and/or transmembrane molecules to identify genes that interacted with ptp-3 or sdn-1. We found that the Wnt ligand, lin-44, was SynLet with sdn-1, but not ptp-3. We used 4-dimensional time-lapse analysis to characterize the interaction between lin-44 and sdn-1. We found evidence that loss of lin-44 caused defects in the polarization and migration of endodermal precursors during gastrulation, a previously undescribed role for lin-44 that is strongly enhanced by the loss of sdn-1. Conclusions PTP-3 and SDN-1 function in compensatory pathways during C. elegans embryonic and larval development, as simultaneous loss of both genes has dire consequences for organismal survival. The Wnt ligand lin-44 contributes to the early stages of gastrulation in parallel to sdn-1, but in a genetic pathway with ptp-3. Overall, the SynLet phenotype provides a robust platform to identify ptp-3 and sdn-1 interacting genes, as well as other genes that function in development, yet might be missed in traditional forward genetic screens. PMID:25938228

  7. Multi-domain utilization by TUT4 and TUT7 in control of let-7 biogenesis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Faehnle, Christopher R.; Walleshauser, Jack; Joshua-Tor, Leemor

    2017-07-03

    The uridyl transferases TUT4 and TUT7 (collectively called TUT4(7)) switch between two modes of activity, either promoting expression of let-7 microRNA (monoU) or marking it for degradation (oligoU). Lin28 modulates the switch via recruitment of TUT4(7) to the precursor pre-let-7 in stem cells and human cancers. We found that TUT4(7) utilize two multidomain functional modules during the switch from monoU to oligoU. The catalytic module (CM) is essential for both activities, while the Lin28-interacting module (LIM) is indispensable for oligoU. A TUT7 CM structure trapped in the monoU activity staterevealed a duplex-RNA-binding pocket that orients group II pre-let-7 hairpins tomore » favor monoU addition. Conversely, the switch to oligoU requires the ZK domain of Lin28 to drive the formation of a stable ternary complex between pre-let-7 and the inactive LIM. Finally, ZK2 of TUT4(7) aids oligoU addition by engaging the growing oligoU tail through uracil-specific interactions.« less

  8. DPL-1 DP, LIN-35 Rb and EFL-1 E2F act with the MCD-1 zinc-finger protein to promote programmed cell death in Caenorhabditis elegans.

    PubMed

    Reddien, Peter W; Andersen, Erik C; Huang, Michael C; Horvitz, H Robert

    2007-04-01

    The genes egl-1, ced-9, ced-4, and ced-3 play major roles in programmed cell death in Caenorhabditis elegans. To identify genes that have more subtle activities, we sought mutations that confer strong cell-death defects in a genetically sensitized mutant background. Specifically, we screened for mutations that enhance the cell-death defects caused by a partial loss-of-function allele of the ced-3 caspase gene. We identified mutations in two genes not previously known to affect cell death, dpl-1 and mcd-1 (modifier of cell death). dpl-1 encodes the C. elegans homolog of DP, the human E2F-heterodimerization partner. By testing genes known to interact with dpl-1, we identified roles in cell death for four additional genes: efl-1 E2F, lin-35 Rb, lin-37 Mip40, and lin-52 dLin52. mcd-1 encodes a novel protein that contains one zinc finger and that is synthetically required with lin-35 Rb for animal viability. dpl-1 and mcd-1 act with efl-1 E2F and lin-35 Rb to promote programmed cell death and do so by regulating the killing process rather than by affecting the decision between survival and death. We propose that the DPL-1 DP, MCD-1 zinc finger, EFL-1 E2F, LIN-35 Rb, LIN-37 Mip40, and LIN-52 dLin52 proteins act together in transcriptional regulation to promote programmed cell death.

  9. Connective tissue growth factor is a substrate of ADAM28

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mochizuki, Satsuki; Tanaka, Rena; Shimoda, Masayuki

    2010-11-26

    Research highlights: {yields} The hyper-variable region in the cysteine-rich domain of ADAM28 binds to C-terminal domain of CTGF. {yields} ADAM28 cleaves CTGF alone and CTGF in the CTGF/VEGF{sub 165} complex. {yields} CTGF digestion by ADAM28 releases biologically active VEGF{sub 165} from the complex. {yields} ADAM28, CTGF and VEGF{sub 165} are commonly co-expressed by carcinoma cells in human breast carcinoma tissues. {yields} These suggest that ADAM28 promotes VEGF{sub 165}-induced angiogenesis in the breast carcinomas by selective CTGF digestion in the CTGF/VEGF{sub 165} complex. -- Abstract: ADAM28, a member of the ADAM (a disintegrin and metalloproteinase) gene family, is over-expressed by carcinomamore » cells and the expression correlates with carcinoma cell proliferation and progression in human lung and breast carcinomas. However, information about substrates of ADAM28 is limited. We screened interacting molecules of ADAM28 in human lung cDNA library by yeast two-hybrid system and identified connective tissue growth factor (CTGF). Binding of CTGF to proADAM28 was demonstrated by yeast two-hybrid assay and protein binding assay. ADAM28 cleaved CTGF in dose- and time-dependent manners at the Ala{sup 181}-Tyr{sup 182} and Asp{sup 191}-Pro{sup 192} bonds in the hinge region of the molecule. ADAM28 selectively digested CTGF in the complex of CTGF and vascular endothelial growth factor{sub 165} (VEGF{sub 165}), releasing biologically active VEGF{sub 165} from the complex. RT-PCR and immunohistochemical analyses demonstrated that ADAM28, CTGF and VEGF are commonly co-expressed in the breast carcinoma tissues. These data provide the first evidence that CTGF is a novel substrate of ADAM28 and suggest that ADAM28 may promote VEGF{sub 165}-induced angiogenesis in the breast carcinomas by the CTGF digestion in the CTGF/VEGF{sub 165} complex.« less

  10. Granulocyte-colony stimulating factor and stem cell factor are the crucial factors in long-term culture of human primitive hematopoietic cells supported by a murine stromal cell line.

    PubMed

    Nishi, N; Ishikawa, R; Inoue, H; Nishikawa, M; Kakeda, M; Yoneya, T; Tsumura, H; Ohashi, H; Yamaguchi, Y; Motoki, K; Sudo, T; Mori, K J

    1996-09-01

    The findings that murine marrow stromal cell line MS-5 supported the proliferation of human lineage-negative (Lin-) CD34+CD38- bone marrow cells in long-term culture have been reported. In this study, we analyzed this proliferating activity of MS-5-conditioned medium (CM) on human primitive hematopoietic cells. When Lin-CD34+CD38- cells of normal human cord blood cells were co-cultured with MS-5, colony forming cells (CFCs) were maintained over 7 weeks in vitro. Prevention of contact between MS-5 and Lin-CD34+CD38- cells by using membrane filter (0.45 micron) was negligible for this activity. This indicated that the activity of MS-5 on human primitive hematopoietic cells is a soluble factor(s) secreted from MS-5, which is not induced by the contact between MS-5 and Lin-CD34+CD38- cells. We tried to purify this soluble activity. An active material with a molecular weight of about 150 kDa, determined by gel filtration chromatography, solely supported the growth of Lin-CD34+CD38- cells and Mo7e, a human megakaryocytic cell line. This activity not only reacted with anti-mouse stem cell factor (mSCF) antibody on Western blots, but it was also neutralized in the presence of anti-mSCF antibody. Another active material with a molecular weight of about 20-30 kDa synergized with mSCF to stimulate the growth of Lin-CD34+CD38- cells but failed to do so alone, although this synergy was inhibited in the presence of soluble mouse granulocyte-colony stimulating factor (mG-CSF) receptor, which is a chimeric protein consisting of the extracellular domain of mG-CSF receptor and the Fe region of human IgG1. In addition, the latter molecule supported the growth of the G-CSF dependent cell line FD/GR3, which is a murine myeloid leukemia cell line, FDC-P2, transfected with mG-CSF receptor cDNA. Adding of anti-mSCF antibody and soluble mG-CSF receptor to the culture completely abrogated the activity of MS-5-CM. Recombinant (r) mSCF and rmG-CSF had synergistic activity on the growth of Lin

  11. Lower Oncogenic Potential of Human Mesenchymal Stem Cells Derived from Cord Blood Compared to Induced Pluripotent Stem Cells

    PubMed Central

    Foroutan, T.; Najmi, M.; Kazemi, N.; Hasanlou, M.; Pedram, A.

    2015-01-01

    Background: In regenerative medicine, use of each of the mesenchymal stem cells derived from bone marrow, cord blood, and adipose tissue, has several cons and pros. Mesenchymal stem cells derived from cord blood have been considered the best source for precursor transplantation. Direct reprogramming of a somatic cell into induced pluripotent stem cells by over-expression of 6 transcription factors Oct4, Sox2, Klf4, lin28, Nanog, and c-Myc has great potential for regenerative medicine, eliminating the ethical issues of embryonic stem cells and the rejection problems of using non-autologous cells. Objective: To compare reprogramming and pluripotent markers OCT4, Sox-2, c-Myc, Klf4, Nanog, and lin28 in mesenchymal stem cells derived from cord blood and induced pluripotent stem cells. Methods: We analyzed the expression level of OCT4, Sox-2, c-Myc, Klf4, Nanog and lin28 genes in human mesenchymal stem cells derived from cord blood and induced pluripotent stem cells by cell culture and RT-PCR. Results: The expression level of pluripotent genes OCT4 and Sox-2, Nanog and lin28 in mesenchymal stem cells derived from cord blood were significantly higher than those in induced pluripotent stem cells. In contrast to OCT-4A and Sox-2, Nanog and lin28, the expression level of oncogenic factors c-Myc and Klf4 were significantly higher in induced pluripotent stem cells than in mesenchymal stem cells derived from cord blood. Conclusion: It could be concluded that mesenchymal stem cells derived from human cord blood have lower oncogenic potential compared to induced pluripotent stem cells. PMID:26306155

  12. A computational study of the dechlorination of β-hexachlorocyclohexane (β-HCH) catalyzed by the haloalkane dehalogenase LinB.

    PubMed

    Manna, Rabindra Nath; Dybala-Defratyka, Agnieszka

    2014-11-15

    LinB, a haloalkane dehalogenase from Sphingomonas paucimobilis UT26, is known to metabolize halohydrocarbons to halide ions and the respective alcohols. Its broad substrate specificity allowed its consideration for bioremediation. Herein, we have shown its catalytic action toward β-hexachlorocyclohexane (β-HCH) - an example of large-size substrates that can be accommodated in its active site. We have analyzed the capability of combined QM/MM schemes to describe in detail the SN2 dechlorination reaction between β-HCH and Asp108 in the active site of LinB. Free energy surfaces have been calculated using one and two dimensional potentials of mean force (PMF) obtained at the PM3/MM (MM=amberff99SB, TIP3P) level of theory. The overestimated energetic barriers by the PM3 Hamiltonian were corrected using a DFT functional (M06-2X). The resulted activation energies (16 and 19 kcal mol(-1) from 1D and 2D-PMF profiles, respectively) for the dechlorination reaction of β-HCH in the active site of LinB enzyme are in qualitative agreement with the experimentally determined value of 17 kcal mol(-1). The binding of β-HCH to the active site of LinB has been compared to the binding of smaller 1-chlorobutane (1-CB) and larger δ-hexabromocyclododecane (δ-HBCD). Copyright © 2014 Elsevier Inc. All rights reserved.

  13. The Value of SCMC in SLA: Comments on Lin, Huang & Liou (2013)

    ERIC Educational Resources Information Center

    Taylor, Alan M.

    2014-01-01

    Meta-analytic methods are often used to determine the effectiveness of certain treatments across studies. However, we are often unaware of how a meta-analysis can provide value to researchers and practitioners. This paper offers a brief commentary on a meta-analysis conducted by Lin, Huang and Liou (2013) in LLT, providing further statistical…

  14. LIN-23, an E3 Ubiquitin Ligase Component, Is Required for the Repression of CDC-25.2 Activity during Intestinal Development in Caenorhabditis elegans.

    PubMed

    Son, Miseol; Kawasaki, Ichiro; Oh, Bong-Kyeong; Shim, Yhong-Hee

    2016-11-30

    Caenorhabditis elegans ( C. elegans ) utilizes two different cell-cycle modes, binucleations during the L1 larval stage and endoreduplications at four larval moltings, for its postembryonic intestinal development. Previous genetic studies indicated that CDC-25.2 is specifically required for binucleations at the L1 larval stage and is repressed before endoreduplications. Furthermore, LIN-23, the C. elegans β-TrCP ortholog, appears to function as a repressor of CDC-25.2 to prevent excess intestinal divisions. We previously reported that intestinal hyperplasia in lin-23(e1883) mutants was effectively suppressed by the RNAi depletion of cdc-25.2 . Nevertheless, LIN-23 targeting CDC-25.2 for ubiquitination as a component of E3 ubiquitin ligase has not yet been tested. In this study, LIN-23 is shown to be the major E3 ubiquitin ligase component, recognizing CDC-25.2 to repress their activities for proper transition of cell-cycle modes during the C. elegans postembryonic intestinal development. In addition, for the first time that LIN-23 physically interacts with both CDC-25.1 and CDC-25.2 and facilitates ubiquitination for timely regulation of their activities during the intestinal development.

  15. Thickness and marking quality of different occlusal contact registration strips

    PubMed Central

    TOLEDO, Maria Fernanda de Souza Mauá Serapião; JÓIAS, Renata Pilli; MARQUES-IASI, Yves Santini; NEVES, Ana Christina Claro; RODE, Sigmar de Mello

    2014-01-01

    Objectives Evaluate the thickness and the marking quality of different occlusal contact registration strips (OCRS) and a possible correlation between them. Material and Methods The following OCRS were selected: Accufilm II, BK20, BK21, BK22, BK23, BK28, and BK31. The thickness was measured in three points of the OCRS with an electronic measuring device (TESA), and the mean was calculated. To produce the marks on the strips, composite resin specimens were adapted to a universal testing machine (Versat 2000) with 40 kgf load cell at a speed of 1.0 mm/min. The mark images were photographed with a stereoscopic microscope (Stemi SV11) and processed and analyzed by the 550-Leica Qwin® analyzer. Results Values (μm) found in the 1st and 2nd thickness measurements were: Accufilm II - 16.4 and 14.2; BK20 - 10.0 and 8.1; BK21 - 9.5 and 8.0; BK22 - 9.7 and 8.7; BK23 - 9.8 and 7.9; BK28 - 12.8 and 10.0; and BK31 - 8.4 and 8.0, respectively. The mean (mm2) values found in the mark areas were: Accufilm II - 0.078; BK20 - 0.035; BK21 - 0.045; BK22 - 0.012; BK23 - 0.022; BK28 - 0.024; and BK31 - 0.024. The results were submitted to the Kruskal-Wallis (p<0.05) and Pearson’s correlation tests. Conclusions Only in the 2nd measurement, the OCRS thickness observed was similar to the value indicated by the manufacturers; the Accufilm II and the BK28 strips showed the better marks; and no correlation was found between the thickness and the marking area. PMID:25591020

  16. Mitotic Vulnerability in Triple-Negative Breast Cancer Associated with LIN9 Is Targetable with BET Inhibitors.

    PubMed

    Sahni, Jennifer M; Gayle, Sylvia S; Webb, Bryan M; Weber-Bonk, Kristen L; Seachrist, Darcie D; Singh, Salendra; Sizemore, Steven T; Restrepo, Nicole A; Bebek, Gurkan; Scacheri, Peter C; Varadan, Vinay; Summers, Matthew K; Keri, Ruth A

    2017-10-01

    Triple-negative breast cancers (TNBC) are highly aggressive, lack FDA-approved targeted therapies, and frequently recur, making the discovery of novel therapeutic targets for this disease imperative. Our previous analysis of the molecular mechanisms of action of bromodomain and extraterminal protein inhibitors (BETi) in TNBC revealed these drugs cause multinucleation, indicating BET proteins are essential for efficient mitosis and cytokinesis. Here, using live cell imaging, we show that BET inhibition prolonged mitotic progression and induced mitotic cell death, both of which are indicative of mitotic catastrophe. Mechanistically, the mitosis regulator LIN9 was a direct target of BET proteins that mediated the effects of BET proteins on mitosis in TNBC. Although BETi have been proposed to function by dismantling super-enhancers (SE), the LIN9 gene lacks an SE but was amplified or overexpressed in the majority of TNBCs. In addition, its mRNA expression predicted poor outcome across breast cancer subtypes. Together, these results provide a mechanism for cancer selectivity of BETi that extends beyond modulation of SE-associated genes and suggest that cancers dependent upon LIN9 overexpression may be particularly vulnerable to BETi. Cancer Res; 77(19); 5395-408. ©2017 AACR . ©2017 American Association for Cancer Research.

  17. Coagulation activation by MC28 fibrosarcoma cells facilitates lung tumor formation.

    PubMed

    Amirkhosravi, M; Francis, J L

    1995-01-01

    Tumor cells interact with the hemostatic system in various ways and may thus influence malignant growth and spread. MC28 fibrosarcoma cells possess a potent procoagulant activity (PCA) and form lung tumors following intravenous injection. The aim of this work was to study the relationship between PCA, intravascular coagulation and lung seeding in the MC28 model. MC28 cells were injected into control, warfarinized and heparinized hooded Lister rats. Coagulation changes were monitored by thromboelastography (TEG) and Sonoclot analysis (SA), lung fibrin formation by light and electron microscopy, tumor seeding by macroscopic counting and tumor cell and platelet deposition in the lungs by radiolabelling. PCA was measured by chromogenic assay. MC28 PCA was characterized as a tissue factor-factor VIIa complex that probably arose during cell culture or disaggregation of solid tumors. Injection of tumor cells caused marked coagulopathy and was rapidly (within 30 min) followed by fibrin deposition in the lungs and accumulation of radiolabelled platelets. Heparin and warfarin significantly reduced lung seeding (p < 0.001) and reduced retention of radiolabelled tumor cells in the pulmonary circulation (p < 0.01). Inhibition of cellular PCA by prior treatment with concanavalin A markedly reduced intravascular coagulation and lung seeding. We conclude that MC28 cells cause intravascular coagulation as a direct result of their procoagulant activity. The data suggest that tumor cells form complexes with platelets and fibrin which are retained in the lungs long enough for extravasation and seeding to occur.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Factors influencing survival and mark retention in postmetamorphic boreal chorus frogs

    USGS Publications Warehouse

    Swanson, Jennifer E; Bailey, Larissa L.; Muths, Erin L.; Funk, W. Chris

    2013-01-01

    The ability to track individual animals is crucial in many field studies and often requires applying marks to captured individuals. Toe clipping has historically been a standard marking method for wild amphibian populations, but more recent marking methods include visual implant elastomer and photo identification. Unfortunately, few studies have investigated the influence and effectiveness of marking methods for recently metamorphosed individuals and as a result little is known about this life-history phase for most amphibians. Our focus was to explore survival probabilities, mark retention, and mark migration in postmetamorphic Boreal Chorus Frogs (Psuedacris maculata) in a laboratory setting. One hundred forty-seven individuals were assigned randomly to two treatment groups or a control group. Frogs in the first treatment group were marked with visual implant elastomer, while frogs in the second treatment group were toe clipped. Growth and mortality were recorded for one year and resulting data were analyzed using known-fate models in Program MARK. Model selection results suggested that survival probabilities of frogs varied with time and showed some variation among marking treatments. We found that frogs with multiple toes clipped on the same foot had lower survival probabilities than individuals in other treatments, but individuals can be marked by clipping a single toe on two different feet without any mark loss or negative survival effects. Individuals treated with visual implant elastomer had a mark migration rate of 4% and mark loss rate of 6%, and also showed very little negative survival impacts relative to control individuals.

  19. Long-term results of endoscopic sympathetic block using the Lin-Telaranta classification.

    PubMed

    Rantanen, Tuomo; Telaranta, Timo

    2013-10-01

    Endoscopic thoracic sympathectomy has been used successfully in the treatment of blushing, excessive sweating, and social phobia. However, the adverse effects of endoscopic thoracic sympathectomy are more severe and frequent than the adverse effects of endoscopic sympathetic block (ESB). The use of different blocking levels for different indications in ESB according to the Lin-Telaranta classification further decreases the postoperative adverse effects. However, there are few data on the long-term results of ESB performed using the Lin-Telaranta classification. Ninety-five patients (55 men, 40 women) were interviewed by before the surgery using our routine questionnaire, and the same questionnaire was answered postoperatively by the patients. In addition, a long-term follow-up questionnaire was sent to all patients whose address was known. Forty-seven patients (24 men, 23 women) answered to this questionnaire. The Davidson brief social phobia scale and the Liebowitz quality of life scale were used. Patients were divided to 3 categories: category 1, patients with sweating problems; category 2, patients with blushing; and category 3, and patients with symptoms other than sweating or blushing. Among patients in category 1, social phobia decreased from 12.43 to 6.71 (p = 0.004), in category 2 from 13.97 to 7.69 (p < 0.001), and in category 3 from 13.18 to 9.64 (p = 0.007) during long-term follow-up. Among patients with severe sweating problems preoperatively, sweating decreased from 2.50 to 1.29 (p = 0.003) among patients in category 1 and from 1.86 to 1.16 (p < 0.001) among patients in category 2. Among patients with unbearable blushing, blushing decreased from 4 to 1.80 (p < 0.001). Patients got a clear help from ESB performed using the Lin-Telaranta classification to treat blushing, excessive sweating, and social phobia with and without physical symptoms. In addition, compensatory sweating increased only slightly.

  20. Soluble factor(s) from bone marrow cells can rescue lethally irradiated mice by protecting endogenous hematopoietic stem cells.

    PubMed

    Zhao, Yi; Zhan, Yuxia; Burke, Kathleen A; Anderson, W French

    2005-04-01

    Ionizing radiation-induced myeloablation can be rescued via bone marrow transplantation (BMT) or administration of cytokines if given within 2 hours after radiation exposure. There is no evidence for the existence of soluble factors that can rescue an animal after a lethal dose of radiation when administered several hours postradiation. We established a system that could test the possibility for the existence of soluble factors that could be used more than 2 hours postirradiation to rescue animals. Animals with an implanted TheraCyte immunoisolation device (TID) received lethal-dose radiation and then normal bone marrow Lin- cells were loaded into the device (thereby preventing direct interaction between donor and recipient cells). Animal survival was evaluated and stem cell activity was tested with secondary bone marrow transplantation and flow cytometry analysis. Donor cell gene expression of five antiapoptotic cytokines was examined. Bone marrow Lin- cells rescued lethally irradiated animals via soluble factor(s). Bone marrow cells from the rescued animals can rescue and repopulate secondary lethally irradiated animals. Within the first 6 hours post-lethal-dose radiation, there is no significant change of gene expression of the known radioprotective factors TPO, SCF, IL-3, Flt-3 ligand, and SDF-1. Hematopoietic stem cells can be protected in lethally irradiated animals by soluble factors produced by bone marrow Lin- cells.

  1. COMBINED ENDOCRINE EFFECTS OF IN UTERO EXPOSURE TO THE ANTIANDROGENS BUTYLBENZYL PHTHALATE (BBP) AND LINURON (LIN) ON FETAL TESTOSTERONE (T) SYNTHESIS AND REPRODUCTIVE TRACT DEVELOPMENT

    EPA Science Inventory

    COMBINED ENDOCRINE EFFECTS OF IN UTERO EXPOSURE TO THE ANTIANDROGENS BUTYLBENZYL PHTHALATE (BBP) AND LINURON (Lin) ON FETAL TESTOSTERONE (T) SYNTHESIS AND REPRODUCTIVE TRACT DEVELOPMENT
    Parks LG , Hotchkiss AK, Ostby J, Lambright C and Gray LE, Jr.

    Lin and BBP are toxic...

  2. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhao, Chen; Tao, Zui; Xue, Langyue

    In lower-order vertebrates, Müller glia exhibit characteristics of retinal progenitor cells, while in higher vertebrates, such as mammals, the regenerative capacity of Müller glia is limited. Recently, we reported that Lin28b promoted the trans-differentiation of Müller cells to rod photoreceptor and bipolar cells in the retina of retinitis pigmentosa rat model, whereas it is unclear whether Lin28b can stimulate the reprogramming of Müller glia in vitro for transplantation into a damaged retina. In the present study, Long-Evens rat Müller glia were infected with Adeno-Lin28b or Adeno-GFP. Over-expression of Lin28b in isolated rat Müller glia resulted in the suppression of GFAP expression,more » enhancement of cell proliferation and a significant increase of the expression of retinal progenitor markers 5 days after infection. Moreover, Lin28b caused a significant reduction of the Let-7 family of microRNAs. Following sub-retinal space transplantation, Müller glia-derived retinal progenitors improved b-wave amplification of 30d Royal College of Surgeons retinitis pigmentosa model (RCS-P+) rats, as detected by electroretinography (ERG) recordings. Taken together, these data suggest that the up-regulation of Lin28b expression facilitated the reprogramming of Müller cells toward characteristics of retinal progenitors. - Highlights: • Lin28b reprograms Müller glia to retinal progenitors. • Let-7 micrRNAs are suppressed by Lin28b. • Transplantation of reprogrammed Müller glia restores retinal function.« less

  3. Hepatocyte nuclear factor-4alpha induces transdifferentiation of hematopoietic cells into hepatocytes.

    PubMed

    Khurana, Satish; Jaiswal, Amit K; Mukhopadhyay, Asok

    2010-02-12

    Hematopoietic stem cells can directly transdifferentiate into hepatocytes because of cellular plasticity, but the molecular basis of transdifferentiation is not known. Here, we show the molecular basis using lineage-depleted oncostatin M receptor beta-expressing (Lin(-)OSMRbeta(+)) mouse bone marrow cells in a hepatic differentiation culture system. Differentiation of the cells was marked by the expression of albumin. Hepatocyte nuclear factor (HNF)-4alpha was expressed and translocated into the nuclei of the differentiating cells. Suppression of its activation in OSM-neutralized culture medium inhibited cellular differentiation. Ectopic expression of full-length HNF4alpha in 32D myeloid cells resulted in decreased myeloid colony-forming potential and increased expression of hepatocyte-specific genes and proteins. Nevertheless, the neohepatocytes produced in culture expressed active P450 enzyme. The obligatory role of HNF4alpha in hepatic differentiation was confirmed by transfecting Lin(-)OSMRbeta(+) cells with dominant negative HNF4alpha in the differentiation culture because its expression inhibited the transcription of the albumin and tyrosine aminotransferase genes. The loss and gain of functional activities strongly suggested that HNF4alpha plays a central role in the transdifferentiation process. For the first time, this report demonstrates the mechanism of transdifferentiation of hematopoietic cells into hepatocytes, in which HNF4alpha serves as a molecular switch.

  4. Roost sites of radio-marked Mexican spotted owls in Arizona and New Mexico: sources of variability and descriptive characteristics

    Treesearch

    Joseph L. Ganey; William M. Block; Rudy M. King

    2000-01-01

    To increase understanding of roosting habitat of Mexican Spotted Owls (Strix occidentalis lucida) and factors that influence use of roosting habitat, we sampled habitat characteristics at 1790 sites used for roosting by 28 radio-marked Mexican Spotted Owls in three study areas in Arizona and New Mexico. We explored potential patterns of variation in...

  5. Human somatic cells subjected to genetic induction with six germ line-related factors display meiotic germ cell-like features

    PubMed Central

    Medrano, Jose V.; Martínez-Arroyo, Ana M.; Míguez, Jose M.; Moreno, Inmaculada; Martínez, Sebastián; Quiñonero, Alicia; Díaz-Gimeno, Patricia; Marqués-Marí, Ana I.; Pellicer, Antonio; Remohí, Jose; Simón, Carlos

    2016-01-01

    The in vitro derivation of human germ cells has attracted interest in the last years, but their direct conversion from human somatic cells has not yet been reported. Here we tested the ability of human male somatic cells to directly convert into a meiotic germ cell-like phenotype by inducing them with a combination of selected key germ cell developmental factors. We started with a pool of 12 candidates that were reduced to 6, demonstrating that ectopic expression of the germ line-related genes PRDM1, PRDM14, LIN28A, DAZL, VASA and SYCP3 induced direct conversion of somatic cells (hFSK (46, XY), and hMSC (46, XY)) into a germ cell-like phenotype in vitro. Induced germ cell-like cells showed a marked switch in their transcriptomic profile and expressed several post-meiotic germ line related markers, showed meiotic progression, evidence of epigenetic reprogramming, and approximately 1% were able to complete meiosis as demonstrated by their haploid status and the expression of several post-meiotic markers. Furthermore, xenotransplantation assays demonstrated that a subset of induced cells properly colonize the spermatogonial niche. Knowledge obtained from this work can be used to create in vitro models to study gamete-related diseases in humans. PMID:27112843

  6. [Characteristics of atmospheric CO2 concentration and variation of carbon source & sink at Lin'an regional background station].

    PubMed

    Pu, Jing-Jiao; Xu, Hong-Hui; Kang, Li-Li; Ma, Qian-Li

    2011-08-01

    Characteristics of Atmospheric CO2 concentration obtained by Flask measurements were analyzed at Lin'an regional background station from August 2006 to July 2009. According to the simulation results of carbon tracking model, the impact of carbon sources and sinks on CO2 concentration was evaluated in Yangtze River Delta. The results revealed that atmospheric CO2 concentrations at Lin'an regional background station were between 368.3 x 10(-6) and 414.8 x 10(-6). The CO2 concentration varied as seasons change, with maximum in winter and minimum in summer; the annual difference was about 20.5 x 10(-6). The long-term trend of CO2 concentration showed rapid growth year by year; the average growth rate was about 3.2 x 10(-6)/a. CO2 flux of Yangtze River Delta was mainly contributed by fossil fuel burning, terrestrial biosphere exchange and ocean exchange, while the contribution of fire emission was small. CO2 flux from fossil fuel burning played an important role in carbon source; terrestrial biosphere and ocean were important carbon sinks in this area. Seasonal variations of CO2 concentration at Lin'an regional background station were consistent with CO2 fluxes from fossil fuel burning and terrestrial biosphere exchange.

  7. Mobilization of Peripheral Blood Stem Cells and Changes in the Concentration of Plasma Factors Influencing their Movement in Patients with Panic Disorder.

    PubMed

    Jabłoński, Marcin; Mazur, Jolanta Kucharska; Tarnowski, Maciej; Dołęgowska, Barbara; Pędziwiatr, Daniel; Kubiś, Ewa; Budkowska, Marta; Sałata, Daria; Wysiecka, Justyna Pełka; Kazimierczak, Arkadiusz; Reginia, Artur; Ratajczak, Mariusz Z; Samochowiec, Jerzy

    2017-04-01

    In this paper we examined whether stem cells and factors responsible for their movement may serve as new biological markers of anxiety disorders. The study was carried out on a group of 30 patients diagnosed with panic disorder (examined before and after treatment), compared to 30 healthy individuals forming the control group. We examined the number of circulating HSCs (hematopoetic stem cells) (Lin-/CD45 +/CD34 +) and HSCs (Lin-/CD45 +/AC133 +), the number of circulating VSELs (very small embryonic-like stem cells) (Lin-/CD45-/CD34 +) and VSELs (Lin-/CD45-/AC133 +), as well as the concentration of complement components: C3a, C5a and C5b-9, SDF-1 (stromal derived factor) and S1P (sphingosine-1-phosphate). Significantly lower levels of HSCs (Lin-/CD45 +/AC133 +) have been demonstrated in the patient group compared to the control group both before and after treatment. The level of VSELs (Lin-/CD45-/CD133 +) was significantly lower in the patient group before treatment as compared to the patient group after treatment.The levels of factors responsible for stem cell movement were significantly lower in the patient group compared to the control group before and after treatment. It was concluded that the study of stem cells and factors associated with their movement can be useful in the diagnostics of panic disorder, as well as differentiating between psychotic and anxiety disorders.

  8. 28 CFR 42.713 - Exception; reasonable factors other than age.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Exception; reasonable factors other than age. 42.713 Section 42.713 Judicial Administration DEPARTMENT OF JUSTICE NONDISCRIMINATION; EQUAL..., otherwise prohibited by § 42.710(a), that affects age groups differently, if such differentiation is based...

  9. LIN-12/Notch signaling instructs postsynaptic muscle arm development by regulating UNC-40/DCC and MADD-2 in Caenorhabditis elegans

    PubMed Central

    Li, Pengpeng; Collins, Kevin M; Koelle, Michael R; Shen, Kang

    2013-01-01

    The diverse cell types and the precise synaptic connectivity between them are the cardinal features of the nervous system. Little is known about how cell fate diversification is linked to synaptic target choices. Here we investigate how presynaptic neurons select one type of muscles, vm2, as a synaptic target and form synapses on its dendritic spine-like muscle arms. We found that the Notch-Delta pathway was required to distinguish target from non-target muscles. APX-1/Delta acts in surrounding cells including the non-target vm1 to activate LIN-12/Notch in the target vm2. LIN-12 functions cell-autonomously to up-regulate the expression of UNC-40/DCC and MADD-2 in vm2, which in turn function together to promote muscle arm formation and guidance. Ectopic expression of UNC-40/DCC in non-target vm1 muscle is sufficient to induce muscle arm extension from these cells. Therefore, the LIN-12/Notch signaling specifies target selection by selectively up-regulating guidance molecules and forming muscle arms in target cells. DOI: http://dx.doi.org/10.7554/eLife.00378.001 PMID:23539368

  10. Crystal structures of MW1337R and lin2004: Representatives of a novel protein family that adopt a four-helical bundle fold

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kozbial, Piotr; Xu, Qingping; Chiu, Hsiu-Ju

    2009-08-28

    To extend the structural coverage of proteins with unknown functions, we targeted a novel protein family (Pfam accession number PF08807, DUF1798) for which we proposed and determined the structures of two representative members. The MW1337R gene of Staphylococcus aureus subsp. aureus Rosenbach (Wood 46) encodes a protein with a molecular weight of 13.8 kDa (residues 1-116) and a calculated isoelectric point of 5.15. The lin2004 gene of the nonspore-forming bacterium Listeria innocua Clip11262 encodes a protein with a molecular weight of 14.6 kDa (residues 1-121) and a calculated isoelectric point of 5.45. MW1337R and lin2004, as well as their homologs,more » which, so far, have been found only in Bacillus, Staphylococcus, Listeria, and related genera (Geobacillus, Exiguobacterium, and Oceanobacillus), have unknown functions and are annotated as hypothetical proteins. The genomic contexts of MW1337R and lin2004 are similar and conserved in related species. In prokaryotic genomes, most often, functionally interacting proteins are coded by genes, which are colocated in conserved operons. Proteins from the same operon as MW1337R and lin2004 either have unknown functions (i.e., belong to DUF1273, Pfam accession number PF06908) or are similar to ypsB from Bacillus subtilis. The function of ypsB is unclear, although it has a strong similarity to the N-terminal region of DivIVA, which was characterized as a bifunctional protein with distinct roles during vegetative growth and sporulation. In addition, members of the DUF1273 family display distant sequence similarity with the DprA/Smf protein, which acts downstream of the DNA uptake machinery, possibly in conjunction with RecA. The RecA activities in Bacillus subtilis are modulated by RecU Holliday-junction resolvase. In all analyzed cases, the gene coding for RecU is in the vicinity of MW1337R, lin2004, or their orthologs, but on a different operon located in the complementary DNA strand. Here, we report the crystal

  11. A Novel Method to Increase LinLog CMOS Sensors’ Performance in High Dynamic Range Scenarios

    PubMed Central

    Martínez-Sánchez, Antonio; Fernández, Carlos; Navarro, Pedro J.; Iborra, Andrés

    2011-01-01

    Images from high dynamic range (HDR) scenes must be obtained with minimum loss of information. For this purpose it is necessary to take full advantage of the quantification levels provided by the CCD/CMOS image sensor. LinLog CMOS sensors satisfy the above demand by offering an adjustable response curve that combines linear and logarithmic responses. This paper presents a novel method to quickly adjust the parameters that control the response curve of a LinLog CMOS image sensor. We propose to use an Adaptive Proportional-Integral-Derivative controller to adjust the exposure time of the sensor, together with control algorithms based on the saturation level and the entropy of the images. With this method the sensor’s maximum dynamic range (120 dB) can be used to acquire good quality images from HDR scenes with fast, automatic adaptation to scene conditions. Adaptation to a new scene is rapid, with a sensor response adjustment of less than eight frames when working in real time video mode. At least 67% of the scene entropy can be retained with this method. PMID:22164083

  12. A novel method to increase LinLog CMOS sensors' performance in high dynamic range scenarios.

    PubMed

    Martínez-Sánchez, Antonio; Fernández, Carlos; Navarro, Pedro J; Iborra, Andrés

    2011-01-01

    Images from high dynamic range (HDR) scenes must be obtained with minimum loss of information. For this purpose it is necessary to take full advantage of the quantification levels provided by the CCD/CMOS image sensor. LinLog CMOS sensors satisfy the above demand by offering an adjustable response curve that combines linear and logarithmic responses. This paper presents a novel method to quickly adjust the parameters that control the response curve of a LinLog CMOS image sensor. We propose to use an Adaptive Proportional-Integral-Derivative controller to adjust the exposure time of the sensor, together with control algorithms based on the saturation level and the entropy of the images. With this method the sensor's maximum dynamic range (120 dB) can be used to acquire good quality images from HDR scenes with fast, automatic adaptation to scene conditions. Adaptation to a new scene is rapid, with a sensor response adjustment of less than eight frames when working in real time video mode. At least 67% of the scene entropy can be retained with this method.

  13. Serviceable pavement marking retroreflectivity levels : technical report.

    DOT National Transportation Integrated Search

    2009-03-01

    This research addressed an array of issues related to measuring pavement markings retroreflectivity, factors : related to pavement marking performance, subjective evaluation process, best practices for using mobile : retroreflectometers, sampling pav...

  14. A laser desorption ionization/matrix-assisted laser desorption ionization target system applicable for three distinct types of instruments (LinTOF/curved field RTOF, LinTOF/RTOF and QqRTOF) with different performance characteristics from three vendors.

    PubMed

    Rados, Edita; Pittenauer, Ernst; Frank, Johannes; Varmuza, Kurt; Allmaier, Günter

    2018-04-30

    We have developed a target system which enables the use of only one target (i.e. target preparation set) for three different laser desorption ionization (LDI)/matrix-assisted laser desorption ionization (MALDI) mass spectrometric instruments. The focus was on analysing small biomolecules with LDI for future use of the system for the study of meteorite samples (carbonaceous chondrites) using devices with different mass spectrometric performance characteristics. Three compounds were selected due to their potential presence in meteoritic chondrites: tryptophan, 2-deoxy-d-ribose and triphenylene. They were prepared (with and without MALDI matrix, i.e. MALDI and LDI) and analysed with three different mass spectrometers (LinTOF/curved field RTOF, LinTOF/RTOF and QqRTOF). The ion sources of two of the instruments were run at high vacuum, and one at intermediate pressure. Two devices used a laser wavelength of 355 nm and one a wavelength of 337 nm. The developed target system operated smoothly with all devices. Tryptophan, 2-deoxy-d-ribose and triphenylene showed similar desorption/ionization behaviour for all instruments using the LDI mode. Interestingly, protonated tryptophan could be observed only with the LinTOF/curved field RTOF device in LDI and MALDI mode, while sodiated molecules were observed with all three instruments (in both ion modes). Deprotonated tryptophan was almost completely obscured by matrix ions in the MALDI mode whereas LDI yielded abundant deprotonated molecules. The presented target system allowed successful analyses of the three compounds using instruments from different vendors with only one preparation showing different analyser performance characteristics. The elemental composition with the QqRTOF analyser and the high-energy 20 keV collision-induced dissociation fragmentation will be important in identifying unknown compounds in chondrites. © 2018 The Authors. Rapid Communications in Mass Spectrometry Published by John Wiley & Sons Ltd.

  15. Building a Rapid Learning Health Care System for Oncology: Why CancerLinQ Collects Identifiable Health Information to Achieve Its Vision.

    PubMed

    Shah, Alaap; Stewart, Andrew K; Kolacevski, Andrej; Michels, Dina; Miller, Robert

    2016-03-01

    The ever-increasing volume of scientific discoveries, clinical knowledge, novel diagnostic tools, and treatment options juxtaposed with rising costs in health care challenge physicians to identify, prioritize, and use new information rapidly to deliver efficient and high-quality care to a growing and aging patient population. CancerLinQ, a rapid learning health care system in oncology, is an initiative of the American Society of Clinical Oncology and its Institute for Quality that addresses these challenges by collecting information from the electronic health records of large numbers of patients with cancer. CancerLinQ is first and foremost a quality measurement and reporting system through which oncologists can harness the depth and power of their patients' clinical records and other data to assess, monitor, and improve the care they deliver. However, in light of privacy and security concerns with regard to collection, use, and disclosure of patient information, this article addresses the need to collect protected health information as defined under the Health Insurance Portability and Accountability Act of 1996 to drive rapid learning through CancerLinQ. © 2016 by American Society of Clinical Oncology.

  16. Verification of Self-Report Temperament Factors.

    ERIC Educational Resources Information Center

    Dermen, Diran; And Others

    In an earlier report, one of the authors describes 28 temperament factors for which there is sufficient consensus in the literature to call them "established". From 1 to 5 distinct bipolar subscales were suggested to mark each factor; 12 or 16 item subscales were written, each balanced in terms of the two defined poles and in terms of numbers of…

  17. Kinetics and stereochemistry of LinB-catalyzed δ-HBCD transformation: Comparison of in vitro and in silico results.

    PubMed

    Heeb, Norbert V; Mazenauer, Manuel; Wyss, Simon; Geueke, Birgit; Kohler, Hans-Peter E; Lienemann, Peter

    2018-05-12

    LinB is a haloalkane dehalogenase found in Sphingobium indicum B90A, an aerobic bacterium isolated from contaminated soils of hexachlorocyclohexane (HCH) dumpsites. We showed that this enzyme also converts hexabromocyclododecanes (HBCDs). Here we give new insights in the kinetics and stereochemistry of the enzymatic transformation of δ-HBCD, which resulted in the formation of two pentabromocyclododecanols (PBCDols) as first- (P 1δ , P 2δ ) and two tetrabromocyclododecadiols (TBCDdiols) as second-generation products (T 1δ , T 2δ ). Enzymatic transformations of δ-HBCD, α 1 -PBCDol, one of the transformation products, and α 2 -PBCDol, its enantiomer, were studied and modeled with Michaelis-Menten (MM) kinetics. Respective MM-parameters K M , v max , k cat /K M indicated that δ-HBCD is the best LinB substrate followed by α 2 - and α 1 -PBCDol. The stereochemistry of these transformations was modeled in silico, investigating respective enzyme-substrate (ES) and enzyme-product (EP) complexes. One of the four predicted ES-complexes led to the PBCDol product P 1δ , identical to α 2 -PBCDol with the 1R,2R,5S,6R,9R,10S-configuration. An S N 2-like substitution of bromine at C6 of δ-HBCD by Asp-108 of LinB and subsequent hydrolysis of the alkyl-enzyme led to α 2 -PBCDol. Modeling results further indicate that backside attacks at C1, C9 and C10 are reasonable too, selectively binding leaving bromide ions in a halide pocket found in LinB. Docking with α 2 -PBCDol, also allowed productive enzyme binding. A TBCD-1,5-diol with the 1S,2S,5R,6R,9S,10R-configuration is the predicted second-generation product T 1δ . In conclusion, in vitro- and in silico findings now allow a detailed description of step-wise enzymatic dehalohydroxylation reactions of δ-HBCD to specific PBCDols and TBCDdiols at Å-resolution and predictions of their stereochemistry. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Mitotic Spindle Positioning in the EMS Cell of Caenorhabditis elegans Requires LET-99 and LIN-5/NuMA.

    PubMed

    Liro, Małgorzata J; Rose, Lesilee S

    2016-11-01

    Asymmetric divisions produce daughter cells with different fates, and thus are critical for animal development. During asymmetric divisions, the mitotic spindle must be positioned on a polarized axis to ensure the differential segregation of cell fate determinants into the daughter cells. In many cell types, a cortically localized complex consisting of Gα, GPR-1/2, and LIN-5 (Gαi/Pins/Mud, Gαi/LGN/NuMA) mediates the recruitment of dynactin/dynein, which exerts pulling forces on astral microtubules to physically position the spindle. The conserved PAR polarity proteins are known to regulate both cytoplasmic asymmetry and spindle positioning in many cases. However, spindle positioning also occurs in response to cell signaling cues that appear to be PAR-independent. In the four-cell Caenorhabditis elegans embryo, Wnt and Mes-1/Src-1 signaling pathways act partially redundantly to align the spindle on the anterior/posterior axis of the endomesodermal (EMS) precursor cell. It is unclear how those extrinsic signals individually contribute to spindle positioning and whether either pathway acts via conserved spindle positioning regulators. Here, we genetically test the involvement of Gα, LIN-5, and their negative regulator LET-99, in transducing EMS spindle positioning polarity cues. We also examined whether the C. elegans ortholog of another spindle positioning regulator, DLG-1, is required. We show that LET-99 acts in the Mes-1/Src-1 pathway for spindle positioning. LIN-5 is also required for EMS spindle positioning, possibly through a Gα- and DLG-1-independent mechanism. Copyright © 2016 by the Genetics Society of America.

  19. Mitotic Spindle Positioning in the EMS Cell of Caenorhabditis elegans Requires LET-99 and LIN-5/NuMA

    PubMed Central

    Liro, Małgorzata J.; Rose, Lesilee S.

    2016-01-01

    Asymmetric divisions produce daughter cells with different fates, and thus are critical for animal development. During asymmetric divisions, the mitotic spindle must be positioned on a polarized axis to ensure the differential segregation of cell fate determinants into the daughter cells. In many cell types, a cortically localized complex consisting of Gα, GPR-1/2, and LIN-5 (Gαi/Pins/Mud, Gαi/LGN/NuMA) mediates the recruitment of dynactin/dynein, which exerts pulling forces on astral microtubules to physically position the spindle. The conserved PAR polarity proteins are known to regulate both cytoplasmic asymmetry and spindle positioning in many cases. However, spindle positioning also occurs in response to cell signaling cues that appear to be PAR-independent. In the four-cell Caenorhabditis elegans embryo, Wnt and Mes-1/Src-1 signaling pathways act partially redundantly to align the spindle on the anterior/posterior axis of the endomesodermal (EMS) precursor cell. It is unclear how those extrinsic signals individually contribute to spindle positioning and whether either pathway acts via conserved spindle positioning regulators. Here, we genetically test the involvement of Gα, LIN-5, and their negative regulator LET-99, in transducing EMS spindle positioning polarity cues. We also examined whether the C. elegans ortholog of another spindle positioning regulator, DLG-1, is required. We show that LET-99 acts in the Mes-1/Src-1 pathway for spindle positioning. LIN-5 is also required for EMS spindle positioning, possibly through a Gα- and DLG-1-independent mechanism. PMID:27672093

  20. Scent-marking by coyotes, Canis latrans: the influence of social and ecological factors

    PubMed

    Gese; Ruff

    1997-11-01

    We observed 49 coyotes, Canis latransfrom five resident packs for 2456 h and five transient coyotes for 51 h from January 1991 to June 1993 in the Lamar River Valley, Yellowstone National Park, Wyoming, U.S.A. During these observations we recorded 3042 urinations, 451 defecations, 446 ground scratches and 743 double-marks. The rate of scent-marking (via urination) was influenced by the social organization (resident versus transient) to which the coyote belonged, the social class (alpha, beta or pup) of the animal and the time of the year. Transient coyotes scent-marked at a lower rate than did members of a resident pack. Within the resident packs, alpha coyotes scent-marked at a higher rate than beta coyotes (adults and yearlings subordinant to alphas, but dominant over pups) and pups. Alpha coyotes increased their rate of marking during the breeding season; beta and pup coyotes performed scent-marks at a relatively constant rate throughout the year. There was no influence of social class or time of year on the rate of defecation. The rate of double-marking was highest among alpha coyotes with a peak during the breeding season. Alpha coyotes ground-scratched at a higher rate than did beta and pup coyotes. Alpha and beta coyotes scent-marked more than expected along the periphery of the territory compared to the interior; pups marked in the interior and edge in proportion to expected frequencies. Double-marking and ground-scratching were higher than expected along the periphery of the territory. The distribution of defecations was not different from expected along the edge versus the interior of the territory. Pack size did not influence the rate of scent-marking performed by individuals in the pack or by the alpha pair. We concluded that alpha coyotes were the primary members of the resident pack involved in scent-marking. The large coyote packs and the high rate of marking by the alpha pairs were parallel to the scent-marking behaviour displayed by wolves, C

  1. Factor structure of the General Health Questionnaire-28 (GHQ-28) from infertile women attending the Yazd Research and Clinical Center for Infertility.

    PubMed

    Shayan, Zahra; Pourmovahed, Zahra; Najafipour, Fatemeh; Abdoli, Ali Mohammad; Mohebpour, Fatemeh; Najafipour, Sedighe

    2015-12-01

    Nowadays, infertility problems have become a social concern, and are associated with multiple psychological and social problems. Also, it affects the interpersonal communication between the individual, familial, and social characteristics. Since women are exposed to stressors of physical, mental, social factors, and treatment of infertility, providing a psychometric screening tool is necessary for disorders of this group. The aim of this study was to determine the factor structure of the general health questionnaire-28 to discover mental disorders in infertile women. In this study, 220 infertile women undergoing treatment of infertility were selected from the Yazd Research and Clinical Center for Infertility with convenience sampling in 2011. After completing the general health questionnaire by the project manager, validity and, reliability of the questionnaire were calculated by confirmatory factor structure and Cronbach's alpha, respectively. Four factors, including anxiety and insomnia, social dysfunction, depression, and physical symptoms were extracted from the factor structure. 50.12% of the total variance was explained by four factors. The reliability coefficient of the questionnaire was obtained 0.90. Analysis of the factor structure and reliability of General Health Questionnaire-28 showed that it is suitable as a screening instrument for assessing general health of infertile women.

  2. 46 CFR 108.661 - Unit markings: Draft marks.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Unit markings: Draft marks. 108.661 Section 108.661... AND EQUIPMENT Equipment Markings and Instructions § 108.661 Unit markings: Draft marks. (a) Each unit must have draft marks for each foot of immersion— (1) If the unit is a surface unit, on both the port...

  3. 46 CFR 108.661 - Unit markings: Draft marks.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Unit markings: Draft marks. 108.661 Section 108.661... AND EQUIPMENT Equipment Markings and Instructions § 108.661 Unit markings: Draft marks. (a) Each unit must have draft marks for each foot of immersion— (1) If the unit is a surface unit, on both the port...

  4. 46 CFR 108.661 - Unit markings: Draft marks.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Unit markings: Draft marks. 108.661 Section 108.661... AND EQUIPMENT Equipment Markings and Instructions § 108.661 Unit markings: Draft marks. (a) Each unit must have draft marks for each foot of immersion— (1) If the unit is a surface unit, on both the port...

  5. 46 CFR 108.661 - Unit markings: Draft marks.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Unit markings: Draft marks. 108.661 Section 108.661... AND EQUIPMENT Equipment Markings and Instructions § 108.661 Unit markings: Draft marks. (a) Each unit must have draft marks for each foot of immersion— (1) If the unit is a surface unit, on both the port...

  6. 46 CFR 108.661 - Unit markings: Draft marks.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Unit markings: Draft marks. 108.661 Section 108.661... AND EQUIPMENT Equipment Markings and Instructions § 108.661 Unit markings: Draft marks. (a) Each unit must have draft marks for each foot of immersion— (1) If the unit is a surface unit, on both the port...

  7. Extended Essay Marking on Screen: Is Examiner Marking Accuracy Influenced by Marking Mode?

    ERIC Educational Resources Information Center

    Johnson, Martin; Hopkin, Rebecca; Shiell, Hannah; Bell, John F.

    2012-01-01

    In the UK and elsewhere, large-scale educational assessment agencies are shifting the mode of school examination marking towards having examiners mark examination scripts on screen rather than on paper. This shift has prompted questions about whether the mode of marking might influence examiner marking accuracy, particularly in relation to…

  8. Deficiency of Suppressor Enhancer Lin12 1 Like (SEL1L) in Mice Leads to Systemic Endoplasmic Reticulum Stress and Embryonic Lethality*

    PubMed Central

    Francisco, Adam B.; Singh, Rajni; Li, Shuai; Vani, Anish K.; Yang, Liu; Munroe, Robert J.; Diaferia, Giuseppe; Cardano, Marina; Biunno, Ida; Qi, Ling; Schimenti, John C.; Long, Qiaoming

    2010-01-01

    Stress in the endoplasmic reticulum (ER) plays an important causal role in the pathogenesis of several chronic diseases such as Alzheimer, Parkinson, and diabetes mellitus. Insight into the genetic determinants responsible for ER homeostasis will greatly facilitate the development of therapeutic strategies for the treatment of these debilitating diseases. Suppressor enhancer Lin12 1 like (SEL1L) is an ER membrane protein and was thought to be involved in the quality control of secreted proteins. Here we show that the mice homozygous mutant for SEL1L were embryonic lethal. Electron microscopy studies revealed a severely dilated ER in the fetal liver of mutant embryos, indicative of alteration in ER homeostasis. Consistent with this, several ER stress responsive genes were significantly up-regulated in the mutant embryos. Mouse embryonic fibroblast cells deficient in SEL1L exhibited activated unfolded protein response at the basal state, impaired ER-associated protein degradation, and reduced protein secretion. Furthermore, markedly increased apoptosis was observed in the forebrain and dorsal root ganglions of mutant embryos. Taken together, our results demonstrate an essential role for SEL1L in protein quality control during mouse embryonic development. PMID:20197277

  9. Deficiency of suppressor enhancer Lin12 1 like (SEL1L) in mice leads to systemic endoplasmic reticulum stress and embryonic lethality.

    PubMed

    Francisco, Adam B; Singh, Rajni; Li, Shuai; Vani, Anish K; Yang, Liu; Munroe, Robert J; Diaferia, Giuseppe; Cardano, Marina; Biunno, Ida; Qi, Ling; Schimenti, John C; Long, Qiaoming

    2010-04-30

    Stress in the endoplasmic reticulum (ER) plays an important causal role in the pathogenesis of several chronic diseases such as Alzheimer, Parkinson, and diabetes mellitus. Insight into the genetic determinants responsible for ER homeostasis will greatly facilitate the development of therapeutic strategies for the treatment of these debilitating diseases. Suppressor enhancer Lin12 1 like (SEL1L) is an ER membrane protein and was thought to be involved in the quality control of secreted proteins. Here we show that the mice homozygous mutant for SEL1L were embryonic lethal. Electron microscopy studies revealed a severely dilated ER in the fetal liver of mutant embryos, indicative of alteration in ER homeostasis. Consistent with this, several ER stress responsive genes were significantly up-regulated in the mutant embryos. Mouse embryonic fibroblast cells deficient in SEL1L exhibited activated unfolded protein response at the basal state, impaired ER-associated protein degradation, and reduced protein secretion. Furthermore, markedly increased apoptosis was observed in the forebrain and dorsal root ganglions of mutant embryos. Taken together, our results demonstrate an essential role for SEL1L in protein quality control during mouse embryonic development.

  10. 7 CFR 28.176 - Designation of official certificates, memoranda, marks, other identifications, and devices for...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., other identifications, and devices for purpose of the Agricultural Marketing Act. 28.176 Section 28.176 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE COMMODITY STANDARDS AND STANDARD CONTAINER...

  11. An Approach to Assign Individual Marks from a Team Mark: The Case of Australian Grading System at Universities

    ERIC Educational Resources Information Center

    Nepal, Kali Prasad

    2012-01-01

    This study uses a new approach to assign individual marks from a team mark using individual contributions to a teamwork product. A team member's contribution to a teamwork product, in the form of an individual weighting factor, is calculated using team members' co-assessment. A comparison of the proposed approach with existing methods has been…

  12. [Evaluation of the lifetime of nail markings during polio vaccinations in Chad].

    PubMed

    Quoc Cuong, Huong; Schlumberger, Martin; Garba Tchang, Salomon; Ould Cheikh, Dah; Savès, Marianne; Mallah, Barah; Demtilo Attilo, Jacques; Ngangro Mosurel, Ndeikoundam; Gamatié, Youssouf

    2010-01-01

    days, visually and by photographs, to determine the factors associated with the lifetime of the markings. Kaplan-Meier and log-rank methods were applied to estimate their survival curve and the variables significant for their lifetime; the Cox proportional hazard model was used to determine multivariable-adjusted hazard ratios. Of the 184 children surveyed through the end of the study, the markings disappeared after 35 days of follow-up for 35% of them. The average lifetime of markings on these children was 28 days (SD: 4.95) and was associated, according to the Cox model, with 3 variables: the quality of the marking (RR = 0.335, 95% CI: 0.182-0.617, p < 0.001), playing with soil or mud (RR = 0.38, 95% CI: 0.208-0.697, p = 0.002), and living in different blocks, after stratification for the variable of application of chemical products on the nail. The latter could not be included in the Cox model because it made the markings disappear instantly. WHO experts were right in stating that the lifetime of the markings was sufficient to estimate coverage accurately when external evaluation takes place one or two weeks after SID. The only action found to make markings disappear rapidly was the application of chemical products. Mothers who tell SID attendance evaluation teams that the marking disappeared with bathing are expressing a tacit refusal of vaccination. These evaluations, which take place well before the disappearance of markings, help to determine the precise coverage of SID.

  13. Lin- CD34hi CD117int/hi FcεRI+ cells in human blood constitute a rare population of mast cell progenitors.

    PubMed

    Dahlin, Joakim S; Malinovschi, Andrei; Öhrvik, Helena; Sandelin, Martin; Janson, Christer; Alving, Kjell; Hallgren, Jenny

    2016-01-28

    Mast cells are rare tissue-resident immune cells that are involved in allergic reactions, and their numbers are increased in the lungs of asthmatics. Murine lung mast cells arise from committed bone marrow-derived progenitors that enter the blood circulation, migrate through the pulmonary endothelium, and mature in the tissue. In humans, mast cells can be cultured from multipotent CD34(+) progenitor cells. However, a population of distinct precursor cells that give rise to mast cells has remained undiscovered. To our knowledge, this is the first report of human lineage-negative (Lin(-)) CD34(hi) CD117(int/hi) FcεRI(+) progenitor cells, which represented only 0.0053% of the isolated blood cells in healthy individuals. These cells expressed integrin β7 and developed a mast cell-like phenotype, although with a slow cell division capacity in vitro. Isolated Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood cells had an immature mast cell-like appearance and expressed high levels of many mast cell-related genes as compared with human blood basophils in whole-transcriptome microarray analyses. Furthermore, serglycin, tryptase, and carboxypeptidase A messenger RNA transcripts were detected by quantitative reverse transcription-polymerase chain reaction. Altogether, we propose that the Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood cells are closely related to human tissue mast cells and likely constitute an immediate precursor population, which can give rise to predominantly mast cells. Furthermore, asthmatics with reduced lung function had a higher frequency of Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood mast cell progenitors than asthmatics with normal lung function. © 2016 by The American Society of Hematology.

  14. Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma

    PubMed Central

    Powers, John T; Tsanov, Kaloyan M; Pearson, Daniel S; Roels, Frederik; Spina, Catherine S; Ebright, Richard; Seligson, Marc; de Soysa, Yvanka; Cahan, Patrick; Theiβen, Jessica; Tu, Ho-Chou; Han, Areum; Kurek, Kyle C; LaPier, Grace S; Osborne, Jihan K; Ross, Samantha J; Cesana, Marcella; Collins, James J; Berthold, Frank; Daley, George Q

    2016-01-01

    Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumor suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. However, here we show that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN mRNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B. We found that genetic loss of let-7 is common in neuroblastoma, inversely associated with MYCN-amplification, and independently associated with poor outcomes, providing a rationale for chromosomal loss patterns in neuroblastoma. We propose that let-7 disruption by LIN28B, MYCN sponging, or genetic loss is a unifying mechanism of neuroblastoma pathogenesis with broad implications for cancer pathogenesis. PMID:27383785

  15. A new nuclide transport model in soil in the GENII-LIN health physics code

    NASA Astrophysics Data System (ADS)

    Teodori, F.

    2017-11-01

    The nuclide soil transfer model, originally included in the GENII-LIN software system, was intended for residual contamination from long term activities and from waste form degradation. Short life nuclides were supposed absent or at equilibrium with long life parents. Here we present an enhanced soil transport model, where short life nuclide contributions are correctly accounted. This improvement extends the code capabilities to handle incidental release of contaminant to soil, by evaluating exposure since the very beginning of the contamination event, before the radioactive decay chain equilibrium is reached.

  16. Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity.

    PubMed

    Cousminer, Diana L; Berry, Diane J; Timpson, Nicholas J; Ang, Wei; Thiering, Elisabeth; Byrne, Enda M; Taal, H Rob; Huikari, Ville; Bradfield, Jonathan P; Kerkhof, Marjan; Groen-Blokhuis, Maria M; Kreiner-Møller, Eskil; Marinelli, Marcella; Holst, Claus; Leinonen, Jaakko T; Perry, John R B; Surakka, Ida; Pietiläinen, Olli; Kettunen, Johannes; Anttila, Verneri; Kaakinen, Marika; Sovio, Ulla; Pouta, Anneli; Das, Shikta; Lagou, Vasiliki; Power, Chris; Prokopenko, Inga; Evans, David M; Kemp, John P; St Pourcain, Beate; Ring, Susan; Palotie, Aarno; Kajantie, Eero; Osmond, Clive; Lehtimäki, Terho; Viikari, Jorma S; Kähönen, Mika; Warrington, Nicole M; Lye, Stephen J; Palmer, Lyle J; Tiesler, Carla M T; Flexeder, Claudia; Montgomery, Grant W; Medland, Sarah E; Hofman, Albert; Hakonarson, Hakon; Guxens, Mònica; Bartels, Meike; Salomaa, Veikko; Murabito, Joanne M; Kaprio, Jaakko; Sørensen, Thorkild I A; Ballester, Ferran; Bisgaard, Hans; Boomsma, Dorret I; Koppelman, Gerard H; Grant, Struan F A; Jaddoe, Vincent W V; Martin, Nicholas G; Heinrich, Joachim; Pennell, Craig E; Raitakari, Olli T; Eriksson, Johan G; Smith, George Davey; Hyppönen, Elina; Järvelin, Marjo-Riitta; McCarthy, Mark I; Ripatti, Samuli; Widén, Elisabeth

    2013-07-01

    The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty and cancer progression, pointing to shared underlying mechanisms. To discover genetic loci influencing pubertal height and growth and to place them in context of overall growth and maturation, we performed genome-wide association meta-analyses in 18 737 European samples utilizing longitudinally collected height measurements. We found significant associations (P < 1.67 × 10(-8)) at 10 loci, including LIN28B. Five loci associated with pubertal timing, all impacting multiple aspects of growth. In particular, a novel variant correlated with expression of MAPK3, and associated both with increased prepubertal growth and earlier menarche. Another variant near ADCY3-POMC associated with increased body mass index, reduced pubertal growth and earlier puberty. Whereas epidemiological correlations suggest that early puberty marks a pathway from rapid prepubertal growth to reduced final height and adult obesity, our study shows that individual loci associating with pubertal growth have variable longitudinal growth patterns that may differ from epidemiological observations. Overall, this study uncovers part of the complex genetic architecture linking pubertal height growth, the timing of puberty and childhood obesity and provides new information to pinpoint processes linking these traits.

  17. Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity

    PubMed Central

    Cousminer, Diana L.; Berry, Diane J.; Timpson, Nicholas J.; Ang, Wei; Thiering, Elisabeth; Byrne, Enda M.; Taal, H. Rob; Huikari, Ville; Bradfield, Jonathan P.; Kerkhof, Marjan; Groen-Blokhuis, Maria M.; Kreiner-Møller, Eskil; Marinelli, Marcella; Holst, Claus; Leinonen, Jaakko T.; Perry, John R.B.; Surakka, Ida; Pietiläinen, Olli; Kettunen, Johannes; Anttila, Verneri; Kaakinen, Marika; Sovio, Ulla; Pouta, Anneli; Das, Shikta; Lagou, Vasiliki; Power, Chris; Prokopenko, Inga; Evans, David M.; Kemp, John P.; St Pourcain, Beate; Ring, Susan; Palotie, Aarno; Kajantie, Eero; Osmond, Clive; Lehtimäki, Terho; Viikari, Jorma S.; Kähönen, Mika; Warrington, Nicole M.; Lye, Stephen J.; Palmer, Lyle J.; Tiesler, Carla M.T.; Flexeder, Claudia; Montgomery, Grant W.; Medland, Sarah E.; Hofman, Albert; Hakonarson, Hakon; Guxens, Mònica; Bartels, Meike; Salomaa, Veikko; Murabito, Joanne M.; Kaprio, Jaakko; Sørensen, Thorkild I.A.; Ballester, Ferran; Bisgaard, Hans; Boomsma, Dorret I.; Koppelman, Gerard H.; Grant, Struan F.A.; Jaddoe, Vincent W.V.; Martin, Nicholas G.; Heinrich, Joachim; Pennell, Craig E.; Raitakari, Olli T.; Eriksson, Johan G.; Smith, George Davey; Hyppönen, Elina; Järvelin, Marjo-Riitta; McCarthy, Mark I.; Ripatti, Samuli; Widén, Elisabeth

    2013-01-01

    The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty and cancer progression, pointing to shared underlying mechanisms. To discover genetic loci influencing pubertal height and growth and to place them in context of overall growth and maturation, we performed genome-wide association meta-analyses in 18 737 European samples utilizing longitudinally collected height measurements. We found significant associations (P < 1.67 × 10−8) at 10 loci, including LIN28B. Five loci associated with pubertal timing, all impacting multiple aspects of growth. In particular, a novel variant correlated with expression of MAPK3, and associated both with increased prepubertal growth and earlier menarche. Another variant near ADCY3-POMC associated with increased body mass index, reduced pubertal growth and earlier puberty. Whereas epidemiological correlations suggest that early puberty marks a pathway from rapid prepubertal growth to reduced final height and adult obesity, our study shows that individual loci associating with pubertal growth have variable longitudinal growth patterns that may differ from epidemiological observations. Overall, this study uncovers part of the complex genetic architecture linking pubertal height growth, the timing of puberty and childhood obesity and provides new information to pinpoint processes linking these traits. PMID:23449627

  18. Leniency and halo effects in marking undergraduate short research projects

    PubMed Central

    McKinstry, Brian H; Cameron, Helen S; Elton, Robert A; Riley, Simon C

    2004-01-01

    Background Supervisors are often involved in the assessment of projects they have supervised themselves. Previous research suggests that detailed marking sheets may alleviate leniency and halo effects. We set out to determine if, despite using such a marking schedule, leniency and halo effects were evident in the supervisors' marking of undergraduate short research projects (special study modules (SSM)). Methods Review of grades awarded by supervisors, second markers and control markers to the written reports of 4th year medical students who had participated in an SSM during two full academic years (n = 399). Paired t-tests were used to compare mean marks, Pearson correlation to look at agreement between marks and multiple linear regression to test the prediction of one mark from several others adjusted for one another. Results There was a highly significant difference of approximately half a grade between supervisors and second markers with supervisors marking higher. (t = 3.12, p < 0.01, difference in grade score = 0.42, 95% CI for mean difference 0.18–0.80). There was a high correlation between the two marks awarded for performance of the project and the written report by the supervisor (r = 0.75), but a low-modest correlation between supervisor and second marker (r = 0.28). Linear regression analysis of the influence of the supervisors' mark for performance on their mark for the report gave a non-significant result. This suggests a leniency effect but no halo effect. Conclusions This study shows that with the use of structured marking sheet for assessment of undergraduate medical students, supervisors marks are not associated with a halo effect, but leniency does occur. As supervisor assessment is becoming more common in both under graduate and postgraduate teaching new ways to improve objectivity in marking and to address the leniency of supervisors should be sought. PMID:15569395

  19. Leniency and halo effects in marking undergraduate short research projects.

    PubMed

    McKinstry, Brian H; Cameron, Helen S; Elton, Robert A; Riley, Simon C

    2004-11-29

    Supervisors are often involved in the assessment of projects they have supervised themselves. Previous research suggests that detailed marking sheets may alleviate leniency and halo effects. We set out to determine if, despite using such a marking schedule, leniency and halo effects were evident in the supervisors' marking of undergraduate short research projects (special study modules (SSM)). Review of grades awarded by supervisors, second markers and control markers to the written reports of 4th year medical students who had participated in an SSM during two full academic years (n = 399). Paired t-tests were used to compare mean marks, Pearson correlation to look at agreement between marks and multiple linear regression to test the prediction of one mark from several others adjusted for one another. There was a highly significant difference of approximately half a grade between supervisors and second markers with supervisors marking higher. (t = 3.12, p < 0.01, difference in grade score = 0.42, 95% CI for mean difference 0.18-0.80). There was a high correlation between the two marks awarded for performance of the project and the written report by the supervisor (r = 0.75), but a low-modest correlation between supervisor and second marker (r = 0.28). Linear regression analysis of the influence of the supervisors' mark for performance on their mark for the report gave a non-significant result. This suggests a leniency effect but no halo effect. This study shows that with the use of structured marking sheet for assessment of undergraduate medical students, supervisors marks are not associated with a halo effect, but leniency does occur. As supervisor assessment is becoming more common in both under graduate and postgraduate teaching new ways to improve objectivity in marking and to address the leniency of supervisors should be sought.

  20. A Computational Wireless Network Backplane: Performance in a Distributed Speaker Identification Application Postprint

    DTIC Science & Technology

    2008-12-01

    AUTHOR(S) H.T. Kung, Chit-Kwan Lin, Chia-Yung Su, Dario Vlah, John Grieco, Mark Huggins, and Bruce Suter 5d. PROJECT NUMBER WCNA 5e. TASK NUMBER...APPLICATION H. T. Kung, Chit-Kwan Lin, Chia-Yung Su, Dario Vlah John Grieco†, Mark Huggins‡, Bruce Suter† Harvard University Air Force Research Lab†, Oasis...contributing its C7 processors used in our wireless testbed. REFERENCES [1] R. North, N. Browne, and L. Schiavone , “Joint tactical radio system - connecting

  1. WRKY Transcription Factors: Key Components in Abscisic Acid Signaling

    DTIC Science & Technology

    2011-01-01

    Review article WRKY transcription factors : key components in abscisic acid signalling Deena L. Rushton1, Prateek Tripathi1, Roel C. Rabara1, Jun Lin1...May 2011. *Correspondence (Tel +605 688 5749; fax +605 688 5624; email paul.rushton@sdstate.edu) Keywords: abscisic acid, WRKY transcription factor ...seed germination, drought, abiotic stress. Summary WRKY transcription factors (TFs) are key regulators of many plant processes, including the responses

  2. HOXB7 overexpression in lung cancer is a hallmark of acquired stem-like phenotype.

    PubMed

    Monterisi, Simona; Lo Riso, Pietro; Russo, Karin; Bertalot, Giovanni; Vecchi, Manuela; Testa, Giuseppe; Di Fiore, Pier Paolo; Bianchi, Fabrizio

    2018-03-26

    HOXB7 is a homeodomain (HOX) transcription factor involved in regional body patterning of invertebrates and vertebrates. We previously identified HOXB7 within a ten-gene prognostic signature for lung adenocarcinoma, where increased expression of HOXB7 was associated with poor prognosis. This raises the question of how HOXB7 overexpression can influence the metastatic behavior of lung adenocarcinoma. Here, we analyzed publicly available microarray and RNA-seq lung cancer expression datasets and found that HOXB7-overexpressing tumors are enriched in gene signatures characterizing adult and embryonic stem cells (SC), and induced pluripotent stem cells (iPSC). Experimentally, we found that HOXB7 upregulates several canonical SC/iPSC markers and sustains the expansion of a subpopulation of cells with SC characteristics, through modulation of LIN28B, an emerging cancer gene and pluripotency factor, which we discovered to be a direct target of HOXB7. We validated this new circuit by showing that HOXB7 enhances reprogramming to iPSC with comparable efficiency to LIN28B or its target c-MYC, which is a canonical reprogramming factor.

  3. Mark-recapture with multiple, non-invasive marks.

    PubMed

    Bonner, Simon J; Holmberg, Jason

    2013-09-01

    Non-invasive marks, including pigmentation patterns, acquired scars, and genetic markers, are often used to identify individuals in mark-recapture experiments. If animals in a population can be identified from multiple, non-invasive marks then some individuals may be counted twice in the observed data. Analyzing the observed histories without accounting for these errors will provide incorrect inference about the population dynamics. Previous approaches to this problem include modeling data from only one mark and combining estimators obtained from each mark separately assuming that they are independent. Motivated by the analysis of data from the ECOCEAN online whale shark (Rhincodon typus) catalog, we describe a Bayesian method to analyze data from multiple, non-invasive marks that is based on the latent-multinomial model of Link et al. (2010, Biometrics 66, 178-185). Further to this, we describe a simplification of the Markov chain Monte Carlo algorithm of Link et al. (2010, Biometrics 66, 178-185) that leads to more efficient computation. We present results from the analysis of the ECOCEAN whale shark data and from simulation studies comparing our method with the previous approaches. © 2013, The International Biometric Society.

  4. Recovery of CD45(-)/Lin(-)/SSEA-4(+) very small embryonic-like stem cells by cord blood bank standard operating procedures.

    PubMed

    Chang, Yu-Jen; Tien, Kuei-Erh; Wen, Cheng-Hao; Hsieh, Tzu-Bou; Hwang, Shiaw-Min

    2014-04-01

    Very small embryonic-like (VSEL) stem cells are a rare cell population present in bone marrow, cord blood and other tissues that displays a distinct small cell size and the ability to give rise to cells of the three germ layers. VSEL stem cells were reported to be discarded in the red blood cell fraction by Ficoll-Paque density gradient centrifugation during the processing of bone marrow and cord blood specimens. However, most cord blood banks do not include density gradient centrifugation in their procedures while red blood cells are removed by Hespan sedimentation following the Cord Blood Transplantation Study cord blood bank standard operating procedures (COBLT SOP). To clarify the retention of VSEL stem cells, we investigated the recovery of VSEL stem cells following COBLT SOP guidelines. The recovery of CD45(-)/Lin(-)/SSEA-4(+) VSEL stem cells of umbilical cord blood was examined by flow cytometry before and after COBLT SOP processing, and relative expression of pluripotent genes was analyzed by quantitative polymerase chain reaction. CD45(-)/Lin(-)/SSEA-4(+) VSEL stem cells were mostly recovered in the final products following COBLT SOP guidelines. The expression of pluripotent genes could be maintained at >80% in products after hetastarch (Hespan; B. Braun Medical Inc., Irvine, CA, USA) processing. The rare sub-population of CD45(-)/Lin(-)/SSEA-4(+) VSEL stem cells survived after Hespan sedimentation. This finding suggests that umbilical cord blood units cryopreserved by COBLT SOP in cord blood banks should retain most VSEL stem cells present in the un-processed specimens. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  5. 49 CFR 238.125 - Marking and instructions for emergency egress and rescue access.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... and rescue access. On or after January 28, 2015, emergency signage and markings shall be provided for..., “Standard for Emergency Signage for Egress/Access of Passenger Rail Equipment,” Authorized October 7, 2007...

  6. A classification of marked hijaiyah letters' pronunciation using hidden Markov model

    NASA Astrophysics Data System (ADS)

    Wisesty, Untari N.; Mubarok, M. Syahrul; Adiwijaya

    2017-08-01

    Hijaiyah letters are the letters that arrange the words in Al Qur'an consisting of 28 letters. They symbolize the consonant sounds. On the other hand, the vowel sounds are symbolized by harokat/marks. Speech recognition system is a system used to process the sound signal to be data so that it can be recognized by computer. To build the system, some stages are needed i.e characteristics/feature extraction and classification. In this research, LPC and MFCC extraction method, K-Means Quantization vector and Hidden Markov Model classification are used. The data used are the 28 letters and 6 harakat with the total class of 168. After several are testing done, it can be concluded that the system can recognize the pronunciation pattern of marked hijaiyah letter very well in the training data with its highest accuracy of 96.1% using the feature of LPC extraction and 94% using the MFCC. Meanwhile, when testing system is used, the accuracy decreases up to 41%.

  7. acn-1, a C. elegans homologue of ACE, genetically interacts with the let-7 microRNA and other heterochronic genes.

    PubMed

    Metheetrairut, Chanatip; Ahuja, Yuri; Slack, Frank J

    2017-10-02

    The heterochronic pathway in C. elegans controls the relative timing of cell fate decisions during post-embryonic development. It includes a network of microRNAs (miRNAs), such as let-7, and protein-coding genes, such as the stemness factors, LIN-28 and LIN-41. Here we identified the acn-1 gene, a homologue of mammalian angiotensin-converting enzyme (ACE), as a new suppressor of the stem cell developmental defects of let-7 mutants. Since acn-1 null mutants die during early larval development, we used RNAi to characterize the role of acn-1 in C. elegans seam cell development, and determined its interaction with heterochronic factors, including let-7 and its downstream interactors - lin-41, hbl-1, and apl-1. We demonstrate that although RNAi knockdown of acn-1 is insufficient to cause heterochronic defects on its own, loss of acn-1 suppresses the retarded phenotypes of let-7 mutants and enhances the precocious phenotypes of hbl-1, though not lin-41, mutants. Conversely, the pattern of acn-1 expression, which oscillates during larval development, is disrupted by lin-41 mutants but not by hbl-1 mutants. Finally, we show that acn-1(RNAi) enhances the let-7-suppressing phenotypes caused by loss of apl-1, a homologue of the Alzheimer's disease-causing amyloid precursor protein (APP), while significantly disrupting the expression of apl-1 during the L4 larval stage. In conclusion, acn-1 interacts with heterochronic genes and appears to function downstream of let-7 and its target genes, including lin-41 and apl-1.

  8. 28 CFR 540.19 - Legal correspondence.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Legal correspondence. 540.19 Section 540... WITH PERSONS IN THE COMMUNITY Correspondence § 540.19 Legal correspondence. (a) Staff shall mark each envelope of incoming legal mail (mail from courts or attorneys) to show the date and time of receipt, the...

  9. 28 CFR 540.19 - Legal correspondence.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Legal correspondence. 540.19 Section 540... WITH PERSONS IN THE COMMUNITY Correspondence § 540.19 Legal correspondence. (a) Staff shall mark each envelope of incoming legal mail (mail from courts or attorneys) to show the date and time of receipt, the...

  10. 28 CFR 540.19 - Legal correspondence.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Legal correspondence. 540.19 Section 540... WITH PERSONS IN THE COMMUNITY Correspondence § 540.19 Legal correspondence. (a) Staff shall mark each envelope of incoming legal mail (mail from courts or attorneys) to show the date and time of receipt, the...

  11. 28 CFR 540.19 - Legal correspondence.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Legal correspondence. 540.19 Section 540... WITH PERSONS IN THE COMMUNITY Correspondence § 540.19 Legal correspondence. (a) Staff shall mark each envelope of incoming legal mail (mail from courts or attorneys) to show the date and time of receipt, the...

  12. 28 CFR 540.19 - Legal correspondence.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Legal correspondence. 540.19 Section 540... WITH PERSONS IN THE COMMUNITY Correspondence § 540.19 Legal correspondence. (a) Staff shall mark each envelope of incoming legal mail (mail from courts or attorneys) to show the date and time of receipt, the...

  13. [Risk factors in the results of the colour vision test Roth 28-hue (E) desaturated in glaucoma patients].

    PubMed

    Jass, C M; Böhringer, D; Erb, C; Jordan, J F

    2013-11-01

    Glaucoma is an ocular disease with typical progressive damage of the optic nerve. In the past it was postulated that glaucoma induces acquired colour vision disorders. Until now all studies about glaucoma and colour vision disorders did not include vascular risk factors. In the present study we determined several vascular risk factors concerning the results of the colour vision test Roth 28-hue (E) desaturated in glaucoma patients. On the basis of an analysis of variance (ANOVA) we determined the influence of several risk factors, such as arteriosclerotic and vasospastic risk factors, on the results of the colour vision test Roth 28-hue (E) desaturated in glaucoma patients. 353 glaucoma patients were included in this study. We detected a strong influence of age and mean defect in perimetry and an additional effect of arteriosclerotic and vasospastic risk factors on the results of the colour vision test Roth 28-hue (E) desaturated in glaucoma patients. We suspect that arteriosclerotic and vasospastic risk factors independently to glaucoma have an influence on colour vision. In the future attention additionally has to be given to vascular risk factors in the colour vision testing of glaucoma patients. Georg Thieme Verlag KG Stuttgart · New York.

  14. Far ultraviolet spectrophotometry of BD +28 4211

    NASA Technical Reports Server (NTRS)

    Cook, Timothy A.; Cash, Webster; Green, James C.

    1991-01-01

    The results are reported of a November 1989 rocket flight which recorded a flux-calibrated spectrum of BD +28 4211 from 912 to 1150 A with 1A resolution. BD +28 4211, an SdO-type star, is commonly used as an ultraviolet calibration source in the IUE wavelength band. The present work extends the useful range of this standard shortward of Lyman-alpha. Since previous experiments show marked disparity, this study can be useful in determining a standard in the 912 to 1216 A band.

  15. Mark-resight abundance estimation under incomplete identification of marked individuals

    USGS Publications Warehouse

    McClintock, Brett T.; Hill, Jason M.; Fritz, Lowell; Chumbley, Kathryn; Luxa, Katie; Diefenbach, Duane R.

    2014-01-01

    Often less expensive and less invasive than conventional mark–recapture, so-called 'mark-resight' methods are popular in the estimation of population abundance. These methods are most often applied when a subset of the population of interest is marked (naturally or artificially), and non-invasive sighting data can be simultaneously collected for both marked and unmarked individuals. However, it can often be difficult to identify marked individuals with certainty during resighting surveys, and incomplete identification of marked individuals is potentially a major source of bias in mark-resight abundance estimators. Previously proposed solutions are ad hoc and will tend to underperform unless marked individual identification rates are relatively high (>90%) or individual sighting heterogeneity is negligible.Based on a complete data likelihood, we present an approach that properly accounts for uncertainty in marked individual detection histories when incomplete identifications occur. The models allow for individual heterogeneity in detection, sampling with (e.g. Poisson) or without (e.g. Bernoulli) replacement, and an unknown number of marked individuals. Using a custom Markov chain Monte Carlo algorithm to facilitate Bayesian inference, we demonstrate these models using two example data sets and investigate their properties via simulation experiments.We estimate abundance for grassland sparrow populations in Pennsylvania, USA when sampling was conducted with replacement and the number of marked individuals was either known or unknown. To increase marked individual identification probabilities, extensive territory mapping was used to assign incomplete identifications to individuals based on location. Despite marked individual identification probabilities as low as 67% in the absence of this territorial mapping procedure, we generally found little return (or need) for this time-consuming investment when using our proposed approach. We also estimate rookery abundance

  16. Fibroblast growth factor regulates insulin-like growth factor-binding protein production by vascular smooth muscle cells.

    PubMed

    Ververis, J; Ku, L; Delafontaine, P

    1994-02-01

    Insulin-like growth factor I is an important mitogen for vascular smooth muscle cells, and its effects are regulated by several binding proteins. Western ligand blotting of conditioned medium from rat aortic smooth muscle cells detected a 24 kDa binding protein and a 28 kDa glycosylated variant of this protein, consistent with insulin-like growth factor binding protein-4 by size. Low amounts of a glycosylated 38 to 42 kDa doublet (consistent with binding protein-3) and a 31 kDa non-glycosylated protein also were present. Basic fibroblast growth factor markedly increased secretion of the 24 kDa binding protein and its 28 kDa glycosylated variant. This effect was dose- and time-dependent and was inhibited by co-incubation with cycloheximide. Crosslinking of [125I]-insulin-like growth factor I to cell monolayers revealed no surface-associated binding proteins, either basally or after agonist treatment. Induction of binding protein production by fibroblast growth factor at sites of vascular injury may be important in vascular proliferative responses in vivo.

  17. Risk factors for hospital admission in the 28 days following a community-acquired pneumonia diagnosis in older adults, and their contribution to increasing hospitalisation rates over time: a cohort study

    PubMed Central

    Millett, Elizabeth R C; De Stavola, Bianca L; Smeeth, Liam; Thomas, Sara L

    2015-01-01

    Objectives To determine factors associated with hospitalisation after community-acquired pneumonia (CAP) among older adults in England, and to investigate how these factors have contributed to increasing hospitalisations over time. Design Cohort study. Setting Primary and secondary care in England. Population 39 211 individuals from the Clinical Practice Research Datalink, who were eligible for linkage to Hospital Episode Statistics and mortality data, were aged ≥65 and had at least 1 CAP episode between April 1998 and March 2011. Main outcome measures The association between hospitalisation within 28 days of CAP diagnosis (a ‘post-CAP’ hospitalisation) and a wide range of comorbidities, frailty factors, medications and vaccinations. We examined the role of these factors in post-CAP hospitalisation trends. We also looked at trends in post-CAP mortality and length of hospitalisation over the study period. Results 14 comorbidities, 5 frailty factors and 4 medications/vaccinations were associated with hospitalisation (of 18, 12 and 7 considered, respectively). Factors such as chronic lung disease, severe renal disease and diabetes were associated with increased likelihood of hospitalisation, whereas factors such as recent influenza vaccination and a recent antibiotic prescription decreased the odds of hospitalisation. Despite adjusting for these and other factors, the average predicted probability of hospitalisation after CAP rose markedly from 57% (1998–2000) to 86% (2009–2010). Duration of hospitalisation and 28-day mortality decreased over the study period. Conclusions The risk factors we describe enable identification of patients at increased likelihood of post-CAP hospitalisation and thus in need of proactive case management. Our analyses also provide evidence that while comorbidities and frailty factors contributed to increasing post-CAP hospitalisations in recent years, the trend appears to be largely driven by changes in service provision and

  18. MIB-1 Is Required for Spermatogenesis and Facilitates LIN-12 and GLP-1 Activity in Caenorhabditis elegans.

    PubMed

    Ratliff, Miriam; Hill-Harfe, Katherine L; Gleason, Elizabeth J; Ling, Huiping; Kroft, Tim L; L'Hernault, Steven W

    2018-05-01

    Covalent attachment of ubiquitin to substrate proteins changes their function or marks them for proteolysis, and the specificity of ubiquitin attachment is mediated by the numerous E3 ligases encoded by animals. Mind Bomb is an essential E3 ligase during Notch pathway signaling in insects and vertebrates. While Caenorhabditis elegans encodes a Mind Bomb homolog ( mib-1 ), it has never been recovered in the extensive Notch suppressor/enhancer screens that have identified numerous pathway components. Here, we show that C. elegans mib-1 null mutants have a spermatogenesis-defective phenotype that results in a heterogeneous mixture of arrested spermatocytes, defective spermatids, and motility-impaired spermatozoa. mib-1 mutants also have chromosome segregation defects during meiosis, molecular null mutants are intrinsically temperature-sensitive, and many mib-1 spermatids contain large amounts of tubulin. These phenotypic features are similar to the endogenous RNA intereference (RNAi) mutants, but mib-1 mutants do not affect RNAi. MIB-1 protein is expressed throughout the germ line with peak expression in spermatocytes followed by segregation into the residual body during spermatid formation. C. elegans mib-1 expression, while upregulated during spermatogenesis, also occurs somatically, including in vulva precursor cells. Here, we show that mib-1 mutants suppress both lin-12 and glp-1 ( C. elegans Notch) gain-of-function mutants, restoring anchor cell formation and a functional vulva to the former and partly restoring oocyte production to the latter. However, suppressed hermaphrodites are only observed when grown at 25°, and they are self-sterile. This probably explains why mib-1 was not previously recovered as a Notch pathway component in suppressor/enhancer selection experiments. Copyright © 2018 by the Genetics Society of America.

  19. Identification of key factors regulating self-renewal and differentiation in EML hematopoietic precursor cells by RNA-sequencing analysis.

    PubMed

    Zong, Shan; Deng, Shuyun; Chen, Kenian; Wu, Jia Qian

    2014-11-11

    Hematopoietic stem cells (HSCs) are used clinically for transplantation treatment to rebuild a patient's hematopoietic system in many diseases such as leukemia and lymphoma. Elucidating the mechanisms controlling HSCs self-renewal and differentiation is important for application of HSCs for research and clinical uses. However, it is not possible to obtain large quantity of HSCs due to their inability to proliferate in vitro. To overcome this hurdle, we used a mouse bone marrow derived cell line, the EML (Erythroid, Myeloid, and Lymphocytic) cell line, as a model system for this study. RNA-sequencing (RNA-Seq) has been increasingly used to replace microarray for gene expression studies. We report here a detailed method of using RNA-Seq technology to investigate the potential key factors in regulation of EML cell self-renewal and differentiation. The protocol provided in this paper is divided into three parts. The first part explains how to culture EML cells and separate Lin-CD34+ and Lin-CD34- cells. The second part of the protocol offers detailed procedures for total RNA preparation and the subsequent library construction for high-throughput sequencing. The last part describes the method for RNA-Seq data analysis and explains how to use the data to identify differentially expressed transcription factors between Lin-CD34+ and Lin-CD34- cells. The most significantly differentially expressed transcription factors were identified to be the potential key regulators controlling EML cell self-renewal and differentiation. In the discussion section of this paper, we highlight the key steps for successful performance of this experiment. In summary, this paper offers a method of using RNA-Seq technology to identify potential regulators of self-renewal and differentiation in EML cells. The key factors identified are subjected to downstream functional analysis in vitro and in vivo.

  20. Identification of Key Factors Regulating Self-renewal and Differentiation in EML Hematopoietic Precursor Cells by RNA-sequencing Analysis

    PubMed Central

    Chen, Kenian; Wu, Jia Qian

    2014-01-01

    Hematopoietic stem cells (HSCs) are used clinically for transplantation treatment to rebuild a patient's hematopoietic system in many diseases such as leukemia and lymphoma. Elucidating the mechanisms controlling HSCs self-renewal and differentiation is important for application of HSCs for research and clinical uses. However, it is not possible to obtain large quantity of HSCs due to their inability to proliferate in vitro. To overcome this hurdle, we used a mouse bone marrow derived cell line, the EML (Erythroid, Myeloid, and Lymphocytic) cell line, as a model system for this study. RNA-sequencing (RNA-Seq) has been increasingly used to replace microarray for gene expression studies. We report here a detailed method of using RNA-Seq technology to investigate the potential key factors in regulation of EML cell self-renewal and differentiation. The protocol provided in this paper is divided into three parts. The first part explains how to culture EML cells and separate Lin-CD34+ and Lin-CD34- cells. The second part of the protocol offers detailed procedures for total RNA preparation and the subsequent library construction for high-throughput sequencing. The last part describes the method for RNA-Seq data analysis and explains how to use the data to identify differentially expressed transcription factors between Lin-CD34+ and Lin-CD34- cells. The most significantly differentially expressed transcription factors were identified to be the potential key regulators controlling EML cell self-renewal and differentiation. In the discussion section of this paper, we highlight the key steps for successful performance of this experiment. In summary, this paper offers a method of using RNA-Seq technology to identify potential regulators of self-renewal and differentiation in EML cells. The key factors identified are subjected to downstream functional analysis in vitro and in vivo. PMID:25407807

  1. Geodetic Results from Mark 4 VLBI

    NASA Technical Reports Server (NTRS)

    MacMillan, Daniel; Petrov, Leonid; Ma, Chopo

    2002-01-01

    We present geodetic results of a series of 30 VLBI experiments recorded in Mark 4 mode at rates of 128 and 256 Mbps. The formal uncertainties of UT1, polar motion, and nutation offsets derived from these experiments are better than the corresponding uncertainties from NEOS-A experiments by a factor of 1.3-2. Baseline length repeatability for the series of 32 experiments over a period of one year is about 0.9 ppb. For comparison, NEOS-A length repeatability is about 1.4 ppb. We will discuss optimal use of Mark 4 in the design of future observing networks.

  2. Mark.

    ERIC Educational Resources Information Center

    Lipman, Matthew; Smith, Theresa L., Ed.

    Mark is the central character in this story designed to help adolescents formulate a philosophy of values. The story is well suited for use in high school social studies courses and/or in philosophy or guidance units. Mark's thoughts and actions are reported as he interacts with his family, friends, acquaintances, and individuals of authority…

  3. Enamel-based mark performance for marking Chinese mystery snail Bellamya chinensis

    USGS Publications Warehouse

    Wong, Alec; Allen, Craig R.; Hart, Noelle M.; Haak, Danielle M.; Pope, Kevin L.; Smeenk, Nicholas A.; Stephen, Bruce J.; Uden, Daniel R.

    2013-01-01

    The exoskeleton of gastropods provides a convenient surface for carrying marks, and i the interest of improving future marking methods our laboratory assessed the performance of an enamel paint. The endurance of the paint was also compared to other marking methods assessed in the past. We marked the shells of 30 adult Chinese mystery snails Bellamya chinensis and held them in an aquarium for 181 days. We observed no complete degradation of any enamel-paint mark during the 181 days. The enamel-paint mark was superior to a nai;-polish mark, which lasted a median of 100 days. Enamel-paint marks also have a lower rate of loss (0.00 month-1 181 days) than plastic bee tags (0.01 month-1, 57 days), gouache paint (0.07 month-1, 18.5 days), or car body paint from studies found in scientific literature. Legibility of enamel-paint marks had a median lifetime of 102 days. The use of enamel paint on the shells of gastropods is a viable option for studies lasting up to 6 months. Furthermore, visits to capture-mark-recapture site 1 year after application of enamel-paint marks on B. chinesnis shells produced several individuals on which the enamel paint was still visible, although further testing is required to clarify durability over longer periods.

  4. On denture marking.

    PubMed

    Borrman, H I; DiZinno, J A; Wasén, J; René, N

    1999-06-01

    During the last decades in Sweden dentures have been permanently marked with a stainless steel metal band incorporated into the acrylic and containing the patient's birth date, a special number, and "S" for Sweden. The last recommendation issued by the National Board of Health and Welfare states that "the patients shall always be offered denture marking and be informed about the benefit thereof. Denture marking is not permitted if the patient refuses it". Requirements for denture markers have been that they should be biologically inert (when incorporated into the denture), not be expensive, be easy to inscribe, be possible to retrieve after an accident, and survive elevated temperatures for a reasonable time under normal circumstances. Although the frequency of edentulousness has decreased in recent years due to the improvement in oral health there remains a need to address the issue of marking of complete dentures, because there is a large variation in the oral status of populations in different countries. Given that only one marked denture can reveal the identity of a deceased person when all other methods fail to do so, makes it worthwhile. Furthermore, denture marking is important in long-term care facilities. We have investigated the issue of denture marking in Europe and in the United States. The results from the European survey show that denture marking is, to our knowledge regulated by law only in Sweden and Iceland. In the US denture marking is so far mandatory in 21 states while New York State requires dentures to be marked if the patient requests it and several other states impose the obligation to mark dentures on long-term care facilities. Since there is no international consensus regarding the issue of denture marking it is important to address it. A survey from the Nordic countries has shown that if denture marking was in general use, the contribution to the establishment of identity by forensic odontology in cases of fire would increase by about 10

  5. Herd-level risk factors associated with the presence of Phage type 21/28 E. coli O157 on Scottish cattle farms

    PubMed Central

    Halliday, Jo EB; Chase-Topping, Margo E; Pearce, Michael C; McKendrick, Iain J; Allison, Lesley; Fenlon, Dave; Low, Chris; Mellor, Dominic J; Gunn, George J; Woolhouse, Mark EJ

    2006-01-01

    Background E. coli O157 is a bacterial pathogen that is shed by cattle and can cause severe disease in humans. Phage type (PT) 21/28 is a subtype of E. coli O157 that is found across Scotland and is associated with particularly severe human morbidity. Methods A cross-sectional survey of Scottish cattle farms was conducted in the period Feb 2002-Feb 2004 to determine the prevalence of E. coli O157 in cattle herds. Data from 88 farms on which E. coli O157 was present were analysed using generalised linear mixed models to identify risk factors for the presence of PT 21/28 specifically. Results The analysis identified private water supply, and northerly farm location as risk factors for PT 21/28 presence. There was a significant association between the presence of PT 21/28 and an increased number of E. coli O157 positive pat samples from a farm, and PT 21/28 was significantly associated with larger E. coli O157 counts than non-PT 21/28 E. coli O157. Conclusion PT 21/28 has significant risk factors that distinguish it from other phage types of E. coli O157. This finding has implications for the control of E. coli O157 as a whole and suggests that control could be tailored to target the locally dominant PT. PMID:17140453

  6. The interplay of attention economics and computer-aided detection marks in screening mammography

    NASA Astrophysics Data System (ADS)

    Schwartz, Tayler M.; Sridharan, Radhika; Wei, Wei; Lukyanchenko, Olga; Geiser, William; Whitman, Gary J.; Haygood, Tamara Miner

    2016-03-01

    Introduction: According to attention economists, overabundant information leads to decreased attention for individual pieces of information. Computer-aided detection (CAD) alerts radiologists to findings potentially associated with breast cancer but is notorious for creating an abundance of false-positive marks. We suspected that increased CAD marks do not lengthen mammogram interpretation time, as radiologists will selectively disregard these marks when present in larger numbers. We explore the relevance of attention economics in mammography by examining how the number of CAD marks affects interpretation time. Methods: We performed a retrospective review of bilateral digital screening mammograms obtained between January 1, 2011 and February 28, 2014, using only weekend interpretations to decrease distractions and the likelihood of trainee participation. We stratified data according to reader and used ANOVA to assess the relationship between number of CAD marks and interpretation time. Results: Ten radiologists, with median experience after residency of 12.5 years (range 6 to 24,) interpreted 1849 mammograms. When accounting for number of images, Breast Imaging Reporting and Data System category, and breast density, increasing numbers of CAD marks was correlated with longer interpretation time only for the three radiologists with the fewest years of experience (median 7 years.) Conclusion: For the 7 most experienced readers, increasing CAD marks did not lengthen interpretation time. We surmise that as CAD marks increase, the attention given to individual marks decreases. Experienced radiologists may rapidly dismiss larger numbers of CAD marks as false-positive, having learned that devoting extra attention to such marks does not improve clinical detection.

  7. Characteristics of diving in radio-marked Xantus's Murrelets

    USGS Publications Warehouse

    Hamilton, C.D.; Golightly, R.T.; Takekawa, John Y.

    2005-01-01

    We monitored diving activity of radio-marked Xantus's Murrelets Synthliboramphus hypoleucus near Anacapa Island, California, during the breeding season. Thirteen radio-marked murrelets were remotely monitored from Anacapa Island with a handheld antenna and radio receiver for 29 hours in three sample periods in April and May 2003. Mean dive durations in the sample periods were 18 s ?? 2 s, 28 s ?? 2 s, and 24 s ?? 4 s, suggesting that dives were less than 21 m from the surface. Dive duration and subsequent time on the surface differed between the sample periods. Dive duration and subsequent time on the surface were not correlated in observations stratified by individual bird or by sample period. Further, dive duration and subsequent time on the surface were not correlated within foraging bouts. Dive characteristics measured near Anacapa Island suggested that Xantus's Murrelets have the ability to capture prey found at varying depths, but will feed on prey that is most available near the surface of the water.

  8. Functional Analysis of the Alternative Sigma-28 Factor FliA and Its Anti-Sigma Factor FlgM of the Nonflagellated Legionella Species L. oakridgensis.

    PubMed

    Tlapák, Hana; Rydzewski, Kerstin; Schulz, Tino; Weschka, Dennis; Schunder, Eva; Heuner, Klaus

    2017-06-01

    Legionella oakridgensis causes Legionnaires' disease but is known to be less virulent than Legionella pneumophila L. oakridgensis is one of the Legionella species that is nonflagellated. The genes of the flagellar regulon are absent, except those encoding the alternative sigma-28 factor (FliA) and its anti-sigma-28 factor (FlgM). Similar to L. oakridgensis , Legionella adelaidensis and Legionella londiniensis , located in the same phylogenetic clade, have no flagellar regulon, although both are positive for fliA and flgM Here, we investigated the role and function of both genes to better understand the role of FliA, the positive regulator of flagellin expression, in nonflagellated strains. We demonstrated that the FliA gene of L. oakridgensis encodes a functional sigma-28 factor that enables the transcription start from the sigma-28-dependent promoter site. The investigations have shown that FliA is necessary for full fitness of L. oakridgensis Interestingly, expression of FliA-dependent genes depends on the growth phase and temperature, as already shown for L. pneumophila strains that are flagellated. In addition, we demonstrated that FlgM is a negative regulator of FliA-dependent gene expression. FlgM seems to be degraded in a growth-phase- and temperature-dependent manner, instead of being exported into the medium as reported for most bacteria. The degradation of FlgM leads to an increase of FliA activity. IMPORTANCE A less virulent Legionella species, L. oakridgensis , causes Legionnaires' disease and is known to not have flagella, even though L. oakridgensis has the regulator of flagellin expression (FliA). This protein has been shown to be involved in the expression of virulence factors. Thus, the strain was chosen for use in this investigation to search for FliA target genes and to identify putative virulence factors of L. oakridgensis One of the five major target genes of FliA identified here encodes the anti-FliA sigma factor FlgM. Interestingly, in

  9. Plant Type Selection for Reclamation of Sarcheshmeh Copper Mine Using Fuzzy-Topsis Approach / Wybór Gatunków Roślin Do Wykorzystania W Projekcie Rekultywacji Terenów Kopalni Miedzi Sarcheshmeh Z Wykorzystaniem Metod Logiki Rozmytej Topsis

    NASA Astrophysics Data System (ADS)

    Ebrahimabadi, Arash; Alavi, Iraj

    2013-09-01

    Plant species selection is a multi-criteria evaluation decision and has a strategic importance for many companies. The conventional methods for plant species selection are inadequate for dealing with the imprecise or vague nature of linguistic assessment. To overcome this difficulty, fuzzy multi-criteria decision-making methods are proposed. The aim of this study is to use the fuzzy technique for order preference by similarity to ideal solution (F.TOPSIS) methods for the selection of plant species in mine reclamation plan. Plant type selection and planting to protect the environment and the reclamation of the mine are some of the most important solutions. Therefore, the objective of the current research study is to choose the proper plant types for reclamation of Sarcheshmeh Copper Mine using Fuzzy-topsis method. In this regard, primarily, surrounding area of Sarcheshmeh copper mine, one of the world's 10 biggest copper mine which is located near Kerman city of Iran, are surveyed, to choose the best plant type for reclamation of disturbance area. With this respect, based on reclamation plan, primary criteria were consisted of kinds of post mining land use, climate, and nature of soil. Comparison matrixes were then obtained based on experts' opinion and plant types were subsequently prioritized using the Fuzzy Topsis method. Secondary factors considered through the analysis were as follows: perspective of the region, resistance against disease and insects, strength and method of growth, availability to plant type, economic efficiency, protection of soil, storing water, and prevention of pollution. Finally, suitable plant types in the mining perimeter were prioritized as: Amygdalus scoparia, Tamarix, Pistachio Wild, Ephedra, Astragalus, Salsola, respectively. Wybór gatunków roślin jest decyzją podejmowaną w oparciu o wiele kryteriów i stanowi poważne wyzwanie strategiczne dla wielu firm. Konwencjonalne metody wyboru gatunków roślin okazują si

  10. Laser marking as a result of applying reverse engineering

    NASA Astrophysics Data System (ADS)

    Mihalache, Andrei; Nagîţ, Gheorghe; Rîpanu, Marius Ionuţ; Slǎtineanu, Laurenţiu; Dodun, Oana; Coteaţǎ, Margareta

    2018-05-01

    The elaboration of a modern manufacturing technology needs a certain quantum of information concerning the part to be obtained. When it is necessary to elaborate the technology for an existing object, such an information could be ensured by using the principles specific to the reverse engineering. Essentially, in the case of this method, the analysis of the surfaces and of other characteristics of the part must offer enough information for the elaboration of the part manufacturing technology. On the other hand, it is known that the laser marking is a processing method able to ensure the transfer of various inscriptions or drawings on a part. Sometimes, the laser marking could be based on the analysis of an existing object, whose image could be used to generate the same object or an improved object. There are many groups of factors able to affect the results of applying the laser marking process. A theoretical analysis was proposed to show that the heights of triangles obtained by means of a CNC marking equipment depend on the width of the line generated by the laser spot on the workpiece surface. An experimental research was thought and materialized to highlight the influence exerted by the line with and the angle of lines intersections on the accuracy of the marking process. By mathematical processing of the experimental results, empirical mathematical models were determined. The power type model and the graphical representation elaborated on the base of this model offered an image concerning the influences exerted by the considered input factors on the marking process accuracy.

  11. Stretch marks

    MedlinePlus

    Stretch marks can appear when there is rapid stretching of the skin. The marks appear as parallel ... often disappear after the cause of the skin stretching is gone. Avoiding rapid weight gain helps reduce ...

  12. Stretch Marks

    MedlinePlus

    ... stretch marks. This isn't true with regular tanning or tanning beds , though: Stretch marks are less likely to ... up looking more obvious. Plus, the sun and tanning beds do more harm than good when it ...

  13. Superagonistic CD28 antibody induces donor-specific tolerance in rat renal allografts.

    PubMed

    Azuma, H; Isaka, Y; Li, X; Hünig, T; Sakamoto, T; Nohmi, H; Takabatake, Y; Mizui, M; Kitazawa, Y; Ichimaru, N; Ibuki, N; Ubai, T; Inamoto, T; Katsuoka, Y; Takahara, S

    2008-10-01

    The ultimate goal of organ transplantation is to establish graft tolerance where CD4+CD25+FOXP3+ regulatory T (Treg) cells play an important role. We examined whether a superagonistic monoclonal antibody specific for CD28 (CD28 SA), which expands Treg cells in vivo, would prevent acute rejection and induce tolerance using our established rat acute renal allograft model (Wistar to Lewis). In the untreated or mouse IgG-treated recipients, graft function significantly deteriorated with marked destruction of renal tissue, and all rats died by 13 days with severe azotemia. In contrast, 90% of recipients treated with CD28 SA survived over 100 days, and 70% survived with well-preserved graft function until graft recovery at 180 days. Analysis by flow cytometry and immunohistochemistry demonstrated that CD28 SA induced marked infiltration of FOXP3+ Treg cells into the allografts. Furthermore, these long-surviving recipients showed donor-specific tolerance, accepting secondary (donor-matched) Wistar cardiac allografts, but acutely rejecting third-party BN allografts. We further demonstrated that adoptive transfer of CD4+CD25+ Treg cells, purified from CD28 SA-treated Lewis rats, significantly prolonged allograft survival and succeeded in inducing donor-specific tolerance. In conclusion, CD28 SA treatment successfully induces donor-specific tolerance with the involvement of Treg cells, and thus the therapeutic value of this approach warrants further investigation and preclinical studies.

  14. Pavement markings and safety.

    DOT National Transportation Integrated Search

    2010-11-01

    Previous research on pavement markings from a safety perspective tackled various issues such as pavement marking retroreflectivity : variability, relationship between pavement marking retroreflectivity and driver visibility, or pavement marking impro...

  15. A new measurement of the 6Li(n, α)t cross section at MeV energies using a 252Cf fission chamber and 6Li scintillators

    NASA Astrophysics Data System (ADS)

    Kirsch, Leo E.; Devlin, M.; Mosby, S. M.; Gomez, J. A.

    2017-12-01

    A new measurement is presented of the 6Li(n, α)t cross section from 245 keV to 10 MeV using a 252Cf fission chamber with 6LiI(Eu) and Cs2LiYCl6:Ce (CLYC) scintillators which act as both target and detector. Neutron energies are determined from the time of flight (TOF) method using the signals from spontaneous fission and reaction product recoil. Simulations of neutron downscatter in the crystals and fission chamber bring 6Li(n, α)t cross section values measured with the 6LiI(Eu) into agreement with previous experiments and evaluations, except for two resonances at 4.2 and 6.5 MeV introduced by ENDF/B-VII.1. Suspected neutron transport modeling issues cause the cross section values obtained with CLYC to be discrepant above 2 MeV.

  16. High-water marks from tropical storm Irene for selected river reaches in northwestern Massachusetts, August 2011

    USGS Publications Warehouse

    Bent, Gardner C.; Medalie, Laura; Nielsen, Martha G.

    2013-01-01

    A Presidential Disaster Declaration was issued for Massachusetts, with a focus on the northwestern counties, following flooding from tropical storm Irene on August 28–29, 2011. Three to 10 inches of rain fell during the storm on soils that were susceptible to flash flooding because of wet antecedent conditions. The gage height at one U.S. Geological Survey (USGS) streamgage rose nearly 20 feet in less than 4 hours because of the combination of saturated soils and intense rainfall. Eight of 16 USGS long-term streamgages in western Massachusetts set new peaks of record on August 28 or 29, 2011. To document the historic water levels of the streamflows from tropical storm Irene, the USGS identified, flagged, and surveyed 323 high-water marks in the Deerfield and Hudson- Hoosic River basins in northwestern Massachusetts. Areas targeted for high-water marks were generally upstream and downstream from structures along selected river reaches. Elevations from high-water marks can be used to confirm peak river stages or help compute peak streamflows, to calibrate hydraulic models, or to update flood-inundation and recovery maps. For areas in western Massachusetts that flooded as a result of tropical storm Irene, high-water marks surveyed for this study have helped to confirm or determine instantaneous peak river gage heights at several USGS streamgages.

  17. Marking nut anaphylaxis

    PubMed Central

    Kral, Anita Christine; Hayball, John; Smith, William B

    2016-01-01

    Marking nut Semecarpus anacardium, so-called because it contains a pigment that has been used in the past to mark fabrics, is a known cause of contact hypersensitivity. It may be ingested as an ingredient of some traditional Hindi foods. We describe the first reported case of anaphylaxis to marking nut. PMID:27489793

  18. Mark Mehos | NREL

    Science.gov Websites

    Mehos Photo of Mark Mehos Mark Mehos Group Manager, Thermal Systems R&D Mark.Mehos@nrel.gov Thermal Systems R&D group at NREL, which includes the Concentrating Solar Power (CSP) Program. Since SolarPACES "Solar Thermal Electric Power Systems" task, which focuses on the development of

  19. Leaving A Mark: A Comparison Arthropod Protein Marking Protocols

    USDA-ARS?s Scientific Manuscript database

    Knowledge of arthropod pest and natural enemy disperal patterns is needed for effective and environmentally benign pest control. The most common tactics used to monitor arthropod dispersal patterns include mark-release-recapture (MRR) and mark-capture methodologies. Both methods require the applica...

  20. Mastering Marking Madness

    ERIC Educational Resources Information Center

    Moore, Brooke

    2009-01-01

    Teachers are smart people, so why does marking reduce them to stressed and soulless messes? Because in their hearts they know that students do not learn from it, and that drives them nuts. Researchers like Lorna Earl and Dylan Wiliam have looked closely at marking systems and have proven what teachers already know deep down: marking student work…

  1. An Application of Generalizability Theory on Writing Assessment: Effects of Marking Components Weighting

    ERIC Educational Resources Information Center

    Lam, Ling Chi Tenny

    2010-01-01

    In writing assessment, there are quite a number of factors influencing the marking stability and the reliability of the assessment such as the attitude towards marking and consistency of markers, the physical environment, the design of the items, and marking rubrics. Even the methods to train markers have effects on the reliability of the…

  2. Mark-recapture of Culex erythrothorax in Santa Cruz County, California.

    PubMed

    Tietze, Noor S; Stephenson, Mike F; Sidhom, Nader T; Binding, Paul L

    2003-06-01

    The dispersal of the tule mosquito, Culex erythrothorax, was studied in the proximity of Lake Tynan in the city of Watsonville, CA. From July 18 to 20, 2000, approximately 43,000 female Cx. erythrothorax were marked with luminous powder and released, using a distinct color each day. Recaptures were sampled by using 21 carbon dioxide-baited traps ranging in distance from zero to 2.8 km from the release site. During the 5 days of postrelease sampling, 319 marked mosquitoes were recaptured. The percentage of the marked mosquitoes that were recaptured was 0.46, 0.50, and 0.55% based on the 3 releases, respectively. Overall, the mosquitoes dispersed 0.57 km/day; the mean distance traveled increased during the 5-day sampling period from 0.42 km/day to 0.89 km/day from day 1 to day 5, respectively. Based on the Lincoln index, the estimated total population size for Cx. erythrothorax in the study area ranged from 3.8 to 94 million mosquitoes. This species was found to constitute a nuisance to local residents because of the abundance of this species and its capability to disperse into proximal communities.

  3. Source apportionment of PM2.5 at the Lin'an regional background site in China with three receptor models

    NASA Astrophysics Data System (ADS)

    Deng, Junjun; Zhang, Yanru; Qiu, Yuqing; Zhang, Hongliang; Du, Wenjiao; Xu, Lingling; Hong, Youwei; Chen, Yanting; Chen, Jinsheng

    2018-04-01

    Source apportionment of fine particulate matter (PM2.5) were conducted at the Lin'an Regional Atmospheric Background Station (LA) in the Yangtze River Delta (YRD) region in China from July 2014 to April 2015 with three receptor models including principal component analysis combining multiple linear regression (PCA-MLR), UNMIX and Positive Matrix Factorization (PMF). The model performance, source identification and source contribution of the three models were analyzed and inter-compared. Source apportionment of PM2.5 was also conducted with the receptor models. Good correlations between the reconstructed and measured concentrations of PM2.5 and its major chemical species were obtained for all models. PMF resolved almost all masses of PM2.5, while PCA-MLR and UNMIX explained about 80%. Five, four and seven sources were identified by PCA-MLR, UNMIX and PMF, respectively. Combustion, secondary source, marine source, dust and industrial activities were identified by all the three receptor models. Combustion source and secondary source were the major sources, and totally contributed over 60% to PM2.5. The PMF model had a better performance on separating the different combustion sources. These findings improve the understanding of PM2.5 sources in background region.

  4. Surface laser marking optimization using an experimental design approach

    NASA Astrophysics Data System (ADS)

    Brihmat-Hamadi, F.; Amara, E. H.; Lavisse, L.; Jouvard, J. M.; Cicala, E.; Kellou, H.

    2017-04-01

    Laser surface marking is performed on a titanium substrate using a pulsed frequency doubled Nd:YAG laser ( λ= 532 nm, τ pulse=5 ns) to process the substrate surface under normal atmospheric conditions. The aim of the work is to investigate, following experimental and statistical approaches, the correlation between the process parameters and the response variables (output), using a Design of Experiment method (DOE): Taguchi methodology and a response surface methodology (RSM). A design is first created using MINTAB program, and then the laser marking process is performed according to the planned design. The response variables; surface roughness and surface reflectance were measured for each sample, and incorporated into the design matrix. The results are then analyzed and the RSM model is developed and verified for predicting the process output for the given set of process parameters values. The analysis shows that the laser beam scanning speed is the most influential operating factor followed by the laser pumping intensity during marking, while the other factors show complex influences on the objective functions.

  5. Trivalent chromatin marks the way in.

    PubMed

    Hysolli, Eriona; Park, In-Hyun

    2013-11-07

    Recently in Cell, Wapinski et al. (2013) investigated the epigenetic mechanisms underlying the direct conversion of fibroblasts to induced neurons (iNs). They found that Ascl1 acts as a pioneer factor at neurogenic loci marked by a closed "trivalent" chromatin state in cells permissive to direct conversion, but not in restrictive cell types. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Evidence of cation vacancy induced room temperature ferromagnetism in Li-N codoped ZnO thin films

    NASA Astrophysics Data System (ADS)

    Zhang, B. Y.; Yao, B.; Li, Y. F.; Liu, A. M.; Zhang, Z. Z.; Li, B. H.; Xing, G. Z.; Wu, T.; Qin, X. B.; Zhao, D. X.; Shan, C. X.; Shen, D. Z.

    2011-10-01

    Room temperature ferromagnetism (RTFM) was observed in Li-N codoped ZnO thin films [ZnO:(Li, N)] fabricated by plasma-assisted molecular beam epitaxy, and p-type ZnO:(Li, N) shows the strongest RTFM. Positron annihilation spectroscopy and low temperature photoluminescence measurements indicate that the RTFM in ZnO:(Li, N) is attributed to the defect complex related to VZn, such as VZn and Lii-NO-VZn complex, well supported by first-principles calculations. The incorporation of NO can stabilize and enhance the RTFM of ZnO:(Li, N) by combining with Lii to form Lii-NO complex, which restrains the compensation of Lii for VZn and makes the ZnO:(Li, N) conduct in p-type.

  7. STS-28 Columbia, OV-102, MS Brown juggles food containers on middeck

    NASA Image and Video Library

    1989-08-13

    STS028-13-013 (August 1989) --- Astronaut Mark N. Brown, STS-28 mission specialist, assembles various components of a meal at the stowage locker area of Columbia's middeck, as James C. Adamson, mission specialist, looks on.

  8. Mark Tracking: Position/orientation measurements using 4-circle mark and its tracking experiments

    NASA Technical Reports Server (NTRS)

    Kanda, Shinji; Okabayashi, Keijyu; Maruyama, Tsugito; Uchiyama, Takashi

    1994-01-01

    Future space robots require position and orientation tracking with visual feedback control to track and capture floating objects and satellites. We developed a four-circle mark that is useful for this purpose. With this mark, four geometric center positions as feature points can be extracted from the mark by simple image processing. We also developed a position and orientation measurement method that uses the four feature points in our mark. The mark gave good enough image measurement accuracy to let space robots approach and contact objects. A visual feedback control system using this mark enabled a robot arm to track a target object accurately. The control system was able to tolerate a time delay of 2 seconds.

  9. KSC supplied views of the STS 28 crew suiting up, at breakfast and

    NASA Image and Video Library

    1989-08-09

    S89-41091 (18 July 1989) --- During the Terminal Countdown Demonstration Test (TCDT), STS-28 crew members are assisted with suiting up in the Operations and Checkout Building prior to departing for pad 39-B. STS-28 and the Space Shuttle Columbia are scheduled to be launched in early August on a Department of Defense dedicated mission. The crew for STS-28 are Commander Brewster H. Shaw; Pilot Richard N. Richards; and Mission Specialists Mark N. Brown, James C. Adamson, and David C. Leestma.

  10. Marking Time

    ERIC Educational Resources Information Center

    Foster, Colin

    2011-01-01

    Teachers say that they would gladly teach a day in the classroom if at the end of the day they could leave and have no marking. There is a common staffroom perception that mathematics teachers have it easy when it comes to marking. In arts subjects, setting an essay can be a fairly straightforward matter--a one-line question may suffice--but…

  11. Improving Marking Quality through a Taxonomy of Mark Schemes

    ERIC Educational Resources Information Center

    Ahmed, Ayesha; Pollitt, Alastair

    2011-01-01

    At the heart of most assessments lies a set of questions, and those who write them must achieve "two" things. Not only must they ensure that each question elicits the kind of performance that shows how "good" pupils are at the subject, but they must also ensure that each mark scheme gives more marks to those who are…

  12. Commercialization of LARC(TradeMark)-SI Polyimide Technology

    NASA Technical Reports Server (NTRS)

    Bryant, Robert G.

    2008-01-01

    LARC(TradeMark)-SI, Langley Research Center-Soluble Imide, was developed in 1992. This new polyimide won a 1995 Research and Development 100 Award, with the first patent issuing in 1997 and subsequent issued patents in 1998 and 2000. Currently, this polymer has been successfully licensed by NASA, and has generated revenues in excess of 1.4 million dollars. This might seem insignificant in comparison to industrially developed technology, where the customer is understood, technologies that use a novel assembly of commercial off the shelf (COTS) components, or software patents and "method based" innovations that do not require any material beyond labor, as examples. However, consider that LARC(TradeMark)-SI competes in areas currently dominated by traditional materials at a cost disadvantage ($350/lb) and that the physical-mechanical properties of LARC(TradeMark)-SI are similar to other high performance polymers. Indeed the success of this particular polymer was due to many factors and many lessons learned to the point that the invention was the most important, but least significant part in the commercialization of this material. This brief paper outlines the significant factors that occurred to make this technology available for the public access and application development that led to the licensing success of this material.

  13. 28 CFR 28.28 - Sanctions for violations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Sanctions for violations. 28.28 Section 28.28 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM Preservation of... evidence from being subjected to DNA testing or prevent the production or use of that evidence in an...

  14. 28 CFR 28.28 - Sanctions for violations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Sanctions for violations. 28.28 Section 28.28 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM Preservation of... evidence from being subjected to DNA testing or prevent the production or use of that evidence in an...

  15. 28 CFR 28.28 - Sanctions for violations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Sanctions for violations. 28.28 Section 28.28 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM Preservation of... evidence from being subjected to DNA testing or prevent the production or use of that evidence in an...

  16. 28 CFR 28.28 - Sanctions for violations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Sanctions for violations. 28.28 Section 28.28 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM Preservation of... evidence from being subjected to DNA testing or prevent the production or use of that evidence in an...

  17. 28 CFR 28.28 - Sanctions for violations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 1 2012-07-01 2012-07-01 false Sanctions for violations. 28.28 Section 28.28 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM Preservation of... evidence from being subjected to DNA testing or prevent the production or use of that evidence in an...

  18. STS-28 Columbia, OV-102, official crew portrait

    NASA Image and Video Library

    1989-03-16

    S89-29370 (March 1989) --- These five astronauts have been assigned to man the Space Shuttle Columbia for STS-28, a Department of Defense-devoted mission scheduled for July of this year. Brewster H. Shaw (center, front) is mission commander; and Richard N. Richards (left) is pilot. Mission specialists are, left to right, Mark N. Brown, James C. Adamson and David C. Leestma (seated).

  19. Elemental marking of arthropod pests in agricultural systems: single and multigenerational marking

    Treesearch

    Jane Leslie Hayes

    1991-01-01

    Use of elemental markers to study movement of arthropod pests of field crops is reviewed. Trace elements, rubidium (Rb) and cesium (Cs), have provided a nondisruptive method of marking natural adult populations via developmental stage consumption of treated host plants. Multigenerational marking occurs with the transfer of elemental markers from marked adults to...

  20. 14 CFR 45.10 - Marking.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Marking. 45.10 Section 45.10 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Marking of Products and Articles § 45.10 Marking. No person may mark a product or article...

  1. 14 CFR 45.10 - Marking.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Marking. 45.10 Section 45.10 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Marking of Products and Articles § 45.10 Marking. No person may mark a product or article...

  2. 14 CFR 45.10 - Marking.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Marking. 45.10 Section 45.10 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Marking of Products and Articles § 45.10 Marking. No person may mark a product or article...

  3. 14 CFR 45.10 - Marking.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Marking. 45.10 Section 45.10 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Marking of Products and Articles § 45.10 Marking. No person may mark a product or article...

  4. The RING finger/B-box factor TAM-1 and a retinoblastoma-like protein LIN-35 modulate context-dependent gene silencing in Caenorhabditis elegans.

    PubMed

    Hsieh, J; Liu, J; Kostas, S A; Chang, C; Sternberg, P W; Fire, A

    1999-11-15

    Context-dependent gene silencing is used by many organisms to stably modulate gene activity for large chromosomal regions. We have used tandem array transgenes as a model substrate in a screen for Caenorhabditis elegans mutants that affect context-dependent gene silencing in somatic tissues. This screen yielded multiple alleles of a previously uncharacterized gene, designated tam-1 (for tandem-array-modifier). Loss-of-function mutations in tam-1 led to a dramatic reduction in the activity of numerous highly repeated transgenes. These effects were apparently context dependent, as nonrepetitive transgenes retained activity in a tam-1 mutant background. In addition to the dramatic alterations in transgene activity, tam-1 mutants showed modest alterations in expression of a subset of endogenous cellular genes. These effects include genetic interactions that place tam-1 into a group called the class B synMuv genes (for a Synthetic Multivulva phenotype); this family plays a negative role in the regulation of RAS pathway activity in C. elegans. Loss-of-function mutants in other members of the class-B synMuv family, including lin-35, which encodes a protein similar to the tumor suppressor Rb, exhibit a hypersilencing in somatic transgenes similar to that of tam-1 mutants. Molecular analysis reveals that tam-1 encodes a broadly expressed nuclear protein with RING finger and B-box motifs.

  5. Méthode de prédétermination des caractéristiques électromagnétiques de machines á bobinage global à commutation de flux. Application à un actionneur linéaire

    NASA Astrophysics Data System (ADS)

    Prevond, L.; Ben Ahmed, A.; Multon, B.; Lucidarme, J.

    1997-06-01

    This paper presents a predetermination method of Permanent Magnet (P.M.) multicellular flux switching machines. The non-linear characteristic of the ferromagnetic material is integrated in this method which combines analytical and numerical calculus. This study permits to make a fast parametrical analysis to define optimal parameters of a flux switching cell such as magnetic shear stress and flux concentration factor as function of magnetomotive force. The demagnetisation limit is introduced by a finite element calculus applied. The comparison of the theoritical results and experimental one gives a good correlation. Cet article présente une méthode de prédétermination des caractéristiques de machines multicellulaires (bobinage global) à commutation de flux (aimants permanents) en tenant compte de la non linéarité des matériaux ferromagnétiques. Cette méthode allie le calcul numérique par éléments finis et le calcul analytique. Cette étude nous a permis, d'une part, d'effectuer une analyse paramétrique intrinsèque et, d'autre part, de définir les paramètres optimaux de la cellule à commutation de flux. La notion de désaimantation est introduite en calculant le champ démagnétisant dans l'aimant. Les calculs effectués, dans le cas d'un actionneur linéaire à cômmutation de flux, montrent une bonne corrélation avec les essais directs.

  6. Image-guided system versus manual marking for toric intraocular lens alignment in cataract surgery.

    PubMed

    Webers, Valentijn S C; Bauer, Noel J C; Visser, Nienke; Berendschot, Tos T J M; van den Biggelaar, Frank J H M; Nuijts, Rudy M M A

    2017-06-01

    To compare the accuracy of toric intraocular lens (IOL) alignment using the Verion Image-Guided System versus a conventional manual ink-marking procedure. University Eye Clinic Maastricht, Maastricht, the Netherlands. Prospective randomized clinical trial. Eyes with regular corneal astigmatism of at least 1.25 diopters (D) that required cataract surgery and toric IOL implantation (Acrysof SN6AT3-T9) were randomly assigned to the image-guided group or the manual-marking group. The primary outcome was the alignment of the toric IOL based on preoperative images and images taken immediately after surgery. Secondary outcome measures were residual astigmatism, uncorrected distance visual acuity (UDVA), and complications. The study enrolled 36 eyes (24 patients). The mean toric IOL misalignment was significantly less in the image-guided group than in the manual group 1 hour (1.3 degrees ± 1.6 [SD] versus 2.8 ± 1.8 degrees; P = .02) and 3 months (1.7 ± 1.5 degrees versus 3.1 ± 2.1 degrees; P < .05) postoperatively. The mean residual refractive cylinder was -0.36 ± 0.32 D and -0.47 ± 0.28 D in the image-guided group and manual group, respectively (P > .05). The mean UDVA was 0.03 ± 0.10 logarithm of minimum angle of resolution (logMAR) and 0.04 ± 0.09 logMAR, respectively (both P > .05). No intraoperative complications occurred during any surgery. The IOL misalignment was significantly less with digital marking than with manual marking; this did not result in a better UDVA or lower residual refractive astigmatism. Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  7. Mark-recapture and mark-resight methods for estimating abundance with remote cameras: a carnivore case study

    USGS Publications Warehouse

    Alanso, Robert S.; McClintock, Brett T.; Lyren, Lisa M.; Boydston, Erin E.; Crooks, Kevin R.

    2015-01-01

    Abundance estimation of carnivore populations is difficult and has prompted the use of non-invasive detection methods, such as remotely-triggered cameras, to collect data. To analyze photo data, studies focusing on carnivores with unique pelage patterns have utilized a mark-recapture framework and studies of carnivores without unique pelage patterns have used a mark-resight framework. We compared mark-resight and mark-recapture estimation methods to estimate bobcat (Lynx rufus) population sizes, which motivated the development of a new "hybrid" mark-resight model as an alternative to traditional methods. We deployed a sampling grid of 30 cameras throughout the urban southern California study area. Additionally, we physically captured and marked a subset of the bobcat population with GPS telemetry collars. Since we could identify individual bobcats with photos of unique pelage patterns and a subset of the population was physically marked, we were able to use traditional mark-recapture and mark-resight methods, as well as the new “hybrid” mark-resight model we developed to estimate bobcat abundance. We recorded 109 bobcat photos during 4,669 camera nights and physically marked 27 bobcats with GPS telemetry collars. Abundance estimates produced by the traditional mark-recapture, traditional mark-resight, and “hybrid” mark-resight methods were similar, however precision differed depending on the models used. Traditional mark-recapture and mark-resight estimates were relatively imprecise with percent confidence interval lengths exceeding 100% of point estimates. Hybrid mark-resight models produced better precision with percent confidence intervals not exceeding 57%. The increased precision of the hybrid mark-resight method stems from utilizing the complete encounter histories of physically marked individuals (including those never detected by a camera trap) and the encounter histories of naturally marked individuals detected at camera traps. This new estimator

  8. 28. SONAR CONTROL ROOM FORWARD LOOKING AFT SHOWING AN/SQS23G ...

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

    28. SONAR CONTROL ROOM - FORWARD LOOKING AFT SHOWING AN/SQS-23G DETECTING-RANGING SET, MARK & CONTROL PANEL, CAN-55134 RECORDER, SPEED INDICATOR, VARIOUS ALARMS AND INTERNAL COMMUNICATION CIRCUITS. - U.S.S. HORNET, Puget Sound Naval Shipyard, Sinclair Inlet, Bremerton, Kitsap County, WA

  9. 75 FR 55366 - In the Matter of Mark M. Ficek; Order Prohibiting Involvement in NRC-Licensed Activities...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-10

    ... (Effective Immediately) Mr. Mark M. Ficek is the President, owner, and former radiation safety officer (RSO... new radiation safety officer, and due to expire on February 28, 2016. The license authorizes Mattingly... assessing Mattingly's entire radiation safety program, providing radiation safety training to the Mattingly...

  10. Outbreak of diffuse lamellar keratitis caused by marking-pen toxicity.

    PubMed

    Hadden, Osmond Bruce; McGhee, Charles N J; Morris, Antony Trevor; Gray, Trevor Buchanan; Ring, Charles Peter; Watson, Adam Stewart John

    2008-07-01

    To examine the evidence that a series of cases of diffuse lamellar keratitis (DLK) after laser in situ keratomileusis (LASIK) was caused by a type of marker pen. Eye Institute, Auckland, New Zealand. During a 10-week period, 522 consecutive LASIK procedures were performed using a 60 Hz IntraLase femtosecond laser (IntraLase Corp.) to create the LASIK flap and a 217Z 100 Hz excimer laser (Bausch & Lomb) to perform the refractive ablation. As standard practice, a marking pen was used to enable accurate flap realignment. Three weeks after a sudden increase in the incidence of DLK was identified, one of the 5 surgeons performed 5 consecutive bilateral cases using the marking pen in the right eyes but not in the left eyes. Of the 522 LASIK cases (119 without marking pen, 403 with marking pen), DLK developed in 49 (9.4%). No eye treated without the marking pen developed DLK; of those in which the marking pen was used, 49 (12.2%) developed DLK (P<0.0001, Fischer exact test; odds ratio, 27). In the 5 consecutive bilateral cases in which the marking pen was used in the right eye but not the left eye, 4 right eyes and no left eye developed DLK (P=0.03). Forty-five of the 49 eyes with DLK quickly recovered. The other 4 developed central toxic keratopathy. There is strong statistical evidence that the marking pen was a factor in the occurrence of DLK.

  11. Lujan Mark-4

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mocko, Michael Jeffrey; Zavorka, Lukas; Koehler, Paul E.

    2017-11-13

    This is a review of Mark-IV target neutronics design. It involved the major redesign of the upper tier, offering harder neutron spectra for upper-tier FPs; a redesign of the high-resolution (HR) moderator; and a preservation of the rest of Mark-III features.

  12. Minimal Marking: A Success Story

    ERIC Educational Resources Information Center

    McNeilly, Anne

    2014-01-01

    The minimal-marking project conducted in Ryerson's School of Journalism throughout 2012 and early 2013 resulted in significantly higher grammar scores in two first-year classes of minimally marked university students when compared to two traditionally marked classes. The "minimal-marking" concept (Haswell, 1983), which requires…

  13. 14 CFR 45.10 - Marking.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Marking. 45.10 Section 45.10 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Identification of Aircraft and Related Products § 45.10 Marking. No person may mark a...

  14. Unequal Probability Marking Approach to Enhance Security of Traceback Scheme in Tree-Based WSNs.

    PubMed

    Huang, Changqin; Ma, Ming; Liu, Xiao; Liu, Anfeng; Zuo, Zhengbang

    2017-06-17

    Fog (from core to edge) computing is a newly emerging computing platform, which utilizes a large number of network devices at the edge of a network to provide ubiquitous computing, thus having great development potential. However, the issue of security poses an important challenge for fog computing. In particular, the Internet of Things (IoT) that constitutes the fog computing platform is crucial for preserving the security of a huge number of wireless sensors, which are vulnerable to attack. In this paper, a new unequal probability marking approach is proposed to enhance the security performance of logging and migration traceback (LM) schemes in tree-based wireless sensor networks (WSNs). The main contribution of this paper is to overcome the deficiency of the LM scheme that has a higher network lifetime and large storage space. In the unequal probability marking logging and migration (UPLM) scheme of this paper, different marking probabilities are adopted for different nodes according to their distances to the sink. A large marking probability is assigned to nodes in remote areas (areas at a long distance from the sink), while a small marking probability is applied to nodes in nearby area (areas at a short distance from the sink). This reduces the consumption of storage and energy in addition to enhancing the security performance, lifetime, and storage capacity. Marking information will be migrated to nodes at a longer distance from the sink for increasing the amount of stored marking information, thus enhancing the security performance in the process of migration. The experimental simulation shows that for general tree-based WSNs, the UPLM scheme proposed in this paper can store 1.12-1.28 times the amount of stored marking information that the equal probability marking approach achieves, and has 1.15-1.26 times the storage utilization efficiency compared with other schemes.

  15. Unequal Probability Marking Approach to Enhance Security of Traceback Scheme in Tree-Based WSNs

    PubMed Central

    Huang, Changqin; Ma, Ming; Liu, Xiao; Liu, Anfeng; Zuo, Zhengbang

    2017-01-01

    Fog (from core to edge) computing is a newly emerging computing platform, which utilizes a large number of network devices at the edge of a network to provide ubiquitous computing, thus having great development potential. However, the issue of security poses an important challenge for fog computing. In particular, the Internet of Things (IoT) that constitutes the fog computing platform is crucial for preserving the security of a huge number of wireless sensors, which are vulnerable to attack. In this paper, a new unequal probability marking approach is proposed to enhance the security performance of logging and migration traceback (LM) schemes in tree-based wireless sensor networks (WSNs). The main contribution of this paper is to overcome the deficiency of the LM scheme that has a higher network lifetime and large storage space. In the unequal probability marking logging and migration (UPLM) scheme of this paper, different marking probabilities are adopted for different nodes according to their distances to the sink. A large marking probability is assigned to nodes in remote areas (areas at a long distance from the sink), while a small marking probability is applied to nodes in nearby area (areas at a short distance from the sink). This reduces the consumption of storage and energy in addition to enhancing the security performance, lifetime, and storage capacity. Marking information will be migrated to nodes at a longer distance from the sink for increasing the amount of stored marking information, thus enhancing the security performance in the process of migration. The experimental simulation shows that for general tree-based WSNs, the UPLM scheme proposed in this paper can store 1.12–1.28 times the amount of stored marking information that the equal probability marking approach achieves, and has 1.15–1.26 times the storage utilization efficiency compared with other schemes. PMID:28629135

  16. STS-28 Columbia, OV-102, ET/SRB mating preparations at KSC VAB

    NASA Image and Video Library

    1989-07-03

    S89-39624 (3 July 1989) --- Following rollover from the Orbiter Processing Facility, the orbiter Columbia is prepared for mating with the ET/SRB stack in the Vehicle Assembly Building transfer aisle as work continues toward an early August launch of Space Shuttle Mission STS-28. STS-28 is a Department of Defense dedicated mission. Crew members for the mission are: Commander Brewster H. Shaw, Pilot Richard N. Richards, and Mission Specialists Mark N. Brown, James C. Adamson, and David C. Leestma.

  17. Laser marking as environment technology

    NASA Astrophysics Data System (ADS)

    Sobotova, Lydia; Badida, Miroslav

    2017-11-01

    The contribution deals with the laser marking as one of the progressive and environment friendly technologies with utilisation in many branches of industry. Engraving and other types of laser marking of different types of materials are very actual technologies these days. Laser marking decreases the waste creation in comparison with the other classical marking technologies, which use paintings or created chips. In this experimental investigation the laser marking surface texturing of material AL99,7 according to STN 42 4003:1993-08 (STN EN 573) has been conducted. The laser marking machine TruMark 6020 and software TruTops Mark were used. Laser surface texturing after laser marking has been realised under different combinations of process parameters: pulse frequency, pulse energy and laser beam scanning speed. The morphological characterization of engraving or annealing surfaces has been performed using scanning electron microscopy (SEM) technique. The evaluation of roughness of engraved surfaces has been realized according to STN EN ISO 4287 by using Surftest SJ 301. The aim of the contribution was to show how different laser parameters affect the surface texture and colour change of metallic materials while creating minimal waste.

  18. Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups.

    PubMed

    Sumazin, Pavel; Chen, Yidong; Treviño, Lisa R; Sarabia, Stephen F; Hampton, Oliver A; Patel, Kayuri; Mistretta, Toni-Ann; Zorman, Barry; Thompson, Patrick; Heczey, Andras; Comerford, Sarah; Wheeler, David A; Chintagumpala, Murali; Meyers, Rebecka; Rakheja, Dinesh; Finegold, Milton J; Tomlinson, Gail; Parsons, D Williams; López-Terrada, Dolores

    2017-01-01

    Despite being the most common liver cancer in children, hepatoblastoma (HB) is a rare neoplasm. Consequently, few pretreatment tumors have been molecularly profiled, and there are no validated prognostic or therapeutic biomarkers for HB patients. We report on the first large-scale effort to profile pretreatment HBs at diagnosis. Our analysis of 88 clinically annotated HBs revealed three risk-stratifying molecular subtypes that are characterized by differential activation of hepatic progenitor cell markers and metabolic pathways: high-risk tumors were characterized by up-regulated nuclear factor, erythroid 2-like 2 activity; high lin-28 homolog B, high mobility group AT-hook 2, spalt-like transcription factor 4, and alpha-fetoprotein expression; and high coordinated expression of oncofetal proteins and stem-cell markers, while low-risk tumors had low lin-28 homolog B and lethal-7 expression and high hepatic nuclear factor 1 alpha activity. Analysis of immunohistochemical assays using antibodies targeting these genes in a prospective study of 35 HBs suggested that these candidate biomarkers have the potential to improve risk stratification and guide treatment decisions for HB patients at diagnosis; our results pave the way for clinical collaborative studies to validate candidate biomarkers and test their potential to improve outcome for HB patients. (Hepatology 2017;65:104-121). © 2016 by the American Association for the Study of Liver Diseases.

  19. Productivity and cost of marking activities for single-tree selection and thinning treatments in Arkansas

    Treesearch

    Tymur Sydor; Richard A. Kluender; Rodney L. Busby; Matthew Pelkki

    2004-01-01

    An activity algorithm was developed for standard marking methods for natural pine stands in Arkansas. For the two types of marking methods examined, thinning (selection from below) and single-tree selection (selection from above), cycle time and cost models were developed. Basal area (BA) removed was the major influencing factor in both models. Marking method was...

  20. Influence of the axial rotation angle on tool mark striations.

    PubMed

    Garcia, Derrel Louis; Pieterman, René; Baiker, Martin

    2017-10-01

    A tool's axial rotation influences the geometric properties of a tool mark. The larger the axial rotation angle, the larger the compression of structural details like striations. This complicates comparing tool marks at different axial rotations. Using chisels, tool marks were made from 0° to 75° axial rotation and compared using an automated approach Baiker et al. [10]. In addition, a 3D topographic surface of a chisel was obtained to generate virtual tool marks and to test whether the axial rotation angle of a mark could be predicted. After examination of the tool mark and chisel data-sets it was observed that marks lose information with increasing rotation due to the change in relative distance between geometrical details on the tool and the disappearance of smaller details. The similarity and repeatability were high for comparisons between marks with no difference in axial rotation, but decreasing with increased rotation angle from 0° to 75°. With an increasing difference in the rotation angles, the tool marks had to be corrected to account for the different compression factors between them. For compression up to 7.5%, this was obtained automatically by the tool mark alignment method. For larger compression, manually re-sizing the marks to the uncompressed widths at 0° rotation before the alignment was found suitable for successfully comparing even large differences in axial rotation. The similarity and repeatability were decreasing however, with increasing degree of re-sizing. The quality was assessed by determining the similarity at different detail levels within a tool mark. With an axial rotation up to 75°, tool marks were found to reliably represent structural details down to 100μm. The similarity of structural details below 100μm was dependent on the angle, with the highest similarity at small rotation angles and the lowest similarity at large rotation angles. Filtering to remove the details below 100μm lead to consistently higher similarity

  1. Sampling factors influencing accuracy of sperm kinematic analysis.

    PubMed

    Owen, D H; Katz, D F

    1993-01-01

    Sampling conditions that influence the accuracy of experimental measurement of sperm head kinematics were studied by computer simulation methods. Several archetypal sperm trajectories were studied. First, mathematical models of typical flagellar beats were input to hydrodynamic equations of sperm motion. The instantaneous swimming velocities of such sperm were computed over sequences of flagellar beat cycles, from which the resulting trajectories were determined. In a second, idealized approach, direct mathematical models of trajectories were utilized, based upon similarities to the previous hydrodynamic constructs. In general, it was found that analyses of sampling factors produced similar results for the hydrodynamic and idealized trajectories. A number of experimental sampling factors were studied, including the number of sperm head positions measured per flagellar beat, and the time interval over which these measurements are taken. It was found that when one flagellar beat is sampled, values of amplitude of lateral head displacement (ALH) and linearity (LIN) approached their actual values when five or more sample points per beat were taken. Mean angular displacement (MAD) values, however, remained sensitive to sampling rate even when large sampling rates were used. Values of MAD were also much more sensitive to the initial starting point of the sampling procedure than were ALH or LIN. On the basis of these analyses of measurement accuracy for individual sperm, simulations were then performed of cumulative effects when studying entire populations of motile cells. It was found that substantial (double digit) errors occurred in the mean values of curvilinear velocity (VCL), LIN, and MAD under the conditions of 30 video frames per second and 0.5 seconds of analysis time. Increasing the analysis interval to 1 second did not appreciably improve the results. However, increasing the analysis rate to 60 frames per second significantly reduced the errors. These findings

  2. Marking as Judgment

    ERIC Educational Resources Information Center

    Brooks, Val

    2012-01-01

    An aspect of assessment which has received little attention compared with perennial concerns, such as standards or reliability, is the role of judgment in marking. This paper explores marking as an act of judgment, paying particular attention to the nature of judgment and the processes involved. It brings together studies which have explored…

  3. Crystal Structure of Haloalkane Dehalogenase LinB from Sphingomonas paucimobilis UT26 at 0.95 Å Resolution: Dynamics of Catalytic Residues

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Oakley, Aaron J.; Klvana, Martin; Otyepka, Michal

    We present the structure of LinB, a 33-kDa haloalkane dehalogenase from Sphingomonas paucimobilis UT26, at 0.95 {angstrom} resolution. The data have allowed us to directly observe the anisotropic motions of the catalytic residues. In particular, the side-chain of the catalytic nucleophile, Asp108, displays a high degree of disorder. It has been modeled in two conformations, one similar to that observed previously (conformation A) and one strained (conformation B) that approached the catalytic base (His272). The strain in conformation B was mainly in the C{sub {alpha}}-C{sub {beta}}-C{sub {gamma}} angle (126{sup o}) that deviated by 13.4{sup o} from the 'ideal' bond anglemore » of 112.6{sup o}. On the basis of these observations, we propose a role for the charge state of the catalytic histidine in determining the geometry of the catalytic residues. We hypothesized that double-protonation of the catalytic base (His272) reduces the distance between the side-chain of this residue and that of the Asp108. The results of molecular dynamics simulations were consistent with the structural data showing that protonation of the His272 side-chain nitrogen atoms does indeed reduce the distance between the side-chains of the residues in question, although the simulations failed to demonstrate the same degree of strain in the Asp108 C{sub {alpha}}-C{sub {beta}}-C{sub {gamma}} angle. Instead, the changes in the molecular dynamics structures were distributed over several bond and dihedral angles. Quantum mechanics calculations on LinB with 1-chloro-2,2-dimethylpropane as a substrate were performed to determine which active site conformations and protonation states were most likely to result in catalysis. It was shown that His272 singly protonated at N{sub {delta}1} and Asp108 in conformation A gave the most exothermic reaction ({Delta}H = -22 kcal/mol). With His272 doubly protonated at N{sub {delta}1} and N{sub {epsilon}2}, the reactions were only slightly exothermic or were

  4. Regio- and Enantioselective Sequential Dehalogenation of rac-1,3-Dibromobutane by Haloalkane Dehalogenase LinB.

    PubMed

    Gross, Johannes; Prokop, Zbyněk; Janssen, Dick; Faber, Kurt; Hall, Mélanie

    2016-08-03

    The hydrolytic dehalogenation of rac-1,3-dibromobutane catalyzed by the haloalkane dehalogenase LinB from Sphingobium japonicum UT26 proceeds in a sequential fashion: initial formation of intermediate haloalcohols followed by a second hydrolytic step to produce the final diol. Detailed investigation of the course of the reaction revealed favored nucleophilic displacement of the sec-halogen in the first hydrolytic event with pronounced R enantioselectivity. The second hydrolysis step proceeded with a regioselectivity switch at the primary position, with preference for the S enantiomer. Because of complex competition between all eight possible reactions, intermediate haloalcohols formed with moderate to good ee ((S)-4-bromobutan-2-ol: up to 87 %). Similarly, (S)-butane-1,3-diol was formed at a maximum ee of 35 % before full hydrolysis furnished the racemic diol product. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. 9 CFR 316.9 - Products to be marked with official marks.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... marks. 316.9 Section 316.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... liver, beef tongue, and beef heart which has been inspected and passed shall be marked with the official... round, flank, loin, rib, plate, brisket, chuck, and shank are primal parts of beef carcasses. Veal...

  6. 9 CFR 316.9 - Products to be marked with official marks.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... marks. 316.9 Section 316.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... liver, beef tongue, and beef heart which has been inspected and passed shall be marked with the official... round, flank, loin, rib, plate, brisket, chuck, and shank are primal parts of beef carcasses. Veal...

  7. 9 CFR 316.9 - Products to be marked with official marks.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... marks. 316.9 Section 316.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... liver, beef tongue, and beef heart which has been inspected and passed shall be marked with the official... round, flank, loin, rib, plate, brisket, chuck, and shank are primal parts of beef carcasses. Veal...

  8. 9 CFR 316.9 - Products to be marked with official marks.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... marks. 316.9 Section 316.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... liver, beef tongue, and beef heart which has been inspected and passed shall be marked with the official... round, flank, loin, rib, plate, brisket, chuck, and shank are primal parts of beef carcasses. Veal...

  9. 9 CFR 316.9 - Products to be marked with official marks.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... marks. 316.9 Section 316.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... liver, beef tongue, and beef heart which has been inspected and passed shall be marked with the official... round, flank, loin, rib, plate, brisket, chuck, and shank are primal parts of beef carcasses. Veal...

  10. Solving quantum optimal control problems using Clebsch variables and Lin constraints

    NASA Astrophysics Data System (ADS)

    Delgado-Téllez, M.; Ibort, A.; Rodríguez de la Peña, T.

    2018-01-01

    Clebsch variables (and Lin constraints) are applied to the study of a class of optimal control problems for affine-controlled quantum systems. The optimal control problem will be modelled with controls defined on an auxiliary space where the dynamical group of the system acts freely. The reciprocity between both theories: the classical theory defined by the objective functional and the quantum system, is established by using a suitable version of Lagrange’s multipliers theorem and a geometrical interpretation of the constraints of the system as defining a subspace of horizontal curves in an associated bundle. It is shown how the solutions of the variational problem defined by the objective functional determine solutions of the quantum problem. Then a new way of obtaining explicit solutions for a family of optimal control problems for affine-controlled quantum systems (finite or infinite dimensional) is obtained. One of its main advantages, is the the use of Clebsch variables allows to compute such solutions from solutions of invariant problems that can often be computed explicitly. This procedure can be presented as an algorithm that can be applied to a large class of systems. Finally, some simple examples, spin control, a simple quantum Hamiltonian with an ‘Elroy beanie’ type classical model and a controlled one-dimensional quantum harmonic oscillator, illustrating the main features of the theory, will be discussed.

  11. Assessment of the durability of wet night visible pavement markings : wet visibility project phase IV.

    DOT National Transportation Integrated Search

    2012-06-01

    This project encompassed a research effort to establish the durability of pavement markings in an on-road installation. Six : marking technologies were installed on a portion of Route 460 in Blacksburg, Virginia. A human factors experiment in natural...

  12. STS-28 Columbia, OV-102, crew eats preflight breakfast at KSC O and C Bldg

    NASA Technical Reports Server (NTRS)

    1989-01-01

    STS-28 crewmembers eat preflight breakfast at Kennedy Space Center (KSC) Operations and Checkout (O and C) Building before boarding Columbia, Orbiter Vehicle (OV) 102. Sitting around table (left to right) are Mission Specialist (MS) David C. Leestma, Pilot Richard N. Richards, Commander Brewster H. Shaw, MS James C. Adamson, and MS Mark N. Brown. A cake decorated with the STS-28 mission insignia is in the center of the table.

  13. Pavement marking performance analysis

    DOT National Transportation Integrated Search

    2009-06-30

    This research evaluated pavement marking performance and developed useful degradation models for thermoplastic : and paint pavement markings which can help North Carolina meet the pending FHWA minimum retroreflectivity : requirements. The impacts of ...

  14. GCF Mark IV development

    NASA Technical Reports Server (NTRS)

    Mortensen, L. O.

    1982-01-01

    The Mark IV ground communication facility (GCF) as it is implemented to support the network consolidation program is reviewed. Changes in the GCF are made in the area of increased capacity. Common carrier circuits are the medium for data transfer. The message multiplexing in the Mark IV era differs from the Mark III era, in that all multiplexing is done in a GCF computer under GCF software control, which is similar to the multiplexing currently done in the high speed data subsystem.

  15. Therapeutic Inhibitors of LIN28/let-7 Pathway in Ovarian Cancer

    DTIC Science & Technology

    2015-09-01

    of-function cell lines to complement our already generated shRNA lines, we are developing handson experience with CrispR /Cas9 technology to...generate stable cell lines where our genes of interest will be inactivated. The advantage of the CrispR /Cas9 method is that stable lines can be...ovarian cancer cell lines using two distinct RNAi methods, shRNA and siRNA. We plan to explore the feasibility of using the CrispR /Cas9 system to

  16. Cell type-specific recruitment of Drosophila Lin-7 to distinct MAGUK-based protein complexes defines novel roles for Sdt and Dlg-S97.

    PubMed

    Bachmann, André; Timmer, Marco; Sierralta, Jimena; Pietrini, Grazia; Gundelfinger, Eckart D; Knust, Elisabeth; Thomas, Ulrich

    2004-04-15

    Stardust (Sdt) and Discs-Large (Dlg) are membrane-associated guanylate kinases (MAGUKs) involved in the organization of supramolecular protein complexes at distinct epithelial membrane compartments in Drosophila. Loss of either Sdt or Dlg affects epithelial development with severe effects on apico-basal polarity. Moreover, Dlg is required for the structural and functional integrity of synaptic junctions. Recent biochemical and cell culture studies have revealed that various mammalian MAGUKs can interact with mLin-7/Veli/MALS, a small PDZ-domain protein. To substantiate these findings for their in vivo significance with regard to Sdt- and Dlg-based protein complexes, we analyzed the subcellular distribution of Drosophila Lin-7 (DLin-7) and performed genetic and biochemical assays to characterize its interaction with either of the two MAGUKs. In epithelia, Sdt mediates the recruitment of DLin-7 to the subapical region, while at larval neuromuscular junctions, a particular isoform of Dlg, Dlg-S97, is required for postsynaptic localization of DLin-7. Ectopic expression of Dlg-S97 in epithelia, however, was not sufficient to induce a redistribution of DLin-7. These results imply that the recruitment of DLin-7 to MAGUK-based protein complexes is defined by cell-type specific mechanisms and that DLin-7 acts downstream of Sdt in epithelia and downstream of Dlg at synapses.

  17. Adolescent oligomenorrhea (age 14-19) tracks into the third decade of life (age 20-28) and predicts increased cardiovascular risk factors and metabolic syndrome.

    PubMed

    Glueck, Charles J; Woo, Jessica G; Khoury, Philip R; Morrison, John A; Daniels, Stephen R; Wang, Ping

    2015-04-01

    Assess whether adolescent oligomenorrhea (age 14-19) tracks into young adulthood (age 20-28) and predicts increased cardiometabolic risk factors, metabolic syndrome (MetS), and impaired fasting glucose-type II diabetes mellitus (IFG+T2DM). Prospective study of menstrual cyclicity and its metabolic effects in 865 black and white schoolgirls from age 9 to 19, and 605 of these 865 girls from age 20 to 28. Patterns of menstrual delays (oligomenorrhea) during ages 14-19 and ages 20-28 were closely related (p<.0001). Adolescent menses delay (ages 14-19, p<.0001), mean insulin (ages 20-28, p=.0003), and self-identified polycystic ovary syndrome (PCOS, p=.049) predicted ages 20-28 menses delay. Menses delays during ages 14-19 and 20-28, and, their interaction product were correlated with IFG+T2DM and MetS at ages 20-28. Waist circumference (ages 20-28, p<.0001), mean triglyceride (ages 20-28, p=.005), and the number of average menstrual cycles≥42 days (ages 20-28, p=.04) predicted IFG+T2DM (ages 20-28). MetS (ages 9-19, p<.0001), mean insulin (ages 20-28, p=.0002), the number of ≥42 day gaps between menstrual periods (ages 20-28, p=.02), and cigarette smoking at age 18-19 (p=.04) were significant explanatory variables for MetS at ages 27-28. As MetS status category changed from age 14-19 to 27-28 from best to worst: (no → no), (yes → no), (yes → yes), (no → yes), the number of women with ≥2 menses delays during ages 20-28 rose from 3% to 4% to 15% to 17%, p=.0001. MetS status change from age 9-19 to 27-28 was positively associated with mean insulin (age 20-28, p<.0001), cigarette smoking (age 24-25, p=.01) and the number of menses delays during ages 20-28 (p=.04). Menstrual patterns track from adolescence to young adulthood, and oligomenorrhea predicts MetS and IFG+T2DM. Patterns of menses delays in adolescence should be considered as a significant risk factor for future development of young adult IFG+T2DM, MetS, oligomenorrhea, and polycystic ovary syndrome

  18. 49 CFR 172.304 - Marking requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false Marking requirements. 172.304 Section 172.304 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY... SECURITY PLANS Marking § 172.304 Marking requirements. (a) The marking required in this subpart— (1) Must...

  19. Hematopoietic stem cells found in lineage-positive subsets in the bone marrow of 5-fluorouracil-treated mice.

    PubMed

    Nishi, N; Osawa, M; Ishikawa, R; Nishikawa, M; Tsumura, H; Inoue, H; Sudo, T

    1995-09-01

    It is known that treatment of mice with 5-fluorouracil (5-FU, 150 mg/kg) confers radioprotection. To investigate this effect, we performed bone marrow transplantation (BMT) using C57BL/6-Ly5 congenic mice treated with 5-FU five days prior to experiments. The mononuclear cells (MNC) in 5-FU-treated bone marrow (BM) were 10 times more radioprotective than those in untreated BM. Moreover, the number of BM MNC expressing c-kit on their surface from 5-FU-treated mice was markedly decreased relative to those from untreated controls. These results showed that the surface characteristics of cells that contributed to this radio-protective effect differ from those of stem cells as reported recently. BM MNC of mice treated with 5-FU were separated on the basis of expression of the lineage-specific antigens (Lin), c-kit, and Ly6A/E. When injected into lethally irradiated mice, 1,000 Lin+ and Lin-c-kit+Ly6A/E+ cells showed radioprotective effects such that 100% and 60% survived, respectively. Flow cytometric analysis 165 days after BMT showed that 88.8% and 65.1% of peripheral blood (PB) in mice transplanted with Lin+ and Lin-c-kit+Ly6A/E+ was derived from donor mice, respectively. After six months, donor-derived Lin-c-kit+Ly6A/E+ cells which showed radioprotective effects on a secondary irradiated host were detected from mice transplanted with Lin+ cells from 5-FU-treated mice. Taken together, these findings demonstrated that stem cells expressing Lin+ present in the BM of mice treated with 5-FU other than Lin-c-kit+Ly6A/E+ cells and these Lin+ cells play an important role in the recovery of myeloablative mice.

  20. Classroom Mark-Recapture with Crickets

    ERIC Educational Resources Information Center

    Whiteley, Andrew R.; Woolfe, Jennifer; Kennedy, Kathleen; Oberbillig, David; Brewer, Carol

    2007-01-01

    Mark-recapture techniques are commonly used by ecologists to estimate abundance of naturally occurring animals and are an important component of ecology curricula. This investigation teaches a mark-recapture technique using store-bought crickets in 10-gallon aquaria and provides an inexpensive way to teach students about mark-recapture in a real…

  1. Dietary calcein marking of shovelnose sturgeon and the effect of sunlight on mark retention

    USGS Publications Warehouse

    Honeyfield, D.C.; Kindschi, G.A.; Bell, T.A.; Mohler, J.W.

    2011-01-01

    Calcein, a fluorochrome dye, is a potential fish-marking agent that has not been evaluated in sturgeon. Shovelnose sturgeon Scaphirhynchus platorynchus (average weight, 9.7 g) were fed calcein, immersed in a calcein bath, or left unmarked to determine calcein mark intensity. In the first study, six treatments were evaluated in a two-by-three factorial arrangement. Feed was formulated with 2.0 g of SE-MARK/kg either as powder or in an encapsulated form. Sturgeon were fed the test diets for 5, 10, or 15 d. They readily ate feed containing powdered or encapsulated calcein. Sturgeon fed powdered calcein had more brilliant marks than those fed encapsulated calcein (8.27 versus 4.66 lm; P < 0.03) 6 months postexposure. Fish fed calcein for 15 d (11.26 lm) were more brilliant (P < 0.002) than fish fed for either 5 d (3.02 lm) or 10 d (5.11 lm). Post hoc comparison of the three treatment groups showed that sturgeon fed powdered calcein for 15 d (14.06 lm) were brighter (P < 0.01) than fish fed encapsulated calcein (8.46 lm) or fish immersed in calcein (9.68 lm). In the second study, previouslymarked sturgeon were exposed to sunlight for 14months to determine their retention of calcein marks. Dorsal marks were no longer visible on fish exposed to 100% sunlight after 8 weeks. Most but not all fish exposed to 20% sunlight had no discernable dorsalmarks after 8 weeks, but ventral marks at the pectoral fin girdle were present on all fish in the 0% and 20% sunlight exposure treatments. Feeding calcein for 15 d appears to have excellent potential for practical application, such as distinguishing hatchery-reared from wild fish. Ventral calcein marks remained visible after 14 months of exposure to 20% sunlight when sturgeon were reared in clear water. ?? American Fisheries Society 2011.

  2. Differential effect of 1{alpha},25-dihydroxyvitamin D{sub 3} on Hsp28 and PKC{beta} gene expression in the phorbol ester-resistant human myeloid HL-525 leukemic cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Yong J.; Galoforo, S.S.; Berns, C.M.

    We investigated the effect of 1{alpha},25-dihydroxyvitamin D{sub 3} [1,25-(OH){sub 2}D{sub 3}] on the expression of the 28-kDa heat shock protein gene (hsp28) and the protein kinase C beta gene (PKC{beta}) in the human myeloid HL-60 leukemic cell variant HL-525, which is resistance to phorbol ester-induced macrophage differentiation. Northern and Western blot analysis showed little or no hsp28 gene expression in the HL-60 cell variant, HL-205, which is susceptible to such differentiation, while a relatively high basal level of hps28 gene expression was observed in the HL-525 cells. However, both cell lines demonstrated heat shock-induced expression of this gene. During treatmentmore » with 50-300 nM 1,25-(OH){sub 2}D{sub 3}, a marked reduction of hsp28 gene expression was not associated with heat shock transcription factor-heat shock element (HSF-HSE) binding activity. Our results suggest that the differential effect of 1,25-(OH){sub 2}D{sub 3} on hsp28 and PKC{beta} gene expression is due to the different sequence composition of the vitamin D response element in the in the promoter region as well as an accessory factor for each gene or that 1,25-(OH){sub 2}D{sub 3} increases PKC{beta} gene expression, which in turn negatively regulates the expression of the hsp28 gene, or vice versa.« less

  3. 46 CFR 185.602 - Hull markings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Hull markings. 185.602 Section 185.602 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) OPERATIONS Markings Required § 185.602 Hull markings. (a) Each vessel must be marked as required by part 67...

  4. The effect of preoperative stoma site marking on quality of life.

    PubMed

    Cakir, Selda Karaveli; Ozbayir, Turkan

    2018-01-01

    The objective of the study was to determine the effect of preoperative stoma site marking on the health- related quality of life (HRQOL). A nonrandomized, quasi-experimental design was used for the study performed from June 2013 to August 2014. The study sample (n:60) included patients for whom a stoma was opened after a planned colorectal surgery. The City of Hope Quality of Life-Ostomy Questionnaire (COHQOL-OQ) was used to measure HRQOL. The mean age of the participants in the experimental group was 53.5±12.83, 18(60%) had colostomies, mean BMI was 25.46 ± 4.25 and mean age of that of the control group was 58.00 ± 14.22, 19(63.3%) had colostomies, mean BMI was 25.28 ± 5.00. A comparison of the two groups indicates that the sixth-month total score of the patients in the experimental group on (COHQOL-OQ) is higher than that of the control group (p<0.05). The study results demonstrated that patient who underwent stoma site marking reported higher HRQOL than those who did not.

  5. 14 CFR 23.1555 - Control markings.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Markings and Placards § 23.1555 Control markings. (a) Each cockpit control, other than primary flight controls and simple push button type starter switches, must be plainly marked as to its function and method... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Control markings. 23.1555 Section 23.1555...

  6. 14 CFR 23.1555 - Control markings.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Markings and Placards § 23.1555 Control markings. (a) Each cockpit control, other than primary flight controls and simple push button type starter switches, must be plainly marked as to its function and method... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Control markings. 23.1555 Section 23.1555...

  7. 14 CFR 23.1555 - Control markings.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Markings and Placards § 23.1555 Control markings. (a) Each cockpit control, other than primary flight controls and simple push button type starter switches, must be plainly marked as to its function and method... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Control markings. 23.1555 Section 23.1555...

  8. 14 CFR 23.1555 - Control markings.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Control markings. 23.1555 Section 23.1555... Markings and Placards § 23.1555 Control markings. (a) Each cockpit control, other than primary flight controls and simple push button type starter switches, must be plainly marked as to its function and method...

  9. A Novel Marking Reader for Progressive Addition Lenses Based on Gabor Holography.

    PubMed

    Perucho, Beatriz; Picazo-Bueno, José Angel; Micó, Vicente

    2016-05-01

    Progressive addition lenses (PALs) are marked with permanent engraved marks (PEMs) at standardized locations. Permanent engraved marks are very useful through the manufacturing and mounting processes, act as locator marks to re-ink the removable marks, and contain useful information about the PAL. However, PEMs are often faint and weak, obscured by scratches, partially occluded, and difficult to recognize on tinted lenses or with antireflection or scratch-resistant coatings. The aim of this article is to present a new generation of portable marking reader based on an extremely simplified concept for visualization and identification of PEMs in PALs. Permanent engraved marks on different PALs are visualized using classical Gabor holography as underlying principle. Gabor holography allows phase sample visualization with adjustable magnification and can be implemented in either classical or digital versions. Here, visual Gabor holography is used to provide a magnified defocused image of the PEMs onto a translucent visualization screen where the PEM is clearly identified. Different types of PALs (conventional, personalized, old and scratched, sunglasses, etc.) have been tested to visualize PEMs with the proposed marking reader. The PEMs are visible in every case, and variable magnification factor can be achieved simply moving up and down the PAL in the instrument. In addition, a second illumination wavelength is also tested, showing the applicability of this novel marking reader for different illuminations. A new concept of marking reader ophthalmic instrument has been presented and validated in the laboratory. The configuration involves only a commercial-grade laser diode and a visualization screen for PEM identification. The instrument is portable, economic, and easy to use, and it can be used for identifying patient's current PAL model and for marking removable PALs again or finding test points regardless of the age of the PAL, its scratches, tints, or coatings.

  10. STS-28 Columbia, OV-102, terminal countdown demonstration test (TCDT) at KSC

    NASA Technical Reports Server (NTRS)

    1989-01-01

    STS-28 Columbia, Orbiter Vehicle (OV) 102, crewmembers participate in the terminal countdown demonstration test (TCDT) at the Kennedy Space Center (KSC). Before TCDT, crewmembers eat breakfast. Sitting around the table (left to right) are Mission Specialist (MS) James C. Adamson, Pilot Richard N. Richards, Commander Brewster H. Shaw, Jr, MS David C. Leestma, and MS Mark N. Brown.

  11. Histone Methylation Restrains the Expression of Subtype-Specific Genes during Terminal Neuronal Differentiation in Caenorhabditis elegans

    PubMed Central

    Chiang, Victor; Chalfie, Martin

    2013-01-01

    Although epigenetic control of stem cell fate choice is well established, little is known about epigenetic regulation of terminal neuronal differentiation. We found that some differences among the subtypes of Caenorhabditis elegans VC neurons, particularly the expression of the transcription factor gene unc-4, require histone modification, most likely H3K9 methylation. An EGF signal from the vulva alleviated the epigenetic repression of unc-4 in vulval VC neurons but not the more distant nonvulval VC cells, which kept unc-4 silenced. Loss of the H3K9 methyltransferase MET-2 or H3K9me2/3 binding proteins HPL-2 and LIN-61 or a novel chromodomain protein CEC-3 caused ectopic unc-4 expression in all VC neurons. Downstream of the EGF signaling in vulval VC neurons, the transcription factor LIN-11 and histone demethylases removed the suppressive histone marks and derepressed unc-4. Behaviorally, expression of UNC-4 in all the VC neurons caused an imbalance in the egg-laying circuit. Thus, epigenetic mechanisms help establish subtype-specific gene expression, which are needed for optimal activity of a neural circuit. PMID:24348272

  12. Safety by design: effects of operating room floor marking on the position of surgical devices to promote clean air flow compliance and minimise infection risks.

    PubMed

    de Korne, Dirk F; van Wijngaarden, Jeroen D H; van Rooij, Jeroen; Wauben, Linda S G L; Hiddema, U Frans; Klazinga, Niek S

    2012-09-01

    To evaluate the use of floor marking on the positioning of surgical devices within the clean air flow in an operating room (OR) to minimise infection risk. Laminar flow clean air systems are important in preventing infection in ORs but, for optimal results, surgical devices must be correctly positioned. The authors evaluated floor marking in four ORs at an eye hospital using time series analysis. Through observations during 829 surgeries over a 20-month period, the positions of surgical devices were determined. Eight semistructured interviews with surgical staff were conducted to assess user experiences and team dynamics. Before marking, the instrument table was positioned completely within the laminar flow in only 6.1% of the cases. This increased to 36.1% and finally 53.8%. Mayo stands were increasingly positioned within the laminar flow: from 74.2% to 84.7%. The surgical lamp decreasingly obstructed flow: from 41.8% to 28.7%. At T3 (20 months), however, in 48.6% of the applicable cases the lamp was positioned in the flow again. Discussions and site visits between airside operators and surgical staff resulted in increasing awareness of specific risk areas in the OR. OR floor markings facilitated and stimulated safety awareness and resulted in significantly increased compliance with the positioning of surgical devices in the clean air flow. Safety and quality approaches in hospital care, therefore, should include a human factors approach that focuses on system design in addition to teaching clinical and non-technical skills.

  13. 28 CFR 28.21 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Purpose. 28.21 Section 28.21 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM Preservation of Biological Evidence § 28.21... exceptions. The general purpose of this requirement is to preserve biological evidence for possible DNA...

  14. 28 CFR 28.21 - Purpose.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Purpose. 28.21 Section 28.21 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM Preservation of Biological Evidence § 28.21... exceptions. The general purpose of this requirement is to preserve biological evidence for possible DNA...

  15. 28 CFR 28.21 - Purpose.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Purpose. 28.21 Section 28.21 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM Preservation of Biological Evidence § 28.21... exceptions. The general purpose of this requirement is to preserve biological evidence for possible DNA...

  16. 28 CFR 28.21 - Purpose.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Purpose. 28.21 Section 28.21 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM Preservation of Biological Evidence § 28.21... exceptions. The general purpose of this requirement is to preserve biological evidence for possible DNA...

  17. 28 CFR 28.21 - Purpose.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 1 2012-07-01 2012-07-01 false Purpose. 28.21 Section 28.21 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM Preservation of Biological Evidence § 28.21... exceptions. The general purpose of this requirement is to preserve biological evidence for possible DNA...

  18. Induction of activator protein (AP)-1 and nuclear factor-kappaB by CD28 stimulation involves both phosphatidylinositol 3-kinase and acidic sphingomyelinase signals.

    PubMed

    Edmead, C E; Patel, Y I; Wilson, A; Boulougouris, G; Hall, N D; Ward, S G; Sansom, D M

    1996-10-15

    A major obstacle in understanding the signaling events that follow CD28 receptor ligation arises from the fact that CD28 acts as a costimulus to TCR engagement, making it difficult to assess the relative contribution of CD28 signals as distinct from those of the TCR. To overcome this problem, we have exploited the observation that activated human T cell blasts can be stimulated via the CD28 surface molecule in the absence of antigenic challenge; thus, we have been able to observe the response of normal T cells to CD28 activation in isolation. Using this system, we observed that CD28 stimulation by B7-transfected CHO cells induced a proliferative response in T cells that was not accompanied by measurable IL-2 production. However, subsequent analysis of transcription factor generation revealed that B7 stimulation induced both activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) complexes, but not NF-AT. In contrast, engagement of the TCR by class II MHC/superantigen, either with or without CD28 ligation, resulted in the induction of NF-AT, AP-1, and NF-kappaB as well as IL-2 production. Using selective inhibitors, we investigated the signaling pathways involved in the CD28-mediated induction of AP-1 and NF-kappaB. This revealed that NF-kappaB generation was sensitive to chloroquine, an inhibitor of acidic sphingomyelinase, but not to the phosphatidylinositol 3-kinase inhibitor, wortmannin. In contrast, AP-1 generation was inhibited by wortmannin and was also variably sensitive to chloroquine. These data suggest that in activated normal T cells, CD28-derived signals can stimulate proliferation at least in part via NF-kappaB and AP-1 generation, and that this response uses both acidic sphingomyelinase and phosphatidylinositol 3-kinase-linked pathways.

  19. Synthetic mRNA devices that detect endogenous proteins and distinguish mammalian cells.

    PubMed

    Kawasaki, Shunsuke; Fujita, Yoshihiko; Nagaike, Takashi; Tomita, Kozo; Saito, Hirohide

    2017-07-07

    Synthetic biology has great potential for future therapeutic applications including autonomous cell programming through the detection of protein signals and the production of desired outputs. Synthetic RNA devices are promising for this purpose. However, the number of available devices is limited due to the difficulty in the detection of endogenous proteins within a cell. Here, we show a strategy to construct synthetic mRNA devices that detect endogenous proteins in living cells, control translation and distinguish cell types. We engineered protein-binding aptamers that have increased stability in the secondary structures of their active conformation. The designed devices can efficiently respond to target proteins including human LIN28A and U1A proteins, while the original aptamers failed to do so. Moreover, mRNA delivery of an LIN28A-responsive device into human induced pluripotent stem cells (hiPSCs) revealed that we can distinguish living hiPSCs and differentiated cells by quantifying endogenous LIN28A protein expression level. Thus, our endogenous protein-driven RNA devices determine live-cell states and program mammalian cells based on intracellular protein information. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. Evaluation of coded wire tags for marking lake trout

    USGS Publications Warehouse

    Elrod, Joseph H.; Schneider, Clifford P.

    1986-01-01

    Among hatchery-reared lake trout (Salvelinus namaycush) of the 1979-1982 year classes stocked in New York waters of Lake Ontario, more than 3 million fish were marked with a coded wire tag (CWT) plus an adipose fin clip, and 1.5 million with only conventional fin clips. Altogether, 7,640 tags were recovered from fish collected with bottom trawls and gill nets or caught by anglers during 1980-1983. One person was able to extract and decipher 200 or more CWTs per day with about a 1% error rate in reading and recording codes. Presence of the CWT did not affect growth. The adipose fin clip did not regenerate. The occurrence of fish with an adipose fin clip but no CWT resulted primarily from the regeneration of paired fins among fish marked with a combination of the adipose fin and a paired fin. Loss of CWTs between marking and stocking (generally 4-5 months for fish stocked in spring and 1-8 d for fish stocked in fall) declined from nearly 11% for the 1979 year class stocked as fall fingerlings to less than 3% for the 1981 and 1982 year classes - a difference that primarily reflected improvements in instrumentation and tagging technique. The rate of CWT loss after the marked fish were stocked was probably less than 1% per year. The CWT is a reliable method for marking hatchery-reared lake trout. A large number of experimental groups can be uniquely marked, and fish from each group can be accurately identified throughout their life. Use of this technique should greatly facilitate evaluations of genetic strain, hatchery experience, condition at time of stocking, season of stocking, size at stocking, method of stocking and other factors that affect poststocking survival and performance of lake trout stocked in the Great Lakes.

  1. 1L Mark-IV Target Design Review

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Koehler, Paul E.

    This presentation includes General Design Considerations; Current (Mark-III) Lower Tier; Mark-III Upper Tier; Performance Metrics; General Improvements for Material Science; General Improvements for Nuclear Science; Improving FOM for Nuclear Science; General Design Considerations Summary; Design Optimization Studies; Expected Mark-IV Performance: Material Science; Expected Mark-IV Performance: Nuclear Science (Disk); Mark IV Enables Much Wider Range of Nuclear-Science FOM Gains than Mark III; Mark-IV Performance Summary; Rod or Disk? Center or Real FOV?; and Project Cost and Schedule.

  2. Prayer marks.

    PubMed

    Abanmi, Abdullah A; Al Zouman, Abdulrahman Y; Al Hussaini, Husa; Al-Asmari, Abdulrahman

    2002-07-01

    Prayer marks (PMs) are asymptomatic, chronic skin changes that consist mainly of thickening, lichenification, and hyperpigmentation, and develop over a long period of time as a consequence of repeated, extended pressure on bony prominences during prayer. Three hundred and forty-nine Muslims and 24 non-Muslims were examined for the appearance of PMs at different body sites. The prospective study of 349 Muslims (both males and females) with regular praying habits showed the occurrence of PMs on specific locations, such as the forehead, knees, ankles, and dorsa of the feet, leading to dermatologic changes consisting of lichenification and hyperpigmentation. The incidence of PMs was significantly higher in males than in females. Older subjects (over 50 years of age) demonstrated a significantly higher frequency of lichenification and hyperpigmentation, suggesting that repeated pressure and friction for prolonged periods are the causative factors for the development of PMs. Histologic examination of skin biopsies from the affected sites showed compact orthokeratosis, hypergranulosis, dermal papillary fibrosis, and dermal vascularization. PMs were not associated with any risk of secondary complications, such as erythema, bullous formation, and infections. PMs are commonly occurring dermatologic changes in Muslims who pray for prolonged periods.

  3. The research of laser marking control technology

    NASA Astrophysics Data System (ADS)

    Zhang, Qiue; Zhang, Rong

    2009-08-01

    In the area of Laser marking, the general control method is insert control card to computer's mother board, it can not support hot swap, it is difficult to assemble or it. Moreover, the one marking system must to equip one computer. In the system marking, the computer can not to do the other things except to transmit marking digital information. Otherwise it can affect marking precision. Based on traditional control methods existed some problems, introduced marking graphic editing and digital processing by the computer finish, high-speed digital signal processor (DSP) control marking the whole process. The laser marking controller is mainly contain DSP2812, digital memorizer, DAC (digital analog converting) transform unit circuit, USB interface control circuit, man-machine interface circuit, and other logic control circuit. Download the marking information which is processed by computer to U disk, DSP read the information by USB interface on time, then processing it, adopt the DSP inter timer control the marking time sequence, output the scanner control signal by D/A parts. Apply the technology can realize marking offline, thereby reduce the product cost, increase the product efficiency. The system have good effect in actual unit markings, the marking speed is more quickly than PCI control card to 20 percent. It has application value in practicality.

  4. 3 CFR 8936 - Proclamation 8936 of February 28, 2013. Read Across America Day, 2013

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... America Day, 2013 8936 Proclamation 8936 Presidential Documents Proclamations Proclamation 8936 of February 28, 2013 Proc. 8936 Read Across America Day, 2013By the President of the United States of America A Proclamation Today, people of all ages will mark Read Across America Day by celebrating stories...

  5. [The scent marking of territory of gerbils: a comparative analysis exemplified by 4 species of the genus Meriones].

    PubMed

    Gromov, V S

    1997-01-01

    Sex-age and seasonal variability of the ventral glands and different stereotypes of scent marking behaviour in four Meriones species (M. unguiculatus, M. meridianus, M. libycus, M. tamariscinus) have been studied in nature and under semi-natural conditions. Two major ways of olfactory marking are considered: by secretion of the ventral glands and by "signal heaps" with urine and feces. Intraspecific and inter-species variability of marking activity is investigated. The ventral glands start to function at the period of preparation of a generative system to reproduction. The peak of secretary activity of gland and maximum of two types of marking activity is observed in spring and early summer, i.e. the period of active reproduction. The maximum of two types of the marking activity is observed during this period. In M. tamariscinus and M. meridianus the marking by the ventral gland is prevailing mode of the territory scent marking, while Mongolian gerbils (M. unguiculatus) prefer to use "signal heaps" Libyan gerbils (M. libycus) in this relation take an intermediate position. At the non-productive period a level of marking activity is on 10-20 times lower than at the reproductive season. Besides hormonal, social factors were also important for regulation of marking activity. By influence of these factors the differences in the level of marking activity in high-rank and low-rank individuals and differences in patterns of a spatial distribution of scent marks in individuals of different hierarchical rank is explained. Functional significance of various ways of territory scent marking is discussed.

  6. Meetings with Mark Vishik

    NASA Astrophysics Data System (ADS)

    Kalikinskaya, E. I.

    2014-12-01

    Mark Iosifovich Vishik was my husband Vladimir Chepyzhov's advisor during his years as a student in the Faculty of Mechanics and Mathematics at Moscow State University, and afterwards they worked together for almost 30 years. This is why I knew him personally while not being a mathematician myself: we sometimes talked on the phone, and met during common trips and a few holidays. In his last years, after the death of his devoted wife who was also his best friend, my husband and I decided to visit Mark regularly in order to comfort him in his loneliness, and many other of his friends did the same. I can say without exaggeration that Mark loved to talk with me about everyday matters, to reminisce about his wife Asya Moiseevna, their friends and relatives, to tell stories of his youth and the wonderful encounters that had so enriched his life. We had the idea to write down our conversations and publish them as a book. Unfortunately, few such conversations lay ahead. The last one took place in January 2010. We did not write a book, but we did write an article [1], which was published in English in the form of an interview with Mark. The present article is based on our conversations with Mark. Here I will try to recount his memories about people who played an important role in his life.

  7. 28 CFR 71.28 - Motions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... REMEDIES ACT OF 1986 Implementation for Actions Initiated by the Department of Justice § 71.28 Motions. (a) Any application to the ALJ for an order or ruling shall be by motion. Motions shall state the relief... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Motions. 71.28 Section 71.28 Judicial...

  8. 28 CFR 71.28 - Motions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... REMEDIES ACT OF 1986 Implementation for Actions Initiated by the Department of Justice § 71.28 Motions. (a) Any application to the ALJ for an order or ruling shall be by motion. Motions shall state the relief... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Motions. 71.28 Section 71.28 Judicial...

  9. Swash mark and grain flow

    USGS Publications Warehouse

    Sallenger,, Asbury H.

    1981-01-01

    Swash marks composed entirely of coarse sand are commonly found on coarse-sand beaches. These swash marks are 10 to 30 centimeters in width and a few millimeters to one centimeter in height. Previous observations, mostly on finer-sand beaches, indicate swash marks are seldom over a few millimeters in height and are commonly composed of material readily floated by surface tension (e.g., mica flakes and shell fragments). Swash marks composed of coarse sand have both fining seaward and fining with depth trends in grain size. Apparently, the leading margin of a wave upwash drives a highly concentrated flow of grains in which both grain size and grain velocity decrease with depth. Therefore, large grains are transported at greater velocities than are smaller grains. Thus, at the maximum advance of an upwash, a swash mark is deposited which has the observed fining seaward and fining with depth trends in grain size.

  10. The Mediator Kinase Module Restrains Epidermal Growth Factor Receptor Signaling and Represses Vulval Cell Fate Specification in Caenorhabditis elegans.

    PubMed

    Grants, Jennifer M; Ying, Lisa T L; Yoda, Akinori; You, Charlotte C; Okano, Hideyuki; Sawa, Hitoshi; Taubert, Stefan

    2016-02-01

    Cell signaling pathways that control proliferation and determine cell fates are tightly regulated to prevent developmental anomalies and cancer. Transcription factors and coregulators are important effectors of signaling pathway output, as they regulate downstream gene programs. In Caenorhabditis elegans, several subunits of the Mediator transcriptional coregulator complex promote or inhibit vulva development, but pertinent mechanisms are poorly defined. Here, we show that Mediator's dissociable cyclin dependent kinase 8 (CDK8) module (CKM), consisting of cdk-8, cic-1/Cyclin C, mdt-12/dpy-22, and mdt-13/let-19, is required to inhibit ectopic vulval cell fates downstream of the epidermal growth factor receptor (EGFR)-Ras-extracellular signal-regulated kinase (ERK) pathway. cdk-8 inhibits ectopic vulva formation by acting downstream of mpk-1/ERK, cell autonomously in vulval cells, and in a kinase-dependent manner. We also provide evidence that the CKM acts as a corepressor for the Ets-family transcription factor LIN-1, as cdk-8 promotes transcriptional repression by LIN-1. In addition, we find that CKM mutation alters Mediator subunit requirements in vulva development: the mdt-23/sur-2 subunit, which is required for vulva development in wild-type worms, is dispensable for ectopic vulva formation in CKM mutants, which instead display hallmarks of unrestrained Mediator tail module activity. We propose a model whereby the CKM controls EGFR-Ras-ERK transcriptional output by corepressing LIN-1 and by fine tuning Mediator specificity, thus balancing transcriptional repression vs. activation in a critical developmental signaling pathway. Collectively, these data offer an explanation for CKM repression of EGFR signaling output and ectopic vulva formation and provide the first evidence of Mediator CKM-tail module subunit crosstalk in animals. Copyright © 2016 by the Genetics Society of America.

  11. Formation of positive cluster ions Li(n) Br (n = 2-7) and ionization energies studied by thermal ionization mass spectrometry.

    PubMed

    Veličković, S R; Đustebek, J B; Veljković, F M; Veljković, M V

    2012-05-01

    Clusters of the type Li(n)X (X = halides) can be considered as potential building blocks of cluster-assembly materials. In this work, Li(n)Br (n = 2-7) clusters were obtained by a thermal ionization source of modified design and selected by a magnetic sector mass spectrometer. Positive ions of the Li(n)Br (n = 4-7) cluster were detected for the first time. The order of ion intensities was Li(2)Br(+) > Li(4)Br(+) > Li(5)Br(+) > Li(6)Br(+) > Li(3)Br(+). The ionization energies (IEs) were measured and found to be 3.95 ± 0.20 eV for Li(2)Br, 3.92 ± 0.20 eV for Li(3)Br, 3.93 ± 0.20 eV for Li(4)Br, 4.08 ± 0.20 eV for Li(5)Br, 4.14 ± 0.20 eV for Li(6)Br and 4.19 ± 0.20 eV for Li(7)Br. All of these clusters have a much lower ionization potential than that of the lithium atom, so they belong to the superalkali class. The IEs of Li(n)Br (n = 2-4) are slightly lower than those in the corresponding small Li(n) or Li(n)H clusters, whereas the IEs of Li(n)Br are very similar to those of Li(n) or Li(n)H for n = 5 and 6. The thermal ionization source of modified design is an important means for simultaneously obtaining and measuring the IEs of Li(n)Br (n = 2-7) clusters (because their ions are hermodynamically stable with respect to the loss of lithium atoms in the gas phase) and increasingly contributes toward the development of clusters for practical applications. Copyright © 2012 John Wiley & Sons, Ltd.

  12. 48 CFR 227.7103-10 - Contractor identification and marking of technical data to be furnished with restrictive markings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... and marking of technical data to be furnished with restrictive markings. 227.7103-10 Section 227.7103... DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Technical Data 227.7103-10 Contractor identification and marking of technical data to be furnished with restrictive markings...

  13. Wet night visibility of pavement markings.

    DOT National Transportation Integrated Search

    2004-01-01

    This report describes an investigation into the performance of pavement markings in wet night conditions. The performance of a typical pavement marking will degrade when it gets wet. This is a result of the flooding of the marking optics, thereby red...

  14. 9 CFR 317.3 - Approval of abbreviations of marks of inspection; preparation of marking devices bearing...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... marking device containing any official mark or simulation thereof, or any label bearing any such mark or simulation, without the written authority therefor of the Administrator. However, when any such sample label... inspection legend, or simulation thereof, shown in § 312.2(a), § 312.3(a) (only the legend appropriate for...

  15. 9 CFR 317.3 - Approval of abbreviations of marks of inspection; preparation of marking devices bearing...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... marking device containing any official mark or simulation thereof, or any label bearing any such mark or simulation, without the written authority therefor of the Administrator. However, when any such sample label... inspection legend, or simulation thereof, shown in § 312.2(a), § 312.3(a) (only the legend appropriate for...

  16. 9 CFR 317.3 - Approval of abbreviations of marks of inspection; preparation of marking devices bearing...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... marking device containing any official mark or simulation thereof, or any label bearing any such mark or simulation, without the written authority therefor of the Administrator. However, when any such sample label... inspection legend, or simulation thereof, shown in § 312.2(a), § 312.3(a) (only the legend appropriate for...

  17. 9 CFR 317.3 - Approval of abbreviations of marks of inspection; preparation of marking devices bearing...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... marking device containing any official mark or simulation thereof, or any label bearing any such mark or simulation, without the written authority therefor of the Administrator. However, when any such sample label... inspection legend, or simulation thereof, shown in § 312.2(a), § 312.3(a) (only the legend appropriate for...

  18. 9 CFR 317.3 - Approval of abbreviations of marks of inspection; preparation of marking devices bearing...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... marking device containing any official mark or simulation thereof, or any label bearing any such mark or simulation, without the written authority therefor of the Administrator. However, when any such sample label... inspection legend, or simulation thereof, shown in § 312.2(a), § 312.3(a) (only the legend appropriate for...

  19. Crystal structure, mutational analysis and RNA-dependent ATPase activity of the yeast DEAD-box pre-mRNA splicing factor Prp28

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jacewicz, Agata; Schwer, Beate; Smith, Paul

    Yeast Prp28 is a DEAD-box pre-mRNA splicing factor implicated in displacing U1 snRNP from the 5' splice site. Here we report that the 588-aa Prp28 protein consists of a trypsin-sensitive 126-aa N-terminal segment (of which aa 1–89 are dispensable for Prp28 function in vivo) fused to a trypsin-resistant C-terminal catalytic domain. Purified recombinant Prp28 and Prp28-(127–588) have an intrinsic RNA-dependent ATPase activity, albeit with a low turnover number. The crystal structure of Prp28-(127–588) comprises two RecA-like domains splayed widely apart. AMPPNP•Mg 2+ is engaged by the proximal domain, with proper and specific contacts from Phe194 and Gln201 (Q motif) tomore » the adenine nucleobase. The triphosphate moiety of AMPPNP•Mg 2+ is not poised for catalysis in the open domain conformation. Guided by the Prp28•AMPPNP structure, and that of the Drosophila Vasa•AMPPNP•Mg 2+•RNA complex, we targeted 20 positions in Prp28 for alanine scanning. ATP-site components Asp341 and Glu342 (motif II) and Arg527 and Arg530 (motif VI) and RNA-site constituent Arg476 (motif Va) are essential for Prp28 activity in vivo. Synthetic lethality of double-alanine mutations highlighted functionally redundant contacts in the ATP-binding (Phe194-Gln201, Gln201-Asp502) and RNA-binding (Arg264-Arg320) sites. As a result, overexpression of defective ATP-site mutants, but not defective RNA-site mutants, elicited severe dominant-negative growth defects.« less

  20. Crystal structure, mutational analysis and RNA-dependent ATPase activity of the yeast DEAD-box pre-mRNA splicing factor Prp28

    DOE PAGES

    Jacewicz, Agata; Schwer, Beate; Smith, Paul; ...

    2014-10-10

    Yeast Prp28 is a DEAD-box pre-mRNA splicing factor implicated in displacing U1 snRNP from the 5' splice site. Here we report that the 588-aa Prp28 protein consists of a trypsin-sensitive 126-aa N-terminal segment (of which aa 1–89 are dispensable for Prp28 function in vivo) fused to a trypsin-resistant C-terminal catalytic domain. Purified recombinant Prp28 and Prp28-(127–588) have an intrinsic RNA-dependent ATPase activity, albeit with a low turnover number. The crystal structure of Prp28-(127–588) comprises two RecA-like domains splayed widely apart. AMPPNP•Mg 2+ is engaged by the proximal domain, with proper and specific contacts from Phe194 and Gln201 (Q motif) tomore » the adenine nucleobase. The triphosphate moiety of AMPPNP•Mg 2+ is not poised for catalysis in the open domain conformation. Guided by the Prp28•AMPPNP structure, and that of the Drosophila Vasa•AMPPNP•Mg 2+•RNA complex, we targeted 20 positions in Prp28 for alanine scanning. ATP-site components Asp341 and Glu342 (motif II) and Arg527 and Arg530 (motif VI) and RNA-site constituent Arg476 (motif Va) are essential for Prp28 activity in vivo. Synthetic lethality of double-alanine mutations highlighted functionally redundant contacts in the ATP-binding (Phe194-Gln201, Gln201-Asp502) and RNA-binding (Arg264-Arg320) sites. As a result, overexpression of defective ATP-site mutants, but not defective RNA-site mutants, elicited severe dominant-negative growth defects.« less

  1. 7 CFR 28.5-28.6 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false [Reserved] 28.5-28.6 Section 28.5-28.6 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... §§ 28.5-28.6 [Reserved] ...

  2. 7 CFR 28.5-28.6 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false [Reserved] 28.5-28.6 Section 28.5-28.6 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... §§ 28.5-28.6 [Reserved] ...

  3. Digital cultural heritage and its applications: case studies of Digital Mogao Grottos and Chi Lin Nunnery reconstruction

    NASA Astrophysics Data System (ADS)

    Li, Deren; Du, Zhiqiang; Zhu, Yixuan; Wang, Tingsong

    2009-09-01

    Considerable damage has been done to the cultural heritage sites around the world ranging from natural erosion to artificial destruction. With the development of information sciences, frontier technologies are actively introduced to help protect cultural heritage sites. The new concept of a Digital Cultural Heritage has been presented for culture protection and is gradually becoming an efficient method to solve or to remit various difficult problems. This paper puts forward a digitalization method for cultural heritage sites which rationally integrates and utilizes multiform surveying measurements. These techniques have been successfully implemented into two projects, namely the Digital Mogao Grottos and the Chi Lin Nunnery reconstruction. Our results prove that the concept of and the techniques utilized in Digital Cultural Heritage can not only contribute to research, preservation, management, interpretation, and representation of cultural heritages but can also help resolve the conflicts between tourism and protection.

  4. Digital cultural heritage and its applications: case studies of Digital Mogao Grottos and Chi Lin Nunnery reconstruction

    NASA Astrophysics Data System (ADS)

    Li, Deren; Du, Zhiqiang; Zhu, Yixuan; Wang, Tingsong

    2010-11-01

    Considerable damage has been done to the cultural heritage sites around the world ranging from natural erosion to artificial destruction. With the development of information sciences, frontier technologies are actively introduced to help protect cultural heritage sites. The new concept of a Digital Cultural Heritage has been presented for culture protection and is gradually becoming an efficient method to solve or to remit various difficult problems. This paper puts forward a digitalization method for cultural heritage sites which rationally integrates and utilizes multiform surveying measurements. These techniques have been successfully implemented into two projects, namely the Digital Mogao Grottos and the Chi Lin Nunnery reconstruction. Our results prove that the concept of and the techniques utilized in Digital Cultural Heritage can not only contribute to research, preservation, management, interpretation, and representation of cultural heritages but can also help resolve the conflicts between tourism and protection.

  5. Bench-marking effects in the blaming of professionals for incidents of aggression and assault.

    PubMed

    Carifio, J; Lanza, M

    1994-01-01

    This study compared all possible orders of responding to three vignettes describing incidents between a male patient and a female nurse in which the nurse is mildly assaulted, severely assaulted, or verbally abused by the patient (the control condition). Subjects were 32 female senior-year nursing students and 28 practicing nurses. It was found that response levels to a given vignette could predict a respondent's response to the other vignettes. Also, a significant "bench-marking" effect was found: if a subject responded to the mild assault vignette first, the subject's overall response pattern best fit the general nonlinear assignment-of-blame pattern observed, but if the subject responded to the severe assault or control vignette first, this vignette set a bench mark for responding from which the subject's subsequent responses did not deviate greatly, which slightly distorted the subject's V-shaped nonlinear response pattern.

  6. 49 CFR 15.13 - Marking SSI.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Office of the Secretary of Transportation PROTECTION OF SENSITIVE SECURITY INFORMATION § 15.13 Marking... document. (b) Protective marking. The protective marking is: SENSITIVE SECURITY INFORMATION. (c... Sensitive Security Information that is controlled under 49 CFR parts 15 and 1520. No part of this record may...

  7. 49 CFR 15.13 - Marking SSI.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Office of the Secretary of Transportation PROTECTION OF SENSITIVE SECURITY INFORMATION § 15.13 Marking... document. (b) Protective marking. The protective marking is: SENSITIVE SECURITY INFORMATION. (c... Sensitive Security Information that is controlled under 49 CFR parts 15 and 1520. No part of this record may...

  8. 46 CFR 160.060-8 - Marking.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Specification for a Buoyant Vest, Unicellular Polyethylene Foam, Adult and Child § 160.060-8 Marking. (a) Each buoyant vest must have the following information clearly... manufacturer or distributor). (Lot No.). (b) Waterproof marking. Marking of buoyant vests shall be sufficiently...

  9. 46 CFR 160.060-8 - Marking.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Specification for a Buoyant Vest, Unicellular Polyethylene Foam, Adult and Child § 160.060-8 Marking. (a) Each buoyant vest must have the following information clearly... manufacturer or distributor). (Lot No.). (b) Waterproof marking. Marking of buoyant vests shall be sufficiently...

  10. 46 CFR 160.060-8 - Marking.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Specification for a Buoyant Vest, Unicellular Polyethylene Foam, Adult and Child § 160.060-8 Marking. (a) Each buoyant vest must have the following information clearly... manufacturer or distributor). (Lot No.). (b) Waterproof marking. Marking of buoyant vests shall be sufficiently...

  11. Evaluation of pavement marking performance.

    DOT National Transportation Integrated Search

    2008-06-01

    The objective of the investigation was to evaluate the useful life of pavement markings. The Manual on Uniform Traffic Control Devices (MUTCD) provides general guidelines for the application and installation of pavement markings. However, performance...

  12. 49 CFR 180.515 - Markings.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) Pressure converted tank cars must have the new specification and conversion date permanently marked in... the manway nozzle flange on the left side of the car. The marking may have the last numeral of the...

  13. 49 CFR 28.132-28.139 - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false [Reserved] 28.132-28.139 Section 28.132-28.139 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION §§ 28.132-28.139 [Reserved] ...

  14. 49 CFR 28.104-28.109 - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false [Reserved] 28.104-28.109 Section 28.104-28.109 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION §§ 28.104-28.109 [Reserved] ...

  15. 49 CFR 28.141-28.148 - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false [Reserved] 28.141-28.148 Section 28.141-28.148 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION §§ 28.141-28.148 [Reserved] ...

  16. 49 CFR 28.112-28.129 - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false [Reserved] 28.112-28.129 Section 28.112-28.129 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION §§ 28.112-28.129 [Reserved] ...

  17. 49 CFR 28.161-28.169 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false [Reserved] 28.161-28.169 Section 28.161-28.169 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION §§ 28.161-28.169 [Reserved] ...

  18. 49 CFR 28.141-28.148 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false [Reserved] 28.141-28.148 Section 28.141-28.148 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION §§ 28.141-28.148 [Reserved] ...

  19. 49 CFR 28.104-28.109 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false [Reserved] 28.104-28.109 Section 28.104-28.109 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION §§ 28.104-28.109 [Reserved] ...

  20. 49 CFR 28.171-28.999 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false [Reserved] 28.171-28.999 Section 28.171-28.999 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION §§ 28.171-28.999 [Reserved] ...

  1. 49 CFR 28.152-28.159 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false [Reserved] 28.152-28.159 Section 28.152-28.159 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION §§ 28.152-28.159 [Reserved] ...

  2. 49 CFR 28.132-28.139 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false [Reserved] 28.132-28.139 Section 28.132-28.139 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION §§ 28.132-28.139 [Reserved] ...

  3. 49 CFR 28.112-28.129 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false [Reserved] 28.112-28.129 Section 28.112-28.129 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION §§ 28.112-28.129 [Reserved] ...

  4. Marking Student Programs Using Graph Similarity

    ERIC Educational Resources Information Center

    Naude, Kevin A.; Greyling, Jean H.; Vogts, Dieter

    2010-01-01

    We present a novel approach to the automated marking of student programming assignments. Our technique quantifies the structural similarity between unmarked student submissions and marked solutions, and is the basis by which we assign marks. This is accomplished through an efficient novel graph similarity measure ("AssignSim"). Our experiments…

  5. 14 CFR 27.1555 - Control markings.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Control markings. (a) Each cockpit control, other than primary flight controls or control whose function... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Control markings. 27.1555 Section 27.1555... fuel controls— (1) Each fuel tank selector control must be marked to indicate the position...

  6. 14 CFR 27.1555 - Control markings.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Control markings. (a) Each cockpit control, other than primary flight controls or control whose function... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Control markings. 27.1555 Section 27.1555... fuel controls— (1) Each fuel tank selector control must be marked to indicate the position...

  7. 14 CFR 27.1555 - Control markings.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Control markings. (a) Each cockpit control, other than primary flight controls or control whose function... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Control markings. 27.1555 Section 27.1555... fuel controls— (1) Each fuel tank selector control must be marked to indicate the position...

  8. 14 CFR 27.1555 - Control markings.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Control markings. (a) Each cockpit control, other than primary flight controls or control whose function... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Control markings. 27.1555 Section 27.1555... fuel controls— (1) Each fuel tank selector control must be marked to indicate the position...

  9. 14 CFR 27.1555 - Control markings.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Control markings. 27.1555 Section 27.1555... Control markings. (a) Each cockpit control, other than primary flight controls or control whose function... fuel controls— (1) Each fuel tank selector control must be marked to indicate the position...

  10. The effect of preoperative stoma site marking on quality of life

    PubMed Central

    Cakir, Selda Karaveli; Ozbayir, Turkan

    2018-01-01

    Objective: The objective of the study was to determine the effect of preoperative stoma site marking on the health- related quality of life (HRQOL). Methods: A nonrandomized, quasi-experimental design was used for the study performed from June 2013 to August 2014. The study sample (n:60) included patients for whom a stoma was opened after a planned colorectal surgery. The City of Hope Quality of Life-Ostomy Questionnaire (COHQOL-OQ) was used to measure HRQOL. Results: The mean age of the participants in the experimental group was 53.5±12.83, 18(60%) had colostomies, mean BMI was 25.46 ± 4.25 and mean age of that of the control group was 58.00 ± 14.22, 19(63.3%) had colostomies, mean BMI was 25.28 ± 5.00. A comparison of the two groups indicates that the sixth-month total score of the patients in the experimental group on (COHQOL-OQ) is higher than that of the control group (p<0.05). Conclusions: The study results demonstrated that patient who underwent stoma site marking reported higher HRQOL than those who did not. PMID:29643897

  11. Mark IVA microprocessor support

    NASA Technical Reports Server (NTRS)

    Burford, A. L.

    1982-01-01

    The requirements and plans for the maintenance support of microprocessor-based controllers in the Deep Space Network Mark IVA System are discussed. Additional new interfaces and 16-bit processors have introduced problems not present in the Mark III System. The need for continuous training of maintenance personnel to maintain a level of expertise consistent with the sophistication of the required tools is also emphasized.

  12. 14 CFR 45.11 - Marking of products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Marking of Products and Articles § 45.11 Marking of products. (a) Aircraft. A manufacturer of aircraft covered under § 21.182 of this chapter must mark each aircraft by attaching a...

  13. 14 CFR 45.11 - Marking of products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Marking of Products and Articles § 45.11 Marking of products. (a) Aircraft. A manufacturer of aircraft covered under § 21.182 of this chapter must mark each aircraft by attaching a...

  14. 14 CFR 45.11 - Marking of products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Marking of Products and Articles § 45.11 Marking of products. (a) Aircraft. A manufacturer of aircraft covered under § 21.182 of this chapter must mark each aircraft by attaching a...

  15. 14 CFR 29.1555 - Control markings.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ....1555 Control markings. (a) Each cockpit control, other than primary flight controls or control whose... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Control markings. 29.1555 Section 29.1555... fuel controls— (1) Each fuel tank selector valve control must be marked to indicate the position...

  16. 14 CFR 29.1555 - Control markings.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ....1555 Control markings. (a) Each cockpit control, other than primary flight controls or control whose... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Control markings. 29.1555 Section 29.1555... fuel controls— (1) Each fuel tank selector valve control must be marked to indicate the position...

  17. 14 CFR 29.1555 - Control markings.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ....1555 Control markings. (a) Each cockpit control, other than primary flight controls or control whose... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Control markings. 29.1555 Section 29.1555... fuel controls— (1) Each fuel tank selector valve control must be marked to indicate the position...

  18. 14 CFR 29.1555 - Control markings.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ....1555 Control markings. (a) Each cockpit control, other than primary flight controls or control whose... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Control markings. 29.1555 Section 29.1555... fuel controls— (1) Each fuel tank selector valve control must be marked to indicate the position...

  19. 14 CFR 29.1555 - Control markings.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ....1555 Control markings. (a) Each cockpit control, other than primary flight controls or control whose... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Control markings. 29.1555 Section 29.1555... fuel controls— (1) Each fuel tank selector valve control must be marked to indicate the position...

  20. 46 CFR 122.602 - Hull markings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Hull markings. 122.602 Section 122.602 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS CARRYING MORE THAN 150....602 Hull markings. (a) Each vessel must be marked as required by part 67, subpart I, of this chapter...

  1. STS-28 Columbia, OV-102, crewmembers pose for group portrait on middeck

    NASA Image and Video Library

    1989-08-13

    STS028-22-030 (August 1989) --- An in-space crew portrait of the astronauts for the STS-28 mission. Brewster H. Shaw Jr., mission commander, is at lower left corner. Others are, clockwise from Shaw's position, James C. Adamson, David C. Leestma and Mark N. Brown, all mission specialists; and Richard N. Richards, pilot. The photo was taken on the middeck of the earth-orbiting Columbia.

  2. High contrast laser marking of alumina

    NASA Astrophysics Data System (ADS)

    Penide, J.; Quintero, F.; Riveiro, A.; Fernández, A.; del Val, J.; Comesaña, R.; Lusquiños, F.; Pou, J.

    2015-05-01

    Alumina serves as raw material for a broad range of advanced ceramic products. These elements should usually be identified by some characters or symbols printed directly on them. In this sense, laser marking is an efficient, reliable and widely implemented process in industry. However, laser marking of alumina still leads to poor results since the process is not able to produce a dark mark, yielding bad contrast. In this paper, we present an experimental study on the process of marking alumina by three different lasers working in two wavelengths: 1064 nm (Near-infrared) and 532 nm (visible, green radiation). A colorimetric analysis has been carried out in order to compare the resulting marks and its contrast. The most suitable laser operating conditions were also defined and are reported here. Moreover, the physical process of marking by NIR lasers is discussed in detail. Field Emission Scanning Electron Microscopy, High Resolution Transmission Electron Microscopy and X-ray Photoelectron Spectroscopy were also employed to analyze the results. Finally, we propose an explanation for the differences of the coloration induced under different atmospheres and laser parameters. We concluded that the atmosphere is the key parameter, being the inert one the best choice to produce the darkest marks.

  3. 46 CFR 111.25-5 - Marking.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Marking. 111.25-5 Section 111.25-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Motors § 111.25-5 Marking. (a) Each motor must have a marking or nameplate that meets either Section 430...

  4. 46 CFR 111.25-5 - Marking.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Marking. 111.25-5 Section 111.25-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Motors § 111.25-5 Marking. (a) Each motor must have a marking or nameplate that meets either Section 430...

  5. 46 CFR 111.25-5 - Marking.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Marking. 111.25-5 Section 111.25-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Motors § 111.25-5 Marking. (a) Each motor must have a marking or nameplate that meets either Section 430...

  6. 46 CFR 111.25-5 - Marking.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Marking. 111.25-5 Section 111.25-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Motors § 111.25-5 Marking. (a) Each motor must have a marking or nameplate that meets either Section 430...

  7. 46 CFR 111.25-5 - Marking.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Marking. 111.25-5 Section 111.25-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Motors § 111.25-5 Marking. (a) Each motor must have a marking or nameplate that meets either Section 430...

  8. A case of squamous cell carcinoma of the head and neck producing granulocyte-colony stimulating factor with marked leukocytosis.

    PubMed

    Toyoda, Minoru; Chikamatsu, Kazuaki; Sakakura, Koichi; Fukuda, Yoichiro; Takahashi, Katsumasa; Miyashita, Motoaki; Shimamura, Kazuo; Furuya, Nobuhiko

    2007-06-01

    In squamous cell carcinoma of the head and neck (SCCHN), tumor cells have been shown to secrete detectable amounts of various cytokines, such as interleukin (IL)-6, IL-10, and transforming growth factor (TGF)-beta. These tumor-derived factors might be responsible for promoting malignancy. Here, we describe a SCCHN patient with tumor produced G-CSF and characterized by marked leukocytosis. In this 45-year-old man, severe leukocytosis developed in parallel with aggressive tumor growth. G-CSF production by the tumor was confirmed by immunohistochemistry (IHC). Serum G-CSF levels were elevated. The leukocyte counts and the blood G-CSF level decreased following a course of radiotherapy. Tumor cells were also positive for G-CSF receptor, suggesting autocrine growth regulation by G-CSF. Moreover, the tumor cells were also investigated by IHC with anti-p53, anti-P-glycoprotein (P-gp), anti-thymidylate synthase (TS), and anti-dihydropyrimidine dehydrogenase (DPD), which molecules are thought to contribute the acquisition of therapeutic resistance. The tumor cells were positively stained for TS and DPD, but neither p53 nor P-gp. These results suggest that a variety of molecules may be responsible for acquisition of high malignancy.

  9. 14 CFR 25.1555 - Control markings.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ....1555 Control markings. (a) Each cockpit control, other than primary flight controls and controls whose... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Control markings. 25.1555 Section 25.1555... aerodynamic control must be marked under the requirements of §§ 25.677 and 25.699. (c) For powerplant fuel...

  10. 14 CFR 25.1555 - Control markings.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ....1555 Control markings. (a) Each cockpit control, other than primary flight controls and controls whose... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Control markings. 25.1555 Section 25.1555... aerodynamic control must be marked under the requirements of §§ 25.677 and 25.699. (c) For powerplant fuel...

  11. 14 CFR 25.1555 - Control markings.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ....1555 Control markings. (a) Each cockpit control, other than primary flight controls and controls whose... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Control markings. 25.1555 Section 25.1555... aerodynamic control must be marked under the requirements of §§ 25.677 and 25.699. (c) For powerplant fuel...

  12. 40 CFR 761.45 - Marking formats.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... POLYCHLORINATED BIPHENYLS (PCBs) MANUFACTURING, PROCESSING, DISTRIBUTION IN COMMERCE, AND USE PROHIBITIONS Marking...) Large PCB Mark—M L. Mark ML shall be as shown in Figure 1, letters and striping on a white or yellow... PCB Mark—M s. Mark Ms shall be as shown in Figure 2, letters and striping on a white or yellow...

  13. 14 CFR 23.1555 - Control markings.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Control markings. 23.1555 Section 23.1555... Markings and Placards § 23.1555 Control markings. Link to an amendment published at 76 FR 75763, December 2, 2011. (a) Each cockpit control, other than primary flight controls and simple push button type starter...

  14. 14 CFR 25.1555 - Control markings.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Control markings. 25.1555 Section 25.1555....1555 Control markings. (a) Each cockpit control, other than primary flight controls and controls whose... aerodynamic control must be marked under the requirements of §§ 25.677 and 25.699. (c) For powerplant fuel...

  15. 14 CFR 25.1555 - Control markings.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Control markings. 25.1555 Section 25.1555....1555 Control markings. (a) Each cockpit control, other than primary flight controls and controls whose... aerodynamic control must be marked under the requirements of §§ 25.677 and 25.699. (c) For powerplant fuel...

  16. 28 CFR 28.1 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Purpose. 28.1 Section 28.1 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM Qualifying Federal Offenses for Purposes of DNA... indexing of a DNA sample from each individual in the custody of the Bureau of Prisons or under the...

  17. 28 CFR 28.1 - Purpose.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Purpose. 28.1 Section 28.1 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM Qualifying Federal Offenses for Purposes of DNA... indexing of a DNA sample from each individual in the custody of the Bureau of Prisons or under the...

  18. 28 CFR 28.1 - Purpose.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Purpose. 28.1 Section 28.1 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM Qualifying Federal Offenses for Purposes of DNA... indexing of a DNA sample from each individual in the custody of the Bureau of Prisons or under the...

  19. 28 CFR 28.1 - Purpose.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Purpose. 28.1 Section 28.1 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM Qualifying Federal Offenses for Purposes of DNA... indexing of a DNA sample from each individual in the custody of the Bureau of Prisons or under the...

  20. 28 CFR 28.1 - Purpose.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 1 2012-07-01 2012-07-01 false Purpose. 28.1 Section 28.1 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM Qualifying Federal Offenses for Purposes of DNA... indexing of a DNA sample from each individual in the custody of the Bureau of Prisons or under the...

  1. 46 CFR 97.40-5 - Hull markings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Hull markings. 97.40-5 Section 97.40-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CARGO AND MISCELLANEOUS VESSELS OPERATIONS Markings on Vessels § 97.40-5 Hull markings. Vessels shall be marked as required by parts 67 and 69 of this...

  2. 46 CFR 196.40-5 - Hull markings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Hull markings. 196.40-5 Section 196.40-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Markings on Vessels § 196.40-5 Hull markings. Vessels shall be marked as required by parts 67 and 69 of this chapter...

  3. 46 CFR 78.50-5 - Hull markings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 3 2010-10-01 2010-10-01 false Hull markings. 78.50-5 Section 78.50-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PASSENGER VESSELS OPERATIONS Markings on Vessels § 78.50-5 Hull markings. Vessels shall be marked as required by parts 67 and 69 of this chapter. [CGD 72...

  4. Implementing New Methods of Laser Marking of Items in the Nuclear Material Control and Accountability System at SSC RF-IPPE: An Automated Laser Marking System

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Regoushevsky, V I; Tambovtsev, S D; Dvukhsherstnov, V G

    2009-05-18

    For over ten years SSC RF-IPPE, together with the US DOE National Laboratories, has been working on implementing automated control and accountability methods for nuclear materials and other items. Initial efforts to use adhesive bar codes or ones printed (painted) onto metal revealed that these methods were inconvenient and lacked durability under operational conditions. For NM disk applications in critical stands, there is the additional requirement that labels not affect the neutron characteristics of the critical assembly. This is particularly true for the many stainless-steel clad disks containing highly enriched uranium (HEU) and plutonium that are used at SSC RF-IPPEmore » for modeling nuclear power reactors. In search of an alternate method for labeling these disks, we tested several technological options, including laser marking and two-dimensional codes. As a result, the method of laser coloring was chosen in combination with Data Matrix ECC200 symbology. To implement laser marking procedures for the HEU disks and meet all the nuclear material (NM) handling standards and rules, IPPE staff, with U.S. technical and financial support, implemented an automated laser marking system; there are also specially developed procedures for NM movements during laser marking. For the laser marking station, a Zenith 10F system by Telesis Technologies (10 watt Ytterbium Fiber Laser and Merlin software) is used. The presentation includes a flowchart for the automated system and a list of specially developed procedures with comments. Among other things, approaches are discussed for human-factor considerations. To date, markings have been applied to numerous steel-clad HEU disks, and the work continues. In the future this method is expected to be applied to other MC&A items.« less

  5. 33 CFR 62.27 - Safe water marks.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Safe water marks. 62.27 Section... UNITED STATES AIDS TO NAVIGATION SYSTEM The U.S. Aids to Navigation System § 62.27 Safe water marks. Safe water marks indicate that there is navigable water all around the mark. They are often used to indicate...

  6. 33 CFR 62.27 - Safe water marks.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Safe water marks. 62.27 Section... UNITED STATES AIDS TO NAVIGATION SYSTEM The U.S. Aids to Navigation System § 62.27 Safe water marks. Safe water marks indicate that there is navigable water all around the mark. They are often used to indicate...

  7. 33 CFR 62.27 - Safe water marks.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Safe water marks. 62.27 Section... UNITED STATES AIDS TO NAVIGATION SYSTEM The U.S. Aids to Navigation System § 62.27 Safe water marks. Safe water marks indicate that there is navigable water all around the mark. They are often used to indicate...

  8. The neonatal marmoset monkey ovary is very primitive exhibiting many oogonia

    PubMed Central

    Fereydouni, B; Drummer, C; Aeckerle, N; Schlatt, S; Behr, R

    2014-01-01

    Oogonia are characterized by diploidy and mitotic proliferation. Human and mouse oogonia express several factors such as OCT4, which are characteristic of pluripotent cells. In human, almost all oogonia enter meiosis between weeks 9 and 22 of prenatal development or undergo mitotic arrest and subsequent elimination from the ovary. As a consequence, neonatal human ovaries generally lack oogonia. The same was found in neonatal ovaries of the rhesus monkey, a representative of the old world monkeys (Catarrhini). By contrast, proliferating oogonia were found in adult prosimians (now called Strepsirrhini), which is a group of ‘lower’ primates. The common marmoset monkey (Callithrix jacchus) belongs to the new world monkeys (Platyrrhini) and is increasingly used in reproductive biology and stem cell research. However, ovarian development in the marmoset monkey has not been widely investigated. Herein, we show that the neonatal marmoset ovary has an extremely immature histological appearance compared with the human ovary. It contains numerous oogonia expressing the pluripotency factors OCT4A, SALL4, and LIN28A (LIN28). The pluripotency factor-positive germ cells also express the proliferation marker MKI67 (Ki-67), which has previously been shown in the human ovary to be restricted to premeiotic germ cells. Together, the data demonstrate the primitiveness of the neonatal marmoset ovary compared with human. This study may introduce the marmoset monkey as a non-human primate model to experimentally study the aspects of primate primitive gonad development, follicle assembly, and germ cell biology in vivo. PMID:24840529

  9. A Comparative Evaluation of Analytical Methods to Allocate Individual Marks from a Team Mark

    ERIC Educational Resources Information Center

    Nepal, Kali

    2012-01-01

    This study presents a comparative evaluation of analytical methods to allocate individual marks from a team mark. Only the methods that use or can be converted into some form of mathematical equations are analysed. Some of these methods focus primarily on the assessment of the quality of teamwork product (product assessment) while the others put…

  10. Resveratrol modulates MED28 (Magicin/EG-1) expression and inhibits epidermal growth factor (EGF)-induced migration in MDA-MB-231 human breast cancer cells.

    PubMed

    Lee, Ming-Fen; Pan, Min-Hsiung; Chiou, Yi-Siou; Cheng, An-Chin; Huang, Han

    2011-11-09

    Resveratrol and pterostilbene exhibit diverse biological activities. MED28, a subunit of the mammalian Mediator complex for transcription, was also identified as magicin, an actin cytoskeleton Grb2-associated protein, and as endothelial-derived gene (EG-1). Several tumors exhibit aberrant MED28 expression, whereas the underlying mechanism is unclear. Triple-negative breast cancers, often expressing epidermal growth factor (EGF) receptor (EGFR), are associated with metastasis and poor survival. The objective of this study is to compare the effect of resveratrol and pterostilbene and to investigate the role of MED28 in EGFR-overexpressing MDA-MB-231 breast cancer cells. Pretreatment of resveratrol, but not pterostlbene, suppressed EGF-mediated migration and expression of MED28 and matrix metalloproteinase (MMP)-9 in MDA-MB-231 cells. Moreover, overexpression of MED28 increased migration, and the addition of EGF further enhanced migration. Our data indicate that resveratrol modulates the effect of MED28 on cellular migration, presumably through the EGFR/phosphatidylinositol 3-kinase (PI3K) signaling pathway, in breast cancer cells.

  11. 22 CFR 226.91 - Marking.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., public communications, and commodities, specified further at paragraph (b)-(e) of this section, partially... funded public communications and program materials for compliance with the approved Marking Plan. (3... marked with the USAID Identity. (1) Any “public communications” as defined in § 226.2, funded by USAID...

  12. 22 CFR 226.91 - Marking.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., public communications, and commodities, specified further at paragraph (b)-(e) of this section, partially... funded public communications and program materials for compliance with the approved Marking Plan. (3... marked with the USAID Identity. (1) Any “public communications” as defined in § 226.2, funded by USAID...

  13. A Descriptive Study Assessing Quality of Life for Adults With a Permanent Ostomy and the Influence of Preoperative Stoma Site Marking.

    PubMed

    Maydick, Diane

    2016-05-01

    Diseases or anomalies of the genitourinary or gastrointestinal tract often require removal of organs and creation of an artificial opening (stoma) to allow for elimination of urine or stool. Preoperative stoma site marking can affect quality of life (QoL). A descriptive study was conducted to assess the relationship between QoL and preoperative stoma site marking in adults with a permanent ostomy. Using convenience sampling methods, 230 eligible participants attending a United Ostomy Association of America conference were invited to complete a survey of demographics regarding age, gender, time since surgeries, and ostomy type and the City of Hope National Medical Center Quality of Life Ostomy Questionnaire. The latter contains 2 sections of 30 and 43 items each that address life impact and quality of life, respectively. The researcher explained the study and provided a study packet to volunteers who were interested in participating. Volunteers were to complete the surveys over a 4-day period while at the conference; the investigator collected all study materials. Inclusion criteria stipulated study participants must be English writing/reading persons at least 18 years of age with a colostomy, ileostomy, or urostomy. All descriptive statistics (means, standard deviation, frequency, and percents) used to describe demographic and surgical history and quantitative data (logistic regression, cross-tabulation, Pearson product moment correlations, and analysis of covariance) used to determine relationships among factors were entered and analyzed using a computer software program. Of the 140 participants who met inclusion criteria and provided data, the majority (85, 60.7%) had their stoma site marked by a wound, ostomy, continence (WOC) nurse. WOC nurse marking was more likely in recent years, and WOC nurse marking was 1.03 times more likely for each year since stoma surgery (M = 13.44, SD = 13.48). Mean QoL was 7.56 (SD = 1.59, range 3.84-10.00) and was positively

  14. 7. ELEVATION SOUTH FACE BLDG. 28B, 28, 28A. Fafnir ...

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

    7. ELEVATION SOUTH FACE BLDG. 28B, 28, 28A. - Fafnir Bearing Plant, Bounded on North side by Myrtle Street, on South side by Orange Street, on East side by Booth Street & on West side by Grove Street, New Britain, Hartford County, CT

  15. Human ovarian cancer stem/progenitor cells are stimulated by doxorubicin but inhibited by Mullerian inhibiting substance

    PubMed Central

    Meirelles, Katia; Benedict, Leo Andrew; Dombkowski, David; Pepin, David; Preffer, Frederic I.; Teixeira, Jose; Tanwar, Pradeep Singh; Young, Robert H.; MacLaughlin, David T.; Donahoe, Patricia K.; Wei, Xiaolong

    2012-01-01

    Women with late-stage ovarian cancer usually develop chemotherapeutic-resistant recurrence. It has been theorized that a rare cancer stem cell, which is responsible for the growth and maintenance of the tumor, is also resistant to conventional chemotherapeutics. We have isolated from multiple ovarian cancer cell lines an ovarian cancer stem cell-enriched population marked by CD44, CD24, and Epcam (3+) and by negative selection for Ecadherin (Ecad−) that comprises less than 1% of cancer cells and has increased colony formation and shorter tumor-free intervals in vivo after limiting dilution. Surprisingly, these cells are not only resistant to chemotherapeutics such as doxorubicin, but also are stimulated by it, as evidenced by the significantly increased number of colonies in treated 3+Ecad− cells. Similarly, proliferation of the 3+Ecad− cells in monolayer increased with treatment, by either doxorubicin or cisplatin, compared with the unseparated or cancer stem cell-depleted 3−Ecad+ cells. However, these cells are sensitive to Mullerian inhibiting substance (MIS), which decreased colony formation. MIS inhibits ovarian cancer cells by inducing G1 arrest of the 3+Ecad− subpopulation through the induction of cyclin-dependent kinase inhibitors. 3+Ecad− cells selectively expressed LIN28, which colocalized by immunofluorescence with the 3+ cancer stem cell markers in the human ovarian carcinoma cell line, OVCAR-5, and is also highly expressed in transgenic murine models of ovarian cancer and in other human ovarian cancer cell lines. These results suggest that chemotherapeutics may be stimulative to cancer stem cells and that selective inhibition of these cells by treating with MIS or targeting LIN28 should be considered in the development of therapeutics. PMID:22308459

  16. Human ovarian cancer stem/progenitor cells are stimulated by doxorubicin but inhibited by Mullerian inhibiting substance.

    PubMed

    Meirelles, Katia; Benedict, Leo Andrew; Dombkowski, David; Pepin, David; Preffer, Frederic I; Teixeira, Jose; Tanwar, Pradeep Singh; Young, Robert H; MacLaughlin, David T; Donahoe, Patricia K; Wei, Xiaolong

    2012-02-14

    Women with late-stage ovarian cancer usually develop chemotherapeutic-resistant recurrence. It has been theorized that a rare cancer stem cell, which is responsible for the growth and maintenance of the tumor, is also resistant to conventional chemotherapeutics. We have isolated from multiple ovarian cancer cell lines an ovarian cancer stem cell-enriched population marked by CD44, CD24, and Epcam (3+) and by negative selection for Ecadherin (Ecad-) that comprises less than 1% of cancer cells and has increased colony formation and shorter tumor-free intervals in vivo after limiting dilution. Surprisingly, these cells are not only resistant to chemotherapeutics such as doxorubicin, but also are stimulated by it, as evidenced by the significantly increased number of colonies in treated 3+Ecad- cells. Similarly, proliferation of the 3+Ecad- cells in monolayer increased with treatment, by either doxorubicin or cisplatin, compared with the unseparated or cancer stem cell-depleted 3-Ecad+ cells. However, these cells are sensitive to Mullerian inhibiting substance (MIS), which decreased colony formation. MIS inhibits ovarian cancer cells by inducing G1 arrest of the 3+Ecad- subpopulation through the induction of cyclin-dependent kinase inhibitors. 3+Ecad- cells selectively expressed LIN28, which colocalized by immunofluorescence with the 3+ cancer stem cell markers in the human ovarian carcinoma cell line, OVCAR-5, and is also highly expressed in transgenic murine models of ovarian cancer and in other human ovarian cancer cell lines. These results suggest that chemotherapeutics may be stimulative to cancer stem cells and that selective inhibition of these cells by treating with MIS or targeting LIN28 should be considered in the development of therapeutics.

  17. The Interrelations of Features of Questions, Mark Schemes and Examinee Responses and Their Impact upon Marker Agreement

    ERIC Educational Resources Information Center

    Black, Beth; Suto, Irenka; Bramley, Tom

    2011-01-01

    In this paper we develop an evidence-based framework for considering many of the factors affecting marker agreement in GCSEs and A levels. A logical analysis of the demands of the marking task suggests a core grouping comprising: (i) question features; (ii) mark scheme features; and (iii) examinee response features. The framework synthesises…

  18. Mark 3 wideband digital recorder in perspective

    NASA Technical Reports Server (NTRS)

    Hinteregger, H. F.

    1980-01-01

    The tape recorder used for the Mark 3 data acquisition and processing system is compared with earlier very long baseline interferometry recorders. Wideband 33-1/3 kbpi digital channel characteristics of instrumentation recorders and of a modern video cassette recorder are illustrated. Factors which influenced selection of the three major commercial components (transport, heads, and tape) are discussed. A brief functional description and the reasons for development of efficient signal electronics and necessary auxiliary control electronics are given. The design and operation of a digital bit synchronizer is illustrated as an example of the high degree of simplicity achieved.

  19. 48 CFR 752.7009 - Marking.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... sites and other project locations be suitably marked with the USAID emblem. Shipping containers are also..., marking is not required for raw materials shipped in bulk (such as coal, grain, etc.), or for semifinished... procurement of commodities to be shipped, and as early as possible for project construction sites and other...

  20. 48 CFR 752.7009 - Marking.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... sites and other project locations be suitably marked with the USAID emblem. Shipping containers are also..., marking is not required for raw materials shipped in bulk (such as coal, grain, etc.), or for semifinished... procurement of commodities to be shipped, and as early as possible for project construction sites and other...

  1. 48 CFR 752.7009 - Marking.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... sites and other project locations be suitably marked with the USAID emblem. Shipping containers are also..., marking is not required for raw materials shipped in bulk (such as coal, grain, etc.), or for semifinished... procurement of commodities to be shipped, and as early as possible for project construction sites and other...

  2. 48 CFR 752.7009 - Marking.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... sites and other project locations be suitably marked with the USAID emblem. Shipping containers are also..., marking is not required for raw materials shipped in bulk (such as coal, grain, etc.), or for semifinished... procurement of commodities to be shipped, and as early as possible for project construction sites and other...

  3. 48 CFR 752.7009 - Marking.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... sites and other project locations be suitably marked with the USAID emblem. Shipping containers are also..., marking is not required for raw materials shipped in bulk (such as coal, grain, etc.), or for semifinished... procurement of commodities to be shipped, and as early as possible for project construction sites and other...

  4. 49 CFR 450.7 - Marking.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... APPROVAL OF CARGO CONTAINERS GENERAL General Provisions § 450.7 Marking. (a) On each container that construction begins on or after January 1, 1984, all maximum gross weight markings on the container must be consistent with the maximum gross weight information on the safety approval plate. (b) On each container that...

  5. 49 CFR 450.7 - Marking.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... APPROVAL OF CARGO CONTAINERS GENERAL General Provisions § 450.7 Marking. (a) On each container that construction begins on or after January 1, 1984, all maximum gross weight markings on the container must be consistent with the maximum gross weight information on the safety approval plate. (b) On each container that...

  6. 49 CFR 450.7 - Marking.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... APPROVAL OF CARGO CONTAINERS GENERAL General Provisions § 450.7 Marking. (a) On each container that construction begins on or after January 1, 1984, all maximum gross weight markings on the container must be consistent with the maximum gross weight information on the safety approval plate. (b) On each container that...

  7. 49 CFR 450.7 - Marking.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... APPROVAL OF CARGO CONTAINERS GENERAL General Provisions § 450.7 Marking. (a) On each container that construction begins on or after January 1, 1984, all maximum gross weight markings on the container must be consistent with the maximum gross weight information on the safety approval plate. (b) On each container that...

  8. 49 CFR 450.7 - Marking.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... APPROVAL OF CARGO CONTAINERS GENERAL General Provisions § 450.7 Marking. (a) On each container that construction begins on or after January 1, 1984, all maximum gross weight markings on the container must be consistent with the maximum gross weight information on the safety approval plate. (b) On each container that...

  9. Identifying and preserving high-water mark data

    USGS Publications Warehouse

    Koenig, Todd A.; Bruce, Jennifer L.; O'Connor, Jim; McGee, Benton D.; Holmes, Robert R.; Hollins, Ryan; Forbes, Brandon T.; Kohn, Michael S.; Schellekens, Mathew; Martin, Zachary W.; Peppler, Marie C.

    2016-03-08

    High-water marks provide valuable data for understanding recent and historical flood events. The proper collection and recording of high-water mark data from perishable and preserved evidence informs flood assessments, research, and water resource management. Given the high cost of flooding in developed areas, experienced hydrographers, using the best available techniques, can contribute high-quality data toward efforts such as public education of flood risk, flood inundation mapping, flood frequency computations, indirect streamflow measurement, and hazard assessments.This manual presents guidance for skilled high-water mark identification, including marks left behind in natural and man-made environments by tranquil and rapid flowing water. This manual also presents pitfalls and challenges associated with various types of flood evidence that help hydrographers identify the best high-water marks and assess the uncertainty associated with a given mark. Proficient high-water mark data collection contributes to better understanding of the flooding process and reduces risk through greater ability to estimate flood probability.The U.S. Geological Survey, operating the Nation’s premier water data collection network, encourages readers of this manual to familiarize themselves with the art and science of high-water mark collection. The U.S. Geological survey maintains a national database at http://water.usgs.gov/floods/FEV/ that includes high-water mark information for many flood events, and local U.S. Geological Survey Water Science Centers can provide information to interested readers about participation in data collection and flood documentation efforts as volunteers or observers.

  10. 49 CFR 178.703 - Marking of IBCs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...). For metal IBCs on which the marking is stamped or embossed, the capital letters “UN” may be applied... the allocation of the mark. The letters ‘USA’ indicate that the IBC is manufactured and marked in the...

  11. Aircraft vortex marking program

    NASA Technical Reports Server (NTRS)

    Pompa, M. F.

    1979-01-01

    A simple, reliable device for identifying atmospheric vortices, principally as generated by in-flight aircraft and with emphasis on the use of nonpolluting aerosols for marking by injection into such vortex (-ices) is presented. The refractive index and droplet size were determined from an analysis of aerosol optical and transport properties as the most significant parameters in effecting vortex optimum light scattering (for visual sighting) and visual persistency of at least 300 sec. The analysis also showed that a steam-ejected tetraethylene glycol aerosol with droplet size near 1 micron and refractive index of approximately 1.45 could be a promising candidate for vortex marking. A marking aerosol was successfully generated with the steam-tetraethylene glycol mixture from breadboard system hardware. A compact 25 lb/f thrust (nominal) H2O2 rocket chamber was the key component of the system which produced the required steam by catalytic decomposition of the supplied H2O2.

  12. 27 CFR 24.259 - Marks.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....259 Marks. (a) Required marks. Each container larger than four liters or each case used to remove wine... contents of each container larger than four liters or each case in wine gallons, or for containers larger than four liters or cases filled according to metric measure, the contents in liters. If wine is...

  13. 28 CFR 28.2 - Determination of offenses.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Determination of offenses. 28.2 Section 28.2 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM Qualifying Federal Offenses for Purposes of DNA Sample Collection § 28.2 Determination of offenses. (a) Felony means a Federal...

  14. 28 CFR 28.2 - Determination of offenses.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Determination of offenses. 28.2 Section 28.2 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM Qualifying Federal Offenses for Purposes of DNA Sample Collection § 28.2 Determination of offenses. (a) Felony means a Federal...

  15. 28 CFR 28.2 - Determination of offenses.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Determination of offenses. 28.2 Section 28.2 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM Qualifying Federal Offenses for Purposes of DNA Sample Collection § 28.2 Determination of offenses. (a) Felony means a Federal...

  16. 28 CFR 28.2 - Determination of offenses.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Determination of offenses. 28.2 Section 28.2 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM Qualifying Federal Offenses for Purposes of DNA Sample Collection § 28.2 Determination of offenses. (a) Felony means a Federal...

  17. 28 CFR 28.2 - Determination of offenses.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 1 2012-07-01 2012-07-01 false Determination of offenses. 28.2 Section 28.2 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM Qualifying Federal Offenses for Purposes of DNA Sample Collection § 28.2 Determination of offenses. (a) Felony means a Federal...

  18. The Text Marking Patterns of College Students.

    ERIC Educational Resources Information Center

    Nist, Sherrie L.; Kirby, Katie

    1989-01-01

    Examines patterns in college students' text markings using texts from three content areas: history, political science, and sociology. Indicates little differential marking between various text-types. Concludes that students seem to have little idea how to mark text efficiently. (MG)

  19. Responses of female rock lizards to multiple scent marks of males: effects of male age, male density and scent over-marking.

    PubMed

    Martín, José; López, Pilar

    2013-03-01

    Scent-marked substrates may inform conspecifics on the characteristics of territorial males. Scent-marks of male Carpetan rock lizards (Iberolacerta cyreni) affect space use of females, which by selecting an area may increase the probability of mating with the male that has scent-marked that area. However, males do not hold exclusive territories, and scent-marks of different individual males are often together. This may provide complex information from multiple sources on the social structure. Here, we examined female preference in response to scent marks of various males and combinations in a laboratory experiment. Females preferred areas scent-marked by territorial old males against those scent-marked by young satellite-sneaker males. This reflected the known preference of females for mating with old males. In a second experiment, females preferred areas scent-marked by two males to areas of similar size marked by a single male. This may increase the probability of obtaining multiple copulations with different males, which may favour sperm competition and cryptic female choice, or may be a way to avoid infertile males. Finally, when we experimentally over-marked the scent-marks of an old male with scent-marks of a young male, females did not avoid, nor prefer, the over-marked area, suggesting that the quality of the old male may override the presence of a satellite male. We suggest that, irrespective of the causes underlying why a female selects a scent-marked area, this strategy may affect her reproductive success, which may have the same evolutionary consequences that "direct" mate choice decisions of other animals. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Normobaric hyperoxia markedly reduces brain damage and sensorimotor deficits following brief focal ischaemia.

    PubMed

    Ejaz, Sohail; Emmrich, Julius V; Sitnikov, Sergey L; Hong, Young T; Sawiak, Stephen J; Fryer, Tim D; Aigbirhio, Franklin I; Williamson, David J; Baron, Jean-Claude

    2016-03-01

    'True' transient ischaemic attacks are characterized not only clinically, but also radiologically by a lack of corresponding changes on magnetic resonance imaging. During a transient ischaemic attack it is assumed that the affected tissue is penumbral but rescued by early spontaneous reperfusion. There is, however, evidence from rodent studies that even brief focal ischaemia not resulting in tissue infarction can cause extensive selective neuronal loss associated with long-lasting sensorimotor impairment but normal magnetic resonance imaging. Selective neuronal loss might therefore contribute to the increasingly recognized cognitive impairment occurring in patients with transient ischaemic attacks. It is therefore relevant to consider treatments to reduce brain damage occurring with transient ischaemic attacks. As penumbral neurons are threatened by markedly constrained oxygen delivery, improving the latter by increasing arterial O2 content would seem logical. Despite only small increases in arterial O2 content, normobaric oxygen therapy experimentally induces significant increases in penumbral O2 pressure and by such may maintain the penumbra alive until reperfusion. Nevertheless, the effects of normobaric oxygen therapy on infarct volume in rodent models have been conflicting, although duration of occlusion appeared an important factor. Likewise, in the single randomized trial published to date, early-administered normobaric oxygen therapy had no significant effect on clinical outcome despite reduced diffusion-weighted imaging lesion growth during therapy. Here we tested the hypothesis that normobaric oxygen therapy prevents both selective neuronal loss and sensorimotor deficits in a rodent model mimicking true transient ischaemic attack. Normobaric oxygen therapy was applied from the onset and until completion of 15 min distal middle cerebral artery occlusion in spontaneously hypertensive rats, a strain representative of the transient ischaemic attack

  1. Diverse and participative learning methodologies: a remedial teaching intervention for low marks dental students in Chile.

    PubMed

    Alcota, Marcela; Muñoz, Andrea; González, Fermín E

    2011-10-01

    The purpose of this educational intervention was to diagnose the learning style of a group of low marks (i.e., grades) dental students in Chile and improve their academic achievement by means of remedial teaching. The intervention group was composed of ten students in endodontics and eleven in pedodontics with low marks. These two groups were mutually exclusive. The Kolb test of learning styles was applied to the low mark students group and to the rest of the class (n=72). Diverse methodologies were applied to the low marks students, such as seminars, case-based learning and problem-based learning, directed study, plenary discussions and debate, integration and questions, and web-based learning in an effort to cover all learning styles. Students' perceptions of the educational intervention were assessed by means of a questionnaire. The learning styles of the low marks group were mainly divergent (52.4 percent) and convergent (19 percent). Accommodators and assimilators were 14.3 percent each. The rest of the class showed a very distinct frequencies distribution: divergent 18 percent, convergent 20 percent, accommodators 28 percent, and assimilators 34 percent. After the educational intervention, the mean of the scores obtained by the intervention group in formal evaluations was higher than the average scores obtained before the intervention for both courses. Students' perceptions of the activities were that they were effective for their learning process (76 percent) and that the teaching methodologies were useful mainly to clarify concepts and contents from both courses (82 percent). We can conclude that the use of diverse and participative teaching methodologies in a remedial teaching intervention, to cover all the different learning styles of the students, contributes to improve their marks in formal evaluations.

  2. 14 CFR 45.11 - Marking of products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Identification of Aircraft and Related Products § 45.11 Marking of products. (a) Aircraft. A manufacturer of aircraft covered under § 21.182 of this chapter must mark each...

  3. STS-28 Columbia, OV-102, MS Brown uses ARRIFLEX camera on aft flight deck

    NASA Image and Video Library

    1989-08-13

    STS028-17-033 (August 1989) --- Astronaut Mark N. Brown, STS-28 mission specialist, pauses from a session of motion-picture photography conducted through one of the aft windows on the flight deck of the Earth-orbiting Space Shuttle Columbia. He is using an Arriflex camera. The horizon of the blue and white appearing Earth and its airglow are visible in the background.

  4. Factors associated with small head circumference at birth among infants born before the 28th week

    PubMed Central

    McElrath, Thomas F.; Allred, Elizabeth N.; Kuban, Karl; Hecht, Jonathan L.; Onderdonk, Andrew; O’Shea, T. Michael; Paneth, Nigel; Leviton, Alan

    2010-01-01

    OBJECTIVE We sought to identify risk factors for congenital microcephaly in extremely low gestational age newborns. STUDY DESIGN Demographic, clinical, and placental characteristics of 1445 infants born before the 28th week were gathered and evaluated for their relationship with congenital microcephaly. RESULTS Almost 10% of newborns (n = 138), rather than the expected 2.2%, had microcephaly defined as a head circumference >2 SD below the median. In multivariable models, microcephaly was associated with nonwhite race, severe intrauterine growth restriction, delivery for preeclampsia, placental infarction, and being female. The risk factors for a head circumference between <1 and >2 SD below the median were similar to those of microcephaly. CONCLUSION Characteristics associated with fetal growth restriction and preeclampsia are among the strongest correlates of microcephaly among children born at extremely low gestational ages. The elevated risk of a small head among nonwhites and females might reflect the lack of appropriate head circumference standards. PMID:20541727

  5. Mark 4A project training evaluation

    NASA Technical Reports Server (NTRS)

    Stephenson, S. N.

    1985-01-01

    A participant evaluation of a Deep Space Network (DSN) is described. The Mark IVA project is an implementation to upgrade the tracking and data acquisition systems of the dSN. Approximately six hundred DSN operations and engineering maintenance personnel were surveyed. The survey obtained a convenience sample including trained people within the population in order to learn what training had taken place and to what effect. The survey questionnaire used modifications of standard rating scales to evaluate over one hundred items in four training dimensions. The scope of the evaluation included Mark IVA vendor training, a systems familiarization training seminar, engineering training classes, a on-the-job training. Measures of central tendency were made from participant rating responses. Chi square tests of statistical significance were performed on the data. The evaluation results indicated that the effects of different Mark INA training methods could be measured according to certain ratings of technical training effectiveness, and that the Mark IVA technical training has exhibited positive effects on the abilities of DSN personnel to operate and maintain new Mark IVA equipment systems.

  6. 30 CFR 7.409 - Approval marking.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... approval number in addition to the number and size (gauge) of conductors and cable type. For cables containing electric conductors, the marking shall also include the voltage rating. For splices, the marking...

  7. 30 CFR 7.409 - Approval marking.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... approval number in addition to the number and size (gauge) of conductors and cable type. For cables containing electric conductors, the marking shall also include the voltage rating. For splices, the marking...

  8. 30 CFR 7.29 - Approval marking.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Brattice Cloth and Ventilation Tubing § 7.29 Approval marking. (a) Approved brattice cloth shall be legibly and permanently marked with the assigned MSHA...

  9. 30 CFR 7.29 - Approval marking.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Brattice Cloth and Ventilation Tubing § 7.29 Approval marking. (a) Approved brattice cloth shall be legibly and permanently marked with the assigned MSHA...

  10. 30 CFR 7.29 - Approval marking.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Brattice Cloth and Ventilation Tubing § 7.29 Approval marking. (a) Approved brattice cloth shall be legibly and permanently marked with the assigned MSHA...

  11. 30 CFR 7.29 - Approval marking.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Brattice Cloth and Ventilation Tubing § 7.29 Approval marking. (a) Approved brattice cloth shall be legibly and permanently marked with the assigned MSHA...

  12. 30 CFR 7.29 - Approval marking.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Brattice Cloth and Ventilation Tubing § 7.29 Approval marking. (a) Approved brattice cloth shall be legibly and permanently marked with the assigned MSHA...

  13. 7 CFR 160.32 - Marking containers.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... STANDARDS FOR NAVAL STORES Analysis, Inspection, and Grading on Request § 160.32 Marking containers. The interested person shall provide any labor necessary for marking the containers, after the contents have been...

  14. Artillery ammunition marking tests

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Weil, B.S.; Lewis, J.C.

    1995-04-01

    This report describes the testing results of two approaches being considered for marking ink artillery ammunition with machine-readable data symbols. The first approach used ink-jet printing directly onto projectiles, and the second approach employed thermal-transfer printing onto self-adhesive labels that are subsequently applied automatically to projectiles. The objectives of this evaluation for each marking technology were to (1) determine typical system performance characteristics using the best commercially available equipment and (2) identify any special requirements necessary for handling ammunition when these technologies are employed.

  15. 9 CFR 352.7 - Marking inspected products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Section 352.7 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE..., the inspection mark applied to inspected and passed exotic animal carcasses, meat or meat food... abbreviations shall have the same force and effect as the inspection mark. The inspection mark or approved...

  16. 9 CFR 352.7 - Marking inspected products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Section 352.7 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE..., the inspection mark applied to inspected and passed exotic animal carcasses, meat or meat food... abbreviations shall have the same force and effect as the inspection mark. The inspection mark or approved...

  17. 9 CFR 352.7 - Marking inspected products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Section 352.7 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE..., the inspection mark applied to inspected and passed exotic animal carcasses, meat or meat food... abbreviations shall have the same force and effect as the inspection mark. The inspection mark or approved...

  18. Significance of lobular intraepithelial neoplasia at margins of breast conservation specimens: a report of 38 cases and literature review

    PubMed Central

    2010-01-01

    Background Presence of lobular intraepithelial neoplasia (LIN) is not routinely reported as part of margin assessment in breast conservation therapy (BCT) as in ductal carcinoma in situ (DCIS). With new emerging evidence of LIN as possible precursor lesion, the hypothesis is that LIN at the margin may increase the risk of local recurrence with BCT. The aim is to determine whether there is an increase incidence of recurrence when LIN is found at surgical margins on BCT. Methods We retrospectively reviewed a total of 1,334 BCT at a single institution in a 10 year period. Inclusion criteria are positive margin with LIN from primary BCT containing invasive and/or in situ carcinoma with comparison to the negative control group who had similar diseases with negative margin for LIN. Results We identified 38 cases (2.8%) with LIN either lobular carcinoma in situ/atypical lobular hyperplasia (LCIS/ALH) at a margin on initial BCT with 36% recurrence rate. Of the 38 cases: 5 (13%) were lost to follow-up, 12 (32%) had no further procedures performed and 21 (55%) had re-excision. Out of 21 patients who had re-excisions, 12 (57%) had residual invasive carcinoma or DCIS, three (14%) had pleomorphic LCIS and 4 (19%) showed residual classic type LCIS. 71% had significant residual disease (local recurrence) and 29% had no residual disease. A negative control group consisted of 38 cases. We found two patients with bone or brain metastasis and one local recurrence. Clinical follow up periods range from 1 to 109 months. Conclusions LIN found at a margin on BCT showed a significant recurrent ipsilateral disease. Our study supports the view that LIN seen at the margin may play a role in recurrence. PMID:20727142

  19. 14 CFR 45.31 - Marking of export aircraft.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Marking of export aircraft. 45.31 Section 45.31 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Nationality and Registration Marks § 45.31 Marking of export aircraft. A...

  20. 14 CFR 45.31 - Marking of export aircraft.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Marking of export aircraft. 45.31 Section 45.31 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Nationality and Registration Marks § 45.31 Marking of export aircraft. A...

  1. 14 CFR 45.31 - Marking of export aircraft.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Marking of export aircraft. 45.31 Section 45.31 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Nationality and Registration Marks § 45.31 Marking of export aircraft. A...

  2. 14 CFR 45.31 - Marking of export aircraft.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Marking of export aircraft. 45.31 Section 45.31 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Nationality and Registration Marks § 45.31 Marking of export aircraft. A...

  3. 14 CFR 45.31 - Marking of export aircraft.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Marking of export aircraft. 45.31 Section 45.31 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Nationality and Registration Marks § 45.31 Marking of export aircraft. A...

  4. User’s guide for MapMark4GUI—A graphical user interface for the MapMark4 R package

    USGS Publications Warehouse

    Shapiro, Jason

    2018-05-29

    MapMark4GUI is an R graphical user interface (GUI) developed by the U.S. Geological Survey to support user implementation of the MapMark4 R statistical software package. MapMark4 was developed by the U.S. Geological Survey to implement probability calculations for simulating undiscovered mineral resources in quantitative mineral resource assessments. The GUI provides an easy-to-use tool to input data, run simulations, and format output results for the MapMark4 package. The GUI is written and accessed in the R statistical programming language. This user’s guide includes instructions on installing and running MapMark4GUI and descriptions of the statistical output processes, output files, and test data files.

  5. 76 FR 6541 - Airworthiness Directives; Fokker Services B.V. Model F.28 Mark 0100, 1000, 2000, 3000, and 4000...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-07

    ..., an ignition source can develop in the wing tank vapour space during fuel transfer from bag tank CWT..., an ignition source can develop in the wing tank vapour space during fuel transfer from bag tank CWT..., all serial numbers, equipped with a center wing tank (CWT); and Model F.28 [[Page 6543

  6. 6. ELEVATION WEST AND SOUTH FACES BLDG. 28B, 28, 28A. ...

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

    6. ELEVATION WEST AND SOUTH FACES BLDG. 28B, 28, 28A. - Fafnir Bearing Plant, Bounded on North side by Myrtle Street, on South side by Orange Street, on East side by Booth Street & on West side by Grove Street, New Britain, Hartford County, CT

  7. 19 CFR 145.14 - Marking requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... officer shall place in the envelope containing the mail entry a copy of Customs Form 3475, containing...) Failure to mark. If the addressee fails to comply with the marking requirements, the mail article will be...

  8. 14 CFR 133.49 - Markings and placards.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Markings and placards. 133.49 Section 133...-LOAD OPERATIONS Airworthiness Requirements § 133.49 Markings and placards. The following markings and... combination for which the rotorcraft has been approved and the occupancy limitation prescribed in § 133.45(a...

  9. High-water marks from flooding in Lake Champlain from April through June 2011 and Tropical Storm Irene in August 2011 in Vermont

    USGS Publications Warehouse

    Medalie, Laura; Olson, S.A.

    2013-01-01

    The U.S. Geological Survey, in cooperation with the Federal Emergency Management Agency, identified high-water marks after two floods in Vermont during 2011. Following a snowy winter, new monthly precipitation records were set in Burlington, Vermont, in April and May 2011, causing extensive flooding from April through June. The spring 2011 flooding resulted in a new record for stage (103.27 feet, referenced to the National Geodetic Vertical Datum of 1929) at the Lake Champlain at Burlington, Vt., gaging station (04294500). During August 28 and 29, 2011, tropical storm Irene delivered rainfall totals of 3 to more than 7 inches throughout Vermont, which resulted in extensive flooding and new streamflow records at nine streamgaging stations. Four presidential declarations of disaster were made following the 2011 flood events in Vermont. Thirty-nine high-water marks were identified and flagged to mark the highest levels of Lake Champlain from the May 2011 flooding, and 1,138 high-water marks were identified and flagged along Vermont rivers after flooding from tropical storm Irene in August 2011. Seventy-four percent of the high-water marks that were flagged were later found and surveyed to the North American Vertical Datum of 1988.

  10. 46 CFR 67.121 - Official number marking requirement.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Official number marking requirement. 67.121 Section 67... VESSELS DOCUMENTATION OF VESSELS Marking Requirements for Vessel Documentation § 67.121 Official number marking requirement. The official number of the vessel, preceded by the abbreviation “NO.” must be marked...

  11. 46 CFR 67.121 - Official number marking requirement.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Official number marking requirement. 67.121 Section 67... VESSELS DOCUMENTATION OF VESSELS Marking Requirements for Vessel Documentation § 67.121 Official number marking requirement. The official number of the vessel, preceded by the abbreviation “NO.” must be marked...

  12. Magnetic detection of underground pipe using timed-release marking droplets

    DOEpatents

    Powell, James R.; Reich, Morris

    1996-12-17

    A system 10 and method of detecting an underground pipe 12 injects magnetic marking droplets 16 into the underground pipe 12 which coat the inside of the pipe 12 and may be detected from aboveground by a magnetometer 28. The droplets 16 include a non-adhesive cover 32 which allows free flow thereof through the pipe 12, with the cover 32 being ablatable for the timed-release of a central core 30 containing magnetic particles 30a which adhere to the inside of the pipe 12 and are detectable from aboveground. The rate of ablation of the droplet covers 32 is selectively variable to control a free flowing incubation zone 12a for the droplets 16 and a subsequent deposition zone 12b in which the magnetic particles 30a are released for coating the pipe 12.

  13. Preoperative breast marking in reduction mammaplasty.

    PubMed

    Gasperoni, C; Salgarello, M

    1987-10-01

    A simple method of preoperative marking for reduction mammaplasty is described. This method may be used in macromastias when the technique chosen implies a postoperative scar with the shape of an inverted T. The marking sequence follows standard steps, but the drawing is always different because it is a consequence of the shape of the breast. This marking method reduces the chance of making mistakes due to excessive personal evaluations or to the use of standard drawing patterns that may be not suitable for all breast shapes.

  14. 10 CFR 603.850 - Marking of data.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Marking of data. 603.850 Section 603.850 Energy DEPARTMENT... Other Administrative Matters Intellectual Property § 603.850 Marking of data. To protect the recipient's interests in data, the TIA should require the recipient to mark any particular data that it wishes to...

  15. 10 CFR 603.850 - Marking of data.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Marking of data. 603.850 Section 603.850 Energy DEPARTMENT... Other Administrative Matters Intellectual Property § 603.850 Marking of data. To protect the recipient's interests in data, the TIA should require the recipient to mark any particular data that it wishes to...

  16. In vitro and in vivo antimicrobial activities of seeds of Caesalpinia bonduc (Lin.) Roxb.

    PubMed

    Arif, Tasleem; Mandal, T K; Kumar, Naresh; Bhosale, J D; Hole, Archana; Sharma, G L; Padhi, M M; Lavekar, G S; Dabur, Rajesh

    2009-05-04

    Caesalpinia bonduc (Lin.) Roxb. is a known drug in Ayurveda to treat various diseases specifically tumors, cysts and cystic fibrosis (CF). The aim of this study was to assess in vitro as well as in vivo antimicrobial activity of Caesalpinia bonduc seeds. The in vitro antimicrobial activities of seed coat and seed kernel extracts were investigated by microbroth dilution assay. In vivo activities of hydro-alcoholic extracts were investigated in rat models of chronic Pseudomonas aeruginosa pneumonia mimicking that in patients with cystic fibrosis. Various extracts of plant seeds exhibited in vitro antimicrobial activities in a range of 22-350 microg/ml. The extracts also showed activity against methicillin resistant (MR) Staphylococcus aureus and ampicillin resistant (AR) Pseudomonas aeruginosa as in the sensitive strains. In rat model of chronic Pseudomonas aeruginosa pneumonia, hydro-alcoholic extracts of Caesalpinia bonduc seed kernel (CBSK) and Caesalpinia bonduc seed coat (CBSC) were injected subcutaneously in the test groups of animals. The control groups were treated with cortisone and saline. Two weeks after challenge with Pseudomonas aeruginosa, the CBSK treated animals showed a significant bacterial clearance from the lungs (P<0.04) and less severe incidence of lung abscess (P<0.05). Results showed that Caesalpinia bonduc may have the potential to be promising natural medicine, with other forms of treatments, for CF patients with chronic Pseudomonas aeruginosa lung infections.

  17. Topics in Library Technology: Labeling Techniques *

    PubMed Central

    Truelson, Stanley D.

    1966-01-01

    Labels which do not fit on the spines of books should be placed on the upper rather than lower left corner of the front cover, because the upper corner becomes visible first when a volume is tilted from the shelf. None of the past methods of marking call numbers on the spines or covers of books—direct hand lettering by pen, brush, or stylus; affixing cold release characters; embossing by hot type; or gluing labels which are handlettered, typed, or printed—nor even present automatic data processing systems have offered all the advantages of the relatively new Se-Lin labeling system: legibility, reasonable speed of application, automatic protective covering, permanent bonding, and no need for a skilled letterer. Labels seem unaesthetic to some librarians, but their advantages outweigh this consideration. When only one or a few copies of the same call number are required, Se-Lin is the best system now available for libraries marking over 1,000 books a year. PMID:5901359

  18. Pavement marking extensions for deceleration lanes.

    DOT National Transportation Integrated Search

    1974-01-01

    Pavement markings have definite and important functions in a proper scheme of traffic control. One such marking, the pavement edge line, has received much favorable public reaction. One of the limitations of the edge line as conventionally applied is...

  19. STS-28 crewmembers don LESs prior to Columbia, OV-102, launch

    NASA Image and Video Library

    1989-08-08

    STS028-S-005 (8 Aug 1989) --- Three of five STS-28 astronaut crewmembers are pictured during their suiting up process in preparation for spending several days aboard space shuttle Columbia in earth orbit. Astronaut Brewster H. Shaw Jr., mission commander, is in the foreground. Others pictured in the orange suits used for ascent and entry are Richard N. Richards (center), pilot; and James C. Adamson, one of three mission specialists. Out of the frame are David C. Leestma and Mark N. Brown, mission specialists.

  20. Soyuz Ms_06 Post LAnding VF 2-28-18_623721_hires

    NASA Image and Video Library

    2018-03-01

    Expedition 54 Commander Alexander Misurkin of Roscosmos and Flight Engineers Mark Vande Hei and Joe Acaba of NASA were greeted in a traditional ceremony at the airport in Karaganda, Kazakhstan Feb. 28, a few hours after landing in their Soyuz MS-06 spacecraft in Kazakhstan near the town of Dzhezkazgan. After the ceremony, Misurkin returned to his training base in Star City, Russia, while Vande Hei and Acaba flew back to their homes in Houston on a NASA jet. The trio spent almost six months in space.

  1. [Verification of the eclossion mark on the sagittal otolith of the larvae of Sardinella aurita (Pisces: Clupeidae)].

    PubMed

    Balza, M A; Marín, B

    2000-12-01

    The study of otolith in larvae is important to determine fish age and growth, essential parameters in the study and management of fisheries resources. In this study, the formation of the hatching mark in Sardinella aurita was verified on ichthyoplankton samples collected off southern Cubagua island, Venezuela, from May 1998 to January 1999. The embryos were kept alive using a culture system until they hatched and daily a group of 10 to 30 larvae were fixed in 95% ethanol. An image analysis system was used to measure morphometric characteristics of larvae and sagittal otoliths. Following are mean values in newly hatched larvae: otolith hatching mark distance from nucleus 4.78 m (I.C. 0.36 m, p 0.05 n = 30), increase width 1.46 m (I.C. 0.17 microm, p 0.05, n = 30) and diameter 14.28 m (IC 1.11 m, p 0.05, n = 30). The mean standard length of larvae at age 0 was 3.31 mm (I.C. 0.08 mm, p 0.05, n = 200). The identification of the hatching mark allows the exact calculation of the number of rings in larvae from the natural environment.

  2. Markedly severe dystonia in Japanese encephalitis.

    PubMed

    Kalita, J; Misra, U K

    2000-11-01

    Encephalitis has been reported to be a rare cause of severe dystonia. We describe five patients with markedly severe dystonia from Japanese encephalitis. These patients with markedly severe dystonia were seen during the past 8 years as a subgroup of 50 patients with Japanese encephalitis. The diagnosis of markedly severe dystonia was based on increasingly frequent episodes of generalized dystonia with bulbar, respiratory, or metabolic derangement or leading to exhaustion or pain. The diagnosis of JE was based on clinicoradiologic features and a fourfold increase of hemagglutination-inhibiting antibody titers in paired serum. The outcome of the patients was defined as a good, partial, or poor recovery on the basis of 1-year clinical status. All the patients were males, and their ages ranged from 6 to 19 years. Movement disorders appeared 1 to 3 weeks after the illness as the level of consciousness started improving. During the next 1 to 4 weeks, patients began to experience markedly severe dystonia. It was associated with marked axial dystonia resulting in opisthotonus and retrocollis in five patients, jaw-opening dystonia in two patients, teeth clenching in one patient, and oculogyric crisis and neck deviation in another patient. The attacks of markedly severe dystonia lasted for 2 to 30 minutes and occurred as many as 20 to 30 times daily. Other developments included fixed limb dystonia in one patient, severe spasticity and rigidity in five patients, and focal muscle wasting in one patient. These patients had only a modest improvement after treatment. Markedly severe dystonia abated by 2 to 6 months in all the patients who were followed up. Cranial magnetic resonance imaging showed bilateral thalamic involvement in all patients, brainstem involvement in three patients, and basal ganglia involvement in two patients. At the 3-month follow-up, all patients had a poor outcome. At 1 year, one patient had a complete recovery; one had a partial recovery; and two were

  3. 19 CFR 134.43 - Methods of marking specific articles.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Methods of marking specific articles. 134.43...; DEPARTMENT OF THE TREASURY COUNTRY OF ORIGIN MARKING Method and Location of Marking Imported Articles § 134.43 Methods of marking specific articles. (a) Marking previously required by certain provisions of the...

  4. 19 CFR 134.43 - Methods of marking specific articles.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Methods of marking specific articles. 134.43...; DEPARTMENT OF THE TREASURY COUNTRY OF ORIGIN MARKING Method and Location of Marking Imported Articles § 134.43 Methods of marking specific articles. (a) Marking previously required by certain provisions of the...

  5. 19 CFR 134.43 - Methods of marking specific articles.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Methods of marking specific articles. 134.43...; DEPARTMENT OF THE TREASURY COUNTRY OF ORIGIN MARKING Method and Location of Marking Imported Articles § 134.43 Methods of marking specific articles. (a) Marking previously required by certain provisions of the...

  6. 49 CFR 1520.13 - Marking SSI.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY SECURITY RULES FOR ALL MODES OF TRANSPORTATION PROTECTION OF SENSITIVE SECURITY INFORMATION § 1520.13 Marking SSI. (a) Marking of paper records. In the case of paper records...

  7. 46 CFR 160.174-23 - Marking.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... the Coast Guard approval number. (b) Each storage case must be marked with the words “Thermal... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Thermal Protective Aids § 160.174-23 Marking. (a) Each thermal...

  8. Lessons learned : pavement marking warranty contract.

    DOT National Transportation Integrated Search

    2013-12-01

    In 2012, UDOT implemented a performance-based warranty on a portion of an I-15 pavement marking : project. The awarded contract requested a contractor warranty on the implemented markings for a total : duration of six years. This is the first time th...

  9. Virtual Tool Mark Generation for Efficient Striation Analysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ekstrand, Laura; Zhang, Song; Grieve, Taylor

    2014-02-16

    This study introduces a tool mark analysis approach based upon 3D scans of screwdriver tip and marked plate surfaces at the micrometer scale from an optical microscope. An open-source 3D graphics software package is utilized to simulate the marking process as the projection of the tip's geometry in the direction of tool travel. The edge of this projection becomes a virtual tool mark that is compared to cross-sections of the marked plate geometry using the statistical likelihood algorithm introduced by Chumbley et al. In a study with both sides of six screwdriver tips and 34 corresponding marks, the method distinguishedmore » known matches from known nonmatches with zero false-positive matches and two false-negative matches. For matches, it could predict the correct marking angle within ±5–10°. Individual comparisons could be made in seconds on a desktop computer, suggesting that the method could save time for examiners.« less

  10. 33 CFR 62.27 - Safe water marks.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Safe water marks. 62.27 Section 62.27 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION UNITED STATES AIDS TO NAVIGATION SYSTEM The U.S. Aids to Navigation System § 62.27 Safe water marks. Safe water marks indicate that there is...

  11. 31 CFR 100.18 - Counterfeit notes to be marked; “redemption” of notes wrongfully so marked.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 false Counterfeit notes to be marked; âredemptionâ of notes wrongfully so marked. 100.18 Section 100.18 Money and Finance: Treasury Regulations Relating to Money and Finance MONETARY OFFICES, DEPARTMENT OF THE TREASURY EXCHANGE OF PAPER CURRENCY AND...

  12. 31 CFR 100.18 - Counterfeit notes to be marked; “redemption” of notes wrongfully so marked.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 1 2014-07-01 2014-07-01 false Counterfeit notes to be marked; âredemptionâ of notes wrongfully so marked. 100.18 Section 100.18 Money and Finance: Treasury Regulations Relating to Money and Finance MONETARY OFFICES, DEPARTMENT OF THE TREASURY EXCHANGE OF PAPER CURRENCY AND...

  13. Minnesota Local Agency Pavement Marking : Mining Existing Data

    DOT National Transportation Integrated Search

    2017-11-01

    Pavement marking is important for safety. Maximizing pavement marking performance in terms of increased retroreflectivity, within limited budget constraints, allows agencies to make better decisions toward providing more effective pavement marking pe...

  14. Speed Isn't Everything: A Study of Examination Marking

    ERIC Educational Resources Information Center

    Nadas, Rita; Suto, Irenka

    2010-01-01

    The question of whether marking speed is related to marking accuracy is important for training examiners and planning realistic marking schedules. We explored marking speed in the context of a past examination for an international biology qualification for 14- to 16-year-olds. Forty-two markers with differing backgrounds experimentally marked 23…

  15. [Immunological balance of CD8+CD28+/CD8+CD28- T lymphocytes can predict gastrointestinal hemorrhage in patients with inflammatory bowel disease].

    PubMed

    Dai, Shi-Xue; Gu, Hong-Xiang; Wu, Gang; Zhong, Tao; Jian, Hong-Jian; Zhan, Yong-le; Zhang, Min-Hai; Gao, Yong; Xu, Jun; Chen, Dong-Sheng; Liao, Guang-Jie; Feng, Yan-Ling; Liu, Hong-Bo; Zou, Ying; Chi, Hong-Gang

    2016-12-20

    To evaluate the sensitivity and specificity of CD8 + CD28 + /CD8 + CD28 - T lymphocyte balance in predicting the gastrointestinal hemorrhage (GH) in patients with inflammatory bowel disease (IBD). Forty-nine IBD patients, including 30 with ulcerous colitis (UC) and 19 with Crohn's disease (CD), were enrolled to test peripheral blood CD8 + CD28 + and CD8 + CD28 - T cells using flow cytometry. All the patients were followed up for one year. The receiver-operating characteristic (ROC) curves were used to test the efficiency of CD8 + CD28 + /CD8 + CD28 - T lymphocyte balance to predict GH. The differences in lasting time of remission (LTR) under different factors were compared using Kaplan-Meier survival analysis, and the correlation between CD8 + T lymphocytes and the factors were analyzed. The utilization rates of immunosuppressant, steroids, and biological agent (BA) were significantly higher in CD patients than in UC patients (P=0.003, 0.043 and 0.002, respectively). The frequencies of CD8 + CD28 + T cells were obviously higher in UC patients than those in CD patients (t=3.022, P=0.004). CD8 + CD28 + T cells, CD8 + CD28 - T cells, and especially CD8 + CD28 + /CD8 + CD28 - ratio (area under curve of 0.977, P=0.000; cut-off value of 1.14 [13.95%/12.24%] with a sensitivity of 93.3% and a specificity of 91.2%) showed good efficiencies in predicting GH (P<0.01). The mean and median of LTR of IBD patients who did not receive BA or surgical treatment were significantly longer (Χ 2 =9.730, P=0.002; Χ 2 =15.981, P=0.000). CD8 + CD28 + /CD8 + CD28 - ratio was significantly related to both BA (P=0.009) and surgery (P=0.038). Both decreased CD8 + CD28 + T cells and elevated CD8 + CD28 - T cells are closely correlated with GH, and their ratio can predict the occurrence of GH with a high sensitivity and specificity and is correlated with BA and surgery at the cut-off value of 1.14.

  16. 46 CFR 160.016-4 - Marking.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Lamps, Safety, Flame, for Merchant Vessels § 160.016-4 Marking. (a) Flame safety lamps shall be permanently and legibly marked with the name and address of the manufacturer and the type or model designation for the lamp. (b) [Reserved] ...

  17. 46 CFR 160.016-4 - Marking.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Lamps, Safety, Flame, for Merchant Vessels § 160.016-4 Marking. (a) Flame safety lamps shall be permanently and legibly marked with the name and address of the manufacturer and the type or model designation for the lamp. (b) [Reserved] ...

  18. 46 CFR 160.016-4 - Marking.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Lamps, Safety, Flame, for Merchant Vessels § 160.016-4 Marking. (a) Flame safety lamps shall be permanently and legibly marked with the name and address of the manufacturer and the type or model designation for the lamp. (b) [Reserved] ...

  19. 46 CFR 160.016-4 - Marking.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Lamps, Safety, Flame, for Merchant Vessels § 160.016-4 Marking. (a) Flame safety lamps shall be permanently and legibly marked with the name and address of the manufacturer and the type or model designation for the lamp. (b) [Reserved] ...

  20. 46 CFR 160.016-4 - Marking.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Lamps, Safety, Flame, for Merchant Vessels § 160.016-4 Marking. (a) Flame safety lamps shall be permanently and legibly marked with the name and address of the manufacturer and the type or model designation for the lamp. (b) [Reserved] ...

  1. Mechanism of insulin-stimulated clearance of plasma nonesterified fatty acids in humans.

    PubMed

    Carpentier, André C; Frisch, Frédérique; Brassard, Pascal; Lavoie, François; Bourbonnais, Annie; Cyr, Denis; Giguère, Robert; Baillargeon, Jean-Patrice

    2007-03-01

    Insulin increases plasma nonesterified fatty acid (NEFA) clearance in humans, but whether this is independent of change in plasma NEFA appearance is currently unknown. Nine nondiabetic men (age: 28+/-3 yr, body mass index: 27.2+/-1.7 kg/m2) underwent euglycemic clamps to maintain low (LINS) vs. high (HINS) physiological insulin levels for 6 h. An intravenous infusion of heparin+Intralipid (HI) was performed during 4 of the 6 h of the clamps (in the last 4 h at LINS and in the first 4 h at HINS), whereas saline infusion (SAL) was administered in the remaining 2 h to modulate plasma NEFA levels independently of plasma insulin levels. Four experimental conditions were obtained in each individual: LINS with saline (LINS/SAL) and with HI infusion (LINS/HI) and HINS with saline (HINS/SAL) and with HI infusion (HINS/HI). Plasma palmitate appearance during HINS/SAL was lower than during the three other experimental conditions (P<0.05). In contrast, plasma linoleate appearance, as expected, was increased by HI independently of insulin level (P<0.02). Plasma palmitate clearance during HINS/SAL was higher than LINS/SAL and LINS/HI (P<0.008), and this increase was blunted during HINS/HI. We observed a linear decrease in plasma palmitate clearance with increasing plasma NEFA appearance independent of insulin levels. Plasma NEFA levels increased exponentially with increase in plasma NEFA appearance. We conclude that insulin stimulates plasma NEFA clearance by reducing the endogenous appearance rate of NEFA. The relationship between plasma NEFA level and appearance rate is nonlinear.

  2. An Analysis of Peer-Reviewed Scores and Impact Factors with Different Citation Time Windows: A Case Study of 28 Ophthalmologic Journals.

    PubMed

    Liu, Xue-Li; Gai, Shuang-Shuang; Zhang, Shi-Le; Wang, Pu

    2015-01-01

    An important attribute of the traditional impact factor was the controversial 2-year citation window. So far, several scholars have proposed using different citation time windows for evaluating journals. However, there is no confirmation whether a longer citation time window would be better. How did the journal evaluation effects of 3IF, 4IF, and 6IF comparing with 2IF and 5IF? In order to understand these questions, we made a comparative study of impact factors with different citation time windows with the peer-reviewed scores of ophthalmologic journals indexed by Science Citation Index Expanded (SCIE) database. The peer-reviewed scores of 28 ophthalmologic journals were obtained through a self-designed survey questionnaire. Impact factors with different citation time windows (including 2IF, 3IF, 4IF, 5IF, and 6IF) of 28 ophthalmologic journals were computed and compared in accordance with each impact factor's definition and formula, using the citation analysis function of the Web of Science (WoS) database. An analysis of the correlation between impact factors with different citation time windows and peer-reviewed scores was carried out. Although impact factor values with different citation time windows were different, there was a high level of correlation between them when it came to evaluating journals. In the current study, for ophthalmologic journals' impact factors with different time windows in 2013, 3IF and 4IF seemed the ideal ranges for comparison, when assessed in relation to peer-reviewed scores. In addition, the 3-year and 4-year windows were quite consistent with the cited peak age of documents published by ophthalmologic journals. Our study is based on ophthalmology journals and we only analyze the impact factors with different citation time window in 2013, so it has yet to be ascertained whether other disciplines (especially those with a later cited peak) or other years would follow the same or similar patterns. We designed the survey questionnaire

  3. 28 CFR 28.12 - Collection of DNA samples.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Collection of DNA samples. 28.12 Section 28.12 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM DNA Sample Collection, Analysis, and Indexing § 28.12 Collection of DNA samples. (a) The Bureau of Prisons shall collect a DNA...

  4. 28 CFR 28.12 - Collection of DNA samples.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Collection of DNA samples. 28.12 Section 28.12 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM DNA Sample Collection, Analysis, and Indexing § 28.12 Collection of DNA samples. (a) The Bureau of Prisons shall collect a DNA...

  5. 28 CFR 28.12 - Collection of DNA samples.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 1 2012-07-01 2012-07-01 false Collection of DNA samples. 28.12 Section 28.12 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM DNA Sample Collection, Analysis, and Indexing § 28.12 Collection of DNA samples. (a) The Bureau of Prisons shall collect a DNA...

  6. 28 CFR 28.12 - Collection of DNA samples.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Collection of DNA samples. 28.12 Section 28.12 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM DNA Sample Collection, Analysis, and Indexing § 28.12 Collection of DNA samples. (a) The Bureau of Prisons shall collect a DNA...

  7. 28 CFR 28.12 - Collection of DNA samples.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Collection of DNA samples. 28.12 Section 28.12 Judicial Administration DEPARTMENT OF JUSTICE DNA IDENTIFICATION SYSTEM DNA Sample Collection, Analysis, and Indexing § 28.12 Collection of DNA samples. (a) The Bureau of Prisons shall collect a DNA...

  8. [Werkgartner's muzzle imprint mark--a literature study].

    PubMed

    Geserick, Gunther; Vendura, Klaus; Wirth, Ingo

    2009-01-01

    Since Werkgartner described and correctly interpreted the muzzle imprint mark around the gunshot entrance wound in 1922, this finding has been generally accepted as a sign of a contact shot. In further studies, it could finally be clarified that the muzzle imprint mark is caused by the expansive power of the powder gases with pressure on and abrasion of the skin at the muzzle (weapon imprint). Its shape depends on the firearm, the ammunition and the anatomical conditions, but does not require a bullet. Examinations under a magnifying glass microscope and histological investigations can complete the macroscopic findings. Occasionally, the muzzle imprint mark requires a certain "drying period" in order to become clearly visible. In rare cases, muzzle imprint marks also form on textiles perforated by the projectile. Characteristically shaped muzzled imprint marks can provide clues to the type of the firearm and its position at the time of discharge.

  9. Psychosocial and behavioural factors in the explanation of socioeconomic inequalities in adolescent health: a multilevel analysis in 28 European and North American countries.

    PubMed

    Moor, Irene; Rathmann, Katharina; Stronks, Karien; Levin, Kate; Spallek, Jacob; Richter, Matthias

    2014-10-01

    The relative contribution of different pathways leading to health inequalities in adolescence was rarely investigated, especially in a cross-national perspective. The aim of the study is to analyse the contribution of psychosocial and behavioural factors in the explanation of inequalities in adolescent self-rated health (SRH) by family wealth in 28 countries. This study was based on the international WHO 'Health Behaviour in School-aged Children' (HBSC) study carried out in 2005/2006. The total sample included 117 460 adolescents aged 11-15 in 28 European and North American countries. Socioeconomic position was measured using the Family Affluence Scale (FAS). Multilevel logistic regression models were conducted to analyse the direct (independent) and indirect contribution of psychosocial and behavioural factors on SRH. Across all countries, adolescents from low affluent families had a higher risk of reporting fair/poor SRH (OR1.76, CI 1.69 to 1.84). Separate adjustments for psychosocial and behavioural factors reduced the OR of students with low family affluence by 39% (psychosocial) and 22% (behavioural). Together, both approaches explained about 50-60% of inequalities by family affluence in adolescent SRH. Separate analyses showed that relationship to father and academic achievement (psychosocial factors) as well as physical activity and consumption of fruits/vegetables (behavioural factors) were the most important factors in explaining inequalities in SRH. More than half of the inequalities by family affluence in adolescent SRH were explained by an unequal distribution of psychosocial and behavioural factors. Combining both approaches showed that the contribution of psychosocial factors was higher due to their direct (independent) and indirect impact through behavioural factors. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  10. 19 CFR 11.9 - Special marking on certain articles.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Special marking on certain articles. 11.9 Section... OF THE TREASURY PACKING AND STAMPING; MARKING Marking § 11.9 Special marking on certain articles. (a... of additional U.S. Note 4, Chapter 91. If any article so required to be marked is found not to be...

  11. 19 CFR 11.9 - Special marking on certain articles.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Special marking on certain articles. 11.9 Section... OF THE TREASURY PACKING AND STAMPING; MARKING Marking § 11.9 Special marking on certain articles. (a... of additional U.S. Note 4, Chapter 91. If any article so required to be marked is found not to be...

  12. 46 CFR 160.053-5 - Marking.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 6 2011-10-01 2011-10-01 false Marking. 160.053-5 Section 160.053-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Work Vests, Unicellular Plastic Foam § 160.053-5 Marking. (a...

  13. 46 CFR 160.053-5 - Marking.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Marking. 160.053-5 Section 160.053-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Work Vests, Unicellular Plastic Foam § 160.053-5 Marking. (a...

  14. 46 CFR 160.047-6 - Marking.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Marking. 160.047-6 Section 160.047-6 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS... and Child § 160.047-6 Marking. (a) Each buoyant vest must have the following information clearly...

  15. 46 CFR 160.036-5 - Marking.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Hand-Held Rocket-Propelled Parachute Red Flare Distress Signals § 160.036-5 Marking. (a) General. Each hand-held rocket-propelled parachute red flare distress signal shall be legibly marked or labeled as follows: (Company brand or style designation) Hand-Held Rocket...

  16. 46 CFR 160.036-5 - Marking.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Hand-Held Rocket-Propelled Parachute Red Flare Distress Signals § 160.036-5 Marking. (a) General. Each hand-held rocket-propelled parachute red flare distress signal shall be legibly marked or labeled as follows: (Company brand or style designation) Hand-Held Rocket...

  17. 46 CFR 160.036-5 - Marking.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Hand-Held Rocket-Propelled Parachute Red Flare Distress Signals § 160.036-5 Marking. (a) General. Each hand-held rocket-propelled parachute red flare distress signal shall be legibly marked or labeled as follows: (Company brand or style designation) Hand-Held Rocket...

  18. 46 CFR 160.036-5 - Marking.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Hand-Held Rocket-Propelled Parachute Red Flare Distress Signals § 160.036-5 Marking. (a) General. Each hand-held rocket-propelled parachute red flare distress signal shall be legibly marked or labeled as follows: (Company brand or style designation) Hand-Held Rocket...

  19. 46 CFR 160.036-5 - Marking.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Hand-Held Rocket-Propelled Parachute Red Flare Distress Signals § 160.036-5 Marking. (a) General. Each hand-held rocket-propelled parachute red flare distress signal shall be legibly marked or labeled as follows: (Company brand or style designation) Hand-Held Rocket...

  20. Bumblebees can discriminate between scent-marks deposited by conspecifics

    PubMed Central

    Pearce, Richard F.; Giuggioli, Luca; Rands, Sean A.

    2017-01-01

    Bumblebees secrete a substance from their tarsi wherever they land, which can be detected by conspecifics. These secretions are referred to as scent-marks, which bumblebees are able to use as social cues. Although it has been found that bumblebees can detect and associate scent-marks with rewarding or unrewarding flowers, their ability at discriminating between scent-marks from bumblebees of differing relatedness is unknown. We performed three separate experiments with bumblebees (Bombus terrestris), where they were repeatedly exposed to rewarding and unrewarding artificial flowers simultaneously. Each flower type carried scent-marks from conspecifics of differing relatedness or were unmarked. We found that bumblebees are able to distinguish between 1. Unmarked flowers and flowers that they themselves had scent-marked, 2. Flowers scent-marked by themselves and flowers scent-marked by others in their nest (nestmates), and 3. Flowers scent-marked by their nestmates and flowers scent-marked by non-nestmates. The bumblebees found it more difficult to discriminate between each of the flower types when both flower types were scent-marked. Our findings show that bumblebees have the ability to discriminate between scent-marks of conspecifics, which are potentially very similar in their chemical composition, and they can use this ability to improve their foraging success. PMID:28266572