Sample records for early passage mouse

  1. Intracerebral Inoculation of Mouse-Passaged Saffold Virus Type 3 Affects Cerebellar Development in Neonatal Mice

    PubMed Central

    Kotani, Osamu; Suzuki, Tadaki; Yokoyama, Masaru; Iwata-Yoshikawa, Naoko; Nakajima, Noriko; Sato, Hironori; Hasegawa, Hideki; Taguchi, Fumihiro; Shimizu, Hiroyuki

    2016-01-01

    picornaviruses, these isolates showed mild infectivity of glial and neural progenitor cells, but not of large neurons, in the cerebellum. However, the outcome of this viral infection in the cerebellum has not been clarified. Here, we examined the tropism of SAFV in the cerebellum. We obtained an in vivo-passaged strain from the cerebella of neonatal mice and examined its genome and its neurovirulence in the neonatal mouse brain. The passaged virus showed high infectivity and neurovirulence in the brain, especially the cerebellum, and affected cerebellar development. This unique neonatal mouse model will be helpful for elucidating the neuropathogenesis of SAFV infections occurring early in life. PMID:27581974

  2. Selective propagation of mouse-passaged scrapie prions with long incubation period from a mixed prion population using GT1-7 cells.

    PubMed

    Miyazawa, Kohtaro; Masujin, Kentaro; Okada, Hiroyuki; Ushiki-Kaku, Yuko; Matsuura, Yuichi; Yokoyama, Takashi

    2017-01-01

    In our previous study, we demonstrated the propagation of mouse-passaged scrapie isolates with long incubation periods (L-type) derived from natural Japanese sheep scrapie cases in murine hypothalamic GT1-7 cells, along with disease-associated prion protein (PrPSc) accumulation. We here analyzed the susceptibility of GT1-7 cells to scrapie prions by exposure to infected mouse brains at different passages, following interspecies transmission. Wild-type mice challenged with a natural sheep scrapie case (Kanagawa) exhibited heterogeneity of transmitted scrapie prions in early passages, and this mixed population converged upon one with a short incubation period (S-type) following subsequent passages. However, when GT1-7 cells were challenged with these heterologous samples, L-type prions became dominant. This study demonstrated that the susceptibility of GT1-7 cells to L-type prions was at least 105 times higher than that to S-type prions and that L-type prion-specific biological characteristics remained unchanged after serial passages in GT1-7 cells. This suggests that a GT1-7 cell culture model would be more useful for the economical and stable amplification of L-type prions at the laboratory level. Furthermore, this cell culture model might be used to selectively propagate L-type scrapie prions from a mixed prion population.

  3. Selective propagation of mouse-passaged scrapie prions with long incubation period from a mixed prion population using GT1-7 cells

    PubMed Central

    Masujin, Kentaro; Okada, Hiroyuki; Ushiki-Kaku, Yuko; Matsuura, Yuichi; Yokoyama, Takashi

    2017-01-01

    In our previous study, we demonstrated the propagation of mouse-passaged scrapie isolates with long incubation periods (L-type) derived from natural Japanese sheep scrapie cases in murine hypothalamic GT1-7 cells, along with disease-associated prion protein (PrPSc) accumulation. We here analyzed the susceptibility of GT1-7 cells to scrapie prions by exposure to infected mouse brains at different passages, following interspecies transmission. Wild-type mice challenged with a natural sheep scrapie case (Kanagawa) exhibited heterogeneity of transmitted scrapie prions in early passages, and this mixed population converged upon one with a short incubation period (S-type) following subsequent passages. However, when GT1-7 cells were challenged with these heterologous samples, L-type prions became dominant. This study demonstrated that the susceptibility of GT1-7 cells to L-type prions was at least 105 times higher than that to S-type prions and that L-type prion-specific biological characteristics remained unchanged after serial passages in GT1-7 cells. This suggests that a GT1-7 cell culture model would be more useful for the economical and stable amplification of L-type prions at the laboratory level. Furthermore, this cell culture model might be used to selectively propagate L-type scrapie prions from a mixed prion population. PMID:28636656

  4. Different effects of resveratrol on early and late passage mesenchymal stem cells through β-catenin regulation

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

    Yoon, Dong Suk; Choi, Yoorim; Choi, Seong Mi

    2015-11-27

    Resveratrol is a sirtuin 1 (SIRT1) activator and can function as an anti-inflammatory and antioxidant factor. In mesenchymal stem cells (MSCs), resveratrol enhances the proliferation and differentiation potential and has an anti-aging effect. However, contradictory effects of resveratrol on MSC cultures have been reported. In this study, we found that resveratrol had different effects on MSC cultures according to their cell passage and SIRT1 expression. Resveratrol enhanced the self-renewal potential and multipotency of early passage MSCs, but accelerated cellular senescence of late passage MSCs. In early passage MSCs expressing SIRT1, resveratrol decreased ERK and GSK-3β phosphorylation, suppressing β-catenin activity. Inmore » contrast, in late passage MSCs, which did not express SIRT1, resveratrol increased ERK and GSK-3β phosphorylation, activating β-catenin. We confirmed that SIRT1-deficient early passage MSCs treated with resveratrol lost their self-renewal potential and multipotency, and became senescent due to increased β-catenin activity. Sustained treatment with resveratrol at early passages maintained the self-renewal potential and multipotency of MSCs up to passage 10. Our findings suggest that resveratrol can be effectively applied to early passage MSC cultures, whereas parameters such as cell passage and SIRT1 expression must be taken into consideration before applying resveratrol to late passage MSCs. - Highlights: • Resveratrol enhances self-renewal potential and multipotency of early passage MSCs. • Resveratrol accelerates the cellular senescence of late passage MSCs. • The effects of resveratrol on MSCs are dependent on the presence of SIRT1. • SIRT1 modulates ERK/GSK-3β/β-catenin signaling. • Sustained resveratrol treatment maintains MSC stemness up to P10.« less

  5. Selection of early-occurring mutations dictates hormone-independent progression in mouse mammary tumor lines.

    PubMed

    Gattelli, Albana; Zimberlin, María N; Meiss, Roberto P; Castilla, Lucio H; Kordon, Edith C

    2006-11-01

    Mice harboring three mouse mammary tumor virus (MMTV) variants develop pregnancy-dependent (PD) tumors that progress to pregnancy-independent (PI) behavior through successive passages. Herein, we identified 10 predominant insertions in PI transplants from 8 independent tumor lines. These mutations were also detected in small cell populations in the early PD passages. In addition, we identified a new viral insertion upstream of the gene Rspo3, which is overexpressed in three of the eight independent tumor lines and codes for a protein very similar to the recently described protein encoded by Int7. This study suggests that during progression towards hormone independence, clonal expansion of cells with specific mutations might be more relevant than the occurrence of new MMTV insertions.

  6. Selection of Early-Occurring Mutations Dictates Hormone-Independent Progression in Mouse Mammary Tumor Lines▿

    PubMed Central

    Gattelli, Albana; Zimberlin, María N.; Meiss, Roberto P.; Castilla, Lucio H.; Kordon, Edith C.

    2006-01-01

    Mice harboring three mouse mammary tumor virus (MMTV) variants develop pregnancy-dependent (PD) tumors that progress to pregnancy-independent (PI) behavior through successive passages. Herein, we identified 10 predominant insertions in PI transplants from 8 independent tumor lines. These mutations were also detected in small cell populations in the early PD passages. In addition, we identified a new viral insertion upstream of the gene Rspo3, which is overexpressed in three of the eight independent tumor lines and codes for a protein very similar to the recently described protein encoded by Int7. This study suggests that during progression towards hormone independence, clonal expansion of cells with specific mutations might be more relevant than the occurrence of new MMTV insertions. PMID:16971449

  7. Hydroacoustic Evaluation of Overwintering Summer Steelhead Fallback and Kelt Passage at The Dalles Dam Turbines, Early Spring 2011

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

    Khan, Fenton; Royer, Ida M.

    2012-02-01

    This report presents the results of an evaluation of overwintering summer steelhead (Oncorhynchus mykiss) fallback and early out-migrating steelhead kelts downstream passage at The Dalles Dam turbines during early spring 2011. The study was conducted by Pacific Northwest National Laboratory (PNNL) for the U.S. Army Corps of Engineers, Portland District (USACE) to investigate whether adult steelhead are passing through turbines during early spring before annual sluiceway operations typically begin. The sluiceway surface flow outlet is the optimal non-turbine route for adult steelhead, although operating the sluiceway reduces hydropower production. This is a follow-up study to similar studies of adult steelheadmore » passage at the sluiceway and turbines we conducted in the fall/winter 2008, early spring 2009, fall/winter 2009, and early spring 2010. The goal of the 2011 study was to characterize adult steelhead passage rates at the turbines while the sluiceway was closed so fisheries managers would have additional information to use in decision-making relative to sluiceway operations. Sluiceway operations were not scheduled to begin until April 10, 2011. However, based on a management decision in late February, sluiceway operations commenced on March 1, 2011. Therefore, this study provided estimates of fish passage rates through the turbines, and not the sluiceway, while the sluiceway was open. The study period was March 1 through April 10, 2011 (41 days total). The study objective was to estimate the number and distribution of adult steelhead and kelt-sized targets passing into turbine units. We obtained fish passage data using fixed-location hydroacoustics with transducers deployed at all 22 main turbine units at The Dalles Dam. Adult steelhead passage through the turbines occurred on 9 days during the study (March 9, 12, 30, and 31 and April 2, 3, 5, 7, and 9). We estimated a total of 215 {+-} 98 (95% confidence interval) adult steelhead targets passed through

  8. [Effects of in vitro continuous passaging on the phenotype of mouse hyaline chondrocytes and the balance of the extra- cellular matrix].

    PubMed

    Linyi, Cai; Xiangli, Kong; Jing, Xie

    2016-06-01

    This study aimed to investigate the effects of in vitro continuous passaging on the morphological phenotype and differentiation characteristics of mouse hyaline chondrocytes, as well as on the balance of the extracellular matrix (ECM). Enzymatic digestion was conducted to isolate mouse hyaline chondrocytes, which expanded over five passages in vitro. Hematoxylin-eosin stain was used to show the changes in chondrocyte morphology. Semi-quantitative polymerase chain reaction was performed to analyze the mRNA changes in the marker genes, routine genes, matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs (TIMPs) in chondrocytes. Zymography was carried out to elucidate changes in gelatinase activities. After continuous expansion in vitro, the morphology of round or polygonal chondrocytes changed to elongated and spindled shape. The expression of marker genes significantly decreased (P < 0.05), and it was almost negatively expressed by P5 chondrocytes. By contrast, the down regulation of routine genes was insignificant. The gene expression levels of MMPs and TIMPs both decreased (P < 0.05), but the change in MMP-1 and TIMP-1 was not statistically significant (P > 0.05). Meanwhile, the ratio of MMPs/TIMPs was altered. At the protein level, the activities of gelatinases decreased after passaging, especially for P4 and P5 chondrocytes (P < 0.05). Serially passaged chondrocytes dedifferentiated and lost specific phenotypic characteristics during in vitro expansion culture. Simultaneously, the anabolism and catabolism of the cartilage ECM became uncontrollable and led to the imbalance of ECM homeostasis. When hyaline chondrocytes are applied in research on relevant diseases or cartilage tissue engineering, P0-P2 chondrocytes should be used.

  9. Pre-crisis mouse cells show strain-specific covariation in the amount of 54-kilodalton phosphoprotein and in susceptibility to transformation by simian virus 40.

    PubMed

    Chen, S; Blanck, G; Pollack, R E

    1983-09-01

    We have used several inbred mouse strains to examine the role of the 54-kilodalton (kDa) cellular phosphoprotein in transformation by the papovavirus simian virus 40. We have measured the endogenous 54-kDa phosphoprotein in cells obtained from these inbred mouse strains. To study the effect of passage, cell cultures were measured for amount of the 54-kDa phosphoprotein at the 2nd and 12th passages. In the absence of any transforming agent, the amount of endogenous 54-kDa phosphoprotein in early pre-crisis mouse cells varied in a strain-specific way. Transformation frequency varied coordinately with endogenous 54-kDa expression. Mouse strains whose cells produced a high level of endogenous 54-kDa phosphoprotein on passage did not further increase its expression after simian virus 40 transformation.

  10. Pre-crisis mouse cells show strain-specific covariation in the amount of 54-kilodalton phosphoprotein and in susceptibility to transformation by simian virus 40.

    PubMed Central

    Chen, S; Blanck, G; Pollack, R E

    1983-01-01

    We have used several inbred mouse strains to examine the role of the 54-kilodalton (kDa) cellular phosphoprotein in transformation by the papovavirus simian virus 40. We have measured the endogenous 54-kDa phosphoprotein in cells obtained from these inbred mouse strains. To study the effect of passage, cell cultures were measured for amount of the 54-kDa phosphoprotein at the 2nd and 12th passages. In the absence of any transforming agent, the amount of endogenous 54-kDa phosphoprotein in early pre-crisis mouse cells varied in a strain-specific way. Transformation frequency varied coordinately with endogenous 54-kDa expression. Mouse strains whose cells produced a high level of endogenous 54-kDa phosphoprotein on passage did not further increase its expression after simian virus 40 transformation. Images PMID:6310588

  11. iTRAQ-Based Quantitative Proteomic Comparison of Early- and Late-Passage Human Dermal Papilla Cell Secretome in Relation to Inducing Hair Follicle Regeneration.

    PubMed

    Zhang, Huan; Zhu, Ning-Xia; Huang, Keng; Cai, Bo-Zhi; Zeng, Yang; Xu, Yan-Ming; Liu, Yang; Yuan, Yan-Ping; Lin, Chang-Min

    2016-01-01

    Alopecia is an exceedingly prevalent problem that lacks effective therapy. Recently, research has focused on early-passage dermal papilla cells (DPCs), which have hair inducing activity both in vivo and in vitro. Our previous study indicated that factors secreted from early-passage DPCs contribute to hair follicle (HF) regeneration. To identify which factors are responsible for HF regeneration and why late-passage DPCs lose this potential, we collected 48-h-culture medium (CM) from both of passage 3 and 9 DPCs, and subcutaneously injected the DPC-CM into NU/NU mice. Passage 3 DPC-CM induced HF regeneration, based on the emergence of a white hair coat, but passage 9 DPC-CM did not. In order to identify the key factors responsible for hair induction, CM from passage 3 and 9 DPCs was analyzed by iTRAQ-based quantitative proteomic technology. We identified 1360 proteins, of which 213 proteins were differentially expressed between CM from early-passage vs. late-passage DPCs, including SDF1, MMP3, biglycan and LTBP1. Further analysis indicated that the differentially-expressed proteins regulated the Wnt, TGF-β and BMP signaling pathways, which directly and indirectly participate in HF morphogenesis and regeneration. Subsequently, we selected 19 proteins for further verification by multiple reaction monitoring (MRM) between the two types of CM. These results indicate DPC-secreted proteins play important roles in HF regeneration, with SDF1, MMP3, biglycan, and LTBP1 being potential key inductive factors secreted by dermal papilla cells in the regeneration of hair follicles.

  12. Therapeutic Benefit for Late, but Not Early, Passage Mesenchymal Stem Cells on Pain Behaviour in an Animal Model of Osteoarthritis

    PubMed Central

    Chapman, Victoria; Markides, Hareklea; Sagar, Devi Rani; Xu, Luting; Burston, James J.; Mapp, Paul; Kay, Alasdair; Kehoe, Oksana

    2017-01-01

    Background Mesenchymal stem cells (MSCs) have a therapeutic potential for the treatment of osteoarthritic (OA) joint pathology and pain. The aims of this study were to determine the influence of a passage number on the effects of MSCs on pain behaviour and cartilage and bone features in a rodent model of OA. Methods Rats underwent either medial meniscal transection (MNX) or sham surgery under anaesthesia. Rats received intra-articular injection of either 1.5 × 106 late passage MSCs labelled with 10 μg/ml SiMAG, 1.5 × 106 late passage mesenchymal stem cells, the steroid Kenalog (200 μg/20 μL), 1.5 × 106 early passage MSCs, or serum-free media (SFM). Sham-operated rats received intra-articular injection of SFM. Pain behaviour was quantified until day 42 postmodel induction. Magnetic resonance imaging (MRI) was used to localise the labelled cells within the knee joint. Results Late passage MSCs and Kenalog attenuated established pain behaviour in MNX rats, but did not alter MNX-induced joint pathology at the end of the study period. Early passage MSCs exacerbated MNX-induced pain behaviour for up to one week postinjection and did not alter joint pathology. Conclusion Our data demonstrate for the first time the role of a passage number in influencing the therapeutic effects of MSCs in a model of OA pain. PMID:29434641

  13. Expression profiling of the mouse early embryo: Reflections and Perspectives

    PubMed Central

    Ko, Minoru S. H.

    2008-01-01

    Laboratory mouse plays important role in our understanding of early mammalian development and provides invaluable model for human early embryos, which are difficult to study for ethical and technical reasons. Comprehensive collection of cDNA clones, their sequences, and complete genome sequence information, which have been accumulated over last two decades, have provided even more advantages to mouse models. Here the progress in global gene expression profiling in early mouse embryos and, to some extent, stem cells are reviewed and the future directions and challenges are discussed. The discussions include the restatement of global gene expression profiles as snapshot of cellular status, and subsequent distinction between the differentiation state and physiological state of the cells. The discussions then extend to the biological problems that can be addressed only through global expression profiling, which include: bird’s-eye view of global gene expression changes, molecular index for developmental potency, cell lineage trajectory, microarray-guided cell manipulation, and the possibility of delineating gene regulatory cascades and networks. PMID:16739220

  14. The roles of ERAS during cell lineage specification of mouse early embryonic development.

    PubMed

    Zhao, Zhen-Ao; Yu, Yang; Ma, Huai-Xiao; Wang, Xiao-Xiao; Lu, Xukun; Zhai, Yanhua; Zhang, Xiaoxin; Wang, Haibin; Li, Lei

    2015-08-01

    Eras encodes a Ras-like GTPase protein that was originally identified as an embryonic stem cell-specific Ras. ERAS has been known to be required for the growth of embryonic stem cells and stimulates somatic cell reprogramming, suggesting its roles on mouse early embryonic development. We now report a dynamic expression pattern of Eras during mouse peri-implantation development: its expression increases at the blastocyst stage, and specifically decreases in E7.5 mesoderm. In accordance with its expression pattern, the increased expression of Eras promotes cell proliferation through controlling AKT activation and the commitment from ground to primed state through ERK activation in mouse embryonic stem cells; and the reduced expression of Eras facilitates primitive streak and mesoderm formation through AKT inhibition during gastrulation. The expression of Eras is finely regulated to match its roles in mouse early embryonic development during which Eras expression is negatively regulated by the β-catenin pathway. Thus, beyond its well-known role on cell proliferation, ERAS may also play important roles in cell lineage specification during mouse early embryonic development. © 2015 The Authors.

  15. Dual effects of fluoxetine on mouse early embryonic development

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

    Kim, Chang-Woon; Department of Obstetrics and Gynecology, Samsung Changwon Hospital, Sungkyunkwan University, Changwon 630-723; Choe, Changyong

    2012-11-15

    Fluoxetine, a selective serotonin reuptake inhibitor, regulates a variety of physiological processes, such as cell proliferation and apoptosis, in mammalian cells. Little is known about the role of fluoxetine in early embryonic development. This study was undertaken to investigate the effect of fluoxetine during mouse early embryonic development. Late two-cell stage embryos (2-cells) were cultured in the presence of various concentrations of fluoxetine (1 to 50 μM) for different durations. When late 2-cells were incubated with 5 μM fluoxetine for 6 h, the percentage that developed into blastocysts increased compared to the control value. However, late 2-cells exposed to fluoxetinemore » (5 μM) over 24 h showed a reduction in blastocyst formation. The addition of fluoxetine (5 μM) together with KN93 or KN62 (calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitors) failed to increase blastocyst formation. Fluoxetine treatment inhibited TREK-1 and TREK-2, members of the two-pore domain K{sup +} channel family expressed in mouse embryos, activities, indicating that fluoxetine-induced membrane depolarization in late 2-cells might have resulted from TREK inhibition. In addition, long-term exposure to fluoxetine altered the TREK mRNA expression levels. Furthermore, injection of siRNA targeting TREKs significantly decreased blastocyst formation by ∼ 30% compared to injection of scrambled siRNA. Long-term exposure of fluoxetine had no effect on blastocyst formation of TREK deficient embryos. These results indicate that low-dose and short-term exposures of late 2-cells to fluoxetine probably increase blastocyst formation through activation of CaMKII-dependent signal transduction pathways, whereas long-term exposure decreases mouse early embryonic development through inhibition of TREK channel gating. Highlights: ► Short-term exposure of 2-cells to fluoxetine enhances mouse blastocyst formation. ► The enhancive effect of fluoxetine is resulted from Ca

  16. Recognition of the CDEI motif GTCACATG by mouse nuclear proteins and interference with the early development of the mouse embryo.

    PubMed Central

    Blangy, A; Léopold, P; Vidal, F; Rassoulzadegan, M; Cuzin, F

    1991-01-01

    We have reported previously (1) two unexpected consequences of the microinjection into fertilized mouse eggs of a recombinant plasmid designated p12B1, carrying a 343 bp insert of non-repetitive mouse DNA. Injected at very low concentrations, this plasmid could be established as an extrachromosomal genetic element. When injected in greater concentration, an early arrest of embryonic development resulted. In the present work, we have studied this toxic effect in more detail by microinjecting short synthetic oligonucleotides with sequences from the mouse insert. Lethality was associated with the nucleotide sequence GTCACATG, identical with the CDEl element of yeast centromeres. Development of injected embryos was arrested between the one-cell and the early morula stages, with abnormal structures and DNA contents. Electrophoretic mobility shift and DNAse foot-printing assays demonstrated the binding of mouse nuclear protein(s) to the CDEl-like box. Base changes within the CDEl sequence prevented both the toxic effects in embryos and the formation of protein complex in vitro, suggesting that protein binding at such sites in chromosomal DNA plays an important role in early development. Images PMID:1766880

  17. Virulence-Associated Genome Mutations of Murine Rotavirus Identified by Alternating Serial Passages in Mice and Cell Cultures

    PubMed Central

    Tatsumi, Masatoshi; Tsutsumi, Hiroyuki

    2014-01-01

    ABSTRACT Although significant clinical efficacy and safety of rotavirus vaccines were recently revealed in many countries, the mechanism of their attenuation is not well understood. We passaged serially a cell culture-adapted murine rotavirus EB strain in mouse pups or in cell cultures alternately and repeatedly and fully sequenced all 11 genes of 21 virus samples passaged in mice or in cell cultures. Sequence analysis revealed that mouse-passaged viruses that regained virulence almost consistently acquired four kinds of amino acid (aa) substitutions in VP4 and substitution in aa 37 (Val to Ala) in NSP4. In addition, they gained and invariably conserved the 3′ consensus sequence in NSP1. The molecular changes occurred along with the acquisition of virulence during passages in mice and then disappeared following passages in cell cultures. Intraperitoneal injection of recombinant NSP4 proteins confirmed the aa 37 site as important for its diarrheagenic activity in mice. These genome changes are likely to be correlated with rotavirus virulence. IMPORTANCE Serial passage of a virulent wild-type virus in vitro often results in loss of virulence of the virus in an original animal host, while serial passage of a cell culture-adapted avirulent virus in vivo often gains virulence in an animal host. Actually, live attenuated virus vaccines were originally produced by serial passage in cell cultures. Although clinical efficacy and safety of rotavirus vaccines were recently revealed, the mechanism of their attenuation is not well understood. We passaged serially a murine rotavirus by alternating switch of host (mice or cell cultures) repeatedly and sequenced the eleven genes of the passaged viruses to identify mutations associated with the emergence or disappearance of virulence. Sequence analysis revealed that changes in three genes (VP4, NSP1, and NSP4) were associated with virulence in mice. Intraperitoneal injection of recombinant NSP4 proteins confirmed its

  18. Virulence-associated genome mutations of murine rotavirus identified by alternating serial passages in mice and cell cultures.

    PubMed

    Tsugawa, Takeshi; Tatsumi, Masatoshi; Tsutsumi, Hiroyuki

    2014-05-01

    Although significant clinical efficacy and safety of rotavirus vaccines were recently revealed in many countries, the mechanism of their attenuation is not well understood. We passaged serially a cell culture-adapted murine rotavirus EB strain in mouse pups or in cell cultures alternately and repeatedly and fully sequenced all 11 genes of 21 virus samples passaged in mice or in cell cultures. Sequence analysis revealed that mouse-passaged viruses that regained virulence almost consistently acquired four kinds of amino acid (aa) substitutions in VP4 and substitution in aa 37 (Val to Ala) in NSP4. In addition, they gained and invariably conserved the 3' consensus sequence in NSP1. The molecular changes occurred along with the acquisition of virulence during passages in mice and then disappeared following passages in cell cultures. Intraperitoneal injection of recombinant NSP4 proteins confirmed the aa 37 site as important for its diarrheagenic activity in mice. These genome changes are likely to be correlated with rotavirus virulence. Serial passage of a virulent wild-type virus in vitro often results in loss of virulence of the virus in an original animal host, while serial passage of a cell culture-adapted avirulent virus in vivo often gains virulence in an animal host. Actually, live attenuated virus vaccines were originally produced by serial passage in cell cultures. Although clinical efficacy and safety of rotavirus vaccines were recently revealed, the mechanism of their attenuation is not well understood. We passaged serially a murine rotavirus by alternating switch of host (mice or cell cultures) repeatedly and sequenced the eleven genes of the passaged viruses to identify mutations associated with the emergence or disappearance of virulence. Sequence analysis revealed that changes in three genes (VP4, NSP1, and NSP4) were associated with virulence in mice. Intraperitoneal injection of recombinant NSP4 proteins confirmed its diarrheagenic activity in mice

  19. Passage of Campylobacter jejuni through the chicken reservoir or mice promotes phase variation in contingency genes Cj0045 and Cj0170 that strongly associates with colonization and disease in a mouse model

    PubMed Central

    Kim, Joo-Sung; Artymovich, Katherine A.; Hall, David F.; Smith, Eric J.; Fulton, Richard; Bell, Julia; Dybas, Leslie; Mansfield, Linda S.; Tempelman, Robert; Wilson, David L.

    2012-01-01

    Human illness due to Camplyobacter jejuni infection is closely associated with consumption of poultry products. We previously demonstrated a 50 % shift in allele frequency (phase variation) in contingency gene Cj1139 (wlaN) during passage of C. jejuni NCTC11168 populations through Ross 308 broiler chickens. We hypothesized that phase variation in contingency genes during chicken passage could promote subsequent colonization and disease in humans. To test this hypothesis, we passaged C. jejuni strains NCTC11168, 33292, 81-176, KanR4 and CamR2 through broiler chickens and analysed the ability of passaged and non-passaged populations to colonize C57BL6 IL-10-deficient mice, our model for human colonization and disease. We utilized fragment analysis and nucleotide sequence analysis to measure phase variation in contingency genes. Passage through the chicken reservoir promoted phase variation in five specific contingency genes, and these ‘successful’ populations colonized mice. When phase variation did not occur in these same five contingency genes during chicken passage, these ‘unsuccessful’ populations failed to colonize mice. Phase variation during chicken passage generated small insertions or deletions (indels) in the homopolymeric tract (HT) in contingency genes. Single-colony isolates of C. jejuni strain KanR4 carrying an allele of contingency gene Cj0170 with a10G HT colonized mice at high frequency and caused disease symptoms, whereas single-colony isolates carrying the 9G allele failed to colonize mice. Supporting results were observed for the successful 9G allele of Cj0045 in strain 33292. These data suggest that phase variation in Cj0170 and Cj0045 is strongly associated with mouse colonization and disease, and that the chicken reservoir can play an active role in natural selection, phase variation and disease. PMID:22343355

  20. Passage of Campylobacter jejuni through the chicken reservoir or mice promotes phase variation in contingency genes Cj0045 and Cj0170 that strongly associates with colonization and disease in a mouse model.

    PubMed

    Kim, Joo-Sung; Artymovich, Katherine A; Hall, David F; Smith, Eric J; Fulton, Richard; Bell, Julia; Dybas, Leslie; Mansfield, Linda S; Tempelman, Robert; Wilson, David L; Linz, John E

    2012-05-01

    Human illness due to Camplyobacter jejuni infection is closely associated with consumption of poultry products. We previously demonstrated a 50 % shift in allele frequency (phase variation) in contingency gene Cj1139 (wlaN) during passage of C. jejuni NCTC11168 populations through Ross 308 broiler chickens. We hypothesized that phase variation in contingency genes during chicken passage could promote subsequent colonization and disease in humans. To test this hypothesis, we passaged C. jejuni strains NCTC11168, 33292, 81-176, KanR4 and CamR2 through broiler chickens and analysed the ability of passaged and non-passaged populations to colonize C57BL6 IL-10-deficient mice, our model for human colonization and disease. We utilized fragment analysis and nucleotide sequence analysis to measure phase variation in contingency genes. Passage through the chicken reservoir promoted phase variation in five specific contingency genes, and these 'successful' populations colonized mice. When phase variation did not occur in these same five contingency genes during chicken passage, these 'unsuccessful' populations failed to colonize mice. Phase variation during chicken passage generated small insertions or deletions (indels) in the homopolymeric tract (HT) in contingency genes. Single-colony isolates of C. jejuni strain KanR4 carrying an allele of contingency gene Cj0170 with a10G HT colonized mice at high frequency and caused disease symptoms, whereas single-colony isolates carrying the 9G allele failed to colonize mice. Supporting results were observed for the successful 9G allele of Cj0045 in strain 33292. These data suggest that phase variation in Cj0170 and Cj0045 is strongly associated with mouse colonization and disease, and that the chicken reservoir can play an active role in natural selection, phase variation and disease.

  1. Dual effects of fluoxetine on mouse early embryonic development.

    PubMed

    Kim, Chang-Woon; Choe, Changyong; Kim, Eun-Jin; Lee, Jae-Ik; Yoon, Sook-Young; Cho, Young-Woo; Han, Sunkyu; Tak, Hyun-Min; Han, Jaehee; Kang, Dawon

    2012-11-15

    Fluoxetine, a selective serotonin reuptake inhibitor, regulates a variety of physiological processes, such as cell proliferation and apoptosis, in mammalian cells. Little is known about the role of fluoxetine in early embryonic development. This study was undertaken to investigate the effect of fluoxetine during mouse early embryonic development. Late two-cell stage embryos (2-cells) were cultured in the presence of various concentrations of fluoxetine (1 to 50μM) for different durations. When late 2-cells were incubated with 5μM fluoxetine for 6h, the percentage that developed into blastocysts increased compared to the control value. However, late 2-cells exposed to fluoxetine (5μM) over 24h showed a reduction in blastocyst formation. The addition of fluoxetine (5μM) together with KN93 or KN62 (calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitors) failed to increase blastocyst formation. Fluoxetine treatment inhibited TREK-1 and TREK-2, members of the two-pore domain K(+) channel family expressed in mouse embryos, activities, indicating that fluoxetine-induced membrane depolarization in late 2-cells might have resulted from TREK inhibition. In addition, long-term exposure to fluoxetine altered the TREK mRNA expression levels. Furthermore, injection of siRNA targeting TREKs significantly decreased blastocyst formation by ~30% compared to injection of scrambled siRNA. Long-term exposure of fluoxetine had no effect on blastocyst formation of TREK deficient embryos. These results indicate that low-dose and short-term exposures of late 2-cells to fluoxetine probably increase blastocyst formation through activation of CaMKII-dependent signal transduction pathways, whereas long-term exposure decreases mouse early embryonic development through inhibition of TREK channel gating. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Sluiceway Operations for Adult Steelhead Downstream Passage at The Dalles Dam, Columbia River, USA

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

    Khan, Fenton; Royer, Ida M.; Johnson, Gary E.

    2013-10-01

    This study evaluated adult steelhead (Oncorhynchus mykiss; fallbacks and kelts) downstream passage at The Dalles Dam in the Columbia River, USA, during the late fall, winter, and early spring months between 2008 and 2011. The purpose of the study was to determine the efficacy of operating the dam’s ice-and-trash sluiceway during non-spill months to provide a relatively safe, non-turbine, surface outlet for overwintering steelhead fallbacks and downstream migrating steelhead kelts. We applied the fixed-location hydroacoustic technique to estimate fish passage rates at the sluiceway and turbines of the dam. The spillway was closed during our sampling periods, which generally occurredmore » in late fall, winter, and early spring. The sluiceway was highly used by adult steelhead (91–99% of total fish sampled passing the dam) during all sampling periods. Turbine passage was low when the sluiceway was not operated. This implies that lack of a sluiceway route did not result in increased turbine passage. However, when the sluiceway was open, adult steelhead used it to pass through the dam. The sluiceway may be operated during late fall, winter, and early spring to provide an optimal, non-turbine route for adult steelhead (fallbacks and kelts) downstream passage at The Dalles Dam.« less

  3. Influence of early life exposure, host genetics and diet on the mouse gut microbiome and metabolome

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

    Snijders, Antoine M.; Langley, Sasha A.; Kim, Young-Mo

    Although the gut microbiome plays important roles in host physiology, health and disease1, we lack understanding of the complex interplay between host genetics and early life environment on the microbial and metabolic composition of the gut.We used the genetically diverse Collaborative Cross mouse system2 to discover that early life history impacts themicrobiome composition, whereas dietary changes have only a moderate effect. By contrast, the gut metabolome was shaped mostly by diet, with specific non-dietary metabolites explained by microbial metabolism. Quantitative trait analysis identified mouse genetic trait loci (QTL) that impact the abundances of specific microbes. Human orthologues of genes inmore » the mouse QTL are implicated in gastrointestinal cancer. Additionally, genes located in mouse QTL for Lactobacillales abundance are implicated in arthritis, rheumatic disease and diabetes. Furthermore, Lactobacillales abundance was predictive of higher host T-helper cell counts, suggesting an important link between Lactobacillales and host adaptive immunity.« less

  4. Comparison of textbook passages, nonfiction trade book passages and fiction trade book passages as instructional tools for learning science

    NASA Astrophysics Data System (ADS)

    Kelly, Cynthia

    This study examined the impact of different types of text on student achievement in elementary school science. Gender was also examined to see if the type of text passage read had any differential effect on boys' and girls' achievement. This study was a pretest/posttest/retention test design. Eighty-four fourth grade students from a public charter elementary school in South Florida were randomly assigned a passage from a physical science textbook, a physical science nonfiction trade book, a physical science fiction trade book, a biological science textbook or a biological science nonfiction trade book. Results in the physical science content area revealed that students in the textbook passage group had higher posttest and retention test results than students in the nonfiction and fiction trade book passage groups. There was no difference on the posttest results of students in the biological science textbook and nonfiction trade book passage groups. Students in the biological science textbook passage group had higher retention results than students in the biological science nonfiction passage group. Gender results in the physical science content area revealed that boys had a higher retention score than girls in the fiction trade book passage group. There were no gender achievement differences as a result of the text passage read in the biological science content area. It was concluded that no definitive answer as to the efficacy of textbooks versus trade books was possible based upon results of the study. Recommendations for future research include examining the effects of different types of texts in conjunction with other authentic teaching methods.

  5. High-Frequency Ultrasound for the Study of Early Mouse Embryonic Cardiovascular System.

    PubMed

    Greco, Adelaide; Coda, Anna Rita Daniela; Albanese, Sandra; Ragucci, Monica; Liuzzi, Raffaele; Auletta, Luigi; Gargiulo, Sara; Lamagna, Francesco; Salvatore, Marco; Mancini, Marcello

    2015-12-01

    An accurate diagnosis of congenital heart defects during fetal development is critical for interventional planning. Mice can be used to generate animal models with heart defects, and high-frequency ultrasound (HFUS) imaging enables in utero imaging of live mouse embryos. A wide range of physiological measurements is possible using Doppler-HFUS imaging; limitations of any single measurement warrant a multiparameter approach to characterize cardiovascular function. Doppler-HFUS was used to explore the embryonic (heart, aorta) and extraembryonic (umbilical blood flow) circulatory systems to create a database in normal mouse embryos between 9.5 and 16.5 days of gestation. Multivariate analyses were performed to explore correlations between gestational age and embryo echocardiographic parameters. Heart rate and peak velocity in the aorta were positively correlated with gestational time, whereas cardiac cycle length, isovolumetric relaxation time, myocardial performance index, and arterial deceleration time of the umbilical cord were negatively correlated with it. Doppler-HFUS facilitated detailed characterization of the embryonic mouse circulation and represents a useful tool for investigation of the early mouse embryonic cardiovascular system. © The Author(s) 2015.

  6. The cell cycle of early mammalian embryos: lessons from genetic mouse models.

    PubMed

    Artus, Jérôme; Babinet, Charles; Cohen-Tannoudji, Michel

    2006-03-01

    Genes coding for cell cycle components predicted to be essential for its regulation have been shown to be dispensable in mice, at the whole organism level. Such studies have highlighted the extraordinary plasticity of the embryonic cell cycle and suggest that many aspects of in vivo cell cycle regulation remain to be discovered. Here, we discuss the particularities of the mouse early embryonic cell cycle and review the mutations that result in cell cycle defects during mouse early embryogenesis, including deficiencies for genes of the cyclin family (cyclin A2 and B1), genes involved in cell cycle checkpoints (Mad2, Bub3, Chk1, Atr), genes involved in ubiquitin and ubiquitin-like pathways (Uba3, Ubc9, Cul1, Cul3, Apc2, Apc10, Csn2) as well as genes the function of which had not been previously ascribed to cell cycle regulation (Cdc2P1, E4F and Omcg1).

  7. Immunocytochemical localisation of the nucleolar protein fibrillarin and RNA polymerase I during mouse early embryogenesis.

    PubMed

    Cuadros-Fernández, J M; Esponda, P

    1996-02-01

    We have employed immunocytochemical procedures to localise the nucleolar protein fibrillarin and the enzyme RNA polymerase I in the numerous dense fibrillar bodies (nucleolar precursor bodies) which appear in the nuclei of mammalian early embryos. The aim of this study was to search for relationships between the localisation of these proteins, the changes in the structure of the nucleolar precursor bodies and the resumption of rRNA gene transcription during mouse early embryogenesis. Three human autoimmune sera which recognised fibrillarin and a rabbit antiserum created against RNA polymerase I were employed for fluorescence and electron microscopic immunocytochemical assays. A statistical analysis was also applied. Immunocytochemistry revealed that fibrillarin and RNA polymerase I showed the same localisation in the nucleolar precursor bodies. These proteins were immunolocalised only from the late 2-cell stage onward. Fibrillarin was initially detected at the periphery of the nucleolar precursor bodies and the labelling gradually increased until the morula and blastocyst stages, where normally active nucleoli are found. The pattern of increase of fibrillarin during early embryogenesis shows a parallelism with the rise in rRNA gene transcription occurring during these embryonic stages, and a possible correlation between these two phenomena is suggested. Results demonstrated that nucleolar precursor bodies differ in their biochemical composition from the nucleolus and also from the prenucleolar bodies which appear during mitosis. When anti-fibrillarin antibodies were microinjected into the male pronucleus of mouse embryos to analyse the functions of fibrillarin during early development, they partially blocked the early development of mouse embryos and only 23.8% of injected embryos reach the blastocyst stage.

  8. Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation

    PubMed Central

    Liu, Yunlong; Balaraman, Yokesh; Wang, Guohua; Nephew, Kenneth P.; Zhou, Feng C.

    2009-01-01

    Alcohol exposure during development can cause variable neurofacial deficit and growth retardation known as fetal alcohol spectrum disorders (FASD). The mechanism underlying FASD is not fully understood. However, alcohol, which is known to affect methyl donor metabolism, may induce aberrant epigenetic changes contributing to FASD. Using a tightly controlled whole-embryo culture, we investigated the effect of alcohol exposure (88 mM) at early embryonic neurulation on genome-wide DNA methylation and gene expression in the C57BL/6 mouse. The DNA methylation landscape around promoter CpG islands at early mouse development was analyzed using MeDIP (methylated DNA immunoprecipitation) coupled with microarray (MeDIP-chip). At early neurulation, genes associated with high CpG promoters (HCP) had a lower ratio of methylation but a greater ratio of expression. Alcohol-induced alterations in DNA methylation were observed, particularly in genes on chromosomes 7, 10 and X; remarkably, a >10 fold increase in the number of genes with increased methylation on chromosomes 10 and X was observed in alcohol-exposed embryos with a neural tube defect phenotype compared to embryos without a neural tube defect. Significant changes in methylation were seen in imprinted genes, genes known to play roles in cell cycle, growth, apoptosis, cancer, and in a large number of genes associated with olfaction. Altered methylation was associated with significant (p < 0.01) changes in expression for 84 genes. Sequenom EpiTYPER DNA methylation analysis was used for validation of the MeDIP-chip data. Increased methylation of genes known to play a role in metabolism (Cyp4f13) and decreased methylation of genes associated with development (Nlgn3, Elavl2, Sox21 and Sim1), imprinting (Igf2r) and chromatin (Hist1h3d) was confirmed. In a mouse model for FASD, we show for the first time that alcohol exposure during early neurulation can induce aberrant changes in DNA methylation patterns with associated changes

  9. Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation.

    PubMed

    Liu, Yunlong; Balaraman, Yokesh; Wang, Guohua; Nephew, Kenneth P; Zhou, Feng C

    2009-10-01

    Alcohol exposure during development can cause variable neurofacial deficit and growth retardation known as fetal alcohol spectrum disorders (FASD). The mechanism underlying FASD is not fully understood. However, alcohol, which is known to affect methyl donor metabolism, may induce aberrant epigenetic changes contributing to FASD. Using a tightly controlled whole-embryo culture, we investigated the effect of alcohol exposure (88mM) at early embryonic neurulation on genome-wide DNA methylation and gene expression in the C57BL/6 mouse. The DNA methylation landscape around promoter CpG islands at early mouse development was analyzed using MeDIP (methylated DNA immunoprecipitation) coupled with microarray (MeDIP-chip). At early neurulation, genes associated with high CpG promoters (HCP) had a lower ratio of methylation but a greater ratio of expression. Alcohol-induced alterations in DNA methylation were observed, particularly in genes on chromosomes 7, 10, and X; remarkably, a >10 fold increase in the number of genes with increased methylation on chromosomes 10 and X was observed in alcohol-exposed embryos with a neural tube defect phenotype compared to embryos without a neural tube defect. Significant changes in methylation were seen in imprinted genes, genes known to play roles in cell cycle, growth, apoptosis, cancer, and in a large number of genes associated with olfaction. Altered methylation was associated with significant (p<0.01) changes in expression for 84 genes. Sequenom EpiTYPER DNA methylation analysis was used for validation of the MeDIP-chip data. Increased methylation of genes known to play a role in metabolism (Cyp4f13) and decreased methylation of genes associated with development (Nlgn3, Elavl2, Sox21 and Sim1), imprinting (Igf2r) and chromatin (Hist1h3d) was confirmed. In a mouse model for FASD, we show for the first time that alcohol exposure during early neurulation can induce aberrant changes in DNA methylation patterns with associated changes in

  10. MiRNA-mediated regulation of cell signaling and homeostasis in the early mouse embryo.

    PubMed

    Pernaute, Barbara; Spruce, Thomas; Rodriguez, Tristan A; Manzanares, Miguel

    2011-02-15

    At the time of implantation the mouse embryo is composed of three tissues the epiblast, trophectoderm and primitive endoderm. As development progresses the epiblast goes on to form the foetus whilst the trophectoderm and primitive endoderm give rise to extra-embryonic structures with important roles in embryo patterning and nutrition. Dramatic changes in gene expression occur during early embryo development and these require regulation at different levels. miRNAs are small non coding RNAs that have emerged over the last decade as important post-transcriptional repressors of gene expression. The roles played by miRNAs during early mammalian development are only starting to be elucidated. In order to gain insight into the function of miRNAs in the different lineages of the early mouse embryo we have analysed in depth the phenotype of embryos and extra-embryonic stem cells mutant for the miRNA maturation protein Dicer. This study revealed that miRNAs are involved in regulating cell signaling and homeostasis in the early embryo. Specifically, we identified a role for miRNAs in regulating the Erk signaling pathway in the extra-embryonic endoderm, cell cycle progression in extra-embryonic tissues and apoptosis in the epiblast.

  11. Analysis of Stroma Labeling During Multiple Passage of a Sarcoma Imageable Patient-Derived Orthotopic Xenograft (iPDOX) in Red Fluorescent Protein Transgenic Nude Mice.

    PubMed

    Kiyuna, Tasuku; Murakami, Takashi; Tome, Yasunori; Kawaguchi, Kei; Igarashi, Kentaro; Miyake, Kentaro; Kanaya, Fuminori; Singh, Arun; Eilber, Fritz C; Hoffman, Robert M

    2017-10-01

    A patient-derived orthotopic xenograft (PDOX) model of undifferentiated pleomorphic sarcoma (UPS) was previously established that acquired red fluorescent protein (RFP)-expressing stroma by growth in an RFP transgenic nude mouse. In the present study, an imageable PDOX model (iPDOX) of UPS was established by orthotopic implantation in the biceps femoris of transgenic RFP nude mice. After the tumors grew to a diameter of 10 mm, they were harvested and the brightest portion of the tumors were subsequently orthotopically transplanted to both RFP and non-colored nude mice. The UPS PDOX tumor was again transplanted to RFP transgenic and non-colored nude mice, and finally a 3rd passage was made in the same manner. Five UPS tumors from each passage in both RFP and non-colored mouse models were harvested. The FV1,000 confocal microscope was used to visualize and quantitate the RFP area of the resected tumors. The average percent fluorescent area in the first passage of RFP mice was 34 ± 22%; in the second passage, 34 ± 20%; and 36 ± 11% in the third passage of RFP transgenic nude mice. The average tumor RFP area in the first passage from RFP mice to non-colored mice was 20 ± 7%; in the second passage, 28 ± 11%; in the third passage was 27 ± 13%. The present results demonstrate the extensive and stable acquisition of stroma by the UPS-tumor growing orthotopically in transgenic RFP nude mice (iPDOX). This model can be used for screening for effective drugs for individual patients and drug discovery. J. Cell. Biochem. 118: 3367-3371, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. Tissue morphodynamics shaping the early mouse embryo.

    PubMed

    Sutherland, Ann E

    2016-07-01

    Generation of the elongated vertebrate body plan from the initially radially symmetrical embryo requires comprehensive changes to tissue form. These shape changes are generated by specific underlying cell behaviors, coordinated in time and space. Major principles and also specifics are emerging, from studies in many model systems, of the cell and physical biology of how region-specific cell behaviors produce regional tissue morphogenesis, and how these, in turn, are integrated at the level of the embryo. New technical approaches have made it possible more recently, to examine the morphogenesis of the mouse embryo in depth, and to elucidate the underlying cellular mechanisms. This review focuses on recent advances in understanding the cellular basis for the early fundamental events that establish the basic form of the embryo. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Hydroacoustic Evaluation of Juvenile Salmonid Passage and Distribution at Lookout Point Dam, 2010

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

    Khan, Fenton; Johnson, Gary E.; Royer, Ida M.

    Pacific Northwest National Laboratory evaluated juvenile salmonid passage and distribution at Lookout Point Dam (LOP) on the Middle Fork Willamette River for the U.S. Army Corps of Engineers, Portland District (USACE), to provide data to support decisions on long-term measures to enhance downstream passage at LOP and others dams in USACE's Willamette Valley Project. This study was conducted in response to the listing of Upper Willamette River Spring Chinook salmon (Oncorhynchus tshawytscha) and Upper Willamette River steelhead (O. mykiss) as threatened under the Endangered Species Act. We conducted a hydroacoustic evaluation of juvenile salmonid passage and distribution at LOP duringmore » February 2010 through January 2011. Findings from this 1 year of study should be applied carefully because annual variation can be expected due to variability in adult salmon escapement, egg-to-fry and fry-to-smolt survival rates, reservoir rearing and predation, dam operations, and weather. Fish passage rates for smolt-size fish (> {approx}90 mm and < 300 mm) were highest during December-January and lowest in mid-summer through early fall. Passage peaks were also evident in early spring, early summer, and late fall. During the entire study period, an estimated total of 142,463 fish {+-} 4,444 (95% confidence interval) smolt-size fish passed through turbine penstock intakes. Of this total, 84% passed during December-January. Run timing for small-size fish ({approx}65-90 mm) peaked (702 fish) on December 18. Diel periodicity of smolt-size fish showing crepuscular peaks was evident in fish passage into turbine penstock intakes. Relatively few fish passed into the Regulating Outlets (ROs) when they were open in summer (2 fish/d) and winter (8 fish/d). Overall, when the ROs were open, RO efficiency (RO passage divided by total project passage) was 0.004. In linear regression analyses, daily fish passage (turbines and ROs combined) for smolt-size fish was significantly related to

  14. Profiling analysis of long non-coding RNAs in early postnatal mouse hearts

    PubMed Central

    Sun, Xiongshan; Han, Qi; Luo, Hongqin; Pan, Xiaodong; Ji, Yan; Yang, Yao; Chen, Hanying; Wang, Fangjie; Lai, Wenjing; Guan, Xiao; Zhang, Qi; Tang, Yuan; Chu, Jianhong; Yu, Jianhua; Shou, Weinian; Deng, Youcai; Li, Xiaohui

    2017-01-01

    Mammalian cardiomyocytes undergo a critical hyperplastic-to-hypertrophic growth transition at early postnatal age, which is important in establishing normal physiological function of postnatal hearts. In the current study, we intended to explore the role of long non-coding (lnc) RNAs in this transitional stage. We analyzed lncRNA expression profiles in mouse hearts at postnatal day (P) 1, P7 and P28 via microarray. We identified 1,146 differentially expressed lncRNAs with more than 2.0-fold change when compared the expression profiles of P1 to P7, P1 to P28, and P7 to P28. The neighboring genes of these differentially expressed lncRNAs were mainly involved in DNA replication-associated biological processes. We were particularly interested in one novel cardiac-enriched lncRNA, ENSMUST00000117266, whose expression was dramatically down-regulated from P1 to P28 and was also sensitive to hypoxia, paraquat, and myocardial infarction. Knockdown ENSMUST00000117266 led to a significant increase of neonatal mouse cardiomyocytes in G0/G1 phase and reduction in G2/M phase, suggesting that ENSMUST00000117266 is involved in regulating cardiomyocyte proliferative activity and is likely associated with hyperplastic-to-hypertrophic growth transition. In conclusion, our data have identified a large group of lncRNAs presented in the early postnatal mouse heart. Some of these lncRNAs may have important functions in cardiac hyperplastic-to-hypertrophic growth transition. PMID:28266538

  15. Low p16INK4a Expression in Early Passage Human Prostate Basal Epithelial Cells Enables Immortalization by Telomerase Expression Alone.

    PubMed

    Graham, Mindy Kim; Principessa, Lorenzo; Antony, Lizamma; Meeker, Alan K; Isaacs, John T

    2017-03-01

    There are two principal senescence barriers that must be overcome to successfully immortalize primary human epithelial cells in culture, stress-induced senescence, and replicative senescence. The p16 INK4a /retinoblastoma protein (p16/Rb) pathway mediates stress-induced senescence, and is generally upregulated by primary epithelial cells in response to the artificial conditions from tissue culture. Replicative senescence is associated with telomere loss. Following each round of cell division, telomeres progressively shorten. Once telomeres shorten to a critical length, the DNA damage response pathway is activated, and the tumor suppressor p53 pathway triggers replicative senescence. Exogenous expression of telomerase in normal human epithelial cells extends the replicative capacity of cells, and in some cases, immortalizes cells. However reliable immortalization of epithelial cells usually requires telomerase activity coupled with inactivation of the p16/Rb pathway. A lentiviral vector, pLOX-TERT-iresTK (Addgene #12245), containing a CMV promoter upstream of a bicistronic coding cassette that includes loxP sites flanking the catalytic subunit of human telomerase gene (TERT) and herpes simplex virus type-1 thymidine kinase gene (HSV1-tk) was used to transduce normal prostate basal epithelial cells (PrECs) initiated in cell culture from prostate cancer patients undergoing radical prostatectomies. Transduction of early (i.e., <7) passage PrECs with TERT led to successful immortalization. However, attempts to immortalize late (i.e., >7) passage PrECs were unsuccessful. Late passage PrECs, which acquired elevated p16, were unable to overcome the senescence barrier. Immortalized PrECs (TERT-PrECs) retained a normal male karyotype and low p16 expression. Additionally, TERT-PrECs were non-tumorigenic when inoculated into intact male immunodeficient NSG mice. The present studies document that early passage human PrECs have sufficiently low p16 to permit immortalization by

  16. Effects of Passage Number and Differentiation Protocol on the Generation of Dopaminergic Neurons from Rat Bone Marrow-Derived Mesenchymal Stem Cells.

    PubMed

    Shall, Gabrielle; Menosky, Megan; Decker, Sarah; Nethala, Priya; Welchko, Ryan; Leveque, Xavier; Lu, Ming; Sandstrom, Michael; Hochgeschwender, Ute; Rossignol, Julien; Dunbar, Gary

    2018-03-02

    Multiple studies have demonstrated the ability of mesenchymal stem cells (MSCs) to differentiate into dopamine-producing cells, in vitro and in vivo, indicating their potential to be used in the treatment of Parkinson's disease (PD). However, there are discrepancies among studies regarding the optimal time (i.e., passage number) and method for dopaminergic induction, in vitro. In the current study, we compared the ability of early (P4) and later (P40) passaged bone marrow-derived MSCs to differentiate into dopaminergic neurons using two growth-factor-based approaches. A direct dopaminergic induction (DDI) was used to directly convert MSCs into dopaminergic neurons, and an indirect dopaminergic induction (IDI) was used to direct MSCs toward a neuronal lineage prior to terminal dopaminergic differentiation. Results indicate that both early and later passaged MSCs exhibited positive expression of neuronal and dopaminergic markers following either the DDI or IDI protocols. Additionally, both early and later passaged MSCs released dopamine and exhibited spontaneous neuronal activity following either the DDI or IDI. Still, P4 MSCs exhibited significantly higher spiking and bursting frequencies as compared to P40 MSCs. Findings from this study provide evidence that early passaged MSCs, which have undergone the DDI, are more efficient at generating dopaminergic-like cells in vitro, as compared to later passaged MSCs or MSCs that have undergone the IDI.

  17. Intra-spindle Microtubule Assembly Regulates Clustering of Microtubule-Organizing Centers during Early Mouse Development.

    PubMed

    Watanabe, Sadanori; Shioi, Go; Furuta, Yasuhide; Goshima, Gohta

    2016-04-05

    Errors during cell division in oocytes and early embryos are linked to birth defects in mammals. Bipolar spindle assembly in early mouse embryos is unique in that three or more acentriolar microtubule-organizing centers (MTOCs) are initially formed and are then clustered into two spindle poles. Using a knockout mouse and live imaging of spindles in embryos, we demonstrate that MTOC clustering during the blastocyst stage requires augmin, a critical complex for MT-dependent MT nucleation within the spindle. Functional analyses in cultured cells with artificially increased numbers of centrosomes indicate that the lack of intra-spindle MT nucleation, but not loss of augmin per se or overall reduction of spindle MTs, is the cause of clustering failure. These data suggest that onset of mitosis with three or more MTOCs is turned into a typical bipolar division through augmin-dependent intra-spindle MT assembly. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Culturing primary mouse pancreatic ductal cells.

    PubMed

    Reichert, Maximilian; Rhim, Andrew D; Rustgi, Anil K

    2015-06-01

    The most common subtype of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC). PDAC resembles ductal cells morphologically. To study pancreatic ductal cell (PDC) and pancreatic intraepithelial neoplasia (PanIN)/PDAC biology, it is essential to have reliable in vitro culture conditions. Here we describe a methodology to isolate, culture, and passage PDCs and duct-like cells from the mouse pancreas. It can be used to isolate cells from genetically engineered mouse models (GEMMs), providing a valuable tool to study disease models in vitro to complement in vivo findings. The culture conditions allow epithelial cells to outgrow fibroblast and other "contaminating" cell types within a few passages. However, the resulting cultures, although mostly epithelial, are not completely devoid of fibroblasts. Regardless, this protocol provides guidelines for a robust in vitro culture system to isolate, maintain, and expand primary pancreatic ductal epithelial cells. It can be applied to virtually all GEMMs of pancreatic disease and other diseases and cancers that arise from ductal structures. Because most carcinomas resemble ductal structures, this protocol has utility in the study of other cancers in addition to PDAC, such as breast and prostate cancers. © 2015 Cold Spring Harbor Laboratory Press.

  19. Passage-dependent morphological and phenotypical changes of a canine histiocytic sarcoma cell line (DH82 cells).

    PubMed

    Heinrich, Franziska; Contioso, Vanessa Bono; Stein, Veronika M; Carlson, Regina; Tipold, Andrea; Ulrich, Reiner; Puff, Christina; Baumgärtner, Wolfgang; Spitzbarth, Ingo

    2015-01-15

    DH82 cells represent a permanent macrophage cell line isolated from a dog with histiocytic sarcoma (HS) and are commonly used in various fields of research upon infection and cancer, respectively. Despite its frequent use, data on cell surface antigen expression of this cell line are fragmentary and in part inconsistent. We therefore aimed at a detailed morphological and antigenic characterization of DH82 cells with respect to passage-dependent differences. Cellular morphology of early (≤ 13) and late (≥ 66) passages of DH82 cells was evaluated via scanning electron microscopy. Moreover, cells were labelled with 10 monoclonal antibodies directed against CD11c, CD14, CD18, CD44, CD45, CD80, CD86, MHC-I, MHC-II, and ICAM-1 for flow cytometric analysis. Early passage cells were characterized by round cell bodies with abundant small cytoplasmic projections whereas later passages exhibited a spindle-shaped morphology with large processes. The percentage of CD11c-, CD14-, CD18-, CD45-, and CD80 positive cells significantly decreased in late passages whereas the expression of CD44, CD86, MHC-I, MHC-II and ICAM-1 remained unchanged. DH82 cells represent a remarkably heterogeneous cell line with divergent antigenic and morphologic properties. The present findings have important implications for future studies, which should consider distinct characteristics with regard to the used passage. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. PASSAGES experiment

    NASA Image and Video Library

    2010-10-19

    ISS025-E-008371 (20 Oct. 2010) --- NASA astronaut Doug Wheelock, Expedition 25 commander, uses Neurospat hardware to perform a science session with the European Space Agency PASSAGES experiment in the Columbus laboratory of the International Space Station. PASSAGES is designed to test how astronauts interpret visual information in weightlessness. It aims at studying the effects of microgravity on the use of the ‘Eye-Height’ strategy for estimating allowed actions in an environment, and whether this could possibly decrease after a long exposure to weightlessness.

  1. Hydroacoustic Evaluation of Overwintering Summer Steelhead Fallback and Kelt Passage at The Dalles Dam, 2009-2010

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

    Khan, Fenton; Johnson, Gary E.; Weiland, Mark A.

    2010-07-31

    This report presents the results of an evaluation of overwintering summer steelhead (Oncorhynchus mykiss) fallback and early out-migrating steelhead kelts downstream passage at The Dalles Dam (TDA) sluiceway and turbines during fall/winter 2009 through early spring 2010. The study was conducted by the Pacific Northwest National Laboratory (PNNL) for the U.S. Army Corps of Engineers, Portland District (USACE). The goal of this study was to characterize adult steelhead spatial and temporal distributions and passage rates at the sluiceway and turbines for fisheries managers and engineers to use in decision-making relative to sluiceway operations. The study was from November 1, 2009more » to April 10, 2010. The study was divided into three study periods: Period 1, November 1 - December 15, 2009 for a fall/winter sluiceway and turbine study; Period 2, December 16, 2009 - February 28, 2010 for a turbine only study; Period 3, March 1 - April 10, 2010 for a spring sluiceway and turbine study. Sluiceway operations were scheduled to begin on March 1 for this study; however, because of an oil spill cleanup near the sluice outfall, sluiceway operations were delayed until March 8, 2010, therefore the spring study period did not commence until March 8. The study objectives were to (1) estimate the number and distribution of overwintering summer steelhead fallbacks and kelt-sized acoustic targets passing into the sluiceway and turbines at TDA between November 1 and December 15, 2009 and March 1 and April 10, 2010, and (2) estimate the numbers and distribution of adult steelhead and kelt-sized targets passing into turbine units between December 16, 2009 and February 28, 2010. We obtained fish passage data using fixed-location hydroacoustics. For Period 1, overwintering summer steelhead fallback occurred throughout the 45-day study period. A total of 879 {+-} 165 (95% CI) steelhead targets passed through the powerhouse and sluiceway during November 1 to December 15, 2009. Ninety

  2. Effect of passage number on electrophoretic mobility distributions of cultured human embryonic kidney cells

    NASA Technical Reports Server (NTRS)

    Kunze, M. E.

    1985-01-01

    A systematic investigation was undertaken to characterize population shifts that occur in cultured human embryonic kidney cells as a function of passage number in vitro after original explantation. This approach to cell population shift analysis follows the suggestion of Mehreshi, Klein and Revesz that perturbed cell populations can be characterized by electrophoretic mobility distributions if they contain subpopulations with different electrophoretic mobilities. It was shown that this is the case with early passage cultured human embryo cells.

  3. Early Microglia Activation Precedes Photoreceptor Degeneration in a Mouse Model of CNGB1-Linked Retinitis Pigmentosa.

    PubMed

    Blank, Thomas; Goldmann, Tobias; Koch, Mirja; Amann, Lukas; Schön, Christian; Bonin, Michael; Pang, Shengru; Prinz, Marco; Burnet, Michael; Wagner, Johanna E; Biel, Martin; Michalakis, Stylianos

    2017-01-01

    Retinitis pigmentosa (RP) denotes a family of inherited blinding eye diseases characterized by progressive degeneration of rod and cone photoreceptors in the retina. In most cases, a rod-specific genetic defect results in early functional loss and degeneration of rods, which is followed by degeneration of cones and loss of daylight vision at later stages. Microglial cells, the immune cells of the central nervous system, are activated in retinas of RP patients and in several RP mouse models. However, it is still a matter of debate whether activated microglial cells may be responsible for the amplification of the typical degenerative processes. Here, we used Cngb1 -/- mice, which represent a slow degenerative mouse model of RP, to investigate the extent of microglia activation in retinal degeneration. With a combination of FACS analysis, immunohistochemistry and gene expression analysis we established that microglia in the Cngb1 -/- retina were already activated in an early, predegenerative stage of the disease. The evidence available so far suggests that early retinal microglia activation represents a first step in RP, which might initiate or accelerate photoreceptor degeneration.

  4. Expression of the proliferation marker Ki-67 during early mouse development.

    PubMed

    Winking, H; Gerdes, J; Traut, W

    2004-01-01

    In somatic tissues, the mouse Ki-67 protein (pKi-67) is expressed in proliferating cells only. Depending on the stage of the cell cycle, pKi-67 is associated with different nuclear domains: with euchromatin as part of the perichromosomal layer, with centromeric heterochromatin, and with the nucleolus. In gametes, sex-specific expression is evident. Mature MII oocytes contain pKi-67, whereas pKi-67 is not detectable in mature sperm. We investigated the re-establishment of the cell cycle-dependent distribution of pKi-67 during early mouse development. After fertilization, male and female pronuclei exhibited very little or no pKi-67, while polar bodies were pKi-67 positive. Towards the end of the first cell cycle, prophase chromosomes of male and female pronuclei simultaneously got decorated with pKi-67. In 2-cell embryos, the distribution pattern changed, presumably depending on the progress of development of the embryo, from a distribution all over the nucleus to a preferential location in the nucleolus precursor bodies (NPBs). From the 4-cell stage onwards, pKi-67 showed the regular nuclear relocations known from somatic tissues: during mitosis the protein was found covering the chromosome arms as a constituent of the perichromosomal layer, in early G1 it was distributed in the whole nucleus, and for the rest of the cell cycle it was associated with NPBs or with the nucleolus. Copyright 2004 S. Karger AG, Basel

  5. Early biomarkers of doxorubicin-induced heart injury in a mouse model

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

    Desai, Varsha G., E-mail: varsha.desai@fda.hhs.gov; Kwekel, Joshua C.; Vijay, Vikrant

    Cardiac troponins, which are used as myocardial injury markers, are released in plasma only after tissue damage has occurred. Therefore, there is a need for identification of biomarkers of earlier events in cardiac injury to limit the extent of damage. To accomplish this, expression profiling of 1179 unique microRNAs (miRNAs) was performed in a chronic cardiotoxicity mouse model developed in our laboratory. Male B6C3F{sub 1} mice were injected intravenously with 3 mg/kg doxorubicin (DOX; an anti-cancer drug), or saline once a week for 2, 3, 4, 6, and 8 weeks, resulting in cumulative DOX doses of 6, 9, 12, 18,more » and 24 mg/kg, respectively. Mice were euthanized a week after the last dose. Cardiac injury was evidenced in mice exposed to 18 mg/kg and higher cumulative DOX dose whereas examination of hearts by light microscopy revealed cardiac lesions at 24 mg/kg DOX. Also, 24 miRNAs were differentially expressed in mouse hearts, with the expression of 1, 1, 2, 8, and 21 miRNAs altered at 6, 9, 12, 18, and 24 mg/kg DOX, respectively. A pro-apoptotic miR-34a was the only miRNA that was up-regulated at all cumulative DOX doses and showed a significant dose-related response. Up-regulation of miR-34a at 6 mg/kg DOX may suggest apoptosis as an early molecular change in the hearts of DOX-treated mice. At 12 mg/kg DOX, up-regulation of miR-34a was associated with down-regulation of hypertrophy-related miR-150; changes observed before cardiac injury. These findings may lead to the development of biomarkers of earlier events in DOX-induced cardiotoxicity that occur before the release of cardiac troponins. - Highlights: • Upregulation of miR-34a before doxorubicin-induced cardiac tissue injury • Apoptosis might be an early event in mouse heart during doxorubicin treatment. • Expression of miR-150 declined before doxorubicin-induced cardiac tissue injury.« less

  6. Hydroacoustic Evaluation of Overwintering Summer Steelhead Fallback and Kelt Passage at The Dalles Dam 2008-2009

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

    Khan, Fenton; Johnson, Gary E.; Weiland, Mark A.

    2009-09-01

    This report presents the results of an evaluation of overwintering summer steelhead (Oncorhynchus mykiss) fallback and early out-migrating steelhead kelts downstream passage at The Dalles Dam (TDA) sluiceway and turbines during fall/winter 2008 and early spring 2009, respectively. The study was conducted by the Pacific Northwest National Laboratory (PNNL) for the U.S. Army Corps of Engineers, Portland District (USACE). Operating the sluiceway reduces the potential for hydropower production. However, this surface flow outlet may be the optimal non-turbine route for fallbacks in late fall after the sluiceway is typically closed for juvenile fish passage and for overwintering summer steelhead andmore » kelt passage in the early spring before the start of the voluntary spill season. The goal of this study was to characterize adult steelhead spatial and temporal distributions and passage rates at the sluiceway and turbines, and their movements in front of the sluiceway at TDA to inform fisheries managers’ and engineers’ decision-making relative to sluiceway operations. The study periods were from November 1 to December 15, 2008 (45 days) and from March 1 to April 9, 2009 (40 days). The study objectives were to 1) estimate the number and distribution of overwintering summer steelhead fallbacks and kelt-sized acoustic targets passing into the sluiceway and turbines at TDA during the two study periods, respectively, and 2) assess the behavior of these fish in front of sluice entrances. We obtained fish passage data using fixed-location hydroacoustics and fish behavior data using acoustic imaging. For the overwintering summer steelhead, fallback occurred throughout the 45-day study period. We estimated that a total of 1790 ± 250 (95% confidence interval) summer steelhead targets passed through the powerhouse intakes and operating sluices during November 1 to December 15, 2008. Ninety five percent of these fish passed through the sluiceway. Therefore, without the

  7. Hydroacoustic Evaluation of Juvenile Salmonid Passage and Distribution at Detroit Dam, 2011

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

    Khan, Fenton; Royer, Ida M.; Johnson, Gary E.

    Pacific Northwest National Laboratory evaluated juvenile salmonid passage and distribution at Detroit Dam (DET) on the North Santiam River, Oregon for the U.S. Army Corps of Engineers (USACE) to provide data to support decisions on long-term measures to enhance downstream passage at DET and others dams in USACE’s Willamette Valley Project. This study was conducted in response to regulatory requirements necessitated by the listing of Upper Willamette River Spring Chinook salmon (Oncorhynchus tshawytscha) and Upper Willamette River steelhead (O. mykiss) as threatened under the Endangered Species Act. The goal of the study was to provide information of juvenile salmonid passagemore » and distribution at DET from February 2011 through February 2012. The results of the hydroacoustic study provide new and, in some cases, first-ever data on passage estimates, run timing, distributions, and relationships between fish passage and environmental variables at the dam. This information will inform management decisions on the design and development of surface passage and collection devices to help restore Chinook salmon populations in the North Santiam River watershed above DET. During the entire study period, an estimated total of 182,526 smolt-size fish (±4,660 fish, 95% CI) passed through turbine penstock intakes. Run timing peaked in winter and early spring months. Passage rates were highest during late fall, winter and early spring months and low during summer. Horizontal distribution for hours when both turbine units were operated simultaneously indicated Unit 2 passed almost twice as much fish as Unit 1. Diel distribution for smolt-size fish during the study period was fairly uniform, indicating fish were passing the turbines at all times of the day. A total of 5,083 smolt-size fish (± 312 fish, 95% CI) were estimated passed via the spillway when it was open between June 23 and September 27, 2011. Daily passage was low at the spillway during the June-August period

  8. Identification and functional analysis of long non-coding RNAs in human and mouse early embryos based on single-cell transcriptome data

    PubMed Central

    Qiu, Jia-jun; Ren, Zhao-rui; Yan, Jing-bin

    2016-01-01

    Epigenetics regulations have an important role in fertilization and proper embryonic development, and several human diseases are associated with epigenetic modification disorders, such as Rett syndrome, Beckwith-Wiedemann syndrome and Angelman syndrome. However, the dynamics and functions of long non-coding RNAs (lncRNAs), one type of epigenetic regulators, in human pre-implantation development have not yet been demonstrated. In this study, a comprehensive analysis of human and mouse early-stage embryonic lncRNAs was performed based on public single-cell RNA sequencing data. Expression profile analysis revealed that lncRNAs are expressed in a developmental stage–specific manner during human early-stage embryonic development, whereas a more temporal-specific expression pattern was identified in mouse embryos. Weighted gene co-expression network analysis suggested that lncRNAs involved in human early-stage embryonic development are associated with several important functions and processes, such as oocyte maturation, zygotic genome activation and mitochondrial functions. We also found that the network of lncRNAs involved in zygotic genome activation was highly preservative between human and mouse embryos, whereas in other stages no strong correlation between human and mouse embryo was observed. This study provides insight into the molecular mechanism underlying lncRNA involvement in human pre-implantation embryonic development. PMID:27542205

  9. Characterization of a novel genetically obese mouse model demonstrating early onset hyperphagia and hyperleptinemia.

    PubMed

    Nakahara, Keiko; Bannai, Makoto; Maruyama, Keisuke; Suzuki, Yoshihiro; Okame, Rieko; Murakami, Noboru

    2013-08-01

    Obesity is a critical risk factor for the development of metabolic syndrome, and many obese animal models are used to investigate the mechanisms responsible for the appearance of symptoms. To establish a new obese mouse model, we screened ∼13,000 ICR mice and discovered a mouse demonstrating spontaneous obesity. We named this mouse "Daruma" after a traditional Japanese ornament. Following the fixation of the genotype, these animals exhibited obese phenotypes according to Mendel's law of inheritance. In the Daruma mouse, the leptin receptor gene sequence carried two base mutations that are good candidates for the variation(s) responsible for the obese phenotype. The Daruma mice developed characteristic visceral fat accumulation at 4 wk of age, and the white adipose and liver tissues exhibited increases in cell size and lipid droplets, respectively. No histological abnormalities were observed in other tissues of the Daruma mice, even after the mice reached 25 wk of age. Moreover, the onset of impaired leptin signaling was early and manifested as hyperleptinemia and hyperinsulinemia. Pair feeding completely inhibited obesity, although these mice rapidly developed hyperphagia and obesity followed by hyperleptinemia when pair feeding ceased and free-access feeding was permitted. Therefore, the Daruma mice exhibited unique characteristics and may be a good model for studying human metabolic syndrome.

  10. In vivo characterization of early-stage radiation skin injury in a mouse model by two-photon microscopy

    PubMed Central

    Jang, Won Hyuk; Shim, Sehwan; Wang, Taejun; Yoon, Yeoreum; Jang, Won-Suk; Myung, Jae Kyung; Park, Sunhoo; Kim, Ki Hean

    2016-01-01

    Ionizing radiation (IR) injury is tissue damage caused by high energy electromagnetic waves such as X-ray and gamma ray. Diagnosis and treatment of IR injury are difficult due to its characteristics of clinically latent post-irradiation periods and the following successive and unpredictable inflammatory bursts. Skin is one of the many sensitive organs to IR and bears local injury upon exposure. Early-stage diagnosis of IR skin injury is essential in order to maximize treatment efficiency and to prevent the aggravation of IR injury. In this study, early-stage changes of the IR injured skin at the cellular level were characterized in an in vivo mouse model by two-photon microscopy (TPM). Various IR doses were applied to the mouse hind limbs and the injured skin regions were imaged daily for 6 days after IR irradiation. Changes in the morphology and distribution of the epidermal cells and damage of the sebaceous glands were observed before clinical symptoms. These results showed that TPM is sensitive to early-stage changes of IR skin injury and may be useful for its diagnosis. PMID:26755422

  11. First Passage under Restart

    NASA Astrophysics Data System (ADS)

    Pal, Arnab; Reuveni, Shlomi

    2017-01-01

    First passage under restart has recently emerged as a conceptual framework suitable for the description of a wide range of phenomena, but the endless variety of ways in which restart mechanisms and first passage processes mix and match hindered the identification of unifying principles and general truths. Hope that these exist came from a recently discovered universality displayed by processes under optimal, constant rate, restart—but extensions and generalizations proved challenging as they marry arbitrarily complex processes and restart mechanisms. To address this challenge, we develop a generic approach to first passage under restart. Key features of diffusion under restart—the ultimate poster boy for this wide and diverse class of problems—are then shown to be completely universal.

  12. Early life exposure to bisphenol A investigated in mouse models of airway allergy, food allergy and oral tolerance.

    PubMed

    Nygaard, Unni Cecilie; Vinje, Nina Eriksen; Samuelsen, Mari; Andreassen, Monica; Groeng, Else-Carin; Bølling, Anette Kocbach; Becher, Rune; Lovik, Martinus; Bodin, Johanna

    2015-09-01

    The impact of early life exposure to bisphenol A (BPA) through drinking water was investigated in mouse models of respiratory allergy, food allergy and oral tolerance. Balb/c mice were exposed to BPA (0, 10 or 100 μg/ml), and the offspring were intranasally exposed to the allergen ovalbumin (OVA). C3H/HeJ offspring were sensitized with the food allergen lupin by intragastric gavage, after exposure to BPA (0, 1, 10 or 100 μg/ml). In separate offspring, oral tolerance was induced by gavage of 5 mg lupin one week before entering the protocol for the food allergy induction. In the airway allergy model, BPA (100 μg/ml) caused increased eosinophil numbers in bronchoalveolar lavage fluid (BALF) and a trend of increased OVA-specific IgE levels. In the food allergy and tolerance models, BPA did not alter the clinical anaphylaxis or antibody responses, but induced alterations in splenocyte cytokines and decreased mouse mast cell protease (MMCP)-1 serum levels. In conclusion, early life exposure to BPA through drinking water modestly augmented allergic responses in a mouse model of airway allergy only at high doses, and not in mouse models for food allergy and tolerance. Thus, our data do not support that BPA promotes allergy development at exposure levels relevant for humans. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. ESA PASSAGES experiment

    NASA Image and Video Library

    2011-10-06

    ISS029-E-021641 (6 Oct. 2011) --- NASA astronaut Mike Fossum, Expedition 29 commander, uses Neurospat hardware to perform a science session with the European Space Agency PASSAGES experiment in the Columbus laboratory of the International Space Station. PASSAGES is designed to test how astronauts interpret visual information in weightlessness. It aims at studying the effects of microgravity on the use of the 'Eye-Height' strategy for estimating allowed actions in an environment, and whether this could possibly decrease after a long exposure to weightlessness.

  14. Brook trout passage performance through culverts

    USGS Publications Warehouse

    Goerig, Elsa; Castro-Santos, Theodore R.; Bergeron, Normand

    2016-01-01

    Culverts can restrict access to habitat for stream-dwelling fishes. We used passive integrated transponder telemetry to quantify passage performance of >1000 wild brook trout (Salvelinus fontinalis) attempting to pass 13 culverts in Quebec under a range of hydraulic and environmental conditions. Several variables influenced passage success, including complex interactions between physiology and behavior, hydraulics, and structural characteristics. The probability of successful passage was greater through corrugated metal culverts than through smooth ones, particularly among smaller fish. Trout were also more likely to pass at warmer temperatures, but this effect diminished above 15 °C. Passage was impeded at higher flows, through culverts with steep slopes, and those with deep downstream pools. This study provides insight on factors influencing brook trout capacity to pass culverts as well as a model to estimate passage success under various conditions, with an improved resolution and accuracy over existing approaches. It also presents methods that could be used to investigate passage success of other species, with implications for connectivity of the riverscape.

  15. ESA PASSAGES experiment

    NASA Image and Video Library

    2011-10-06

    ISS029-E-021636 (6 Oct. 2011) --- Japan Aerospace Exploration Agency astronaut Satoshi Furukawa, Expedition 29 flight engineer, uses Neurospat hardware to perform a science session with the European Space Agency PASSAGES experiment in the Columbus laboratory of the International Space Station. PASSAGES is designed to test how astronauts interpret visual information in weightlessness. It aims at studying the effects of microgravity on the use of the 'Eye-Height' strategy for estimating allowed actions in an environment, and whether this could possibly decrease after a long exposure to weightlessness.

  16. Tetraploid cells from cytokinesis failure induce aneuploidy and spontaneous transformation of mouse ovarian surface epithelial cells.

    PubMed

    Lv, Lei; Zhang, Tianwei; Yi, Qiyi; Huang, Yun; Wang, Zheng; Hou, Heli; Zhang, Huan; Zheng, Wei; Hao, Qiaomei; Guo, Zongyou; Cooke, Howard J; Shi, Qinghua

    2012-08-01

    Most ovarian cancers originate from the ovarian surface epithelium and are characterized by aneuploid karyotypes. Aneuploidy, a consequence of chromosome instability, is an early event during the development of ovarian cancers. However, how aneuploid cells are evolved from normal diploid cells in ovarian cancers remains unknown. In the present study, cytogenetic analyses of a mouse syngeneic ovarian cancer model revealed that diploid mouse ovarian surface epithelial cells (MOSECs) experienced an intermediate tetraploid cell stage, before evolving to aneuploid (mainly near-tetraploid) cells. Using long-term live-cell imaging followed by fluorescence in situ hybridization (FISH), we demonstrated that tetraploid cells originally arose from cytokinesis failure of bipolar mitosis in diploid cells, and gave rise to aneuploid cells through chromosome mis-segregation during both bipolar and multipolar mitoses. Injection of the late passage aneuploid MOSECs resulted in tumor formation in C57BL/6 mice. Therefore, we reveal a pathway for the evolution of diploid to aneuploid MOSECs and elucidate a mechanism for the development of near-tetraploid ovarian cancer cells.

  17. Transhilar passage in right graft live donor liver transplantation: intrahilar anatomy and its impact on operative strategy.

    PubMed

    Radtke, A; Sotiropoulos, G C; Molmenti, E P; Sgourakis, G; Schroeder, T; Beckebaum, S; Peitgen, H-O; Cicinnati, V R; Broelsch, C E; Broering, D C; Malagó, M

    2012-03-01

    The passage through the hilar plate during right graft live donor liver transplantation (LDLT) can have dangerous consequences for both donors and recipients. The purpose of our study was to delineate hilar transection and biliary reconstruction strategies in right graft LDLT, with special consideration of central and peripheral hilar anatomical variants. A total of 71 consecutive donors underwent preoperative three-dimensional (3D) CT reconstructions and virtual 3D hepatectomies. A three-modal hilar passage strategy was applied, and its impact on operative strategy analyzed. In 68.4% of cases, type I and II anatomical configurations allowed for an en block hilar transection with simple anastomotic reconstructions. In 23.6% of cases, donors had "difficult" type II and types III/IV hilar bile duct anatomy that required stepwise hilar transections and complex graft biliary reconstructions. Morbidity rates for our early (A) and recent (B) experience periods were 67% and 39%, respectively. (1) Our two-level classification and 3D imaging technique allowed for donor-individualized transhilar passage. (2) A stepwise transhilar passage was favored in types III and IV inside the right-sided hilar corridor. (3) Reconstruction techniques showed no ameliorating effect on early/late biliary morbidity rates. © copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

  18. Precision-cut rat, mouse, and human intestinal slices as novel models for the early-onset of intestinal fibrosis.

    PubMed

    Pham, Bao Tung; van Haaften, Wouter Tobias; Oosterhuis, Dorenda; Nieken, Judith; de Graaf, Inge Anne Maria; Olinga, Peter

    2015-04-01

    Intestinal fibrosis (IF) is a major complication of inflammatory bowel disease. IF research is limited by the lack of relevant in vitro and in vivo models. We evaluated precision-cut intestinal slices (PCIS) prepared from human, rat, and mouse intestine as ex vivo models mimicking the early-onset of (human) IF. Precision-cut intestinal slices prepared from human (h), rat (r), and mouse (m) jejunum, were incubated up to 72 h, the viability of PCIS was assessed by ATP content and morphology, and the gene expression of several fibrosis markers was determined. The viability of rPCIS decreased after 24 h of incubation, whereas mPCIS and hPCIS were viable up to 72 h of culturing. Furthermore, during this period, gene expression of heat shock protein 47 and plasminogen activator inhibitor 1 increased in all PCIS in addition to augmented expression of synaptophysin in hPCIS, fibronectin (Fn2) and TGF-β1 in rPCIS, and Fn2 and connective tissue growth factor (Ctgf) in mPCIS. Addition of TGF-β1 to rPCIS or mPCIS induced the gene expression of the fibrosis markers Pro-collagen1a1, Fn2, and Ctgf in both species. However, none of the fibrosis markers was further elevated in hPCIS. We successfully developed a novel ex vivo model that can mimic the early-onset of fibrosis in the intestine using human, rat, and mouse PCIS. Furthermore, in rat and mouse PCIS, TGF-β1 was able to even further increase the gene expression of fibrosis markers. This indicates that PCIS can be used as a model for the early-onset of IF. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  19. Hot Wax Sweeps Debris From Narrow Passages

    NASA Technical Reports Server (NTRS)

    Ricklefs, Steven K.

    1990-01-01

    Safe and effective technique for removal of debris and contaminants from narrow passages involves entrainment of undesired material in thermoplastic casting material. Semisolid wax slightly below melting temperature pushed along passage by pressurized nitrogen to remove debris. Devised to clean out fuel passages in main combustion chamber of Space Shuttle main engine. Also applied to narrow, intricate passages in internal-combustion-engine blocks, carburetors, injection molds, and other complicated parts.

  20. Drake Passage opening history: a synthesis of existing and new data from diverse proxies

    NASA Astrophysics Data System (ADS)

    Barbeau, D. L.; Scotia Project Team

    2011-12-01

    The tectonic opening of the Drake Passage marine gateway between the Antarctic Peninsula and southern South America enabled development of the Antarctic circumpolar current, which has been variably ascribed to establishment and/or expansion of Cenozoic ice caps on Antarctica. Despite the importance of this gateway, interpretations of its opening history vary greatly, and are widely debated. Using data collected using a variety of geologic, geochemical, geophysical, and paleobiologic techniques, I summarize existing and new constraints on the tectonic history of Drake Passage, and evaluate temporal and kinematic models for its opening. In particular, new data from sediment provenance and thermochronology of Drake Passage margins integrated with independent paleoclimate, eustasy and paleobiology studies suggest that this gateway may have begun opening at least as early as the Paleocene -- 15 Myr prior to the oldest previous estimates.

  1. Adaptation of influenza A(H1N1)pdm09 virus in experimental mouse models.

    PubMed

    Prokopyeva, E A; Sobolev, I A; Prokopyev, M V; Shestopalov, A M

    2016-04-01

    In the present study, three mouse-adapted variants of influenza A(H1N1)pdm09 virus were obtained by lung-to-lung passages of BALB/c, C57BL/6z and CD1 mice. The significantly increased virulence and pathogenicity of all of the mouse-adapted variants induced 100% mortality in the adapted mice. Genetic analysis indicated that the increased virulence of all of the mouse-adapted variants reflected the incremental acquisition of several mutations in PB2, PB1, HA, NP, NA, and NS2 proteins. Identical amino acid substitutions were also detected in all of the mouse-adapted variants of A(H1N1)pdm09 virus, including PB2 (K251R), PB1 (V652A), NP (I353V), NA (I106V, N248D) and NS1 (G159E). Apparently, influenza A(H1N1)pdm09 virus easily adapted to the host after serial passages in the lungs, inducing 100% lethality in the last experimental group. However, cross-challenge revealed that not all adapted variants are pathogenic for different laboratory mice. Such important results should be considered when using the influenza mice model. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Chromatin Immunoprecipitation in Early Mouse Embryos.

    PubMed

    García-González, Estela G; Roque-Ramirez, Bladimir; Palma-Flores, Carlos; Hernández-Hernández, J Manuel

    2018-01-01

    Epigenetic regulation is achieved at many levels by different factors such as tissue-specific transcription factors, members of the basal transcriptional apparatus, chromatin-binding proteins, and noncoding RNAs. Importantly, chromatin structure dictates the availability of a specific genomic locus for transcriptional activation as well as the efficiency with which transcription can occur. Chromatin immunoprecipitation (ChIP) is a method that allows elucidating gene regulation at the molecular level by assessing if chromatin modifications or proteins are present at a specific locus. Initially, the majority of ChIP experiments were performed on cultured cell lines and more recently this technique has been adapted to a variety of tissues in different model organisms. Using ChIP on mouse embryos, it is possible to document the presence or absence of specific proteins and chromatin modifications at genomic loci in vivo during mammalian development and to get biological meaning from observations made on tissue culture analyses. We describe here a ChIP protocol on freshly isolated mouse embryonic somites for in vivo analysis of muscle specific transcription factor binding on chromatin. This protocol has been easily adapted to other mouse embryonic tissues and has also been successfully scaled up to perform ChIP-Seq.

  3. Membrane with supported internal passages

    NASA Technical Reports Server (NTRS)

    Gonzalez-Martin, Anuncia (Inventor); Salinas, Carlos E. (Inventor); Cisar, Alan J. (Inventor); Hitchens, G. Duncan (Inventor); Murphy, Oliver J. (Inventor)

    2000-01-01

    The invention provides an improved proton exchange membrane for use in electrochemical cells having internal passages parallel to the membrane surface comprising permanent tubes preferably placed at the ends of the fluid passages. The invention also provides an apparatus and process for making the membrane, membrane and electrode assemblies fabricated using the membrane, and the application of the membrane and electrode assemblies to a variety of devices, both electrochemical and otherwise. The passages in the membrane extend from one edge of the membrane to another and allow fluid flow through the membrane and give access directly to the membrane.

  4. Detection and Evaluation of Early Breast Cancer via Magnetic Resonance Imaging: Studies of Mouse Models and Clinical Implementation

    DTIC Science & Technology

    2008-03-01

    CONTRACT NUMBER Detection and Evaluation of Early Breast Cancer via Magnetic Resonance Imaging: Studies of Mouse Models and Clinical Implementation...research proposed here can directly lead to clinical improvements in both early breast cancer detection, as well as effective breast cancer therapy. To date... cancer is a major prognostic factor in the management of the disease. In particular, detecting breast cancer in its pre-invasive form as ductal carcinoma

  5. Overlapping DNA Methylation Dynamics in Mouse Intestinal Cell Differentiation and Early Stages of Malignant Progression

    PubMed Central

    Forn, Marta; Díez-Villanueva, Anna; Merlos-Suárez, Anna; Muñoz, Mar; Lois, Sergi; Carriò, Elvira; Jordà, Mireia; Bigas, Anna; Batlle, Eduard; Peinado, Miguel A.

    2015-01-01

    Mouse models of intestinal crypt cell differentiation and tumorigenesis have been used to characterize the molecular mechanisms underlying both processes. DNA methylation is a key epigenetic mark and plays an important role in cell identity and differentiation programs and cancer. To get insights into the dynamics of cell differentiation and malignant transformation we have compared the DNA methylation profiles along the mouse small intestine crypt and early stages of tumorigenesis. Genome-scale analysis of DNA methylation together with microarray gene expression have been applied to compare intestinal crypt stem cells (EphB2high), differentiated cells (EphB2negative), ApcMin/+ adenomas and the corresponding non-tumor adjacent tissue, together with small and large intestine samples and the colon cancer cell line CT26. Compared with late stages, small intestine crypt differentiation and early stages of tumorigenesis display few and relatively small changes in DNA methylation. Hypermethylated loci are largely shared by the two processes and affect the proximities of promoter and enhancer regions, with enrichment in genes associated with the intestinal stem cell signature and the PRC2 complex. The hypermethylation is progressive, with minute levels in differentiated cells, as compared with intestinal stem cells, and reaching full methylation in advanced stages. Hypomethylation shows different signatures in differentiation and cancer and is already present in the non-tumor tissue adjacent to the adenomas in ApcMin/+ mice, but at lower levels than advanced cancers. This study provides a reference framework to decipher the mechanisms driving mouse intestinal tumorigenesis and also the human counterpart. PMID:25933092

  6. Passage of American shad: paradigms and realities

    USGS Publications Warehouse

    Haro, Alex; Castro-Santos, Theodore

    2012-01-01

    Despite more than 250 years of development, the passage of American shad Alosa sapidissima at dams and other barriers frequently remains problematic. Few improvements in design based on knowledge of the swimming, schooling, and migratory behaviors of American shad have been incorporated into passage structures. Large-scale technical fishways designed for the passage of adult salmonids on the Columbia River have been presumed to have good performance for American shad but have never been rigorously evaluated for this species. Similar but smaller fishway designs on the East Coast frequently have poor performance. Provision of effective downstream passage for both juvenile and postspawning adult American shad has been given little consideration in most passage projects. Ways to attract and guide American shad to both fishway entrances and downstream bypasses remain marginally understood. The historical development of passage structures for American shad has resulted in assumptions and paradigms about American shad behavior and passage that are frequently unsubstantiated by supporting data or appropriate experimentation. We propose that many of these assumptions and paradigms are either unfounded or invalid and that significant improvements to American shad upstream and downstream passage can be made via a sequential program of behavioral experimentation, application of experimental results to the physical and hydraulic design of new structures, and controlled tests of large-scale prototype structures in the laboratory and field.

  7. Activated ovarian endothelial cells promote early follicular development and survival.

    PubMed

    Kedem, Alon; Aelion-Brauer, Anate; Guo, Peipei; Wen, Duancheng; Ding, Bi-Sen; Lis, Raphael; Cheng, Du; Sandler, Vladislav M; Rafii, Shahin; Rosenwaks, Zev

    2017-09-19

    New data suggests that endothelial cells (ECs) elaborate essential "angiocrine factors". The aim of this study is to investigate the role of activated ovarian endothelial cells in early in-vitro follicular development. Mouse ovarian ECs were isolated using magnetic cell sorting or by FACS and cultured in serum free media. After a constitutive activation of the Akt pathway was initiated, early follicles (50-150 um) were mechanically isolated from 8-day-old mice and co-cultured with these activated ovarian endothelial cells (AOEC) (n = 32), gel (n = 24) or within matrigel (n = 27) in serum free media for 14 days. Follicular growth, survival and function were assessed. After 6 passages, flow cytometry showed 93% of cells grown in serum-free culture were VE-cadherin positive, CD-31 positive and CD 45 negative, matching the known EC profile. Beginning on day 4 of culture, we observed significantly higher follicular and oocyte growth rates in follicles co-cultured with AOECs compared with follicles on gel or matrigel. After 14 days of culture, 73% of primary follicles and 83% of secondary follicles co-cultured with AOEC survived, whereas the majority of follicles cultured on gel or matrigel underwent atresia. This is the first report of successful isolation and culture of ovarian ECs. We suggest that co-culture with activated ovarian ECs promotes early follicular development and survival. This model is a novel platform for the in vitro maturation of early follicles and for the future exploration of endothelial-follicular communication. In vitro development of early follicles necessitates a complex interplay of growth factors and signals required for development. Endothelial cells (ECs) may elaborate essential "angiocrine factors" involved in organ regeneration. We demonstrate that co-culture with ovarian ECs enables culture of primary and early secondary mouse ovarian follicles.

  8. Coupled climate impacts of the Drake Passage and the Panama Seaway

    NASA Astrophysics Data System (ADS)

    Yang, Simon; Galbraith, Eric; Palter, Jaime

    2014-07-01

    Tectonically-active gateways between ocean basins have modified ocean circulation over Earth history. Today, the Atlantic and Pacific are directly connected via the Drake Passage, which forms a barrier to the time-mean geostrophic transport between the subtropics and Antarctica. In contrast, during the warm early Cenozoic era, when Antarctica was ice-free, the Drake Passage was closed. Instead, at that time, the separation of North and South America provided a tropical seaway between the Atlantic and Pacific that remained open until the Isthmus of Panama formed in the relatively recent geological past. Ocean circulation models have previously been used to explore the individual impacts of the Drake Passage and the Panama Seaway, but rarely have the two gateways been considered together, and most explorations have used very simple atmospheric models. Here we use a coupled ocean-ice-atmosphere model (GFDL's CM2Mc), to simulate the impacts of a closed Drake Passage both with and without a Panama Seaway. We find that the climate response to a closed Drake Passage is relatively small when the Panama Seaway is absent, similar to prior studies, although the coupling to a dynamical atmosphere does increase the temperature change. However, with a Panama Seaway, closing Drake Passage has a much larger effect, due to the cessation of deep water formation in the northern hemisphere. Both gateways alter the transport of salt by ocean circulation, with the Panama Seaway allowing fresh Pacific water to be imported to the North Atlantic, and the Drake Passage preventing the flow of saline subtropical water to the circum-Antarctic, a flow that is particularly strong when the Panama Seaway is open. Thus, with a Panama Seaway and a closed Drake Passage, the Southern Ocean tends to be relatively salty, while the North Atlantic tends to be relatively fresh, such that the deep ocean is ventilated from the circum-Antarctic. Ensuing changes in the ocean heat transport drive a bi

  9. Cell death and morphogenesis during early mouse development: Are they interconnected?

    PubMed Central

    Bedzhov, Ivan; Zernicka-Goetz, Magdalena

    2015-01-01

    Shortly after implantation the embryonic lineage transforms from a coherent ball of cells into polarized cup shaped epithelium. Recently we elucidated a previously unknown apoptosis-independent morphogenic event that reorganizes the pluripotent lineage. Polarization cues from the surrounding basement membrane rearrange the epiblast into a polarized rosette-like structure, where subsequently a central lumen is established. Thus, we provided a new model revising the current concept of apoptosis-dependent epiblast morphogenesis. Cell death however has to be tightly regulated during embryogenesis to ensure developmental success. Here, we follow the stages of early mouse development and take a glimpse at the critical signaling and morphogenic events that determine cells destiny and reshape the embryonic lineage. PMID:25640415

  10. Generation of monoclonal antibodies specific for cell surface molecules expressed on early mouse endoderm.

    PubMed

    Gadue, Paul; Gouon-Evans, Valerie; Cheng, Xin; Wandzioch, Ewa; Zaret, Kenneth S; Grompe, Markus; Streeter, Philip R; Keller, Gordon M

    2009-09-01

    The development of functional cell populations such as hepatocytes and pancreatic beta cells from embryonic stem cell (ESC) is dependent on the efficient induction of definitive endoderm early in the differentiation process. To monitor definitive endoderm formation in mouse ESC differentiation cultures in a quantitative fashion, we generated a reporter cell line that expresses human CD25 from the Foxa3 locus and human CD4 from the Foxa2 locus. Induction of these reporter ESCs with high concentrations of activin A led to the development of a CD25-Foxa3+CD4-Foxa2+ population within 4-5 days of culture. Isolation and characterization of this population showed that it consists predominantly of definitive endoderm that is able to undergo hepatic specification under the appropriate conditions. To develop reagents that can be used for studies on endoderm development from unmanipulated ESCs, from induced pluripotent stem cells, and from the mouse embryo, we generated monoclonal antibodies against the CD25-Foxa3+CD4-Foxa2+ population. With this approach, we identified two antibodies that react specifically with endoderm from ESC cultures and from the early embryo. The specificity of these antibodies enables one to quantitatively monitor endoderm development in ESC differentiation cultures, to study endoderm formation in the embryo, and to isolate pure populations of culture- or embryo-derived endodermal cells.

  11. Early Passage Dependence of Mesenchymal Stem Cell Mechanics Influences Cellular Invasion and Migration.

    PubMed

    Spagnol, Stephen T; Lin, Wei-Chun; Booth, Elizabeth A; Ladoux, Benoit; Lazarus, Hillard M; Dahl, Kris Noel

    2016-07-01

    The cellular structures and mechanical properties of human mesenchymal stem cells (hMSCs) vary significantly during culture and with differentiation. Previously, studies to measure mechanics have provided divergent results using different quantitative parameters and mechanical models of deformation. Here, we examine hMSCs prepared for clinical use and subject them to mechanical testing conducive to the relevant deformability associated with clinical injection procedures. Micropipette aspiration of hMSCs shows deformation as a viscoelastic fluid, with little variation from cell to cell within a population. After two passages, hMSCs deform as viscoelastic solids. Further, for clinical applicability during stem cell migration in vivo, we investigated the ability of hMSCs to invade into micropillar arrays of increasing confinement from 12 to 8 μm spacing between adjacent micropillars. We find that hMSC samples with reduced deformability and cells that are more solid-like with passage are more easily able to enter the micropillar arrays. Increased cell fluidity is an advantage for injection procedures and optimization of cell selection based on mechanical properties may enhance efficacy of injected hMSC populations. However, the ability to invade and migrate within tight interstitial spaces appears to be increased with a more solidified cytoskeleton, likely from increased force generation and contractility. Thus, there may be a balance between optimal injection survival and in situ tissue invasion.

  12. Analysis and Down Select of Flow Passages for Thermal Hydraulic Testing of a SNAP Derived Reactor

    NASA Technical Reports Server (NTRS)

    Godfroy, T. J.; Sadasivan, P.; Masterson, S.

    2007-01-01

    As past of the Vision for Space Exploration, man will return to the moon. To enable safe and productive time on the lunar surface will require adequate power resources. To provide the needed power and to give mission planners all landing site possibilities, including a permanently dark crater, a nuclear reactor provides the most options. Designed to be l00kWt providing approx. 25kWe this power plants would be very effective in delivering dependable, site non-specific power to crews or robotic missions on the lunar surface. An affordable reference reactor based upon the successful SNAP program of the 1960's and early 1970's has been designed by Los Alamos National Laboratory that will meet such a requirement. Considering current funding, environmental, and schedule limitations this lunar surface power reactor will be tested using non-nuclear simulators to simulate the heat from fission reactions. Currently a 25kWe surface power SNAP derivative reactor is in the early process of design and testing with collaboration between Los Alamos National Laboratory, Idaho National Laboratory, Glenn Research Center, Marshall Space Flight Center, and Sandia National Laboratory to ensure that this new design is affordable and can be tested using non-nuclear methods as have proven so effective in the past. This paper will discuss the study and down selection of a flow passage concept for a approx. 25kWe lunar surface power reactor. Several different flow passages designs were evaluated using computational fluid dynamics to determine pressure drop and a structural assessment to consider thermal and stress of the passage walls. The reactor design basis conditions are discussed followed by passage problem setup and results for each concept. A recommendation for passage design is made with rationale for selection.

  13. Fish passage in a western Iowa stream modified by grade control structures

    USGS Publications Warehouse

    Litvan, M.E.; Pierce, C.L.; Stewart, T.W.; Larson, C.J.

    2008-01-01

    Grade control structures (GCSs) are commonly used in streams of western Iowa to control bank erosion and channel headcutting but may be barriers to fish passage. From May 2002 to May 2006, we used mark-recapture methods to evaluate fish passage over a total of five GCSs, ranging in slope (run : rise) from 13:1 to 18:1 in Turkey Creek, Cass County, Iowa. Three structures, over which limited fish movement was documented from 2002 to 2004, were modified in the winter of 2004-2005 to facilitate fish passage. Before modification, the majority of recaptured fish were recaptured at the station where they were originally marked; only 1% displayed movement between sites and either upstream or downstream over a GCS. After modification fish passage improved, 14% of recaptured fish displayed movement either upstream or downstream over a GCS. Individuals of four target species - channel catfish Ictalurus punctatus, yellow bullhead Ameiurus natalis, black bullhead A. melas, and creek chub Semotilus atromaculatus - passed over at least one modified structure. The majority of documented movements over GCSs were in the upstream direction and occurred in late spring and early summer, when streamflow was relatively high. Although we documented low numbers of fish passing both upstream and downstream over GCSs, these structures are probably barriers to fish movement during periods of low flow and when there is a structural failure, such as in-channel movement of riprap. Grade control structures are pervasive in western Iowa streams; nearly every low-order stream contains at least one instream structure. To sustain fish populations, management efforts should focus on constructing or modifying GCSs to allow fish passage. ?? Copyright by the American Fisheries Society 2008.

  14. How Important Is Passage Dependence in Reading Comprehension?

    ERIC Educational Resources Information Center

    Hanna, Gerald S.; Oaster, Thomas R.

    1978-01-01

    A higher than expected correlation between "passages in" and "passages out" scores on reading comprehension tests indicated that the practical importance of passage dependence is probably not as great as has been commonly believed. (Editor)

  15. Downstream migration and multiple dam passage by Atlantic Salmon smolts

    USGS Publications Warehouse

    Nyqvist, D.; McCormick, Stephen; Greenberg, L.; Ardren, W.R.; Bergman, E.; Calles, O.; Castro-Santos, Theodore R.

    2017-01-01

    The purpose of this study was to investigate behavior and survival of radio-tagged wild and hatchery-reared landlocked Atlantic Salmon Salmo salar smolts as they migrated past three hydropower dams equipped with fish bypass solutions in the Winooski River, Vermont. Among hatchery-reared smolts, those released early were more likely to initiate migration and did so after less delay than those released late. Once migration was initiated, however, the late-released hatchery smolts migrated at greater speeds. Throughout the river system, hatchery-reared fish performed similarly to wild fish. Dam passage rates varied between the three dams and was highest at the dam where unusually high spill levels occurred throughout the study period. Of the 50 fish that did migrate downstream, only 10% managed to reach the lake. Migration success was low despite the presence of bypass solutions, underscoring the need for evaluations of remedial measures; simply constructing a fishway is not synonymous with providing fish passage.

  16. Numerical simulation of blade-passage noise.

    PubMed

    Yauwenas, Yendrew; Zajamšek, Branko; Reizes, John; Timchenko, Victoria; Doolan, Con J

    2017-09-01

    Numerical simulations are used to investigate the noise generated by the passage of a rotor blade past a fixed object (the blade-passage effects), which was studied by simulating a three-bladed rotor that is supported by a vertical cylindrical tower. To isolate the blade-passage effects, no incoming wind was introduced in the simulation. The symmetric blade was set to zero pitch angle relative to the plane of rotation and two blade-tower distances were investigated. The sliding mesh method was used to simulate the rotation of the blades and Curle's acoustic analogy was used to predict the noise generated from the simulated flow data. Intense force fluctuations occur during the interaction on both the tower and the passing blade, and these are the primary sources of blade-passage noise. The contribution of the force fluctuations on the support tower to blade-passage noise, which previously had been ignored, was revealed to be more significant than that of the blades. The numerical model successfully predicts the noise spectra, which are validated by the very good agreement with experimental measurements. The simulations provide a framework to better understand blade-tower interaction noise in various applications.

  17. Passage relevance models for genomics search.

    PubMed

    Urbain, Jay; Frieder, Ophir; Goharian, Nazli

    2009-03-19

    We present a passage relevance model for integrating syntactic and semantic evidence of biomedical concepts and topics using a probabilistic graphical model. Component models of topics, concepts, terms, and document are represented as potential functions within a Markov Random Field. The probability of a passage being relevant to a biologist's information need is represented as the joint distribution across all potential functions. Relevance model feedback of top ranked passages is used to improve distributional estimates of query concepts and topics in context, and a dimensional indexing strategy is used for efficient aggregation of concept and term statistics. By integrating multiple sources of evidence including dependencies between topics, concepts, and terms, we seek to improve genomics literature passage retrieval precision. Using this model, we are able to demonstrate statistically significant improvements in retrieval precision using a large genomics literature corpus.

  18. Cell death and morphogenesis during early mouse development: are they interconnected?

    PubMed

    Bedzhov, Ivan; Zernicka-Goetz, Magdalena

    2015-04-01

    Shortly after implantation the embryonic lineage transforms from a coherent ball of cells into polarized cup shaped epithelium. Recently we elucidated a previously unknown apoptosis-independent morphogenic event that reorganizes the pluripotent lineage. Polarization cues from the surrounding basement membrane rearrange the epiblast into a polarized rosette-like structure, where subsequently a central lumen is established. Thus, we provided a new model revising the current concept of apoptosis-dependent epiblast morphogenesis. Cell death however has to be tightly regulated during embryogenesis to ensure developmental success. Here, we follow the stages of early mouse development and take a glimpse at the critical signaling and morphogenic events that determine cells destiny and reshape the embryonic lineage. © 2015 The Authors. Bioessays published by WILEY Periodicals, Inc.

  19. Flow in serpentine coolant passages with trip strips

    NASA Technical Reports Server (NTRS)

    Tse, D. G.-N.

    1995-01-01

    Under the subject contract, an effort is being conducted at Scientific Research Associates, Inc. (SRA) to obtain flow field measurements in the coolant passage of a rotating turbine blade with ribbed walls, both in the stationary and rotating frames. The data obtained will be used for validation of computational tools and assessment of turbine blade cooling strategies. The configuration of the turbine blade passage model is given, and the measuring plane locations are given. The model has a four-pass passage with three 180 turns. This geometry was chosen to allow analyses of the velocity measurements corresponding to the heat transfer results obtained by Wagner. Two passes of the passage have a rectangular cross-section of 1.0 in x 0.5 in. Another two passes have a square cross-section of 0.5 in x 0.5 in. Trips with a streamwise pitch to trip height (P/e) = 5 and trip height to coolant passage width (e/Z) = 0.1, were machined along the leading and trailing walls. These dimensions are typical of those used in turbine blade coolant passages. The trips on these walls are staggered by the half-pitch. The trips are skewed at +/- 45 deg, and this allows the effect of trip orientation to be examined. Experiments will be conducted with flow entering the model through the 1.0 in x 0.5 in rectangular passage (Configuration C) and the 0.5 in x 0. 5 in square passage (Configuration D) to examine the effect of passage aspect ratio. Velocity measurements were obtained with a Reynolds number (Re) of 25,000, based on the hydraulic diameter of and bulk mean velocity in the half inch square passage. The coordinate system used in presenting the results for configurations C and D, respectively, is shown. The first, second and third passes of the passage will be referred to as the first, second and third passages, respectively, in later discussion. Streamwise distance (x) from the entrance is normalized by the hydraulic diameter (D). Vertical (y) and tangential (z) distances are

  20. Chimeric elk/mouse prion proteins in transgenic mice.

    PubMed

    Tamgüney, Gültekin; Giles, Kurt; Oehler, Abby; Johnson, Natrina L; DeArmond, Stephen J; Prusiner, Stanley B

    2013-02-01

    Chronic wasting disease (CWD) of deer and elk is a highly communicable neurodegenerative disorder caused by prions. Investigations of CWD are hampered by slow bioassays in transgenic (Tg) mice. Towards the development of Tg mice that will be more susceptible to CWD prions, we created a series of chimeric elk/mouse transgenes that encode the N terminus of elk PrP (ElkPrP) up to residue Y168 and the C terminus of mouse PrP (MoPrP) beyond residue 169 (mouse numbering), designated Elk3M(SNIVVK). Between codons 169 and 219, six residues distinguish ElkPrP from MoPrP: N169S, T173N, V183I, I202V, I214V and R219K. Using chimeric elk/mouse PrP constructs, we generated 12 Tg mouse lines and determined incubation times after intracerebral inoculation with the mouse-passaged RML scrapie or Elk1P CWD prions. Unexpectedly, one Tg mouse line expressing Elk3M(SNIVVK) exhibited incubation times of <70 days when inoculated with RML prions; a second line had incubation times of <90 days. In contrast, mice expressing full-length ElkPrP had incubation periods of >250 days for RML prions. Tg(Elk3M,SNIVVK) mice were less susceptible to CWD prions than Tg(ElkPrP) mice. Changing three C-terminal mouse residues (202, 214 and 219) to those of elk doubled the incubation time for mouse RML prions and rendered the mice resistant to Elk1P CWD prions. Mutating an additional two residues from mouse to elk at codons 169 and 173 increased the incubation times for mouse prions to >300 days, but made the mice susceptible to CWD prions. Our findings highlight the role of C-terminal residues in PrP that control the susceptibility and replication of prions.

  1. An Immunocompetent Mouse Model of Zika Virus Infection.

    PubMed

    Gorman, Matthew J; Caine, Elizabeth A; Zaitsev, Konstantin; Begley, Matthew C; Weger-Lucarelli, James; Uccellini, Melissa B; Tripathi, Shashank; Morrison, Juliet; Yount, Boyd L; Dinnon, Kenneth H; Rückert, Claudia; Young, Michael C; Zhu, Zhe; Robertson, Shelly J; McNally, Kristin L; Ye, Jing; Cao, Bin; Mysorekar, Indira U; Ebel, Gregory D; Baric, Ralph S; Best, Sonja M; Artyomov, Maxim N; Garcia-Sastre, Adolfo; Diamond, Michael S

    2018-05-09

    Progress toward understanding Zika virus (ZIKV) pathogenesis is hindered by lack of immunocompetent small animal models, in part because ZIKV fails to effectively antagonize Stat2-dependent interferon (IFN) responses in mice. To address this limitation, we first passaged an African ZIKV strain (ZIKV-Dak-41525) through Rag1 -/- mice to obtain a mouse-adapted virus (ZIKV-Dak-MA) that was more virulent than ZIKV-Dak-41525 in mice treated with an anti-Ifnar1 antibody. A G18R substitution in NS4B was the genetic basis for the increased replication, and resulted in decreased IFN-β production, diminished IFN-stimulated gene expression, and the greater brain infection observed with ZIKV-Dak-MA. To generate a fully immunocompetent mouse model of ZIKV infection, human STAT2 was introduced into the mouse Stat2 locus (hSTAT2 KI). Subcutaneous inoculation of pregnant hSTAT2 KI mice with ZIKV-Dak-MA resulted in spread to the placenta and fetal brain. An immunocompetent mouse model of ZIKV infection may prove valuable for evaluating countermeasures to limit disease. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. First passage times and asymmetry of DNA translocation

    NASA Astrophysics Data System (ADS)

    Lua, Rhonald C.; Grosberg, Alexander Y.

    2005-12-01

    Motivated by experiments in which single-stranded DNA with a short hairpin loop at one end undergoes unforced diffusion through a narrow pore, we study the first passage times for a particle, executing one-dimensional Brownian motion in an asymmetric sawtooth potential, to exit one of the boundaries. We consider the first passage times for the case of classical diffusion, characterized by a mean-square displacement of the form ⟨(Δx)2⟩˜t , and for the case of anomalous diffusion or subdiffusion, characterized by a mean-square displacement of the form ⟨(Δx)2⟩˜tγ with 0<γ<1 . In the context of classical diffusion, we obtain an expression for the mean first passage time and show that this quantity changes when the direction of the sawtooth is reversed or, equivalently, when the reflecting and absorbing boundaries are exchanged. We discuss at which numbers of “teeth” N (or number of DNA nucleotides) and at which heights of the sawtooth potential this difference becomes significant. For large N , it is well known that the mean first passage time scales as N2 . In the context of subdiffusion, the mean first passage time does not exist. Therefore, we obtain instead the distribution of first passage times in the limit of long times. We show that the prefactor in the power relation for this distribution is simply the expression for the mean first passage time in classical diffusion. We also describe a hypothetical experiment to calculate the average of the first passage times for a fraction of passage events that each end within some time t* . We show that this average first passage time scales as N2/γ in subdiffusion.

  3. Lepidoptera outbreaks in response to successional changes after the passage of Hurricane Hugo in Puerto Rico Rico

    Treesearch

    J.A. Torres

    1992-01-01

    Fifteen species of Lepidoptera occurred in large numbers in spring and early summer after the passage of Hurricane Hugo over the north-east of Puerto Rico. Spodoptera eridania (Noctuidae) was the most common of the larvae and fed on 56 plant species belonging to 31 families. All the Lepidoptera fed on early successional vegetation. Some of the plants represent new host...

  4. Extension in Mona Passage, Northeast Caribbean

    USGS Publications Warehouse

    Chaytor, J.D.; ten Brink, Uri S.

    2010-01-01

    As shown by the recent Mw 7.0 Haiti earthquake, intra-arc deformation, which accompanies the subduction process, can present seismic and tsunami hazards to nearby islands. Spatially-limited diffuse tectonic deformation within the Northeast Caribbean Plate Boundary Zone likely led to the development of the submerged Mona Passage between Puerto Rico and the Dominican Republic. GPS geodetic data and a moderate to high level of seismicity indicate that extension within the region is ongoing. Newly-collected high-resolution multibeam bathymetry and multi-channel seismic reflection profiles and previously-collected samples are used here to determine the tectonic evolution of the Mona Passage intra-arc region. The passage is floored almost completely by Oligocene-Pliocene carbonate platform strata, which have undergone submarine and subaerial erosion. Structurally, the passage is characterized by W- to NNW-trending normal faults that offset the entire thickness of the Oligo-Pliocene carbonate platform rocks. The orientation of these faults is compatible with the NE-oriented extension vector observed in GPS data. Fault geometry best fits an oblique extension model rather than previously proposed single-phase, poly-phase, bending-moment, or rotation extension models. The intersection of these generally NW-trending faults in Mona Passage with the N-S oriented faults of Mona Canyon may reflect differing responses of the brittle upper-crust, along an arc-forearc rheological boundary, to oblique subduction along the Puerto Rico trench. Several faults within the passage, if ruptured completely, are long enough to generate earthquakes with magnitudes on the order of Mw 6.5-7. ?? 2010.

  5. Changing Sea Ice Conditions in the Northwest Passage

    NASA Astrophysics Data System (ADS)

    Tivy, A. C.; Howell, S.; Agnew, T.; Derksen, C.

    2010-12-01

    The Northwest Passage lies in the middle of Canadian Arctic Archipelago providing a potential deepwater route that links the Atlantic and Pacific Oceans. Discovered by Sir Robert M’Clure in the 1850s, ever-present multi-year ice (MYI) has always prevented its practical navigation. 2007 marked extreme low MYI conditions in the Arctic and temporarily cleared the Northwest Passage. However, is one single clearing event within the Northwest Passage over the past 40 years indicative of future clearings? This analysis addressed two inter-related questions: i) why has the Northwest Passage contained historically heavy amounts of MYI? and ii) will decreases in MYI within the Northwest Passage continue into the future? Results indicate that for nearly 4 decades, the southern regions of the Canadian Arctic Archipelago have continuously operated as a drain-trap for MYI and this mechanism is responsible for maintaining the heavy MYI conditions within the Northwest Passage. The oldest and thickest MYI in the world resides along the northern flank of the Canadian Arctic Archipelago therefore, as the transition to a sea ice-free Arctic continues, MYI from this region will continue to migrate southward to the channels of the Northwest Passage. Results also find that 2007 was indeed an anomalously light sea ice year in the Northwest Passage but record low ice conditions have since been observed as of mid-August 2010.

  6. A Method for the Immortalization of Newborn Mouse Skin Keratinocytes

    PubMed Central

    Hammiller, Brianna O.; El-Abaseri, Taghrid Bahig; Dlugosz, Andrzej A.; Hansen, Laura A.

    2015-01-01

    Isolation and culture of mouse primary epidermal keratinocytes is a common technique that allows for easy genetic and environmental manipulation. However, due to their limited lifespan in culture, experiments utilizing primary keratinocytes require large numbers of animals, and are time consuming and expensive. To avoid these issues, we developed a method for the immortalization of primary mouse epidermal keratinocytes. Upon isolation of newborn epidermal keratinocytes according to established methods, the cells were cultured long-term in keratinocyte growth factor-containing medium. The cells senesced within a few weeks and eventually, small, slowly growing colonies emerged. After they regained confluency, the cells were passaged and slowly refilled the dish. With several rounds of subculture, the cells adapted to culture conditions, were easily subcultured, maintained normal morphology, and were apparently immortal. The immortalized cells retained the ability to differentiate with increased calcium concentrations, and were maintained to high passage numbers while maintaining a relatively stable karyotype. Analysis of multiple immortalized cell lines as well as primary keratinocyte cultures revealed increased numbers of chromosomes, especially in the primary keratinocytes, and chromosomal aberrations in most of the immortalized cultures and in the primary keratinocytes. Orthotopic grafting of immortalized keratinocytes together with fibroblasts onto nude mouse hosts produced skin while v-rasHa infection of the immortalized keratinocytes prior to grafting produced squamous cell carcinoma. In summary, this method of cell line generation allows for decreased use of animals, reduces the expense and time involved in research, and provides a useful model for cutaneous keratinocyte experimentation. PMID:26284198

  7. Hydroacoustic Evaluation of Juvenile Salmonid Passage and Distribution at Lookout Point Dam, 2010

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

    Khan, Fenton; Johnson, Gary E.; Royer, Ida M.

    2011-07-01

    This report presents the results of an evaluation of juvenile salmonid passage and distribution at Lookout Point Dam (LOP) on the Middle Fork Willamette River. The study was conducted by the Pacific Northwest National Laboratory for the U.S. Army Corps of Engineers, Portland District (USACE). The goal of the study was to provide fish passage and distribution data to support decisions on long-term measures to enhance downstream passage at LOP and others dams in USACE’s Willamette Valley Project in response to the listing of Upper Willamette River Spring Chinook salmon (Oncorhynchus tshawytscha) and Upper Willamette River steelhead (O. mykiss) asmore » threatened under the Endangered Species Act. During the year-long study period - February 1, 2010 to January 31, 2011the objectives of the hydroacoustic evaluation of fish passage and distribution at LOP were to: 1. Estimate passage rates, run timing, horizontal distribution, and diel distribution at turbine penstock intakes for smolt-size fish. 2. Estimate passage rates, run timing and diel distribution at turbine penstock intakes for small-size fish. 3. Estimate passage rates and run timing at the regulating outlets for smolt-size fish. 4. Estimate vertical distribution of smolt-size fish in the forebay near the upstream face of the dam. The fixed-location hydroacoustic technique was used to accomplish the objectives of this study. Transducers (420 kHz) were deployed in each penstock intake, above each RO entrance, and on the dam face; a total of nine transducers (2 single-beam and 7 split-beam) were used. We summarize the findings from the hydroacoustic evaluation of juvenile salmonid passage and distribution at LOP during February 2010 through January 2011 as follows. • Fish passage rates for smolt-size fish (> ~90 mm) were highest during December-January and lowest in mid-summer through early fall. • During the entire study period, an estimated total of 142,463 fish ± 4,444 (95% confidence interval) smolt

  8. Risk Taking and Rites of Passage

    ERIC Educational Resources Information Center

    Larson, Scott; Martin, Lloyd

    2012-01-01

    Throughout history, young people earned adult roles through observing, imitating, and interacting with adults around them. Rituals of initiation such as the Jewish bar mitzvah and bat mitzvah are very important rite of passage ceremonies. Many churches confer baptism, confirmation, or catechism as rites of passage to adulthood. Without such…

  9. Modeling of First-Passage Processes in Financial Markets

    NASA Astrophysics Data System (ADS)

    Inoue, Jun-Ichi; Hino, Hikaru; Sazuka, Naoya; Scalas, Enrico

    2010-03-01

    In this talk, we attempt to make a microscopic modeling the first-passage process (or the first-exit process) of the BUND future by minority game with market history. We find that the first-passage process of the minority game with appropriate history length generates the same properties as the BTP future (the middle and long term Italian Government bonds with fixed interest rates), namely, both first-passage time distributions have a crossover at some specific time scale as is the case for the Mittag-Leffler function. We also provide a macroscopic (or a phenomenological) modeling of the first-passage process of the BTP future and show analytically that the first-passage time distribution of a simplest mixture of the normal compound Poisson processes does not have such a crossover.

  10. Effects of rotation on coolant passage heat transfer. Volume 1: Coolant passages with smooth walls

    NASA Technical Reports Server (NTRS)

    Hajek, T. J.; Wagner, J. H.; Johnson, B. V.; Higgins, A. W.; Steuber, G. D.

    1991-01-01

    An experimental program was conducted to investigate heat transfer and pressure loss characteristics of rotating multipass passages, for configurations and dimensions typical of modern turbine blades. The immediate objective was the generation of a data base of heat transfer and pressure loss data required to develop heat transfer correlations and to assess computational fluid dynamic techniques for rotating coolant passages. Experiments were conducted in a smooth wall large scale heat transfer model.

  11. A spontaneously arising mutation in connexin32 with repeated passage of FRTL-5 cells coincides with increased growth rate and reduced thyroxine release

    NASA Technical Reports Server (NTRS)

    Green, L. M.; Murray, D. K.; Tran, D. T.; Nelson, G. A.; Shah, M. M.; Luben, R. A.

    2001-01-01

    In this study we examine changes in the cellular properties of FRTL-5 cells as a function of passage number, with particular emphasis on gap junction expression, karyotype, morphology, growth rate and thyroxine (T(4)) release. Early passage FRTL-5 follicular cells transfer dye through gap junctions from injected cell(s) to third-order neighboring cells and beyond within their respective follicles and have immuno-detectable connexin32 (Cx32) type gap junctional plaques in their lateral contacting plasma membranes. By contrast, FRTL-5 cells established as monolayers, or as follicles from cultures passed more than 15 times, did not transfer microinjected Lucifer Yellow dye to contiguous neighboring cells and did not express any immuno-detectable rat thyroid specific connexins (Cx43, Cx32 or Cx26). Western blots confirmed that total, membrane and cytosolic Cx32 protein was present only in early pass follicular cultures. To better understand the passage-dependent loss of Cx32 expression, RT-PCR primers were made to the most unique sequences of the rat Cx32 molecule, the cytoplasmic and carboxyl-terminal regions. These primers were used to screen FRTL-5 RNA from cultures of various passage numbers. The results revealed that later passage cultures had a single base deletion in the middle of the Cx32 cytoplasmic loop region at nucleotide position 378. This base deletion was in the middle position of the codon for amino acid 116, which is normally a CAC (histidine) but read with the frame shift was a CCC (proline). The four amino acids that followed this deletion were also altered with the fourth one becoming UAA, the ochre translation stop codon. This premature stopping of translation resulted in a truncation of 60% of the protein, which included the remaining cytoplasmic loop, third and fourth transmembrane regions and the carboxyl-terminus. The later passage cultures did not produce a carboxyl-terminal RT-PCR product, indicating that the mRNA was also truncated. These

  12. Terrestrial passage theory of the moon illusion.

    PubMed

    Reed, C F

    1984-12-01

    Theories of the celestial, or moon, illusion have neglected geometric characteristics of movement along and above the surface of the earth. The illusion occurs because the characteristics of terrestrial passage are attributed to celestial passage. In terrestrial passage, the visual angle subtended by an object changes discriminably as an essentially invariant function of elevation above the horizon. In celestial passage, by contrast, change in visual angle is indiscriminable at all elevations. If a terrestrial object gains altitude, its angular subtense fails to follow the expansion projected for an orbital course: Angular diminution or constancy is equivalent to distancing. On the basis of terrestrial projections, a similar failure of celestial objects in successive elevations is also equivalent to distancing. The illusion occurs because of retinal image constancy, not--as traditionally stated--despite it.

  13. Early Maternal Alcohol Consumption Alters Hippocampal DNA Methylation, Gene Expression and Volume in a Mouse Model

    PubMed Central

    Marjonen, Heidi; Sierra, Alejandra; Nyman, Anna; Rogojin, Vladimir; Gröhn, Olli; Linden, Anni-Maija; Hautaniemi, Sampsa; Kaminen-Ahola, Nina

    2015-01-01

    The adverse effects of alcohol consumption during pregnancy are known, but the molecular events that lead to the phenotypic characteristics are unclear. To unravel the molecular mechanisms, we have used a mouse model of gestational ethanol exposure, which is based on maternal ad libitum ingestion of 10% (v/v) ethanol for the first 8 days of gestation (GD 0.5-8.5). Early neurulation takes place by the end of this period, which is equivalent to the developmental stage early in the fourth week post-fertilization in human. During this exposure period, dynamic epigenetic reprogramming takes place and the embryo is vulnerable to the effects of environmental factors. Thus, we hypothesize that early ethanol exposure disrupts the epigenetic reprogramming of the embryo, which leads to alterations in gene regulation and life-long changes in brain structure and function. Genome-wide analysis of gene expression in the mouse hippocampus revealed altered expression of 23 genes and three miRNAs in ethanol-exposed, adolescent offspring at postnatal day (P) 28. We confirmed this result by using two other tissues, where three candidate genes are known to express actively. Interestingly, we found a similar trend of upregulated gene expression in bone marrow and main olfactory epithelium. In addition, we observed altered DNA methylation in the CpG islands upstream of the candidate genes in the hippocampus. Our MRI study revealed asymmetry of brain structures in ethanol-exposed adult offspring (P60): we detected ethanol-induced enlargement of the left hippocampus and decreased volume of the left olfactory bulb. Our study indicates that ethanol exposure in early gestation can cause changes in DNA methylation, gene expression, and brain structure of offspring. Furthermore, the results support our hypothesis of early epigenetic origin of alcohol-induced disorders: changes in gene regulation may have already taken place in embryonic stem cells and therefore can be seen in different tissue

  14. Memory retrieval by activating engram cells in mouse models of early Alzheimer's disease.

    PubMed

    Roy, Dheeraj S; Arons, Autumn; Mitchell, Teryn I; Pignatelli, Michele; Ryan, Tomás J; Tonegawa, Susumu

    2016-03-24

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions. Memory decline in the early stages of AD is mostly limited to episodic memory, for which the hippocampus has a crucial role. However, it has been uncertain whether the observed amnesia in the early stages of AD is due to disrupted encoding and consolidation of episodic information, or an impairment in the retrieval of stored memory information. Here we show that in transgenic mouse models of early AD, direct optogenetic activation of hippocampal memory engram cells results in memory retrieval despite the fact that these mice are amnesic in long-term memory tests when natural recall cues are used, revealing a retrieval, rather than a storage impairment. Before amyloid plaque deposition, the amnesia in these mice is age-dependent, which correlates with a progressive reduction in spine density of hippocampal dentate gyrus engram cells. We show that optogenetic induction of long-term potentiation at perforant path synapses of dentate gyrus engram cells restores both spine density and long-term memory. We also demonstrate that an ablation of dentate gyrus engram cells containing restored spine density prevents the rescue of long-term memory. Thus, selective rescue of spine density in engram cells may lead to an effective strategy for treating memory loss in the early stages of AD.

  15. Dysregulation of mitotic machinery genes precedes genome instability during spontaneous pre-malignant transformation of mouse ovarian surface epithelial cells.

    PubMed

    Urzúa, Ulises; Ampuero, Sandra; Roby, Katherine F; Owens, Garrison A; Munroe, David J

    2016-10-25

    Based in epidemiological evidence, repetitive ovulation has been proposed to play a role in the origin of ovarian cancer by inducing an aberrant wound rupture-repair process of the ovarian surface epithelium (OSE). Accordingly, long term cultures of isolated OSE cells undergo in vitro spontaneous transformation thus developing tumorigenic capacity upon extensive subcultivation. In this work, C57BL/6 mouse OSE (MOSE) cells were cultured up to passage 28 and their RNA and DNA copy number profiles obtained at passages 2, 5, 7, 10, 14, 18, 23, 25 and 28 by means of DNA microarrays. Gene ontology, pathway and network analyses were focused in passages earlier than 20, which is a hallmark of malignancy in this model. At passage 14, 101 genes were up-regulated in absence of significant DNA copy number changes. Among these, the top-3 enriched functions (>30 fold, adj p < 0.05) comprised 7 genes coding for centralspindlin, chromosome passenger and minichromosome maintenance protein complexes. The genes Ccnb1 (Cyclin B1), Birc5 (Survivin), Nusap1 and Kif23 were the most recurrent in over a dozen GO terms related to the mitotic process. On the other hand, Pten plus the large non-coding RNAs Malat1 and Neat1 were among the 80 down-regulated genes with mRNA processing, nuclear bodies, ER-stress response and tumor suppression as relevant terms. Interestingly, the earliest discrete segmental aneuploidies arose by passage 18 in chromosomes 7, 10, 11, 13, 15, 17 and 19. By passage 23, when MOSE cells express the malignant phenotype, the dysregulated gene expression repertoire expanded, DNA imbalances enlarged in size and covered additional loci. Prior to early aneuploidies, overexpression of genes coding for the mitotic apparatus in passage-14 pre-malignant MOSE cells indicate an increased proliferation rate suggestive of replicative stress. Concomitant down-regulation of nuclear bodies and RNA processing related genes suggests altered control of nuclear RNA maturation

  16. Skeptical notes on a physics of passage.

    PubMed

    Huggett, Nick

    2014-10-01

    This paper investigates the mathematical representation of time in physics. In existing theories, time is represented by the real numbers, hence their formal properties represent properties of time: these are surveyed. The central question of the paper is whether the existing representation of time is adequate, or whether it can or should be supplemented: especially, do we need a physics incorporating some kind of "dynamical passage" of time? The paper argues that the existing mathematical framework is resistant to such changes, and might have to be rejected by anyone seeking a physics of passage. Then it rebuts two common arguments for incorporating passage into physics, especially the claim that it is an element of experience. Finally, the paper investigates whether, as has been claimed, causal set theory provides a physics of passage. © 2014 New York Academy of Sciences.

  17. Duroquinone reduction during passage through the pulmonary circulation.

    PubMed

    Audi, Said H; Bongard, Robert D; Dawson, Christopher A; Siegel, David; Roerig, David L; Merker, Marilyn P

    2003-11-01

    The lungs can substantially influence the redox status of redox-active plasma constituents. Our objective was to examine aspects of the kinetics and mechanisms that determine pulmonary disposition of redox-active compounds during passage through the pulmonary circulation. Experiments were carried out on rat and mouse lungs with 2,3,5,6-tetramethyl-1,4-benzoquinone [duroquinone (DQ)] as a model amphipathic quinone reductase substrate. We measured DQ and durohydroquinone (DQH2) concentrations in the lung venous effluent after injecting, or while infusing, DQ or DQH2 into the pulmonary arterial inflow. The maximum net rates of DQ reduction to DQH2 in the rat and mouse lungs were approximately 4.9 and 2.5 micromol. min(-1).g dry lung wt(-1), respectively. The net rate was apparently the result of freely permeating access of DQ and DQH2 to tissue sites of redox reactions, dominated by dicumarol-sensitive DQ reduction to DQH2 and cyanide-sensitive DQH2 reoxidation back to DQ. The dicumarol sensitivity along with immunodetectable expression of NAD(P)H-quinone oxidoreductase 1 (NQO1) in the rat lung tissue suggest cytoplasmic NQO1 as the dominant site of DQ reduction. The effect of cyanide on DQH2 oxidation suggests that the dominant site of oxidation is complex III of the mitochondrial electron transport chain. If one envisions DQ as a model compound for examining the disposition of amphipathic NQO1 substrates in the lungs, the results are consistent with a role for lung NQO1 in determining the redox status of such compounds in the circulation. For DQ, the effect is conversion of a redox-cycling, oxygen-activating quinone into a stable hydroquinone.

  18. Bipolar membranes with fluid distribution passages

    NASA Technical Reports Server (NTRS)

    Hitchens, G. Duncan (Inventor); Archer, Shivaun (Inventor); Tennakoon, Charles L. (Inventor); Gonzalez-Martin, Anuncia (Inventor); Cisar, Alan J. (Inventor)

    1999-01-01

    The present invention provides a bipolar membrane and methods for making and using the membrane. The bipolar membrane comprises a cation-selective region, an anion-selective region, an interfacial region between the anion-selective region and the cation-selective region, and means for delivering fluid directly into the interfacial region. The means for delivering fluid includes passages that may comprise a fluid-permeable material, a wicking material, an open passage disposed within the membrane or some combination thereof. The passages may be provided in many shapes, sizes and configurations, but preferably deliver fluid directly to the interfacial region so that the rate of electrodialysis is no longer limited by the diffusion of fluid through the cation- or anion-selective regions to the interfacial region.

  19. 76 FR 34692 - Inside Passage Electric Cooperative

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-14

    ... Electric Cooperative Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments..., the Inside Passage Electric Cooperative filed an application for a preliminary permit, pursuant to..., Operations Manager, Inside Passage Electric Cooperative, P.O. Box 210149, 12480 Mendenhall Loop Road, Auke...

  20. Navigable windows of the Northwest Passage

    NASA Astrophysics Data System (ADS)

    Liu, Xing-he; Ma, Long; Wang, Jia-yue; Wang, Ye; Wang, Li-na

    2017-09-01

    Artic sea ice loss trends support a greater potential for Arctic shipping. The information of sea ice conditions is important for utilizing Arctic passages. Based on the shipping routes given by ;Arctic Marine Shipping Assessment 2009 Report;, the navigable windows of these routes and the constituent legs were calculated by using sea ice concentration product data from 2006 to 2015, by which a comprehensive knowledge of the sea ice condition of the Northwest Passage was achieved. The results showed that Route 4 (Lancaster Sound - Barrow Strait - Prince Regent Inlet and Bellot Strait - Franklin Strait - Larsen Sound - Victoria Strait - Queen Maud Gulf - Dease Strait - Coronation Gulf - Dolphin and Union Strait - Amundsen Gulf) had the best navigable expectation, Route 2 (Parry Channel - M'Clure Strait) had the worst, and the critical legs affecting the navigation of Northwest Passage were Viscount Melville Sound, Franklin Strait, Victoria Strait, Bellot Strait, M'Clure Strait and Prince of Wales Strait. The shortest navigable period of the routes of Northwest Passage was up to 69 days. The methods used and the results of the study can help the selection and evaluation of Arctic commercial routes.

  1. Mouse Polyomavirus Enters Early Endosomes, Requires Their Acidic pH for Productive Infection, and Meets Transferrin Cargo in Rab11-Positive Endosomes

    PubMed Central

    Liebl, David; Difato, Francesco; Horníková, Lenka; Mannová, Petra; Štokrová, Jitka; Forstová, Jitka

    2006-01-01

    Mouse polyomavirus (PyV) virions enter cells by internalization into smooth monopinocytic vesicles, which fuse under the cell membrane with larger endosomes. Caveolin-1 was detected on monopinocytic vesicles carrying PyV particles in mouse fibroblasts and epithelial cells (33). Here, we show that PyV can be efficiently internalized by Jurkat cells, which do not express caveolin-1 and lack caveolae, and that overexpression of a caveolin-1 dominant-negative mutant in mouse epithelial cells does not prevent their productive infection. Strong colocalization of VP1 with early endosome antigen 1 (EEA1) and of EEA1 with caveolin-1 in mouse fibroblasts and epithelial cells suggests that the monopinocytic vesicles carrying the virus (and vesicles containing caveolin-1) fuse with EEA1-positive early endosomes. In contrast to SV40, PyV infection is dependent on the acidic pH of endosomes. Bafilomycin A1 abolished PyV infection, and an increase in endosomal pH by NH4Cl markedly reduced its efficiency when drugs were applied during virion transport towards the cell nucleus. The block of acidification resulted in the retention of a fraction of virions in early endosomes. To monitor further trafficking of PyV, we used fluorescent resonance energy transfer (FRET) to determine mutual localization of PyV VP1 with transferrin and Rab11 GTPase at a 2- to 10-nm resolution. Positive FRET between PyV VP1 and transferrin cargo and between PyV VP1 and Rab11 suggests that during later times postinfection (1.5 to 3 h), the virus meets up with transferrin in the Rab11-positive recycling endosome. These results point to a convergence of the virus and the cargo internalized by different pathways in common transitional compartments. PMID:16611921

  2. The passage and initial implementation of Oregon's Measure 44

    PubMed Central

    Goldman, L.; Glantz, S.

    1999-01-01

    OBJECTIVE—To prepare a history of the passage and early implementation of Ballot Measure 44, "An Act to Support the Oregon Health Plan", and tobacco control policymaking in Oregon. Measure 44 raised cigarette taxes in Oregon by US$0.30 per pack, and dedicated 10% of the revenues to tobacco control.
METHODS—Data were gathered from interviews with members of the Committee to Support the Oregon Health Plan, Measure 44's campaign committee, as well as with state and local officials, and tobacco control advocates. Additional information was obtained from public documents, internal memoranda, and news reports.
RESULTS—Although the tobacco industry outspent Measure 44's supporters 7 to 1, the initiative passed with 56% of the vote. Even before the election, tobacco control advocates were working to develop an implementation plan for the tobacco control programme. They mounted a successful lobbying campaign to see that the legislature did not divert tobacco control funds to other uses. They also stopped industry efforts to limit the scope of the programme. The one shortcoming of the tobacco control forces was not getting involved in planning the initiative early enough to influence the amount of money that was devoted to tobacco control. Although public health groups provided 37% of the money it cost to pass Measure 44, only 10% of revenues were devoted to tobacco control.
CONCLUSIONS—Proactive planning and aggressive implementation can secure passage of tobacco control initiatives and see that the associated implementing legislation follows good public health practice.


Keywords: advocacy; legislation; implementation; tobacco tax PMID:10599577

  3. Partially turbulated trailing edge cooling passages for gas turbine nozzles

    DOEpatents

    Thatcher, Jonathan Carl; Burdgick, Steven Sebastian

    2001-01-01

    A plurality of passages are spaced one from the other along the length of a trailing edge of a nozzle vane in a gas turbine. The passages lie in communication with a cavity in the vane for flowing cooling air from the cavity through the passages through the tip of the trailing edge into the hot gas path. Each passage is partially turbulated and includes ribs in an aft portion thereof to provide enhanced cooling effects adjacent the tip of the trailing edge. The major portions of the passages are smooth bore. By this arrangement, reduced temperature gradients across the trailing edge metal are provided. Additionally, the inlets to each of the passages have a restriction whereby a reduced magnitude of compressor bleed discharge air is utilized for trailing edge cooling purposes.

  4. Early neurotrophic pharmacotherapy rescues developmental delay and Alzheimer’s-like memory deficits in the Ts65Dn mouse model of Down syndrome

    PubMed Central

    Kazim, Syed Faraz; Blanchard, Julie; Bianchi, Riccardo; Iqbal, Khalid

    2017-01-01

    Down syndrome (DS), caused by trisomy 21, is the most common genetic cause of intellectual disability and is associated with a greatly increased risk of early-onset Alzheimer’s disease (AD). The Ts65Dn mouse model of DS exhibits several key features of the disease including developmental delay and AD-like cognitive impairment. Accumulating evidence suggests that impairments in early brain development caused by trisomy 21 contribute significantly to memory deficits in adult life in DS. Prenatal genetic testing to diagnose DS in utero, provides the novel opportunity to initiate early pharmacological treatment to target this critical period of brain development. Here, we report that prenatal to early postnatal treatment with a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic, Peptide 021 (P021), rescued developmental delay in pups and AD-like hippocampus-dependent memory impairments in adult life in Ts65Dn mice. Furthermore, this treatment prevented pre-synaptic protein deficit, decreased glycogen synthase kinase-3beta (GSK3β) activity, and increased levels of synaptic plasticity markers including brain derived neurotrophic factor (BNDF) and phosphorylated CREB, both in young (3-week-old) and adult (~ 7-month-old) Ts65Dn mice. These findings provide novel evidence that providing neurotrophic support during early brain development can prevent developmental delay and AD-like memory impairments in a DS mouse model. PMID:28368015

  5. The future of fish passage science, engineering, and practice

    USGS Publications Warehouse

    Silva, Ana T.; Lucas, Martyn C.; Castro-Santos, Theodore R.; Katopodis, Christos; Baumgartner, Lee J.; Thiem, Jason D.; Aarestrup, Kim; Pompeu, Paulo S.; O'Brien, Gordon C.; Braun, Douglas C.; Burnett, Nicholas J.; Zhu, David Z.; Fjeldstad, Hans-Petter; Forseth, Torbjorn; Rajarathnam, Nallamuthu; Williams, John G.; Cooke, Steven J.

    2018-01-01

    Much effort has been devoted to developing, constructing and refining fish passage facilities to enable target species to pass barriers on fluvial systems, and yet, fishway science, engineering and practice remain imperfect. In this review, 17 experts from different fish passage research fields (i.e., biology, ecology, physiology, ecohydraulics, engineering) and from different continents (i.e., North and South America, Europe, Africa, Australia) identified knowledge gaps and provided a roadmap for research priorities and technical developments. Once dominated by an engineering‐focused approach, fishway science today involves a wide range of disciplines from fish behaviour to socioeconomics to complex modelling of passage prioritization options in river networks. River barrier impacts on fish migration and dispersal are currently better understood than historically, but basic ecological knowledge underpinning the need for effective fish passage in many regions of the world, including in biodiversity hotspots (e.g., equatorial Africa, South‐East Asia), remains largely unknown. Designing efficient fishways, with minimal passage delay and post‐passage impacts, requires adaptive management and continued innovation. While the use of fishways in river restoration demands a transition towards fish passage at the community scale, advances in selective fishways are also needed to manage invasive fish colonization. Because of the erroneous view in some literature and communities of practice that fish passage is largely a proven technology, improved international collaboration, information sharing, method standardization and multidisciplinary training are needed. Further development of regional expertise is needed in South America, Asia and Africa where hydropower dams are currently being planned and constructed.

  6. The role of early development in mammalian limb diversification: a descriptive comparison of early limb development between the Natal long-fingered bat (Miniopterus natalensis) and the mouse (Mus musculus).

    PubMed

    Hockman, Dorit; Mason, Mandy K; Jacobs, David S; Illing, Nicola

    2009-04-01

    Comparative embryology expands our understanding of unique limb structures, such as that found in bats. Bat forelimb digits 2 to 5 are differentially elongated and joined by webbing, while the hindlimb digits are of similar length in many species. We compare limb development between the mouse and the Natal long-fingered bat, Miniopterus natalensis, to pinpoint the stage at which their limbs begin to differ. The bat forelimb differs from the mouse at Carollia stage (CS) 14 with the appearance of the wing membrane primordia. This difference is enhanced at CS 15 with the posterior expansion of the hand plate. The bat hindlimb begins to differ from the mouse between CS 15 and 16 when the foot plate undergoes a proximal expansion resulting in digit primordia of very similar length. Our findings support recent gene expression studies, which reveal a role for early patterning in the development of the bat limb. Copyright 2009 Wiley-Liss, Inc.

  7. Adventitial fibroblasts are activated in the early stages of atherosclerosis in the apolipoprotein E knockout mouse

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

    Xu Fang; Ji Jian; Li Li

    2007-01-19

    The role of the adventitia in vascular function and vascular lesion formation has been largely ignored. This study observed the activation of the adventitia and specifically the fibroblasts in the development of atherosclerosis in the apoE(-/-) mouse. The results showed a gradual increase in expression of collagen types I and III after 2, 4, and 8 weeks of hyperlipidic diet. The earliest expression of monocyte chemoattractant protein-1 (MCP-1) protein and mRNA was detected in the adventitial fibroblast before the formation of intimal lesions. Proliferation, too, was first found in the adventitial fibroblasts. We hypothesize that the adventitial fibroblast is activatedmore » in the early stage of atherosclerosis. Adventitial inflammation may be an early event in the development of atherosclerotic lesions.« less

  8. Behaviour and Locomotor Activity of a Migratory Catostomid during Fishway Passage

    PubMed Central

    Silva, Ana T.; Hatry, Charles; Thiem, Jason D.; Gutowsky, Lee F. G.; Hatin, Daniel; Zhu, David Z.; W. Dawson, Jeffery; Katopodis, Christos; J. Cooke, Steven

    2015-01-01

    Fishways have been developed to restore longitudinal connectivity in rivers. Despite their potential for aiding fish passage, fishways may represent a source of significant energetic expenditure for fish as they are highly turbulent environments. Nonetheless, our understanding of the physiological mechanisms underpinning fishway passage of fish is still limited. We examined swimming behaviour and activity of silver redhorse (Moxostoma anisurum) during its upriver spawning migration in a vertical slot fishway. We used an accelerometer-derived instantaneous activity metric (overall dynamic body acceleration) to estimate location-specific swimming activity. Silver redhorse demonstrated progressive increases in activity during upstream fishway passage. Moreover, location-specific passage duration decreased with an increasing number of passage attempts. Turning basins and the most upstream basin were found to delay fish passage. No relationship was found between basin-specific passage duration and activity and the respective values from previous basins. The results demonstrate that successful fishway passage requires periods of high activity. The resultant energetic expenditure may affect fitness, foraging behaviour and increase susceptibility to predation, compromising population sustainability. This study highlights the need to understand the physiological mechanisms underpinning fishway passage to improve future designs and interpretation of biological evaluations. PMID:25853245

  9. Mouse allergen exposure, wheeze and atopy in the first seven years of life

    PubMed Central

    Phipatanakul, W.; Celedón, J. C.; Hoffman, E. B.; Abdulkerim, H.; Ryan, L. M.; Gold, D. R.

    2008-01-01

    Background Little is known about mouse allergen exposure in home environments and the development of wheezing, asthma and atopy in childhood. Objective To examine the relation between mouse allergen exposure and wheezing, atopy, and asthma in the first 7 years of life. Methods Prospective study of 498 children with parental history of allergy or asthma followed from birth to age 7 years, with longitudinal questionnaire ascertainment of reported mouse exposure and dust sample mouse urinary protein allergen levels measured at age 2–3 months. Results Parental report of mouse exposure in the first year of life was associated with increased risk of transient wheeze and wheezing in early life. Current report of mouse exposure was also significantly associated with current wheeze throughout the first 7 years of life in the longitudinal analysis (P = 0.03 for overall relation of current mouse to current wheeze). However, early life mouse exposure did not predict asthma, eczema or allergic rhinitis at age 7 years. Exposure to detectable levels of mouse urinary protein in house dust samples collected at age 2–3 months was associated with a twofold increase in the odds of atopy (sensitization to >=1 allergen) at school age (95% confidence interval for odds ratio = 1.1–3.7; P = 0.03 in a multivariate analysis. Conclusions Among children with parental history of asthma or allergies, current mouse exposure is associated with increased risk of wheeze during the first 7 years of life. Early mouse exposure was associated with early wheeze and atopy later in life. PMID:18616677

  10. Unintended consequences and trade-offs of fish passage

    USGS Publications Warehouse

    McLaughlin, Robert L.; Smyth, Eric R.; Castro-Santos, Theodore; Jones, Michael L.; Koops, Marten A.; Pratt, Thomas C.; Vélez-Espino, Luis-Antonio

    2012-01-01

    We synthesized evidence for unintended consequences and trade-offs associated with the passage of fishes. Provisioning of fish passageways at dams and dam removals are being carried out increasingly as resource managers seek ways to reduce fragmentation of migratory fish populations and restore biodiversity and nature-like ecosystem services in tributaries altered by dams. The benefits of provisioning upstream passage are highlighted widely. Possible unwanted consequences and trade-offs of upstream passage are coming to light, but remain poorly examined and underappreciated. Unintended consequences arise when passage of native and desirable introduced fishes is delayed, undone (fallback), results in patterns of movement and habitat use that reduce Darwinian fitness (e.g. ecological traps), or is highly selective taxonomically and numerically. Trade-offs arise when passage decisions intended to benefit native species interfere with management decisions intended to control the unwanted spread of non-native fishes and aquatic invertebrates, or genes, diseases and contaminants carried by hatchery and wild fishes. These consequences and trade-offs will vary in importance from system to system and can result in large economic and environmental costs. For some river systems, decisions about how to manage fish passage involve substantial risks and could benefit from use of a formal, structured process that allows transparent, objective and, where possible, quantitative evaluation of these risks. Such a process can also facilitate the design of an adaptive framework that provides valuable insights into future decisions.

  11. Turbulence spectra measured during fire front passage

    Treesearch

    Daisuke Seto; Craig B. Clements; Warren E. Heilman

    2013-01-01

    Four field experiments were conducted over various fuel and terrain to investigate turbulence generation during the passage of wildland fire fronts. Our results indicate an increase in horizontal mean winds and friction velocity, horizontal and vertical velocity variances as well as a decreased degree of anisotropy in TKE during fire front passage (FFP) due to fire-...

  12. Complementary Gli activity mediates early patterning of the mouse visual system.

    PubMed

    Furimsky, Marosh; Wallace, Valerie A

    2006-03-01

    The Sonic hedgehog (Shh) signaling pathway plays a key role in the development of the vertebrate central nervous system, including the eye. This pathway is mediated by the Gli transcription factors (Gli1, Gli2, and Gli3) that differentially activate and repress the expression of specific downstream target genes. In this study, we investigated the roles of the three vertebrate Glis in mediating midline Shh signaling in early ocular development. We examined the ocular phenotypes of Shh and Gli combination mutant mouse embryos and monitored proximodistal and dorsoventral patterning by the expression of specific eye development regulatory genes using in situ hybridization. We show that midline Shh signaling relieves the repressor activity of Gli3 adjacent to the midline and then promotes eye pattern formation through the nonredundant activities of all three Gli proteins. Gli3, in particular, is required to specify the dorsal optic stalk and to define the boundary between the optic stalk and the optic cup.

  13. Model for Predicting Passage of Invasive Fish Species Through Culverts

    NASA Astrophysics Data System (ADS)

    Neary, V.

    2010-12-01

    Conservation efforts to promote or inhibit fish passage include the application of simple fish passage models to determine whether an open channel flow allows passage of a given fish species. Derivations of simple fish passage models for uniform and nonuniform flow conditions are presented. For uniform flow conditions, a model equation is developed that predicts the mean-current velocity threshold in a fishway, or velocity barrier, which causes exhaustion at a given maximum distance of ascent. The derivation of a simple expression for this exhaustion-threshold (ET) passage model is presented using kinematic principles coupled with fatigue curves for threatened and endangered fish species. Mean current velocities at or above the threshold predict failure to pass. Mean current velocities below the threshold predict successful passage. The model is therefore intuitive and easily applied to predict passage or exclusion. The ET model’s simplicity comes with limitations, however, including its application only to uniform flow, which is rarely found in the field. This limitation is addressed by deriving a model that accounts for nonuniform conditions, including backwater profiles and drawdown curves. Comparison of these models with experimental data from volitional swimming studies of fish indicates reasonable performance, but limitations are still present due to the difficulty in predicting fish behavior and passage strategies that can vary among individuals and different fish species.

  14. Tick Passage Results in Enhanced Attenuation of Babesia bovis

    PubMed Central

    McElwain, Terry F.; Ueti, Massaro W.; Scoles, Glen A.; Reif, Kathryn E.; Lau, Audrey O. T.

    2014-01-01

    Serial blood passage of virulent Babesia bovis in splenectomized cattle results in attenuated derivatives that do not cause neurologic disease. Tick transmissibility can be lost with attenuation, but when retained, attenuated B. bovis can revert to virulence following tick passage. This study provides data showing that tick passage of the partially attenuated B. bovis T2Bo derivative strain further decreased virulence compared with intravenous inoculation of the same strain in infected animals. Ticks that acquired virulent or attenuated parasites by feeding on infected cattle were transmission fed on naive, splenectomized animals. While there was no significant difference between groups in the number of parasites in the midgut, hemolymph, or eggs of replete female ticks after acquisition feeding, animals infected with the attenuated parasites after tick transmission showed no clinical signs of babesiosis, unlike those receiving intravenous challenge with the same attenuated strain prior to tick passage. Additionally, there were significantly fewer parasites in blood and tissues of animals infected with tick-passaged attenuated parasites. Sequencing analysis of select B. bovis genes before and after tick passage showed significant differences in parasite genotypes in both peripheral blood and cerebral samples. These results provide evidence that not only is tick transmissibility retained by the attenuated T2Bo strain, but also it results in enhanced attenuation and is accompanied by expansion of parasite subpopulations during tick passage that may be associated with the change in disease phenotype. PMID:25114111

  15. Analysis of early thrombus dynamics in a humanized mouse laser injury model.

    PubMed

    Wang, Weiwei; Lindsey, John P; Chen, Jianchun; Diacovo, Thomas G; King, Michael R

    2014-01-01

    Platelet aggregation and thrombus formation at the site of injury is a dynamic process that involves the continuous addition of new platelets as well as thrombus rupture. In the early stages of hemostasis (within minutes after vessel injury) this process can be visualized by transfusing fluorescently labeled human platelets and observing their deposition and detachment. These two counterbalancing events help the developing thrombus reach a steady-state morphology, where it is large enough to cover the injured vessel surface but not too large to form a severe thrombotic occlusion. In this study, the spatial and temporal aspects of early stage thrombus dynamics which result from laser-induced injury on arterioles of cremaster muscle in the humanized mouse were visualized using fluorescent microscopy. It was found that rolling platelets show preference for the upstream region while tethering/detaching platelets were primarily found downstream. It was also determined that the platelet deposition rate is relatively steady, whereas the effective thrombus coverage area does not increase at a constant rate. By introducing a new method to graphically represent the real time in vivo physiological shear stress environment, we conclude that the thrombus continuously changes shape by regional growth and decay, and neither dominates in the high shear stress region.

  16. Proceedings of a workshop on American Eel passage technologies

    USGS Publications Warehouse

    Haro, Alexander J.

    2013-01-01

    Recent concerns regarding a decline in recruitment of American eels (Anguilla rostrata) have prompted efforts to restore this species to historic habitats by providing passage for both upstream migrant juveniles and downstream migrant adults at riverine barriers, including low-head and hydroelectric dams (Castonguay et al. 1994, Haro et al. 2000). These efforts include development of management plans and stock assessment reviews in both the US and Canada (COSEWIC 2006, Canadian Eel Working Group 2009, DFO 2010, MacGregor et al. 2010, ASMFC 2000, ASMFC 2006, ASMFC 2008, Williams and Threader 2007), which target improvement of upstream and downstream passage for eels, as well as identification and prioritization of research needs for development of new and more effective passage technologies for American eels. Traditional upstream fish passage structures, such as fishways and fish lifts, are often ineffective passing juvenile eels, and specialized passage structures for this species are needed. Although designs for such passage structures are available and diverse (Knights and White 1998, Porcher 2002, FAO/DVWK 2002, Solomon and Beach 2004a,b, Environment Agency UK 2011), many biologists, managers, and engineers are unfamiliar with eel pass design and operation, or unaware of the technical options available for upstream eel passage, Better coordination is needed to account for eel passage requirements during restoration efforts for other diadromous fish species. Also, appropriately siting eel passes at hydropower projects is critical, and siting can be difficult and complex due to physical restrictions in access to points of natural concentrations of eels, dynamic hydraulics of tailrace areas, and presence of significant competing flows from turbine outfalls or spill. As a result, some constructed eel passes are sited poorly and may pass only a fraction of the number of eels attempting to pass the barrier. When sited and constructed appropriately, however, eel passes

  17. Neogene sedimentation and erosion in the Amirante Passage, western Indian Ocean

    NASA Astrophysics Data System (ADS)

    Johnson, D. A.; Ledbetter, M. T.; Damuth, J. E.

    1983-02-01

    Twenty piston cores from the northern Mascarene Basin and Amirante Passage reflect the effects of the Deep Western Boundary Current (DWBC) upon the lithologic and stratigraphic record of the late Cenozoic. The cores span a depth interval of 3350 to 5200 m, representing the transition zone between modern North Atlantic Deep Water (NADW)-Circumpolar Water (CPW) and the underlying Antarctic Bottom Water (AABW). During the late Cretaceous and for much of the Paleogene, pelagic sedimentation occurred in the absence of significant bottom current activity. The formation of the global psychrosphere near the Eocene-Oligocene boundary initiated the DWBC, part of which could enter the Madagascar Basin via deep fractures in the Southwest Indian Ridge. The DWBC was well developed before the early Miocene, transporting course detrital sands northward into the passage from turbidite deposits along the continental margin of Madagascar. The DWBC was confined to depths below ˜ 4 km until the middle Miocene, when the flow strengthened and shoaled to depths <3300 m. Strong DWBC flow continued intermittently until the latest Pleistocene, producing extensive erosional surfaces. Today the flow of the DWBC is relatively weak, with strong only below ˜ 3850 m in the western channels. Pleistocene and late Tertiary erosion at intermediate depths (3 to 4 km) in the Indian Ocean contrasts with depositional continuity at the same depths farther 'upstream' in NADW. Fluctuations in the intensity of circumpolar flow rather than in the rate of production of NADW may have been the major controlling factor in the late Tertiary erosional history of the Amirante Passage.

  18. Passage Equivalency and Predictive Validity of Oral Reading Fluency Measures

    ERIC Educational Resources Information Center

    Checca, Christopher Jason

    2012-01-01

    The use of oral reading fluency (ORF) passages within a Response to Intervention (RTI) framework is examined. Significant limitations within the current ORF research are discussed. The passage equivalency and readability scores for DIBELS Next, AIMSweb, and a school district's curriculum's ORF passages are evaluated using Generalizability Theory…

  19. Aym1, a mouse meiotic gene identified by virtue of its ability to activate early meiotic genes in the yeast Saccharomyces cerevisiae.

    PubMed

    Malcov, Mira; Cesarkas, Karen; Stelzer, Gil; Shalom, Sarah; Dicken, Yosef; Naor, Yaniv; Goldstein, Ronald S; Sagee, Shira; Kassir, Yona; Don, Jeremy

    2004-12-01

    Our understanding of the molecular mechanisms that operate during differentiation of mitotically dividing spermatogonia cells into spermatocytes lags way behind what is known about other differentiating systems. Given the evolutionary conservation of the meiotic process, we screened for mouse proteins that could specifically activate early meiotic promoters in Saccharomyces cerevisiae yeast cells, when fused to the Gal4 activation domain (Gal4AD). Our screen yielded the Aym1 gene that encodes a short peptide of 45 amino acids. We show that a Gal4AD-AYM1 fusion protein activates expression of reporter genes through the promoters of the early meiosis-specific genes IME2 and HOP1, and that this activation is dependent on the DNA-binding protein Ume6. Aym1 is transcribed predominantly in mouse primary spermatocytes and in gonads of female embryos undergoing the corresponding meiotic divisions. Aym1 immunolocalized to nuclei of primary spermatocytes and oocytes and to specific type A spermatogonia cells, suggesting it might play a role in the processes leading to meiotic competence. The potential functional relationship between AYM1 and yeast proteins that regulate expression of early meiotic genes is discussed.

  20. Mechanical factors direct mouse aortic remodelling during early maturation

    PubMed Central

    Le, Victoria P.; Cheng, Jeffrey K.; Kim, Jungsil; Staiculescu, Marius C.; Ficker, Shawn W.; Sheth, Saahil C.; Bhayani, Siddharth A.; Mecham, Robert P.; Yanagisawa, Hiromi; Wagenseil, Jessica E.

    2015-01-01

    Numerous diseases have been linked to genetic mutations that lead to reduced amounts or disorganization of arterial elastic fibres. Previous work has shown that mice with reduced amounts of elastin (Eln+/−) are able to live a normal lifespan through cardiovascular adaptations, including changes in haemodynamic stresses, arterial geometry and arterial wall mechanics. It is not known if the timeline and presence of these adaptations are consistent in other mouse models of elastic fibre disease, such as those caused by the absence of fibulin-5 expression (Fbln5−/−). Adult Fbln5−/− mice have disorganized elastic fibres, decreased arterial compliance and high blood pressure. We examined mechanical behaviour of the aorta in Fbln5−/− mice through early maturation when the elastic fibres are being assembled. We found that the physiologic circumferential stretch, stress and modulus of Fbln5−/− aorta are maintained near wild-type levels. Constitutive modelling suggests that elastin contributions to the total stress are decreased, whereas collagen contributions are increased. Understanding how collagen fibre structure and mechanics compensate for defective elastic fibres to meet the mechanical requirements of the maturing aorta may help to better understand arterial remodelling in human elastinopathies. PMID:25652465

  1. Genomic variant representation in a Chlamydia population is dynamic and adaptive with dependence on in vitro and in vivo passage.

    PubMed

    Jasper, Deana K; Sigar, Ira M; Schripsema, Justin H; Sainvil, Carlyn K; Smith, Christopher L; Yeruva, Laxmi; Rank, Roger G; Murthy, Ashlesh K; Widder, Jared R; Ramsey, Kyle H

    2015-02-01

    We have previously shown that Chlamydia muridarum has multiple genomic variants that concomitantly vary in their in vitro and in vivo phenotype. Herein, we used real-time polymerase chain reaction-based genotyping assays to query plaque-cloned isolates of C. muridarum for the frequency of eight selected polymorphisms. These strains had no history of passage in vivo since their original isolation from laboratory mice. There was significant variance in the frequency of two of the eight polymorphisms assessed with the remaining exhibiting a low rate of variance. To determine if any of these polymorphisms were more favorable for in vivo conditions, we blindly passaged non-clonal C. muridarum three times at 7-day intervals through the urogenital tract of mice. Seven of the eight polymorphisms varied in frequency following in vivo passage and four of these varied between C. muridarum strains. Selected isolates displayed variable growth rates and cytopathic effect in vitro. We conclude that multiple genotypic variants are present within the existing known C. muridarum strains and that the frequency of these variants changes upon introduction into the mouse host. These findings lend support to the concept that genotypic proportional representation in a chlamydial population is dynamic and adaptive. © The Author 2015. Published by Oxford University Press on behalf of on behalf of Federation of European Microbiological Society.

  2. The relativistic titls of Giza pyramids' entrance-passages

    NASA Astrophysics Data System (ADS)

    Aboulfotouh, H.

    The tilts of Giza pyramids' entrance-passages have never been considered as if they were the result of relativistic mathematical equations, and never been thought to encode the Earth's obliquity parameters. This paper presents an attempt to retrieve the method of establishing the equations that the pyramids' designer used to quantify the entrance-passages' tilts of these architectonic masterpieces. It proves that the pyramids' designer was able to include the geographic, astronomical and time parameters in one relativistic equation, encoding the date of the design of the Giza pyramids in the tilt of the entrance passage of the great pyramid.

  3. Gamma-ray flare activity from PSR B1259-63 during 2014 Periastron Passage and comparison to its 2010 passage

    DOE PAGES

    Caliandro, G. A.; Cheung, C. C.; Li, J.; ...

    2015-09-22

    PSR B1259–63/LS 2883 is a gamma-ray binary system containing a radio pulsar in a highly elliptical ~3.4-year orbit around a Be star. In its 2010 periastron passage, multiwavelength emission from radio to TeV was observed, as well as an unexpected GeV flare measured by the Fermi Large Area Telescope (LAT). We report the results of LAT monitoring of PSR B1259–63 during its most recent 2014 periastron passage. We also compare the gamma-ray behavior in this periastron with the former in 2010 and find that PSR B1259–63 shows a recurrent GeV flare. Furthermore, the similarities and differences in the phenomenology ofmore » both periastron passages are discussed.« less

  4. Peptide modified nanofibrous scaffold promotes human mesenchymal stem cell proliferation and long-term passaging.

    PubMed

    Mobasseri, Rezvan; Tian, Lingling; Soleimani, Masoud; Ramakrishna, Seeram; Naderi-Manesh, Hossein

    2018-03-01

    Long-term culture, passage and proliferation of human mesenchymal stem cells (hMSCs) cause loss of their stemness properties including self-renewal and multipotency. By optimizing the MSCs environment in vitro, maintaining the stemness state and better controlling the cell fate might be possible. We have recently reported the significant effects of bioactive Tat protein-derived peptide named R-peptide on hMSC adhesion, morphology and proliferation, which has demonstrated R-peptide enhanced MSC early adhesion and proliferation in comparison to other bioactive molecules including RGD peptide, fibronectin and collagen. In this study, R-peptide was used to evaluate stemness properties of MSCs after long-term passaging. R-peptide conjugated poly caprolactone (PCL) nanofibrous scaffold and unmodified nanofibrous scaffold were used to study the impact of R-peptide modified PCL nanofibers and PCL nanofibers on cell behavior. The results showed early formation of focal adhesion (FA) complex on R-peptide modified scaffolds at 30min after cell seeding. The rate of cell proliferation was significantly increased due to presence of R-peptide, and the MSCs marker analyses using flow cytometry and immunocytochemistry staining proved the ability of R-peptide to maintain mesenchymal stem cell properties (high proliferation, expression of multipotent markers and differentiation capacity) even after long-term passage culturing. Accordingly, our (The) results concluded that bioactive R-peptide in combination with nanofibrous scaffold can mimic the native ECM comprising micro/nano architecture and biochemical molecules in a best way. The designed scaffold can link extracellular matrix (ECM) to nucleus via formation of FA and organization of cytoskeleton, causing fast and strong attachment of MSCs and allowing integrin-mediated signaling to start. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease

    PubMed Central

    Roy, Dheeraj S.; Arons, Autumn; Mitchell, Teryn I.; Pignatelli, Michele; Ryan, Tomás J.; Tonegawa, Susumu

    2016-01-01

    Summary Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions1. Memory decline in early stages of Alzheimer’s is mostly limited to episodic memory, for which the hippocampus (HPC) plays a crucial role2. However, it has been uncertain whether the observed amnesia in early stages of Alzheimer’s is due to disrupted encoding and consolidation of episodic information, or an impairment in the retrieval of stored memory information. Here we show that in transgenic mouse models of early Alzheimer’s, direct optogenetic activation of hippocampal memory engram cells results in memory retrieval despite the fact that these mice are amnesic in long-term memory tests when natural recall cues are utilized, revealing a retrieval, rather than a storage impairment. Prior to amyloid plaque deposition, the amnesia in these mice is age-dependent3–5, which correlates with a progressive reduction of spine density of hippocampal dentate gyrus (DG) engram cells. We show that optogenetic induction of long-term potentiation (LTP) at perforant path (PP) synapses of DG engram cells restores both spine density and long-term memory. We also demonstrate that an ablation of DG engram cells containing restored spine density prevents the rescue of long-term memory. Thus, selective rescue of spine density in engram cells may lead to an effective strategy for treating memory loss in early stages of Alzheimer’s disease. PMID:26982728

  6. Single-cell multi-omics sequencing of mouse early embryos and embryonic stem cells.

    PubMed

    Guo, Fan; Li, Lin; Li, Jingyun; Wu, Xinglong; Hu, Boqiang; Zhu, Ping; Wen, Lu; Tang, Fuchou

    2017-08-01

    Single-cell epigenome sequencing techniques have recently been developed. However, the combination of different layers of epigenome sequencing in an individual cell has not yet been achieved. Here, we developed a single-cell multi-omics sequencing technology (single-cell COOL-seq) that can analyze the chromatin state/nucleosome positioning, DNA methylation, copy number variation and ploidy simultaneously from the same individual mammalian cell. We used this method to analyze the reprogramming of the chromatin state and DNA methylation in mouse preimplantation embryos. We found that within < 12 h of fertilization, each individual cell undergoes global genome demethylation together with the rapid and global reprogramming of both maternal and paternal genomes to a highly opened chromatin state. This was followed by decreased openness after the late zygote stage. Furthermore, from the late zygote to the 4-cell stage, the residual DNA methylation is preferentially preserved on intergenic regions of the paternal alleles and intragenic regions of maternal alleles in each individual blastomere. However, chromatin accessibility is similar between paternal and maternal alleles in each individual cell from the late zygote to the blastocyst stage. The binding motifs of several pluripotency regulators are enriched at distal nucleosome depleted regions from as early as the 2-cell stage. This indicates that the cis-regulatory elements of such target genes have been primed to an open state from the 2-cell stage onward, long before pluripotency is eventually established in the ICM of the blastocyst. Genes may be classified into homogeneously open, homogeneously closed and divergent states based on the chromatin accessibility of their promoter regions among individual cells. This can be traced to step-wise transitions during preimplantation development. Our study offers the first single-cell and parental allele-specific analysis of the genome-scale chromatin state and DNA

  7. Single-cell multi-omics sequencing of mouse early embryos and embryonic stem cells

    PubMed Central

    Guo, Fan; Li, Lin; Li, Jingyun; Wu, Xinglong; Hu, Boqiang; Zhu, Ping; Wen, Lu; Tang, Fuchou

    2017-01-01

    Single-cell epigenome sequencing techniques have recently been developed. However, the combination of different layers of epigenome sequencing in an individual cell has not yet been achieved. Here, we developed a single-cell multi-omics sequencing technology (single-cell COOL-seq) that can analyze the chromatin state/nucleosome positioning, DNA methylation, copy number variation and ploidy simultaneously from the same individual mammalian cell. We used this method to analyze the reprogramming of the chromatin state and DNA methylation in mouse preimplantation embryos. We found that within < 12 h of fertilization, each individual cell undergoes global genome demethylation together with the rapid and global reprogramming of both maternal and paternal genomes to a highly opened chromatin state. This was followed by decreased openness after the late zygote stage. Furthermore, from the late zygote to the 4-cell stage, the residual DNA methylation is preferentially preserved on intergenic regions of the paternal alleles and intragenic regions of maternal alleles in each individual blastomere. However, chromatin accessibility is similar between paternal and maternal alleles in each individual cell from the late zygote to the blastocyst stage. The binding motifs of several pluripotency regulators are enriched at distal nucleosome depleted regions from as early as the 2-cell stage. This indicates that the cis-regulatory elements of such target genes have been primed to an open state from the 2-cell stage onward, long before pluripotency is eventually established in the ICM of the blastocyst. Genes may be classified into homogeneously open, homogeneously closed and divergent states based on the chromatin accessibility of their promoter regions among individual cells. This can be traced to step-wise transitions during preimplantation development. Our study offers the first single-cell and parental allele-specific analysis of the genome-scale chromatin state and DNA

  8. Role of nucleation-promoting factors in mouse early embryo development.

    PubMed

    Wang, Qiao-Chu; Liu, Jun; Wang, Fei; Duan, Xing; Dai, Xiao-Xin; Wang, Teng; Liu, Hong-Lin; Cui, Xiang-Shun; Sun, Shao-Chen; Kim, Nam-Hyung

    2013-06-01

    During mitosis nucleation-promoting factors (NPFs) bind to the Arp2/3 complex and activate actin assembly. JMY and WAVE2 are two critical members of the NPFs. Previous studies have demonstrated that NPFs promote multiple processes such as cell migration and cytokinesis. However, the role of NPFs in development of mammalian embryos is still unknown. Results of the present study show that the NPFs JMY and WAVE2 are critical for cytokinesis during development of mouse embryos. Both JMY and WAVE2 are expressed in mouse embryos. After injection of JMY or WAVE2 siRNA, all embryos failed to develop to the morula or blastocyst stages. Moreover, using fluorescence intensity analysis, we found that the expression of actin decreased, and multiple nuclei were observed within a single cell indicating that NPFs-induced actin reduction caused the failure of cell division. In addition, injection of JMY and WAVE2 siRNA also caused ARP2 degradation, indicating that involvement of NPFs in development of mouse embryos is mainly through regulation of ARP2/3-induced actin assembly. Taken together, these data suggested that WAVE2 and JMY are involved in development of mouse embryos, and their regulation may be through a NPFs-Arp2/3-actin pathway.

  9. Sign changes as a universal concept in first-passage-time calculations

    NASA Astrophysics Data System (ADS)

    Braun, Wilhelm; Thul, Rüdiger

    2017-01-01

    First-passage-time problems are ubiquitous across many fields of study, including transport processes in semiconductors and biological synapses, evolutionary game theory and percolation. Despite their prominence, first-passage-time calculations have proven to be particularly challenging. Analytical results to date have often been obtained under strong conditions, leaving most of the exploration of first-passage-time problems to direct numerical computations. Here we present an analytical approach that allows the derivation of first-passage-time distributions for the wide class of nondifferentiable Gaussian processes. We demonstrate that the concept of sign changes naturally generalizes the common practice of counting crossings to determine first-passage events. Our method works across a wide range of time-dependent boundaries and noise strengths, thus alleviating common hurdles in first-passage-time calculations.

  10. Insertable fluid flow passage bridgepiece and method

    DOEpatents

    Jones, Daniel O.

    2000-01-01

    A fluid flow passage bridgepiece for insertion into an open-face fluid flow channel of a fluid flow plate is provided. The bridgepiece provides a sealed passage from a columnar fluid flow manifold to the flow channel, thereby preventing undesirable leakage into and out of the columnar fluid flow manifold. When deployed in the various fluid flow plates that are used in a Proton Exchange Membrane (PEM) fuel cell, bridgepieces of this invention prevent mixing of reactant gases, leakage of coolant or humidification water, and occlusion of the fluid flow channel by gasket material. The invention also provides a fluid flow plate assembly including an insertable bridgepiece, a fluid flow plate adapted for use with an insertable bridgepiece, and a method of manufacturing a fluid flow plate with an insertable fluid flow passage bridgepiece.

  11. 33 CFR 151.2020 - Vessels in innocent passage.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Vessels in innocent passage. 151.2020 Section 151.2020 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY... United States § 151.2020 Vessels in innocent passage. A foreign vessel that is merely traversing the...

  12. 33 CFR 151.2020 - Vessels in innocent passage.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Vessels in innocent passage. 151.2020 Section 151.2020 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY... United States § 151.2020 Vessels in innocent passage. A foreign vessel that is merely traversing the...

  13. 33 CFR 151.2020 - Vessels in innocent passage.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Vessels in innocent passage. 151.2020 Section 151.2020 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY... United States § 151.2020 Vessels in innocent passage. A foreign vessel that is merely traversing the...

  14. Bilingual Listeners' Perception of Temporally Manipulated English Passages

    ERIC Educational Resources Information Center

    Shi, Lu-Feng; Farooq, Nadia

    2012-01-01

    Purpose: The current study measured, objectively and subjectively, how changes in speech rate affect recognition of English passages in bilingual listeners. Method: Ten native monolingual, 20 English-dominant bilingual, and 20 non-English-dominant bilingual listeners repeated target words in English passages at five speech rates (unprocessed, two…

  15. Targeted deletion of p97 (VCP/CDC48) in mouse results in early embryonic lethality.

    PubMed

    Müller, J M M; Deinhardt, K; Rosewell, I; Warren, G; Shima, D T

    2007-03-09

    The highly conserved AAA ATPase p97 (VCP/CDC48) has well-established roles in cell cycle progression, proteasome degradation and membrane dynamics. Gene disruption in Saccromyces cerevisiae, Drosophila melanogaster and Trypanosoma brucei demonstrated that p97 is essential in unicellular and multicellular organisms. To explore the requirement for p97 in mammalian cell function and embryogenesis, we disrupted the p97 locus by gene targeting. Heterozygous p97+/- mice were indistinguishable from their wild-type littermates, whereas homozygous mutants did not survive to birth and died at a peri-implantation stage. These results show that p97 is an essential gene for early mouse development.

  16. CBP and Extracellular Matrix-Induced Apoptosis in p53(-) HMECs: A Model of Early Mammary Carcinogenesis

    DTIC Science & Technology

    2006-09-01

    LAMA3A promoter activity. Early and late passage HMEC-E6 and passage-matched HMEC- LXSN controls were transiently transfected with a CAT reporter...CBP protein expression resulted in decreased LAMA3A promoter activity. LAMA3A- CAT reporter activity was compared in early passage HMEC-LXSN and HMEC...AF279435 was amplified with PCR primers, sense 5-AAG CTT AAG TTT TCC CAT CCG CAA C-3 and antisense 5-TCT AGA GCT GAC CGC CTC ACT GC-3. The PCR

  17. Early development of the circumferential axonal pathway in mouse and chick spinal cord.

    PubMed

    Holley, J A

    1982-03-10

    The early development of the circumferential axonal pathway in the brachial and lumbar spinal cord of mouse and chick embryos was studied by scanning and transmission electron microscopy. The cellular processes which comprise this pathway grow in the transverse plane and along the lateral margin of the marginal zone (i.e., circumferentially oriented), as typified by the early embryonic commissural axons. The first formative event observed was in the ventrolateral margin of the primitive spinal cord ventricular zone. Cellular processes were found near the external limiting membrane that appeared to grow a variable distance either dorsally or ventrally. Later in development, presumptive motor column neurons migrated into the ventrolateral region, distal to these early circumferentially oriented processes. Concurrently, other circumferentially oriented perikarya and processes appeared along the dorsolateral margin. Due to their aligned sites of origin and parallel growth, the circumferential processes formed a more or less continuous line or pathway, which in about 10% of the scanned specimens could be followed along the entire lateral margin of the embryonic spinal cord. Several specimens later in development had two sets of aligned circumferential processes in the ventral region. Large numbers of circumferential axons were then found to follow the preformed pathway by fasciculation, after the primitive motor column had become established. Since the earliest circumferential processes appeared to differentiate into axons and were found nearly 24 hours prior to growth of most circumferential axons, their role in guidance as pioneering axons was suggested.

  18. First passage Brownian functional properties of snowmelt dynamics

    NASA Astrophysics Data System (ADS)

    Dubey, Ashutosh; Bandyopadhyay, Malay

    2018-04-01

    In this paper, we model snow-melt dynamics in terms of a Brownian motion (BM) with purely time dependent drift and difusion and examine its first passage properties by suggesting and examining several Brownian functionals which characterize the lifetime and reactivity of such stochastic processes. We introduce several probability distribution functions (PDFs) associated with such time dependent BMs. For instance, for a BM with initial starting point x0, we derive analytical expressions for : (i) the PDF P(tf|x0) of the first passage time tf which specify the lifetime of such stochastic process, (ii) the PDF P(A|x0) of the area A till the first passage time and it provides us numerous valuable information about the total fresh water availability during melting, (iii) the PDF P(M) associated with the maximum size M of the BM process before the first passage time, and (iv) the joint PDF P(M; tm) of the maximum size M and its occurrence time tm before the first passage time. These P(M) and P(M; tm) are useful in determining the time of maximum fresh water availability and in calculating the total maximum amount of available fresh water. These PDFs are examined for the power law time dependent drift and diffusion which matches quite well with the available data of snowmelt dynamics.

  19. The Use of Ritual in Rites of Passage.

    ERIC Educational Resources Information Center

    Ferguson, Gary

    2001-01-01

    Humans move through difficult transitions best when guided by ceremony and ritual. The components of traditional rites of passage mirror exactly many of today's most promising psychological theories. Four components of rites of passage that comprise life transitions are discussed: letting go of an old identity, the wandering, the new identity, and…

  20. Algorithms for Brownian first-passage-time estimation

    NASA Astrophysics Data System (ADS)

    Adib, Artur B.

    2009-09-01

    A class of algorithms in discrete space and continuous time for Brownian first-passage-time estimation is considered. A simple algorithm is derived that yields exact mean first-passage times (MFPTs) for linear potentials in one dimension, regardless of the lattice spacing. When applied to nonlinear potentials and/or higher spatial dimensions, numerical evidence suggests that this algorithm yields MFPT estimates that either outperform or rival Langevin-based (discrete time and continuous space) estimates.

  1. Flow in Rotating Serpentine Coolant Passages With Skewed Trip Strips

    NASA Technical Reports Server (NTRS)

    Tse, David G.N.; Steuber, Gary

    1996-01-01

    Laser velocimetry was utilized to map the velocity field in serpentine turbine blade cooling passages with skewed trip strips. The measurements were obtained at Reynolds and Rotation numbers of 25,000 and 0.24 to assess the influence of trips, passage curvature and Coriolis force on the flow field. The interaction of the secondary flows induced by skewed trips with the passage rotation produces a swirling vortex and a corner recirculation zone. With trips skewed at +45 deg, the secondary flows remain unaltered as the cross-flow proceeds from the passage to the turn. However, the flow characteristics at these locations differ when trips are skewed at -45 deg. Changes in the flow structure are expected to augment heat transfer, in agreement with the heat transfer measurements of Johnson, et al. The present results show that trips are skewed at -45 deg in the outward flow passage and trips are skewed at +45 deg in the inward flow passage maximize heat transfer. Details of the present measurements were related to the heat transfer measurements of Johnson, et al. to relate fluid flow and heat transfer measurements.

  2. Comparative Study of Barotrauma Risk during Fish Passage through Kaplan Turbines

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

    Richmond, Marshall C.; Romero-Gomez, Pedro; Serkowski, John A.

    Rapid pressure changes in hydroelectric turbine flows can cause barotrauma that can be hazardous to the passage of fish, in particular migratory juvenile salmonids. Although numerous laboratory tests have evaluated the effect of rapid decompression in fish species of relevance, numerical modeling studies offer the advantage of predicting, for new turbine designs, the potential risks of mortality and injury from rapid pressure change during turbine passage. However, rapid pressure change is only one of several hydraulic risks encountered by fish during turbine passage in addition to blade strike, shear, and turbulence. To better understand the role of rapid pressure changes,more » the present work focuses on the application of a computational fluid dynamics based method for evaluating the risk of pressure-related mortality to fish passing through an early 1960s era original hydroelectric Kaplan turbine at Wanapum Dam (Columbia River, Washington), and a modern advanced Kaplan turbine installed in 2005. The results show that the modeling approach acceptably reproduced the nadir pressure distributions compared to field data previously collected at the site using an autonomous sensor. Our findings show that the new advanced-design unit performs better, in terms of reduced barotrauma risk to fish from exposure to low pressures, than the original turbine unit. The outcomes allow for comparative analyses of turbine designs and operations prior to installation, an advantage that can potentially be integrated in the process of designing new turbine units to achieve superior environmental performance. Overall, the results show that modern turbine designs can achieve the multiple objectives of increasing power generation, lowering cavitation potential, and reducing barotrauma risks to passing fish.« less

  3. GAMMA-RAY FLARE ACTIVITY FROM PSR B1259–63 DURING 2014 PERIASTRON PASSAGE AND COMPARISON TO ITS 2010 PASSAGE

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

    Caliandro, G. A.; Cheung, C. C.; Wood, K. S.

    2015-09-20

    PSR B1259–63/LS 2883 is a gamma-ray binary system containing a radio pulsar in a highly elliptical ∼3.4-year orbit around a Be star. In its 2010 periastron passage, multiwavelength emission from radio to TeV was observed, as well as an unexpected GeV flare measured by the Fermi Large Area Telescope (LAT). Here, we report the results of LAT monitoring of PSR B1259–63 during its most recent 2014 periastron passage. We compare the gamma-ray behavior in this periastron with the former in 2010 and find that PSR B1259–63 shows a recurrent GeV flare. The similarities and differences in the phenomenology of bothmore » periastron passages are discussed.« less

  4. Upstream dispersal of an invasive crayfish aided by a fish passage facility

    USGS Publications Warehouse

    Welsh, Stuart A.; Loughman, Zachary J.

    2015-01-01

    Fish passage facilities for reservoir dams have been used to restore habitat connectivity within riverine networks by allowing upstream passage for native species. These facilities may also support the spread of invasive species, an unintended consequence and potential downside of upstream passage structures. We documented dam passage of the invasive virile crayfish, Orconectes virilis (Hagen, 1870), at fish ladders designed for upstream passage of American eels, Anguilla rostrata (Lesueur, 1817), in the Shenandoah River drainage, USA. Ladder use and upstream passage of 11 virile crayfish occurred from 2007–2014 during periods of low river discharge (<30 m3s–1) and within a wide range of water temperatures from 9.0–28.6 °C. Virile crayfish that used the eel ladders were large adults with a mean carapace length and width of 48.0 mm and 24.1 mm, respectively. Our data demonstrated the use of species-specific fish ladders by a non-target non-native species, which has conservation and management implications for the spread of aquatic invasive species and upstream passage facilities. Specifically, managers should consider implementing long-term monitoring of fish passage facilities with emphasis on detection of invasive species, as well as methods to reduce or eliminate passage of invasive species. 

  5. First-Passage-Time Distribution for Variable-Diffusion Processes

    NASA Astrophysics Data System (ADS)

    Barney, Liberty; Gunaratne, Gemunu H.

    2017-05-01

    First-passage-time distribution, which presents the likelihood of a stock reaching a pre-specified price at a given time, is useful in establishing the value of financial instruments and in designing trading strategies. First-passage-time distribution for Wiener processes has a single peak, while that for stocks exhibits a notable second peak within a trading day. This feature has only been discussed sporadically—often dismissed as due to insufficient/incorrect data or circumvented by conversion to tick time—and to the best of our knowledge has not been explained in terms of the underlying stochastic process. It was shown previously that intra-day variations in the market can be modeled by a stochastic process containing two variable-diffusion processes (Hua et al. in, Physica A 419:221-233, 2015). We show here that the first-passage-time distribution of this two-stage variable-diffusion model does exhibit a behavior similar to the empirical observation. In addition, we find that an extended model incorporating overnight price fluctuations exhibits intra- and inter-day behavior similar to those of empirical first-passage-time distributions.

  6. Comparison between reflectance confocal microscopy and two-photon microscopy in early detection of cutaneous radiation injury in a mouse model in-vivo.

    PubMed

    Jang, Won Hyuk; Kwon, Soonjae; Shim, Sehwan; Jang, Won-Suk; Myung, Jae Kyung; Yang, Sejung; Park, Sunhoo; Kim, Ki Hean

    2018-05-12

    Cutaneous radiation injury (CRI) is a skin injury caused by high dose exposure of ionizing radiation (IR). For proper treatment, early detection of CRI before clinical symptoms is important. Optical microscopic techniques such as reflectance confocal microscopy (RCM) and two-photon microscopy (TPM) have been tested as the early diagnosis method by detecting cellular changes. In this study, RCM and TPM were compared in the detection of cellular changes caused by CRI in an in-vivo mouse model. CRI was induced on the mouse hindlimb skin with various IR doses and the injured skin regions were imaged longitudinally by both modalities until the onset of clinical symptoms. Both RCM and TPM detected the changes of epidermal cells and sebaceous glands before clinical symptoms in different optical contrasts. RCM detected changes of cell morphology and scattering property based on light reflection. TPM detected detail changes of cellular structures based on autofluorescence of cells. Since both RCM and TPM were sensitive to the early-stage CRI by using different contrasts, the optimal method for clinical CRI diagnosis could be either individual methods or their combination. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Internal combuston engine having separated cylinder head oil drains and crankcase ventilation passages

    DOEpatents

    Boggs, David Lee; Baraszu, Daniel James; Foulkes, David Mark; Gomes, Enio Goyannes

    1998-01-01

    An internal combustion engine includes separated oil drain-back and crankcase ventilation passages. The oil drain-back passages extend from the cylinder head to a position below the top level of oil in the engine's crankcase. The crankcase ventilation passages extend from passages formed in the main bearing bulkheads from positions above the oil level in the crankcase and ultimately through the cylinder head. Oil dams surrounding the uppermost portions of the crankcase ventilation passages prevent oil from running downwardly through the crankcase ventilation passages.

  8. Optimal Number of Gaps in C-Test Passages

    ERIC Educational Resources Information Center

    Baghaei, Purya

    2011-01-01

    This study addresses the issue of the optimal number of gaps in C-Test passages. An English C-Test battery containing four passages each having 40 blanks was given to 104 undergraduate students of English. The data were entered into SPSS spreadsheet. Out of the complete data with 160 blanks seven additional datasets were constructed. In the first…

  9. Distinct roles for motor neuron autophagy early and late in the SOD1G93A mouse model of ALS

    PubMed Central

    Rudnick, Noam D.; Griffey, Christopher J.; Guarnieri, Paolo; Gerbino, Valeria; Wang, Xueyong; Piersaint, Jason A.; Tapia, Juan Carlos; Rich, Mark M.; Maniatis, Tom

    2017-01-01

    Mutations in autophagy genes can cause familial and sporadic amyotrophic lateral sclerosis (ALS). However, the role of autophagy in ALS pathogenesis is poorly understood, in part due to the lack of cell type-specific manipulations of this pathway in animal models. Using a mouse model of ALS expressing mutant superoxide dismutase 1 (SOD1G93A), we show that motor neurons form large autophagosomes containing ubiquitinated aggregates early in disease progression. To investigate whether this response is protective or detrimental, we generated mice in which the critical autophagy gene Atg7 was specifically disrupted in motor neurons (Atg7 cKO). Atg7 cKO mice were viable but exhibited structural and functional defects at a subset of vulnerable neuromuscular junctions. By crossing Atg7 cKO mice to the SOD1G93A mouse model, we found that autophagy inhibition accelerated early neuromuscular denervation of the tibialis anterior muscle and the onset of hindlimb tremor. Surprisingly, however, lifespan was extended in Atg7 cKO; SOD1G93A double-mutant mice. Autophagy inhibition did not prevent motor neuron cell death, but it reduced glial inflammation and blocked activation of the stress-related transcription factor c-Jun in spinal interneurons. We conclude that motor neuron autophagy is required to maintain neuromuscular innervation early in disease but eventually acts in a non–cell-autonomous manner to promote disease progression. PMID:28904095

  10. Internal combuston engine having separated cylinder head oil drains and crankcase ventilation passages

    DOEpatents

    Boggs, D.L.; Baraszu, D.J.; Foulkes, D.M.; Gomes, E.G.

    1998-12-29

    An internal combustion engine includes separated oil drain-back and crankcase ventilation passages. The oil drain-back passages extend from the cylinder head to a position below the top level of oil in the engine`s crankcase. The crankcase ventilation passages extend from passages formed in the main bearing bulkheads from positions above the oil level in the crankcase and ultimately through the cylinder head. Oil dams surrounding the uppermost portions of the crankcase ventilation passages prevent oil from running downwardly through the crankcase ventilation passages. 4 figs.

  11. A Passage into Critical Theory.

    ERIC Educational Resources Information Center

    Lynn, Steven

    1990-01-01

    Shows how a single passage might be handled by New Criticism, structuralism, deconstructionism, psychological criticism, and feminist criticism. Concludes that a plurality of critical approaches is better than a unity of approach. (RS)

  12. Spontaneous passage of ureteral stones in patients with indwelling ureteral stents.

    PubMed

    Baumgarten, Lee; Desai, Anuj; Shipman, Scott; Eun, Daniel D; Pontari, Michel A; Mydlo, Jack H; Reese, Adam C

    2017-10-01

    To determine rates of spontaneous ureteral stone passage in patients with indwelling ureteral stents, and to identify factors associated with the spontaneous passage of stones while a ureteral stent is in place. From our institutional database, we identified patients who underwent ureteroscopic procedures for stone disease between January 1, 2013 and March 1, 2015. We compared the rates of spontaneous stone passage between patients who had previously undergone ureteral stent placement and those who had not. In patients with indwelling stents, multivariate logistic regression was performed to identify factors associated with spontaneous stone passage. A total of 194 patients met inclusion criteria. Spontaneous stone passage rates were similar in the stented (17/119, 14%) and non-stented (15/75, 20%) groups (p = 0.30). In bivariate analysis of stented patients, smaller stone size (p < 0.001) and distal stone location (p = 0.01) were significantly associated with spontaneous stone passage. Multivariate logistic regression analysis of stented patients showed that only small stone size was significantly associated with the likelihood of stone passage (p = 0.01), whereas stent duration, stone location, and stone laterality were not. A small, but clinically significant percentage of ureteral stones pass spontaneously with a ureteral stent in place. Small stone size is associated with an increased likelihood of spontaneous passage in patients with indwelling stents. These findings may help to identify patients who can potentially avoid additional surgical procedures for definitive stone removal after ureteral stent placement.

  13. 4. BASEMENT WALL BENEATH SOUTH PASSAGE SHOWING STEAM TUNNEL OPENING ...

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

    4. BASEMENT WALL BENEATH SOUTH PASSAGE SHOWING STEAM TUNNEL OPENING IN SOUTH WALL. - Pennsylvania Railroad Station, South Baggage Passage & Canopy, 1101 Liberty Avenue, Pittsburgh, Allegheny County, PA

  14. Early Changes of Articular Cartilage and Subchondral Bone in The DMM Mouse Model of Osteoarthritis.

    PubMed

    Fang, Hang; Huang, Lisi; Welch, Ian; Norley, Chris; Holdsworth, David W; Beier, Frank; Cai, Daozhang

    2018-02-12

    To examine the early changes of articular cartilage and subchondral bone in the DMM mouse model of osteoarthritis, mice were subjected to DMM or SHAM surgery and sacrificed at 2-, 5- and 10-week post-surgery. Catwalk gait analyses, Micro-Computed Tomography, Toluidine Blue, Picrosirius Red and Tartrate-Resistant Acid Phosphatase (TRAP) staining were used to investigate gait patterns, joint morphology, subchondral bone, cartilage, collagen organization and osteoclasts activity, respectively. Results showed OA progressed over 10-week time-course. Gait disparity occurred only at 10-week post-surgery. Osteophyte formed at 2-week post-surgery. BMDs of DMM showed no statistical differences comparing to SHAM at 2 weeks, but BV/TV is much higher in DMM mice. Increased BMD was clearly found at 5- and 10-week post-surgery in DMM mice. TRAP staining showed increased osteoclast activity at the site of osteophyte formation of DMM joints at 5- and 10-week time points. These results showed that subchondral bone turnover might occurred earlier than 2 weeks in this mouse DMM model. Gait disparity only occurred at later stage of OA in DMM mice. Notably, patella dislocation could occur in some of the DMM mice and cause a different pattern of OA in affected knee.

  15. In vitro expansion impaired the stemness of early passage mesenchymal stem cells for treatment of cartilage defects

    PubMed Central

    Jiang, Tongmeng; Xu, Guojie; Wang, Qiuyan; Yang, Lihui; Zheng, Li; Zhao, Jinmin; Zhang, Xingdong

    2017-01-01

    In vitro cultured autologous mesenchymal stem cells (MSCs) within passage 5 have been approved for clinical application in stem cell-based treatment of cartilage defects. However, their chondrogenic potential has not yet been questioned or verified. In this study, the chondrogenic potential of bone marrow MSCs at passage 3 (P3 BMSCs) was investigated both in cartilage repair and in vitro, with freshly isolated bone marrow mononuclear cells (BMMNCs) as controls. The results showed that P3 BMSCs were inferior to BMMNCs not only in their chondrogenic differentiation ability but also as candidates for long-term repair of cartilage defects. Compared with BMMNCs, P3 BMSCs presented a decay in telomerase activity and a change in chromosomal morphology with potential anomalous karyotypes, indicating senescence. In addition, interindividual variability in P3 BMSCs is much higher than in BMMNCs, demonstrating genomic instability. Interestingly, remarkable downregulation in cell cycle, DNA replication and mismatch repair (MMR) pathways as well as in multiple genes associated with telomerase activity and chromosomal stability were found in P3 BMSCs. This result indicates that telomerase and chromosome anomalies might originate from expansion, leading to impaired stemness and pluripotency of stem cells. In vitro culture and expansion are not recommended for cell-based therapy, and fresh BMMNCs are the first choice. PMID:28569773

  16. Hydroacoustic Evaluation of Fish Passage Through Bonneville Dam in 2005

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

    Ploskey, Gene R.; Weiland, Mark A.; Zimmerman, Shon A.

    2006-12-04

    The Portland District of the U.S. Army Corps of Engineers requested that the Pacific Northwest National Laboratory (PNNL) conduct fish-passage studies at Bonneville Dam in 2005. These studies support the Portland District's goal of maximizing fish-passage efficiency (FPE) and obtaining 95% survival for juvenile salmon passing Bonneville Dam. Major passage routes include 10 turbines and a sluiceway at Powerhouse 1 (B1), an 18-bay spillway, and eight turbines and a sluiceway at Powerhouse 2 (B2). In this report, we present results of two studies related to juvenile salmonid passage at Bonneville Dam. The studies were conducted between April 16 and Julymore » 15, 2005, encompassing most of the spring and summer migrations. Studies included evaluations of (1) Project fish passage efficiency and other major passage metrics, and (2) smolt approach and fate at B1 Sluiceway Outlet 3C from the B1 forebay. Some of the large appendices are only presented on the compact disk (CD) that accompanies the final report. Examples include six large comma-separated-variable (.CSV) files of hourly fish passage, hourly variances, and Project operations for spring and summer from Appendix E, and large Audio Video Interleave (AVI) files with DIDSON-movie clips of the area upstream of B1 Sluiceway Outlet 3C (Appendix H). Those video clips show smolts approaching the outlet, predators feeding on smolts, and vortices that sometimes entrained approaching smolts into turbines. The CD also includes Adobe Acrobat Portable Document Files (PDF) of the entire report and appendices.« less

  17. Stokes shift spectroscopy for the early diagnosis of epithelial precancers in DMBA treated mouse skin carcinogenesis

    NASA Astrophysics Data System (ADS)

    Jeyasingh, Ebenezar; Singaravelu, Ganesan; Prakasarao, Aruna

    2018-02-01

    In this study, we aim to characterize the tissue transformation in dimethylbenz(a)anthracene (DMBA) treated mouse skin tumor model using stokes shift spectroscopy (SSS) technique for early detection of the neoplastic changes. Stokes shift (SS) spectra measured by scanning both excitation and emission wavelength simultaneously with a fixed wavelength of interval (Δλ=20 nm) in vivo from 33 DMBA treated animals and 6 control animals. The SS spectra of normal (n=6), hyperplasia (n=10), dysplasia (n=10), and WDSCC (n=13) of mice skin shows the distinct peaks around 300, 350, and 386 nm may be attributed to tryptophan, collagen, and NADH respectively. From the observed spectral differences and the ratio variables that resulted in better classification between groups, it is concluded that tryptophan, collagen, and NADH are the key fluorophores that undergo changes during tissue transformation process and hence they can be targeted as tumor markers for early neoplastic changes.

  18. Antigenic variants of influenza A virus, PR8 strain. I. Their development during serial passage in the lungs of partially immune mice.

    PubMed

    GERBER, P; LOOSLI, C G; HAMBRE, D

    1955-06-01

    Antigenically different strains of mouse-adapted PR8 influenza A virus have been produced by 17 serial passages of the virus in the lungs of mice immunized with the homologous agent. Comparative serological tests show that the variant strains share antigenic components with the parent strain but the dominant antigen is different. By means of antibody absorption it was shown that the "new" antigenic component of the variant was already present in minor amounts up to the eighth passage and thereafter gained prominence with continued passage in vaccinated mice. Groups of mice vaccinated with either the PR8-S or T(21) virus and having comparable antibody titers showed no growth of virus in the lungs following aid-borne challenge with homologous strains. On the other hand, following heterologous air-borne challenge no deaths occurred, but virus grew in the lungs of both groups of vaccinated mice. Almost unrestricted virus multiplication took place in the lungs of mice vaccinated with the parent strain and challenged with the PR8-T(21) virus which resulted in extensive consolidation. Less virus grew in the lungs of the mice vaccinated with the variant strains and challenged with the PR8-S virus. In these animals only microscopic evidence of changes due to virus growth in the lungs was observed. The successful serial passage of PR8 influenza A virus in immunized animals was dependent on the initial selection of mice with uniformly low H.I. antibody titers as determined on tail blood, and the intranasal instillation of sufficient virus to favor the survival of those virus particles least related to the antibodies present. The epidemiological implications of these observations are discussed briefly.

  19. EMG1 is essential for mouse pre-implantation embryo development.

    PubMed

    Wu, Xiaoli; Sandhu, Sumit; Patel, Nehal; Triggs-Raine, Barbara; Ding, Hao

    2010-09-21

    Essential for mitotic growth 1 (EMG1) is a highly conserved nucleolar protein identified in yeast to have a critical function in ribosome biogenesis. A mutation in the human EMG1 homolog causes Bowen-Conradi syndrome (BCS), a developmental disorder characterized by severe growth failure and psychomotor retardation leading to death in early childhood. To begin to understand the role of EMG1 in mammalian development, and how its deficiency could lead to Bowen-Conradi syndrome, we have used mouse as a model. The expression of Emg1 during mouse development was examined and mice carrying a null mutation for Emg1 were generated and characterized. Our studies indicated that Emg1 is broadly expressed during early mouse embryonic development. However, in late embryonic stages and during postnatal development, Emg1 exhibited specific expression patterns. To assess a developmental role for EMG1 in vivo, we exploited a mouse gene-targeting approach. Loss of EMG1 function in mice arrested embryonic development prior to the blastocyst stage. The arrested Emg1-/- embryos exhibited defects in early cell lineage-specification as well as in nucleologenesis. Further, loss of p53, which has been shown to rescue some phenotypes resulting from defects in ribosome biogenesis, failed to rescue the Emg1-/- pre-implantation lethality. Our data demonstrate that Emg1 is highly expressed during mouse embryonic development, and essential for mouse pre-implantation development. The absolute requirement for EMG1 in early embryonic development is consistent with its essential role in yeast. Further, our findings also lend support to the previous study that showed Bowen-Conradi syndrome results from a partial EMG1 deficiency. A complete deficiency would not be expected to be compatible with a live birth.

  20. Early VGLUT1-specific parallel fiber synaptic deficits and dysregulated cerebellar circuit in the KIKO mouse model of Friedreich ataxia.

    PubMed

    Lin, Hong; Magrane, Jordi; Clark, Elisia M; Halawani, Sarah M; Warren, Nathan; Rattelle, Amy; Lynch, David R

    2017-12-19

    Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder with progressive ataxia that affects both the peripheral and central nervous system (CNS). While later CNS neuropathology involves loss of large principal neurons and glutamatergic and GABAergic synaptic terminals in the cerebellar dentate nucleus, early pathological changes in FRDA cerebellum remain largely uncharacterized. Here, we report early cerebellar VGLUT1 (SLC17A7)-specific parallel fiber (PF) synaptic deficits and dysregulated cerebellar circuit in the frataxin knock-in/knockout (KIKO) FRDA mouse model. At asymptomatic ages, VGLUT1 levels in cerebellar homogenates are significantly decreased, whereas VGLUT2 (SLC17A6) levels are significantly increased, in KIKO mice compared with age-matched controls. Additionally, GAD65 (GAD2) levels are significantly increased, while GAD67 (GAD1) levels remain unaltered. This suggests early VGLUT1-specific synaptic input deficits, and dysregulation of VGLUT2 and GAD65 synaptic inputs, in the cerebellum of asymptomatic KIKO mice. Immunohistochemistry and electron microscopy further show specific reductions of VGLUT1-containing PF presynaptic terminals in the cerebellar molecular layer, demonstrating PF synaptic input deficiency in asymptomatic and symptomatic KIKO mice. Moreover, the parvalbumin levels in cerebellar homogenates and Purkinje neurons are significantly reduced, but preserved in other interneurons of the cerebellar molecular layer, suggesting specific parvalbumin dysregulation in Purkinje neurons of these mice. Furthermore, a moderate loss of large principal neurons is observed in the dentate nucleus of asymptomatic KIKO mice, mimicking that of FRDA patients. Our findings thus identify early VGLUT1-specific PF synaptic input deficits and dysregulated cerebellar circuit as potential mediators of cerebellar dysfunction in KIKO mice, reflecting developmental features of FRDA in this mouse model. © 2017. Published by The Company of

  1. Cyclooxygenase activity is important for efficient replication of mouse hepatitis virus at an early stage of infection

    PubMed Central

    Raaben, Matthijs; Einerhand, Alexandra WC; Taminiau, Lucas JA; van Houdt, Michel; Bouma, Janneke; Raatgeep, Rolien H; Büller, Hans A; de Haan, Cornelis AM; Rossen, John WA

    2007-01-01

    Cyclooxygenases (COXs) play a significant role in many different viral infections with respect to replication and pathogenesis. Here we investigated the role of COXs in the mouse hepatitis coronavirus (MHV) infection cycle. Blocking COX activity by different inhibitors or by RNA interference affected MHV infection in different cells. The COX inhibitors reduced MHV infection at a post-binding step, but early in the replication cycle. Both viral RNA and viral protein synthesis were affected with subsequent loss of progeny virus production. Thus, COX activity appears to be required for efficient MHV replication, providing a potential target for anti-coronaviral therapy. PMID:17555580

  2. Elevated streamflows increase dam passage by juvenile coho salmon during winter: Implications of climate change in the Pacific Northwest

    USGS Publications Warehouse

    Kock, Tobias J.; Liedtke, Theresa L.; Rondorf, Dennis W.; Serl, John D.; Kohn, Mike; Bumbaco, Karin A.

    2012-01-01

    A 4-year evaluation was conducted to determine the proportion of juvenile coho salmon Oncorhynchus kisutch passing Cowlitz Falls Dam, on the Cowlitz River, Washington, during winter. River and reservoir populations of coho salmon parr were monitored using radiotelemetry to determine if streamflow increases resulted in increased downstream movement and dam passage. This was of interest because fish that pass downstream of Cowlitz Falls Dam become landlocked in Riffe Lake and are lost to the anadromous population. Higher proportions of reservoir-released fish (0.391-0.480) passed Cowlitz Falls Dam than did river-released fish (0.037-0.119). Event-time analyses demonstrated that streamflow increases were important predictors of dam passage rates during the study. The estimated effect of increasing streamflows on the risk of dam passage varied annually and ranged from 9% to 75% for every 28.3 m3/s increase in streamflow. These results have current management implications because they demonstrate the significance of dam passage by juvenile coho salmon during winter months when juvenile fish collection facilities are typically not operating. The results also have future management implications because climate change predictions suggest that peak streamflow timing for many watersheds in the Pacific Northwest will shift from late spring and early summer to winter. Increased occurrence of intense winter flood events is also expected. Our results demonstrate that juvenile coho salmon respond readily to streamflow increases and initiate downstream movements during winter months, which could result in increased passage at dams during these periods if climate change predictions are realized in the coming decades.

  3. 3. INTERIOR OF SOUTH BAGGAGE PASSAGE LOOKING EAST, SHOWING ROOF ...

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

    3. INTERIOR OF SOUTH BAGGAGE PASSAGE LOOKING EAST, SHOWING ROOF OF WOOD, GLASS, AND STEEL (TARRED ON EXTERIOR, PAINTED ON INTERIOR) - Pennsylvania Railroad Station, South Baggage Passage & Canopy, 1101 Liberty Avenue, Pittsburgh, Allegheny County, PA

  4. Partial Opening of the Northwest Passage

    NASA Image and Video Library

    2017-12-08

    There was a time when the Northwest Passage was a sort of maritime Holy Grail, a route so desired and sought after, but so elusive. For most of the recorded history of North America, the Passage has been nearly impassable and often deadly. But with the modernization of ships and the warming of the Earth, cruising and sailing through the Canadian Archipelago from Baffin Bay to the Beaufort Sea has grown more common and easier. But it’s not necessarily easy. The top image above shows the Northwest Passage as it appeared on August 31, 2015, to the Visible Infrared Imaging Radiometer Suite (VIIRS) on the Suomi-NPP satellite. Read more: earthobservatory.nasa.gov/IOTD/view.php?id=86589 NASA Earth Observatory images by Jesse Allen, using VIIRS data from the Suomi National Polar-orbiting Partnership. Suomi NPP is the result of a partnership between NASA, the National Oceanic and Atmospheric Administration, and the Department of Defense. NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  5. Complete tooth loss as status passage.

    PubMed

    Gibson, Barry John; Sussex, Philip V; Fitzgerald, Ruth P; Thomson, William Murray

    2017-03-01

    The aim of this article is to add to the literature on the sociology of oral health and dentistry by presenting the relevance of status passage to the study of complete tooth loss. The article reports on an analysis of data taken from participants residing in the Nelson region of New Zealand. In total the data include interviews from 20 participants, all of whom had their remaining natural teeth removed before 1960. In total, 12 women and eight men were interviewed. All were from a European background with an age range of 71 to 101 years. Following a narrative approach, participants were interviewed on the nature of the social factors that resulted in complete tooth loss by starting with their family history and then focusing on the factors and events leading up to their total tooth loss. Data were analysed using the methods and techniques of grounded theory. This article provides an outline of the importance of scheduling, prescribing, social factors, 'compound awareness contexts' and reversibility to the status passage into complete tooth loss. We conclude by arguing that the theory of status passage may enable a detailed analysis of the 'time-space extensionality' of trajectories into complete tooth loss. © 2016 Foundation for the Sociology of Health & Illness.

  6. How Genetically Engineered Mouse Tumor Models Provide Insights Into Human Cancers

    PubMed Central

    Politi, Katerina; Pao, William

    2011-01-01

    Genetically engineered mouse models (GEMMs) of human cancer were first created nearly 30 years ago. These early transgenic models demonstrated that mouse cells could be transformed in vivo by expression of an oncogene. A new field emerged, dedicated to generating and using mouse models of human cancer to address a wide variety of questions in cancer biology. The aim of this review is to highlight the contributions of mouse models to the diagnosis and treatment of human cancers. Because of the breadth of the topic, we have selected representative examples of how GEMMs are clinically relevant rather than provided an exhaustive list of experiments. Today, as detailed here, sophisticated mouse models are being created to study many aspects of cancer biology, including but not limited to mechanisms of sensitivity and resistance to drug treatment, oncogene cooperation, early detection, and metastasis. Alternatives to GEMMs, such as chemically induced or spontaneous tumor models, are not discussed in this review. PMID:21263096

  7. Design for fish passage at roadway-stream crossings : synthesis report.

    DOT National Transportation Integrated Search

    2007-06-01

    Cataloging and synthesizing existing methods for the design of roadway-stream crossings for fish passage began in : January 2005 with an extensive literature review covering the topics of culvert design and assessment to facilitate : fish passage. A ...

  8. Conditional Deletion of the Pten Gene in the Mouse Prostate Induces Prostatic Intraepithelial Neoplasms at Early Ages but a Slow Progression to Prostate Tumors

    PubMed Central

    Zhu, Chunfang; Lee, Suk Hyung; Ye, Ding-Wei; Luong, Richard; Sun, Zijie

    2013-01-01

    The PTEN tumor suppressor gene is frequently inactivated in human prostate cancer. Using Osr1 (odd skipped related 1)-Cre mice, we generated a novel conditional Pten knockout mouse strain, PtenLoxP:Osr1-Cre. Conditional biallelic and monoallelic Pten knockout mice were viable. Deletion of Pten expression was detected in the prostate of PtenLoxP/LoxP:Osr1-Cre mice as early as 2 weeks of age. Intriguingly, PtenLoxP/LoxP:Osr1-Cre mice develop high-grade prostatic intraepithelial neoplasms (PINs) with high penetrance as early as one-month of age, and locally invasive prostatic tumors after 12-months of age. PtenLoxP/+:Osr1-Cre mice show only mild oncogenic changes after 8-weeks of age. Castration of PtenLoxP/LoxP:Osr1-Cre mice shows no significant regression of prostate tumors, although a shift of androgen receptor (AR) staining from the nuclei to cytoplasm is observed in Pten null tumor cells of castrated mice. Enhanced Akt activity is observed in Pten null tumor cells of castrated PtenLoxP/LoxP:Osr1-Cre. This study provides a novel mouse model that can be used to investigate a primary role of Pten in initiating oncogenic transformation in the prostate and to examine other genetic and epigenetic changes that are required for tumor progression in the mouse prostate. PMID:23308230

  9. Classification of collected trot, passage and piaffe based on temporal variables.

    PubMed

    Clayton, H M

    1997-05-01

    The objective was to determine whether collected trot, passage and piaffe could be distinguished as separate gaits on the basis of temporal variables. Sagittal plane, 60 Hz videotapes of 10 finalists in the dressage competitions at the 1992 Olympic Games were analysed to measure the temporal variables in absolute terms and as percentages of stride duration. Classification was based on analysis of variance, a graphical method and discriminant analysis. Stride duration was sufficient to distinguish collected trot from passage and piaffe in all horses. The analysis of variance showed that the mean values of most variables differed significantly between passage and piaffe. When hindlimb stance percentage was plotted against diagonal advanced placement percentage, some overlap was found between all 3 movements indicating that individual horses could not be classified reliably in this manner. Using hindlimb stance percentage and diagonal advanced placement percentage as input in a discriminant analysis, 80% of the cases were classified correctly, but at least one horse was misclassified in each movement. When the absolute, rather than percentage, values of the 2 variables were used as input in the discriminant analysis, 90% of the cases were correctly classified and the only misclassifications were between passage and piaffe. However, the 2 horses in which piaffe was misclassified as passage were the gold and silver medallists. In general, higher placed horses tended toward longer diagonal advanced placements, especially in collected trot and passage, and shorter hindlimb stance percentages in passage and piaffe.

  10. Shape design of internal cooling passages within a turbine blade

    NASA Astrophysics Data System (ADS)

    Nowak, Grzegorz; Nowak, Iwona

    2012-04-01

    The article concerns the optimization of the shape and location of non-circular passages cooling the blade of a gas turbine. To model the shape, four Bezier curves which form a closed profile of the passage were used. In order to match the shape of the passage to the blade profile, a technique was put forward to copy and scale the profile fragments into the component, and build the outline of the passage on the basis of them. For so-defined cooling passages, optimization calculations were carried out with a view to finding their optimal shape and location in terms of the assumed objectives. The task was solved as a multi-objective problem with the use of the Pareto method, for a cooling system composed of four and five passages. The tool employed for the optimization was the evolutionary algorithm. The article presents the impact of the population on the task convergence, and discusses the impact of different optimization objectives on the Pareto optimal solutions obtained. Due to the problem of different impacts of individual objectives on the position of the solution front which was noticed during the calculations, a two-step optimization procedure was introduced. Also, comparative optimization calculations for the scalar objective function were carried out and set up against the non-dominated solutions obtained in the Pareto approach. The optimization process resulted in a configuration of the cooling system that allows a significant reduction in the temperature of the blade and its thermal stress.

  11. Augmentation of sensory-evoked hemodynamic response in an early Alzheimer's disease mouse model.

    PubMed

    Kim, Jinho; Jeong, Yong

    2013-01-01

    Based on enlarged blood oxygen level-dependent (BOLD) responses in cognitively normal subjects at risk for Alzheimer's disease (AD), compensatory neuronal hyperactivation has been proposed as an early marker for diagnosis of AD. The BOLD response results from neurovascular coupling, i.e., hemodynamic response induced by neuronal activity. However, there has been no evidence of task-induced increases in hemodynamic response in animal models of AD. Here, we observed an augmented hemodynamic response pattern in a transgenic AβPP(SWE)/PS1ΔE9 mouse model of AD using three in vivo imaging methods: intrinsic optical signal imaging, multi-photon laser scanning microscopy, and laser Doppler flowmetry. Sensory stimulation resulted in augmented and prolonged hemodynamic responses in transgenic mice evidenced by changes in total, oxygenated, and deoxygenated hemoglobin concentration. This difference between transgenic and wild-type mice was significant at 7 months of age when amyloid plaques and cerebral amyloid angiopathy had developed but not at younger or older ages. Correspondingly, sensory stimulation-induced pial arteriole diameter was also augmented and prolonged in transgenic mice at 7 months of age. Cerebral blood flow response in transgenic mice was augmented but not prolonged. These results are consistent with the existence of BOLD signal hyperactivation in non-demented AD-risk human subjects, supporting its potential use as an early diagnostic marker of AD.

  12. Passage and behavior of radio-tagged adult Pacific Lamprey (Entosphenus tridentata) at the Willamette Falls Project, Oregon, 2005-07

    USGS Publications Warehouse

    Mesa, Matthew G.; Magie, Robert J.; Copeland, Elizabeth S.

    2009-01-01

    We used radio telemetry to monitor passage and describe behavior characteristics of adult Pacific lampreys, Entosphenus tridentata, during their upstream migration at the Willamette Falls Project (Project) on the Willamette River near Portland, Oregon. Our objectives were to document: (1) specific routes of passage at the dam and falls; (2) duration of passage through different routes; and (3) overall passage success. During the spring through autumn of 2005 and 2006, fish were captured in a trap located in the fishway at the Project or collected by hand from the falls, surgically implanted with a radio tag, and released 2 kilometers downstream of the Project. We radio tagged 136 lampreys in 2005 and 107 in 2006. In both years, more than 90 percent of the fish returned to the Project with a median travel time of 7-9 hours. Most fish were first detected at the Project from about 20:00-23:00 hours. In 2005, 43 fish (35 percent) successfully passed through the fishway of the Project, which has four separate entrances and three distinct passage channels or legs that converge at one exit. Prior to the installation of flashboards around the perimeter of the falls in July, lampreys used all three legs of the fishway to pass the Project. After flashboards were installed, only fishway leg 1 was used. The peak of passage occurred in August. No fish passed over the falls, but 13 percent of the lampreys that traveled to the Project ascended at least partway up the falls. In 2006, 24 fish (23 percent) passed the Project, again primarily using fishway leg 1. Most fish passed prior to June 9 when the powerhouse was shut down due to construction. Although 19 lampreys ascended the falls, only 2 passed through this route in late June and early July. Flashboards were not installed in 2006. For both years, the time it took for fish to pass through the fishway depended on which leg they used - the median passage time was at least 4-5 hours in fishway legs 2 and 3 and ranged from 23 to

  13. Mitochondrial bioenergetics and drug-induced toxicity in a panel of mouse embryonic fibroblasts with mitochondrial DNA single nucleotide polymorphisms

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

    Pereira, Claudia V.; Oliveira, Paulo J.; Will, Yvonne

    2012-10-15

    Mitochondrial DNA (mtDNA) variations including single nucleotide polymorphisms (SNPs) have been proposed to be involved in idiosyncratic drug reactions. However, current in vitro and in vivo models lack the genetic diversity seen in the human population. Our hypothesis is that different cell strains with distinct mtDNA SNPs may have different mitochondrial bioenergetic profiles and may therefore vary in their response to drug-induced toxicity. Therefore, we used an in vitro system composed of four strains of mouse embryonic fibroblasts (MEFs) with mtDNA polymorphisms. We sequenced mtDNA from embryonic fibroblasts isolated from four mouse strains, C57BL/6J, MOLF/EiJ, CZECHII/EiJ and PERA/EiJ, with themore » latter two being sequenced for the first time. The bioenergetic profile of the four strains of MEFs was investigated at both passages 3 and 10. Our results showed that there were clear differences among the four strains of MEFs at both passages, with CZECHII/EiJ having a lower mitochondrial robustness when compared to C57BL/6J, followed by MOLF/EiJ and PERA/EiJ. Seven drugs known to impair mitochondrial function were tested for their effect on the ATP content of the four strains of MEFs in both glucose- and galactose-containing media. Our results showed that there were strain-dependent differences in the response to some of the drugs. We propose that this model is a useful starting point to study compounds that may cause mitochondrial off-target toxicity in early stages of drug development, thus decreasing the number of experimental animals used. -- Highlights: ► mtDNA SNPs may be linked to individual predisposition to drug-induced toxicity. ► CZECHII/EiJ and PERA/EiJ mtDNA was sequenced for the first time in this study. ► Strain-dependent mitochondrial capacity differences were measured. ► Strain-dependent differences in response to mitochondrial toxicants were observed.« less

  14. Relationship between Numerous Mast Cells and Early Follicular Development in Neonatal MRL/MpJ Mouse Ovaries

    PubMed Central

    Nakamura, Teppei; Otsuka, Saori; Ichii, Osamu; Sakata, Yuko; Nagasaki, Ken-Ichi; Hashimoto, Yoshiharu; Kon, Yasuhiro

    2013-01-01

    In the neonatal mouse ovary, clusters of oocytes called nests break into smaller cysts and subsequently form individual follicles. During this period, we found numerous mast cells in the ovary of MRL/MpJ mice and investigated their appearance and morphology with follicular development. The ovarian mast cells, which were already present at postnatal day 0, tended to localize adjacent to the surface epithelium. Among 11 different mouse strains, MRL/MpJ mice possessed the greatest number of ovarian mast cells. Ovarian mast cells were also found in DBA/1, BALB/c, NZW, and DBA/2 mice but rarely in C57BL/6, NZB, AKR, C3H/He, CBA, and ICR mice. The ovarian mast cells expressed connective tissue mast cell markers, although mast cells around the surface epithelium also expressed a mucosal mast cell marker in MRL/MpJ mice. Some ovarian mast cells migrated into the oocyte nests and directly contacted the compressed and degenerated oocytes. In MRL/MpJ mice, the number of oocytes in the nest was significantly lower than in the other strains, and the number of oocytes showed a positive correlation with the number of ovarian mast cells. The gene expression of a mast cell marker also correlated with the expression of an oocyte nest marker, suggesting a link between the appearance of ovarian ? 4mast cells and early follicular development. Furthermore, the expression of follicle developmental markers was significantly higher in MRL/MpJ mice than in C57BL/6 mice. These results indicate that the appearance of ovarian mast cells is a unique phenotype of neonatal MRL/MpJ mice, and that ovarian mast cells participate in early follicular development, especially nest breakdown. PMID:24124609

  15. Early-onset type 2 diabetes impairs skeletal acquisition in the male TALLYHO/JngJ mouse.

    PubMed

    Devlin, M J; Van Vliet, M; Motyl, K; Karim, L; Brooks, D J; Louis, L; Conlon, C; Rosen, C J; Bouxsein, M L

    2014-10-01

    Type 2 diabetes (T2D) incidence in adolescents is rising and may interfere with peak bone mass acquisition. We tested the effects of early-onset T2D on bone mass, microarchitecture, and strength in the TALLYHO/JngJ mouse, which develops T2D by 8 weeks of age. We assessed metabolism and skeletal acquisition in male TALLYHO/JngJ and SWR/J controls (n = 8-10/group) from 4 weeks to 8 and 17 weeks of age. Tallyho mice were obese; had an approximately 2-fold higher leptin and percentage body fat; and had lower bone mineral density vs SWR at all time points (P < .03 for all). Tallyho had severe deficits in distal femur trabecular bone volume fraction (-54%), trabecular number (-27%), and connectivity density (-82%) (P < .01 for all). Bone formation was higher in Tallyho mice at 8 weeks but lower by 17 weeks of age vs SWR despite similar numbers of osteoblasts. Bone marrow adiposity was 7- to 50-fold higher in Tallyho vs SWR. In vitro, primary bone marrow stromal cell differentiation into osteoblast and adipocyte lineages was similar in SWR and Tallyho, suggesting skeletal deficits were not due to intrinsic defects in Tallyho bone-forming cells. These data suggest the Tallyho mouse might be a useful model to study the skeletal effects of adolescent T2D.

  16. The differential effects of 2% oxygen preconditioning on the subsequent differentiation of mouse and human pluripotent stem cells.

    PubMed

    Fynes, Kate; Tostoes, Rui; Ruban, Ludmila; Weil, Ben; Mason, Christopher; Veraitch, Farlan S

    2014-08-15

    A major challenge facing the development of effective cell therapies is the efficient differentiation of pluripotent stem cells (PSCs) into pure populations. Lowering oxygen tension to physiological levels can affect both the expansion and differentiation stages. However, to date, there are no studies investigating the knock-on effect of culturing PSCs under low oxygen conditions on subsequent lineage commitment at ambient oxygen levels. PSCs were passaged three times at 2% O2 before allowing cells to spontaneously differentiate as embryoid bodies (EBs) in high oxygen (20% O2) conditions. Maintenance of mouse PSCs in low oxygen was associated with a significant increase in the expression of early differentiation markers FGF5 and Eomes, while conversely we observed decreased expression of these genes in human PSCs. Low oxygen preconditioning primed mouse PSCs for their subsequent differentiation into mesodermal and endodermal lineages, as confirmed by increased gene expression of Eomes, Goosecoid, Brachyury, AFP, Sox17, FoxA2, and protein expression of Brachyury, Eomes, Sox17, FoxA2, relative to high oxygen cultures. The effects extended to the subsequent formation of more mature mesodermal lineages. We observed significant upregulation of cardiomyocyte marker Nkx2.5, and critically a decrease in the number of contaminant pluripotent cells after 12 days using a directed cardiomyocyte protocol. However, the impact of low oxygen preconditioning was to prime human cells for ectodermal lineage commitment during subsequent EB differentiation, with significant upregulation of Nestin and β3-tubulin. Our research demonstrates the importance of oxygen tension control during cell maintenance on the subsequent differentiation of both mouse and human PSCs, and highlights the differential effects.

  17. The RNA-binding landscape of RBM10 and its role in alternative splicing regulation in models of mouse early development.

    PubMed

    Rodor, Julie; FitzPatrick, David R; Eyras, Eduardo; Cáceres, Javier F

    2017-01-02

    Mutations in the RNA-binding protein, RBM10, result in a human syndromic form of cleft palate, termed TARP syndrome. A role for RBM10 in alternative splicing regulation has been previously demonstrated in human cell lines. To uncover the cellular functions of RBM10 in a cell line that is relevant to the phenotype observed in TARP syndrome, we used iCLIP to identify its endogenous RNA targets in a mouse embryonic mandibular cell line. We observed that RBM10 binds to pre-mRNAs with significant enrichment in intronic regions, in agreement with a role for this protein in pre-mRNA splicing. In addition to protein-coding transcripts, RBM10 also binds to a variety of cellular RNAs, including non-coding RNAs, such as spliceosomal small nuclear RNAs, U2 and U12. RNA-seq was used to investigate changes in gene expression and alternative splicing in RBM10 KO mouse mandibular cells and also in mouse ES cells. We uncovered a role for RBM10 in the regulation of alternative splicing of common transcripts in both cell lines but also identified cell-type specific events. Importantly, those pre-mRNAs that display changes in alternative splicing also contain RBM10 iCLIP tags, suggesting a direct role of RBM10 in these events. Finally, we show that depletion of RBM10 in mouse ES cells leads to proliferation defects and to gross alterations in their differentiation potential. These results demonstrate a role for RBM10 in the regulation of alternative splicing in two cell models of mouse early development and suggests that mutations in RBM10 could lead to splicing changes that affect normal palate development and cause human disease.

  18. A generalized one-dimensional computer code for turbomachinery cooling passage flow calculations

    NASA Technical Reports Server (NTRS)

    Kumar, Ganesh N.; Roelke, Richard J.; Meitner, Peter L.

    1989-01-01

    A generalized one-dimensional computer code for analyzing the flow and heat transfer in the turbomachinery cooling passages was developed. This code is capable of handling rotating cooling passages with turbulators, 180 degree turns, pin fins, finned passages, by-pass flows, tip cap impingement flows, and flow branching. The code is an extension of a one-dimensional code developed by P. Meitner. In the subject code, correlations for both heat transfer coefficient and pressure loss computations were developed to model each of the above mentioned type of coolant passages. The code has the capability of independently computing the friction factor and heat transfer coefficient on each side of a rectangular passage. Either the mass flow at the inlet to the channel or the exit plane pressure can be specified. For a specified inlet total temperature, inlet total pressure, and exit static pressure, the code computers the flow rates through the main branch and the subbranches, flow through tip cap for impingement cooling, in addition to computing the coolant pressure, temperature, and heat transfer coefficient distribution in each coolant flow branch. Predictions from the subject code for both nonrotating and rotating passages agree well with experimental data. The code was used to analyze the cooling passage of a research cooled radial rotor.

  19. Ultrasound biomicroscopy in mouse cardiovascular development

    NASA Astrophysics Data System (ADS)

    Turnbull, Daniel H.

    2004-05-01

    The mouse is the preferred animal model for studying mammalian cardiovascular development and many human congenital heart diseases. Ultrasound biomicroscopy (UBM), utilizing high-frequency (40-50-MHz) ultrasound, is uniquely capable of providing in vivo, real-time microimaging and Doppler blood velocity measurements in mouse embryos and neonates. UBM analyses of normal and abnormal mouse cardiovascular function will be described to illustrate the power of this microimaging approach. In particular, real-time UBM images have been used to analyze dimensional changes in the mouse heart from embryonic to neonatal stages. UBM-Doppler has been used recently to examine the precise timing of onset of a functional circulation in early-stage mouse embryos, from the first detectable cardiac contractions. In other experiments, blood velocity waveforms have been analyzed to characterize the functional phenotype of mutant mouse embryos having defects in cardiac valve formation. Finally, UBM has been developed for real-time, in utero image-guided injection of mouse embryos, enabling cell transplantation and genetic gain-of-function experiments with transfected cells and retroviruses. In summary, UBM provides a unique and powerful approach for in vivo analysis and image-guided manipulation in normal and genetically engineered mice, over a wide range of embryonic to neonatal developmental stages.

  20. Repeated exposure of mouse dermal fibroblasts at a sub-cytotoxic dose of UVB leads to premature senescence: a robust model of cellular photoaging.

    PubMed

    Zeng, Ji-ping; Bi, Bo; Chen, Liang; Yang, Ping; Guo, Yu; Zhou, Yi-qun; Liu, Tian-yi

    2014-01-01

    Photoaging skin is due to accumulative effect of UV irradiation that mainly imposes its damage on dermal fibroblasts. To mimic the specific cellular responses invoked by long term effect of UVB, it is preferable to develop a photo-damaged model in vitro based on repeated UVB exposure instead of a single exposure. To develop a photo-damaged model of fibroblasts by repeated UVB exposure allowing for investigation of molecular mechanism underlying premature senescence and testing of potential anti-photoaging compounds. Mouse dermal fibroblasts (MDFs) at early passages (passages 1-3) were exposed to a series of 4 sub-cytotoxic dose of UVB. The senescent phenotypes were detected at 24 or 48h after the last irradiation including cell viability, ROS generation, mitochondrial membrane potential, cell cycle, production and degradation of extracellular matrix. Repeated exposure of UVB resulted in remarkable features of senescence. It effectively avoided the disadvantages of single dose such as induction of cell death rather than senescence, inadequate stress resulting in cellular self-rehabilitation. Our work confirms the possibility of detecting cellular machinery that mediates UVB damage to fibroblasts in vitro by repeated exposure, while the potential molecular mechanisms including cell surface receptors, protein kinase signal transduction pathways, and transcription factors remain to be further evaluated. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  1. Gene function in early mouse embryonic stem cell differentiation

    PubMed Central

    Sene, Kagnew Hailesellasse; Porter, Christopher J; Palidwor, Gareth; Perez-Iratxeta, Carolina; Muro, Enrique M; Campbell, Pearl A; Rudnicki, Michael A; Andrade-Navarro, Miguel A

    2007-01-01

    Background Little is known about the genes that drive embryonic stem cell differentiation. However, such knowledge is necessary if we are to exploit the therapeutic potential of stem cells. To uncover the genetic determinants of mouse embryonic stem cell (mESC) differentiation, we have generated and analyzed 11-point time-series of DNA microarray data for three biologically equivalent but genetically distinct mESC lines (R1, J1, and V6.5) undergoing undirected differentiation into embryoid bodies (EBs) over a period of two weeks. Results We identified the initial 12 hour period as reflecting the early stages of mESC differentiation and studied probe sets showing consistent changes of gene expression in that period. Gene function analysis indicated significant up-regulation of genes related to regulation of transcription and mRNA splicing, and down-regulation of genes related to intracellular signaling. Phylogenetic analysis indicated that the genes showing the largest expression changes were more likely to have originated in metazoans. The probe sets with the most consistent gene changes in the three cell lines represented 24 down-regulated and 12 up-regulated genes, all with closely related human homologues. Whereas some of these genes are known to be involved in embryonic developmental processes (e.g. Klf4, Otx2, Smn1, Socs3, Tagln, Tdgf1), our analysis points to others (such as transcription factor Phf21a, extracellular matrix related Lama1 and Cyr61, or endoplasmic reticulum related Sc4mol and Scd2) that have not been previously related to mESC function. The majority of identified functions were related to transcriptional regulation, intracellular signaling, and cytoskeleton. Genes involved in other cellular functions important in ESC differentiation such as chromatin remodeling and transmembrane receptors were not observed in this set. Conclusion Our analysis profiles for the first time gene expression at a very early stage of mESC differentiation, and

  2. Forgetting of Prose as a Function of Interpolated Passage Content and Organization.

    ERIC Educational Resources Information Center

    Andre, Thomas; And Others

    In three studies subjects read two successive passages and then were tested for retention of the first. Each passage described the characteristics of a series of entities (diseases or countries) along a series of dimensions (symptoms, cause, etc., or climate, soil type, etc.). The first passage described five diseases and was organized by name;…

  3. Lack of species-specific difference in pulmonary function when using mouse versus human plasma in a mouse model of hemorrhagic shock.

    PubMed

    Peng, Zhanglong; Pati, Shibani; Fontaine, Magali J; Hall, Kelly; Herrera, Anthony V; Kozar, Rosemary A

    2016-11-01

    Clinical studies have demonstrated that the early and empiric use of plasma improves survival after hemorrhagic shock. We have demonstrated in rodent models of hemorrhagic shock that resuscitation with plasma is protective to the lungs compared with lactated Ringer's solution. As our long-term objective is to determine the molecular mechanisms that modulate plasma's protective effects in injured bleeding patients, we have used human plasma in a mouse model of hemorrhagic shock. The goal of the current experiments is to determine if there are significant adverse effects on lung injury when using human versus mouse plasma in an established murine model of hemorrhagic shock and laparotomy. Mice underwent laparotomy and 90 minutes of hemorrhagic shock to a mean arterial pressure (MAP) of 35 ± 5 mm Hg followed by resuscitation at 1× shed blood using either mouse fresh frozen plasma (FFP), human FFP, or human lyophilized plasma. Mean arterial pressure was recorded during shock and for the first 30 minutes of resuscitation. After 3 hours, animals were killed, and lungs collected for analysis. There was a significant increase in early MAP when mouse FFP was used to resuscitate animals compared with human FFP or human lyophilized plasma. However, despite these differences, analysis of the mouse lungs revealed no significant differences in pulmonary histopathology, lung permeability, or lung edema between all three plasma groups. Analysis of neutrophil infiltration in the lungs revealed that mouse FFP decreased neutrophil influx as measured by neutrophil staining; however, myeloperoxidase immunostaining revealed no significant differences in between groups. The study of human plasma in a mouse model of hemorrhagic shock is feasible but does reveal some differences compared with mouse plasma-based resuscitation in physiologic measures such as MAP postresuscitation. Measures of end organ function such as lung injury appear to be comparable in this acute model of hemorrhagic

  4. Essential Role of Chromatin Remodeling Protein Bptf in Early Mouse Embryos and Embryonic Stem Cells

    PubMed Central

    Landry, Joseph; Sharov, Alexei A.; Piao, Yulan; Sharova, Lioudmila V.; Xiao, Hua; Southon, Eileen; Matta, Jennifer; Tessarollo, Lino; Zhang, Ying E.; Ko, Minoru S. H.; Kuehn, Michael R.; Yamaguchi, Terry P.; Wu, Carl

    2008-01-01

    We have characterized the biological functions of the chromatin remodeling protein Bptf (Bromodomain PHD-finger Transcription Factor), the largest subunit of NURF (Nucleosome Remodeling Factor) in a mammal. Bptf mutants manifest growth defects at the post-implantation stage and are reabsorbed by E8.5. Histological analyses of lineage markers show that Bptf−/− embryos implant but fail to establish a functional distal visceral endoderm. Microarray analysis at early stages of differentiation has identified Bptf-dependent gene targets including homeobox transcriptions factors and genes essential for the development of ectoderm, mesoderm, and both definitive and visceral endoderm. Differentiation of Bptf−/− embryonic stem cell lines into embryoid bodies revealed its requirement for development of mesoderm, endoderm, and ectoderm tissue lineages, and uncovered many genes whose activation or repression are Bptf-dependent. We also provide functional and physical links between the Bptf-containing NURF complex and the Smad transcription factors. These results suggest that Bptf may co-regulate some gene targets of this pathway, which is essential for establishment of the visceral endoderm. We conclude that Bptf likely regulates genes and signaling pathways essential for the development of key tissues of the early mouse embryo. PMID:18974875

  5. Visualization of early post-implantation mouse embryogenesis using 3D imaging modality (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Hsu, Chih-Wei; Le, Henry H.; Li-Villarreal, Nanbing; Piazza, Victor G.; Kalaga, Sowmya; Dickinson, Mary E.

    2017-02-01

    Hemodynamic force is vital to cardiovascular remodeling in the early post-implantation mouse embryo. Here, we present work using microCT and lightsheet microscopy to establish the critical sequence of developmental events required for forming functional vasculature and circulation in the embryo, yolk sac, and placenta in the context of normal and impaired flow. A flow impaired model, Mlc2a+/- will be used to determine how hemodynamic force affects the specific events during embryonic development and vascular remodeling between the 4 and 29-somite stage using microCT. We have recently established high-resolution methods for the generation of 3D image volumes from the whole embryo within the deciduum (Hsu et al., in revision). This method enables the careful characterization of 3D images of vitelline and umbilical vessel remodeling to define how poor blood flow impacts both vitelline and umbilical vessel remodeling. Novel lightsheet live imaging techniques will be used to determine the consequence of impaired blood flow on yolk sac vasculature remodeling and formation of umbilical vessels using transgenic reporters: Flk-myr::mCherry, Flk1-H2B::YFP, or ɛGlobin-GFP. High-resolution 3D imaging of fixed and ScaleA2-cleared whole mount embryos labeled with Ki67 and Caspase3 will also be performed using lightsheet microscopy to quantify the proliferation and apoptotic indexes of early post-implanted embryos and yolk sac. This multi-modality approach is aimed at revealing further information about the cellular mechanisms required for proper vessel remodeling and the initial stages in placentation during early post-implantation development.

  6. Otoprotective effects of mouse nerve growth factor in DBA/2J mice with early-onset progressive hearing loss.

    PubMed

    Wang, Qingzhu; Zhao, Hongchun; Zheng, Tihua; Wang, Wenjun; Zhang, Xiaolin; Wang, Andi; Li, Bo; Wang, Yanfei; Zheng, Qingyin

    2017-10-01

    As it displays progressive hair-cell loss and degeneration of spiral ganglion neurons (SGNs) characterized by early-onset progressive hearing loss (ePHL), DBA/2J is an inbred mouse strain widely used in hearing research. Mouse nerve growth factor (mNGF), as a common exogenous nerve growth factor (NGF), has been studied extensively for its ability to promote neuronal survival and growth. To determine whether mNGF can ameliorate progressive hearing loss (PHL) in DBA/2J mice, saline or mNGF was given to DBA/2J mice of either sex by daily intramuscular injection from the 1st to the 9th week after birth. At 5, 7, and 9 weeks of age, in comparison with vehicle groups, mNGF groups experienced decreased auditory-evoked brainstem response (ABR) thresholds and increased distortion product otoacoustic emission (DPOAE) amplitudes, the prevention of hair cell loss, and the inhibition of apoptosis of SGNs. Downregulation of Bak/Bax and Caspase genes and proteins in cochleae of mice receiving the mNGF treatment was detected by real-time PCR, Western blot, and immunohistochemistry. This suggests that the Bak-dependent mitochondrial apoptosis pathway may be involved in the otoprotective mechanism of mNGF in progressive hearing loss of DBA/2J mice. Our results demonstrate that mNGF can act as an otoprotectant in the DBA/2J mice for the early intervention of PHL and, thus, could become of great value in clinical applications. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Aquatic organism passage at road-stream crossings—synthesis and guidelines for effectiveness monitoring

    USGS Publications Warehouse

    Hoffman, Robert L.; Dunham, Jason B.; Hansen, Bruce P.

    2012-01-01

    Restoration and maintenance of passage for aquatic organisms at road-stream crossings represents a major management priority, involving an investment of hundreds of millions of dollars (for example, U.S. Government Accounting Office, 2001). In recent years, passage at hundreds of crossings has been restored, primarily by replacing barrier road culverts with bridges or stream simulation culverts designed to pass all species and all life stages of aquatic life and simulate natural hydro-geomorphic processes (U.S. Forest Service, 2008). The current situation has motivated two general questions: 1. Are current design standards for stream simulation culverts adequately re-establishing passage for aquatic biota? and 2. How do we monitor and evaluate effectiveness of passage restoration? To address the latter question, a national workshop was held in March 2010, in Portland, Oregon. The workshop included experts on aquatic organism passage from across the nation (see table of participants, APPENDIX) who addressed four classes of methods for monitoring effectiveness of aquatic organism passage—individual movement, occupancy, demography, and genetics. This report has been written, in part, for field biologists who will be undertaking and evaluating the effectiveness of aquatic organism passage restoration projects at road-stream crossings. The report outlines basic methods for evaluating road-stream crossing passage impairment and restoration and discusses under what circumstances and conditions each method will be useful; what questions each method can potentially answer; how to design and implement an evaluation study; and points out the fundamental reality that most evaluation projects will require special funding and partnerships among researchers and resource managers. The report is organized into the following sections, which can be read independently: 1. Historical context: In this section, we provide a brief history of events leading up to the present situation

  8. Prenatal and Early Postnatal Odorant Exposure Heightens Odor-Evoked Mitral Cell Responses in the Mouse Olfactory Bulb

    PubMed Central

    2017-01-01

    Abstract Early sensory experience shapes the anatomy and function of sensory circuits. In the mouse olfactory bulb (OB), prenatal and early postnatal odorant exposure through odorized food (food/odorant pairing) not only increases the volume of activated glomeruli but also increases the number of mitral and tufted cells (M/TCs) connected to activated glomeruli. Given the importance of M/TCs in OB output and in mediating lateral inhibitory networks, increasing the number of M/TCs connected to a single glomerulus may significantly change odorant representation by increasing the total output of that glomerulus and/or by increasing the strength of lateral inhibition mediated by cells connected to the affected glomerulus. Here, we seek to understand the functional impact of this long-term odorant exposure paradigm on the population activity of mitral cells (MCs). We use viral expression of GCaMP6s to examine odor-evoked responses of MCs following prenatal and early postnatal odorant exposure to two dissimilar odorants, methyl salicylate (MS) and hexanal, which are both strong activators of glomeruli on the dorsal OB surface. Previous work suggests that odor familiarity may decrease odor-evoked MC response in rodents. However, we find that early food-based odorant exposure significantly changes MC responses in an unexpected way, resulting in broad increases in the amplitude, number, and reliability of excitatory MC responses across the dorsal OB. PMID:28955723

  9. Roles of Macrophages and Neutrophils in the Early Host Response to Bacillus anthracis Spores in a Mouse Model of Infection

    PubMed Central

    Cote, Christopher K.; Van Rooijen, Nico; Welkos, Susan L.

    2006-01-01

    The development of new approaches to combat anthrax requires that the pathogenesis and host response to Bacillus anthracis spores be better understood. We investigated the roles that macrophages and neutrophils play in the progression of infection by B. anthracis in a mouse model. Mice were treated with a macrophage depletion agent (liposome-encapsulated clodronate) or with a neutrophil depletion agent (cyclophosphamide or the rat anti-mouse granulocyte monoclonal antibody RB6-8C5), and the animals were then infected intraperitoneally or by aerosol challenge with fully virulent, ungerminated B. anthracis strain Ames spores. The macrophage-depleted mice were significantly more susceptible to the ensuing infection than the saline-pretreated mice, whereas the differences observed between the neutropenic mice and the saline-pretreated controls were generally not significant. We also found that augmenting peritoneal neutrophil populations before spore challenge did not increase resistance of the mice to infection. In addition, the bacterial load in macrophage-depleted mice was significantly greater and appeared significantly sooner than that observed with the saline-pretreated mice. However, the bacterial load in the neutropenic mice was comparable to that of the saline-pretreated mice. These data suggest that, in our model, neutrophils play a relatively minor role in the early host response to spores, whereas macrophages play a more dominant role in early host defenses against infection by B. anthracis spores. PMID:16369003

  10. Cancer stem cells from human glioblastoma resemble but do not mimic original tumors after in vitro passaging in serum-free media.

    PubMed

    García-Romero, Noemí; González-Tejedo, Carmen; Carrión-Navarro, Josefa; Esteban-Rubio, Susana; Rackov, Gorjana; Rodríguez-Fanjul, Vanessa; Oliver-De La Cruz, Jorge; Prat-Acín, Ricardo; Peris-Celda, María; Blesa, David; Ramírez-Jiménez, Laura; Sánchez-Gómez, Pilar; Perona, Rosario; Escobedo-Lucea, Carmen; Belda-Iniesta, Cristobal; Ayuso-Sacido, Angel

    2016-10-04

    Human gliomas harbour cancer stem cells (CSCs) that evolve along the course of the disease, forming highly heterogeneous subpopulations within the tumour mass. These cells possess self-renewal properties and appear to contribute to tumour initiation, metastasis and resistance to therapy. CSC cultures isolated from surgical samples are considered the best preclinical in vitro model for primary human gliomas. However, it is not yet well characterized to which extent their biological and functional properties change during in vitro passaging in the serum-free culture conditions. Here, we demonstrate that our CSC-enriched cultures harboured from one to several CSC clones from the human glioma sample. When xenotransplanted into mouse brain, these cells generated tumours that reproduced at least three different dissemination patterns found in original tumours. Along the passages in culture, CSCs displayed increased expression of stem cell markers, different ratios of chromosomal instability events, and a varied response to drug treatment. Our findings highlight the need for better characterization of CSC-enriched cultures in the context of their evolution in vitro, in order to uncover their full potential as preclinical models in the studies aimed at identifying molecular biomarkers and developing new therapeutic approaches of human gliomas.

  11. Vascular smooth muscle cells exhibit a progressive loss of rigidity with serial culture passaging.

    PubMed

    Dinardo, Carla Luana; Venturini, Gabriela; Omae, Samantha Vieira; Zhou, Enhua H; da Motta-Leal-Filho, Joaquim Maurício; Dariolli, Rafael; Krieger, José Eduardo; Alencar, Adriano Mesquita; Costa Pereira, Alexandre

    2012-01-01

    One drawback of in vitro cell culturing is the dedifferentiation process that cells experience. Smooth muscle cells (SMC) also change molecularly and morphologically with long term culture. The main objective of this study was to evaluate if culture passages interfere in vascular SMC mechanical behavior. SMC were obtained from five different porcine arterial beds. Optical magnetic twisting cytometry (OMTC) was used to characterize mechanically vascular SMC from different cultures in distinct passages and confocal microscopy/western blotting, to evaluate cytoskeleton and extracellular matrix proteins. We found that vascular SMC rigidity or viscoelastic complex modulus (G) decreases with progression of passages. A statistically significant negative correlation between G and passage was found in four of our five cultures studied. Phalloidin-stained SMC from higher passages exhibited lower mean signal intensity per cell (confocal microscopy) and quantitative western blotting analysis showed a decrease in collagen I content throughout passages. We concluded that vascular SMC progressively lose their stiffness with serial culture passaging. Thus, limiting the number of passages is essential for any experiment measuring viscoelastic properties of SMC in culture.

  12. Studies of the Seriousness of Three Threats to Passage Dependence.

    ERIC Educational Resources Information Center

    Hanna, Gerald S.; Oaster, Thomas R.

    1980-01-01

    Certain kinds of multiple-choice reading comprehension questions may be answered correctly at the higher-than-chance level when they are administered without the accompanying passage. These high risk questions do not necessarily lead to passage dependence invalidity. They threaten but do not prove invalidity. (Author/CP)

  13. INTERIOR VIEW, PASSAGE AND DOOR LETTING ONTO THE SOUTHEAST BED ...

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

    INTERIOR VIEW, PASSAGE AND DOOR LETTING ONTO THE SOUTHEAST BED CHAMBER. THE ANGLED PASSAGE RUNS PARALLEL TO WHAT WAS AN EXTERIOR WALL OF THE THREE-SIDED WINDOW BOW PRESENT IN THE HOUSE’S ORIGINAL CA. 1770 STATE - The Woodlands, 4000 Woodlands Avenue, Philadelphia, Philadelphia County, PA

  14. Uterine NDRG2 expression is increased at implantation sites during early pregnancy in mice, and its down-regulation inhibits decidualization of mouse endometrial stromal cells.

    PubMed

    Gu, Yan; Zhang, Xuan; Yang, Qian; Wang, Jian-mei; He, Ya-ping; Sun, Zhao-gui; Zhang, Hui-qin; Wang, Jian

    2015-05-27

    N-myc down-regulated gene 2 (NDRG2) is a tumor suppressor involved in cell proliferation and differentiation. The aim of this study was to determine the uterine expression pattern of this gene during early pregnancy in mice. Uterine NDRG2 mRNA and protein expression levels were determined by RT-PCR and Western blot analyses, respectively, during the peri-implantation period in mice. Immunohistochemical (IHC) analysis was performed to examine the spatial localization of NDRG2 expression in mouse uterine tissues. The in vitro decidualization model of mouse endometrial stromal cells (ESCs) was used to evaluate decidualization of ESCs following NDRG2 knock down by small interfering RNA (siRNA). Statistical significance was analyzed by one-way ANOVA using SPSS 19.0 software. Uterine NDRG2 gene expression was significantly up-regulated and was predominantly localized to the secondary decidual zone on days 5 and 8 of pregnancy in mice. Its increased expression was associated with artificial decidualization as well as the activation of delayed implantation. Furthermore, uterine NDRG2 expression was induced by estrogen and progesterone treatments. The in vitro decidualization of mouse ESCs was accompanied by up-regulation of NDRG2 expression, and knock down of its expression in these cells by siRNA inhibited the decidualization process. These results suggest that NDRG2 might play an important role in the process of decidualization during early pregnancy.

  15. Terrestrial-passage theory: failing a test.

    PubMed

    Reed, Charles F; Krupinski, Elizabeth A

    2009-01-01

    Terrestrial-passage theory proposes that the 'moon' and 'sky' illusions occur because observers learn to expect an elevation-dependent transformation of visual angle. The transformation accompanies daily movement through ordinary environments of fixed-altitude objects. Celestial objects display the same visual angle at all elevations, and hence are necessarily non-conforming with the ordinary transformation. On hypothesis, observers should target angular sizes to appear greater at elevation than at horizon. However, in a sample of forty-eight observers there was no significant difference between the perceived angular size of a constellation of stars at horizon and that predicted for a specific elevation. Occurrence of the illusion was not restricted to those observers who expected angular expansion. These findings fail to support the terrestrial-passage theory of the illusion.

  16. Reduplication Facilitates Early Word Segmentation

    ERIC Educational Resources Information Center

    Ota, Mitsuhiko; Skarabela, Barbora

    2018-01-01

    This study explores the possibility that early word segmentation is aided by infants' tendency to segment words with repeated syllables ("reduplication"). Twenty-four nine-month-olds were familiarized with passages containing one novel reduplicated word and one novel non-reduplicated word. Their central fixation times in response to…

  17. Implementation speed of deterministic population passages compared to that of Rabi pulses

    NASA Astrophysics Data System (ADS)

    Chen, Jingwei; Wei, L. F.

    2015-02-01

    Fast Rabi π -pulse technique has been widely applied to various coherent quantum manipulations, although it requires precise designs of the pulse areas. Relaxing the precise pulse designs, various rapid adiabatic passage (RAP) approaches have been alternatively utilized to implement various population passages deterministically. However, the usual RAP protocol could not be implemented desirably fast, as the relevant adiabatic condition should be robustly satisfied during the passage. Here, we propose a modified shortcut to adiabaticity (STA) technique to accelerate significantly the desired deterministic quantum state population passages. This transitionless technique is beyond the usual rotating wave approximation (RWA) performed in the recent STA protocols, and thus can be applied to deliver various fast quantum evolutions wherein the relevant counter-rotating effects cannot be neglected. The proposal is demonstrated specifically with the driven two- and three-level systems. Numerical results show that with the present STA technique beyond the RWA the usual Stark-chirped RAPs and stimulated Raman adiabatic passages could be significantly speeded up; the deterministic population passages could be implemented as fast as the widely used fast Rabi π pulses, but are insensitive to the applied pulse areas.

  18. Novel Approaches to Examine Passage, Student, and Question Effects on Reading Comprehension

    PubMed Central

    Miller, Amanda C.; Davis, Nicole; Gilbert, Jennifer K.; Cho, Sun-Joo; Toste, Jessica R.; Street, James; Cutting, Laurie E.

    2014-01-01

    Reading comprehension is influenced by sources of variance associated with the reader and the task. To gain insight into the complex interplay of multiple sources of influence, we employed crossed random-effects item response models. These models allowed us to simultaneously examine the degree to which variables related to the type of passage and student characteristics influenced students’ (n = 94; mean age = 11.97 years) performance on two indicators of reading comprehension: different types of comprehension questions and passage fluency. We found that variables related to word recognition, language, and executive function were influential across various types of passages and comprehension questions and also predicted a reader’s passage fluency. Further, an exploratory analysis of two-way interaction effects was conducted. Results suggest that understanding the relative influence of passage, question, and student variables has implications for identifying struggling readers and designing interventions to address their individual needs. PMID:24535914

  19. Isolation, identification and multipotential differentiation of mouse adipose tissue-derived stem cells.

    PubMed

    Taha, Masoumeh Fakhr; Hedayati, Vahideh

    2010-08-01

    Bone marrow and adipose tissue have provided two suitable sources of mesenchymal stem cells. Although previous studies have confirmed close similarities between bone marrow-derived stem cells (BM-MSCs) and adipose tissue-derived stem cells (ADSCs), the molecular phenotype of ADSCs is still poorly identified. In the present study, mouse ADSCs were isolated from the inguinal fat pad of 12-14 weeks old mice. Freshly isolated and three passaged ADSCs were analyzed for the expression of OCT4, Sca-1, c-kit and CD34 by RT-PCR. Three passaged ADSCs were analyzed by flow cytometry for the presence of CD11b, CD45, CD31, CD29 and CD44. Moreover, cardiogenic, adipogenic and neurogenic differentiation of ADSCs were induced in vitro. Freshly isolated ADSCs showed the expression of OCT4, Sca-1, c-kit and CD34, and two days cultured ADSCs were positively immunostained with anti-OCT4 monoclonal antibody. After three passages, the expression of OCT4, c-kit and CD34 eliminated, while the expression of Sca-1 showed a striking enhancement. These cells were identified positive for CD29 and CD44 markers, and they showed the lack of CD45 and CD31 expression. Three passaged ADSCs were differentiated to adipocyte-, cardiomyocyte- and neuron-like cells that were identified based on the positive staining with Sudan black, anti-cardiac troponin I antibody and anti-map-2 antibody, respectively. In conclusion, adipose tissue contains a stem cell population that seems to be a good multipotential cell candidate for the future cell replacement therapy. Copyright 2010 Elsevier Ltd. All rights reserved.

  20. ONTOGENY OF TRANSCRIPTION PROFILES DURING MOUSE EARLY CRANIOFACIAL DEVELOPMENT

    EPA Science Inventory

    Using the CD-1 mouse conceptus, we investigated gene expression changes found in vivo from gestational day (GD)8 through GD9 at 6h intervals, and then at 24h intervals through GD11. Data sets were analyzed for patterns in transcriptional expression over a time course as well as t...

  1. EARLY ONSET OF CRANIOSYNOSTOSIS IN AN APERT MOUSE MODEL REVEALS CRITICAL FEATURES OF THIS PATHOLOGY

    PubMed Central

    Holmes, Greg; Rothschild, Gerson; Roy, Upal Basu; Deng, Chu-Xia; Mansukhani, Alka; Basilico, Claudio

    2009-01-01

    Activating mutations of FGFRs1–3 cause craniosynostosis (CS), the premature fusion of cranial bones, in man and mouse. The mechanisms by which such mutations lead to CS have been variously ascribed to increased osteoblast proliferation, differentiation, and apoptosis, but it is not always clear how these disturbances relate to the process of suture fusion. We have reassessed coronal suture fusion in an Apert Fgfr2 (S252W) mouse model. We find that the critical event of CS is the early loss of basal sutural mesenchyme as the osteogenic fronts, expressing activated Fgfr2, unite to form a contiguous skeletogenic membrane. A mild increase in osteoprogenitor proliferation precedes but does not accompany this event, and apoptosis is insignificant. On the other hand, the more apical coronal suture initially forms appropriately but then undergoes fusion, albeit at a slower rate, accompanied by a significant decrease in osteoprogenitor proliferation, and increased osteoblast maturation. Apoptosis now accompanies fusion, but is restricted to bone fronts in contact with one another. We correlated these in vivo observations with the intrinsic effects of the activated Fgfr2 S252W mutation in primary osteoblasts in culture, which show an increased capacity for both proliferation and differentiation. Our studies suggest that the major determinant of Fgfr2-induced craniosynostosis is the failure to respond to signals that would halt the recruitment or the advancement of osteoprogenitor cells at the sites where sutures should normally form. PMID:19389359

  2. Fish passage research: S.O. Conte Anadromous Fish Research Laboratory

    USGS Publications Warehouse

    Garebedian, Steve

    2008-01-01

    The Leetown Science Center’s S.O. Conte Anadromous Fish Research Laboratory conducts basic and applied scientific studies of fish passage and migration to define underlying principles and relationships of fish behavior and hydraulics, and to develop integrated, predictive research that can be applied to a wide range of fish passage problems.

  3. Quality of Vision in Eyes With Epiphora Undergoing Lacrimal Passage Intubation.

    PubMed

    Koh, Shizuka; Inoue, Yasushi; Ochi, Shintaro; Takai, Yoshihiro; Maeda, Naoyuki; Nishida, Kohji

    2017-09-01

    To investigate visual function and optical quality in eyes with epiphora undergoing lacrimal passage intubation. Prospective case series. Thirty-four eyes of 30 patients with lacrimal passage obstruction were enrolled. Before and 1 month after lacrimal passage intubation, functional visual acuity (FVA), higher-order aberrations (HOAs), lower tear meniscus, and tear clearance were assessed. An FVA measurement system was used to examine changes in continuous visual acuity (VA) over time, and visual function parameters such as FVA, visual maintenance ratio, and blink frequency were obtained. Sequential ocular HOAs were measured for 10 seconds after the blink using a wavefront sensor. Aberration data were analyzed in the central 4 mm for coma-like, spherical-like, and total HOAs. Fluctuation and stability indices of the total HOAs over time were calculated. Lower tear meniscus was assessed by anterior segment optical coherence tomography. After lacrimal passage intubation, visual function significantly improved, as indicated by improved FVA (P = .003) and visual maintenance ratio (P < .001). Blink frequency decreased significantly after treatment (P = .01). Optical quality significantly improved, as indicated by a decrease in coma-like aberrations (P = .003), spherical-like aberrations (P = .018), and total HOAs (P = .001). Stability index increased (P < .001) and fluctuation index decreased (P = .019), and tear meniscus dimension decreased (P < .001). Lacrimal passage intubation for eyes with epiphora significantly improved visual function and optical quality via patency of the lacrimal passage. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. A mouse model for creatine transporter deficiency reveals early onset cognitive impairment and neuropathology associated with brain aging.

    PubMed

    Baroncelli, Laura; Molinaro, Angelo; Cacciante, Francesco; Alessandrì, Maria Grazia; Napoli, Debora; Putignano, Elena; Tola, Jonida; Leuzzi, Vincenzo; Cioni, Giovanni; Pizzorusso, Tommaso

    2016-10-01

    Mutations in the creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CCDS1), an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement and autistic-like behavioural disturbances, language and speech impairment. Since no data are available about the neural and molecular underpinnings of this disease, we performed a longitudinal analysis of behavioural and pathological alterations associated with CrT deficiency in a CCDS1 mouse model. We found precocious cognitive and autistic-like defects, mimicking the early key features of human CCDS1. Moreover, mutant mice displayed a progressive impairment of short and long-term declarative memory denoting an early brain aging. Pathological examination showed a prominent loss of GABAergic synapses, marked activation of microglia, reduction of hippocampal neurogenesis and the accumulation of autofluorescent lipofuscin. Our data suggest that brain Cr depletion causes both early intellectual disability and late progressive cognitive decline, and identify novel targets to design intervention strategies aimed at overcoming brain CCDS1 alterations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. PNNL Tests Fish Passage System

    ScienceCinema

    Colotelo, Alison

    2018-01-16

    Scientists from PNNL are testing a fish transportation system developed by Whooshh Innovations. The Whooshh system uses a flexible tube that works a bit like a vacuum, guiding fish over hydroelectric dams or other structures. Compared to methods used today, this system could save money while granting fish quicker, safer passage through dams and hatcheries.

  6. PNNL Tests Fish Passage System

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

    Colotelo, Alison

    2015-03-13

    Scientists from PNNL are testing a fish transportation system developed by Whooshh Innovations. The Whooshh system uses a flexible tube that works a bit like a vacuum, guiding fish over hydroelectric dams or other structures. Compared to methods used today, this system could save money while granting fish quicker, safer passage through dams and hatcheries.

  7. Defining the molecular pathologies in cloaca malformation: similarities between mouse and human

    PubMed Central

    Runck, Laura A.; Method, Anna; Bischoff, Andrea; Levitt, Marc; Peña, Alberto; Collins, Margaret H.; Gupta, Anita; Shanmukhappa, Shiva; Wells, James M.; Guasch, Géraldine

    2014-01-01

    Anorectal malformations are congenital anomalies that form a spectrum of disorders, from the most benign type with excellent functional prognosis, to very complex, such as cloaca malformation in females in which the rectum, vagina and urethra fail to develop separately and instead drain via a single common channel into the perineum. The severity of this phenotype suggests that the defect occurs in the early stages of embryonic development of the organs derived from the cloaca. Owing to the inability to directly investigate human embryonic cloaca development, current research has relied on the use of mouse models of anorectal malformations. However, even studies of mouse embryos lack analysis of the earliest stages of cloaca patterning and morphogenesis. Here we compared human and mouse cloaca development and retrospectively identified that early mis-patterning of the embryonic cloaca might underlie the most severe forms of anorectal malformation in humans. In mouse, we identified that defective sonic hedgehog (Shh) signaling results in early dorsal-ventral epithelial abnormalities prior to the reported defects in septation. This is manifested by the absence of Sox2 and aberrant expression of keratins in the embryonic cloaca of Shh knockout mice. Shh knockout embryos additionally develop a hypervascular stroma, which is defective in BMP signaling. These epithelial and stromal defects persist later, creating an indeterminate epithelium with molecular alterations in the common channel. We then used these animals to perform a broad comparison with patients with mild-to-severe forms of anorectal malformations including cloaca malformation. We found striking parallels with the Shh mouse model, including nearly identical defective molecular identity of the epithelium and surrounding stroma. Our work strongly suggests that early embryonic cloacal epithelial differentiation defects might be the underlying cause of severe forms of anorectal malformations in humans. Moreover

  8. Relocalization of STIM1 in mouse oocytes at fertilization: early involvement of store-operated calcium entry.

    PubMed

    Gómez-Fernández, Carolina; Pozo-Guisado, Eulalia; Gañán-Parra, Miguel; Perianes, Mario J; Alvarez, Ignacio S; Martín-Romero, Francisco Javier

    2009-08-01

    Calcium waves represent one of the most important intracellular signaling events in oocytes at fertilization required for the exit from metaphase arrest and the resumption of the cell cycle. The molecular mechanism ruling this signaling has been described in terms of the contribution of intracellular calcium stores to calcium spikes. In this work, we considered the possible contribution of store-operated calcium entry (SOCE) to this signaling, by studying the localization of the protein STIM1 in oocytes. STIM1 has been suggested to play a key role in the recruitment and activation of plasma membrane calcium channels, and we show here that mature mouse oocytes express this protein distributed in discrete clusters throughout their periphery in resting cells, colocalizing with the endoplasmic reticulum marker calreticulin. However, immunolocalization of the endogenous STIM1 showed considerable redistribution over larger areas or patches covering the entire periphery of the oocyte during Ca(2+) store depletion induced with thapsigargin or ionomycin. Furthermore, pharmacological activation of endogenous phospholipase C induced a similar pattern of redistribution of STIM1 in the oocyte. Finally, fertilization of mouse oocytes revealed a significant and rapid relocalization of STIM1, similar to that found after pharmacological Ca(2+) store depletion. This particular relocalization supports a role for STIM1 and SOCE in the calcium signaling during early stages of fertilization.

  9. In vivo quantitative bioluminescence tomography using heterogeneous and homogeneous mouse models.

    PubMed

    Liu, Junting; Wang, Yabin; Qu, Xiaochao; Li, Xiangsi; Ma, Xiaopeng; Han, Runqiang; Hu, Zhenhua; Chen, Xueli; Sun, Dongdong; Zhang, Rongqing; Chen, Duofang; Chen, Dan; Chen, Xiaoyuan; Liang, Jimin; Cao, Feng; Tian, Jie

    2010-06-07

    Bioluminescence tomography (BLT) is a new optical molecular imaging modality, which can monitor both physiological and pathological processes by using bioluminescent light-emitting probes in small living animal. Especially, this technology possesses great potential in drug development, early detection, and therapy monitoring in preclinical settings. In the present study, we developed a dual modality BLT prototype system with Micro-computed tomography (MicroCT) registration approach, and improved the quantitative reconstruction algorithm based on adaptive hp finite element method (hp-FEM). Detailed comparisons of source reconstruction between the heterogeneous and homogeneous mouse models were performed. The models include mice with implanted luminescence source and tumor-bearing mice with firefly luciferase report gene. Our data suggest that the reconstruction based on heterogeneous mouse model is more accurate in localization and quantification than the homogeneous mouse model with appropriate optical parameters and that BLT allows super-early tumor detection in vivo based on tomographic reconstruction of heterogeneous mouse model signal.

  10. Computational study of fish passage through circular culverts in Northeast Ohio.

    DOT National Transportation Integrated Search

    2013-11-01

    An investigation has been carried out in Northeast Ohio to determine the percentage of culverts that act : as barriers for fish passage and to identify the design parameters that can be associated with passage : success through stream simulation in t...

  11. Functional Genomic and Proteomic Analysis Reveals Disruption of Myelin-Related Genes and Translation in a Mouse Model of Early Life Neglect

    PubMed Central

    Bordner, Kelly A.; George, Elizabeth D.; Carlyle, Becky C.; Duque, Alvaro; Kitchen, Robert R.; Lam, TuKiet T.; Colangelo, Christopher M.; Stone, Kathryn L.; Abbott, Thomas B.; Mane, Shrikant M.; Nairn, Angus C.; Simen, Arthur A.

    2011-01-01

    Early life neglect is an important public health problem which can lead to lasting psychological dysfunction. Good animal models are necessary to understand the mechanisms responsible for the behavioral and anatomical pathology that results. We recently described a novel model of early life neglect, maternal separation with early weaning (MSEW), that produces behavioral changes in the mouse that persist into adulthood. To begin to understand the mechanism by which MSEW leads to these changes we applied cDNA microarray, next-generation RNA-sequencing (RNA-seq), label-free proteomics, multiple reaction monitoring (MRM) proteomics, and methylation analysis to tissue samples obtained from medial prefrontal cortex to determine the molecular changes induced by MSEW that persist into adulthood. The results show that MSEW leads to dysregulation of markers of mature oligodendrocytes and genes involved in protein translation and other categories, an apparent downward biasing of translation, and methylation changes in the promoter regions of selected dysregulated genes. These findings are likely to prove useful in understanding the mechanism by which early life neglect affects brain structure, cognition, and behavior. PMID:21629843

  12. Middle Passage in the Triangular Slave Trade: The West Indies

    ERIC Educational Resources Information Center

    Sawh, Ruth; Scales, Alice M.

    2006-01-01

    Our narrative focuses on the middle passage of the slave trade in the West Indies. Herein we describe why more men, women, and children were imported in the West Indies than other islands. Specifically, our aim was to address how slaves in the middle passage of the triangular slave trade were treated, how they sustained themselves, and how they…

  13. Defining Family-Friendly Early Intervention.

    ERIC Educational Resources Information Center

    Wadsworth, Donna E. Dugger; Wartelle, Noah L.

    Prior to the 1986 passage of PL 99-457, an extension of the special services coverage under the Education for All Handicapped Children Act, early intervention programs were primarily interventionist directed and child focused. The new legislation provided incentives for providing programs that were family-centered and family-driven. The goal of…

  14. Method of creating a controlled interior surface configuration of passages within a substrate

    DOEpatents

    Dembowski, Peter V.; Schilke, Peter W.

    1983-01-01

    A method of creating a controlled interior surface configuration of passages within a substrate, particularly cooling passages of nozzles or buckets of a gas turbine, involves the hot isostatic pressing of a leachable passage insert whose surface carries the female image of the desired interior surface configuration inside the substrate followed by leaching of the insert from the substrate.

  15. Anisodamine accelerates spontaneous passage of single symptomatic bile duct stones ≤ 10 mm

    PubMed Central

    Gao, Jun; Ding, Xue-Mei; Ke, Shan; Zhou, Yi-Ming; Qian, Xiao-Jun; Ma, Rui-Liang; Ning, Chun-Min; Xin, Zong-Hai; Sun, Wen-Bing

    2013-01-01

    AIM: To investigate the rate of spontaneous passage of single and symptomatic common bile duct (CBD) stones ≤ 10 mm in diameter in 4 wk with or without a 2-wk course of anisodamine. METHODS: A multicenter, randomized, placebo-controlled trial was undertaken. A total of 197 patients who met the inclusion criteria were enrolled. Ninety-seven patients were assigned randomly to the control group and the other 100 to the anisodamine group. The anisodamine group received intravenous infusions of anisodamine (10 mg every 8 h) for 2 wk. The control group received the same volume of 0.9% isotonic saline for 2 wk. Patients underwent imaging studies and liver-function tests every week for 4 wk. The rate of spontaneous passage of CBD stones was analyzed. RESULTS: The rate of spontaneous passage of CBD stones was significantly higher in the anisodamine group than that in the control group (47.0% vs 22.7%). Most (87.2%, 41/47) stone passages in the anisodamine group occurred in the first 2 wk, and passages in the control group occurred at a comparable rate each week. Factors significantly increasing the possibility of spontaneous passage by univariate logistic regression analyses were stone diameter (< 5 mm vs ≥ 5 mm and ≤ 10 mm) and anisodamine therapy. Multivariate logistic regression analyses revealed that these two factors were significantly associated with spontaneous passage. CONCLUSION: Two weeks of anisodamine administration can safely accelerate spontaneous passage of single and symptomatic CBD stones ≤ 10 mm in diameter, especially for stones < 5 mm. PMID:24151390

  16. Establishment of a patient-derived orthotopic osteosarcoma mouse model.

    PubMed

    Blattmann, Claudia; Thiemann, Markus; Stenzinger, Albrecht; Roth, Eva K; Dittmar, Anne; Witt, Hendrik; Lehner, Burkhard; Renker, Eva; Jugold, Manfred; Eichwald, Viktoria; Weichert, Wilko; Huber, Peter E; Kulozik, Andreas E

    2015-04-30

    Osteosarcoma (OS) is the most common pediatric primary malignant bone tumor. As the prognosis for patients following standard treatment did not improve for almost three decades, functional preclinical models that closely reflect important clinical cancer characteristics are urgently needed to develop and evaluate new treatment strategies. The objective of this study was to establish an orthotopic xenotransplanted mouse model using patient-derived tumor tissue. Fresh tumor tissue from an adolescent female patient with osteosarcoma after relapse was surgically xenografted into the right tibia of 6 immunodeficient BALB/c Nu/Nu mice as well as cultured into medium. Tumor growth was serially assessed by palpation and with magnetic resonance imaging (MRI). In parallel, a primary cell line of the same tumor was established. Histology and high-resolution array-based comparative genomic hybridization (aCGH) were used to investigate both phenotypic and genotypic characteristics of different passages of human xenografts and the cell line compared to the tissue of origin. A primary OS cell line and a primary patient-derived orthotopic xenotranplanted mouse model were established. MRI analyses and histopathology demonstrated an identical architecture in the primary tumor and in the xenografts. Array-CGH analyses of the cell line and all xenografts showed highly comparable patterns of genomic progression. So far, three further primary patient-derived orthotopic xenotranplanted mouse models could be established. We report the first orthotopic OS mouse model generated by transplantation of tumor fragments directly harvested from the patient. This model represents the morphologic and genomic identity of the primary tumor and provides a preclinical platform to evaluate new treatment strategies in OS.

  17. Investigating passage of ESA-listed juvenile fall Chinook salmon at Lower Granite Dam during winter when the fish bypass system is not operated

    USGS Publications Warehouse

    Kock, Tobias J.; Tiffan, Kenneth F.; Connor, William P.

    2007-01-01

    During the winter of 2006-07, we radio and passive integrated transponder (PIT) tagged, and released 99 juvenile fall Chinook salmon to evaluate over-wintering behavior and dam passage in the lower Snake River, Washington. All fish were released 10 km upstream of Lower Granite Dam at Granite Point in early November, 2006. Fixed radio telemetry detection sites located in the forebay and tailrace areas of Lower Granite, Little Goose, Lower Monumental, Ice Harbor, Bonneville dams, and at Lyle, Washington were used to monitor fish movements and dam passage through early-May 2007. Of the 99 fish released during our study, 80 passed Lower Granite Dam and were detected at downstream detection sites, 37 passed Little Goose Dam, 41 passed Lower Monumental Dam, 31 passed Ice Harbor Dam, 18 passed Lyle, WA, and 13 passed Bonneville Dam. Of the fish that passed Lower Granite Dam in the fall, 63 fish did so during the extended bypass period from November 1 through December 16. Of these fish, 53 were also detected by the PIT-tag interrogation system. Fifteen of the fish that passed Lower Granite Dam in the fall continued to pass lower Snake River dams and exit the system by the end of January. The remaining fish either died, their tags failed, or they resided in Little Goose Reservoir until spring when relatively few continued their seaward migration. Passage of tagged fish past lower Snake River dams generally declined during the winter as temperatures decreased, but increased again in the spring as temperatures and flows increased. Fish residence times in reservoirs and forebays was lengthy during the winter (up to 160 d), and varied by reservoir and time of year. We observed no diel trends in fish passage. Very few fish were detected at PIT-tag interrogation sites in the spring compared to detection by radio telemetry detection sites indicating that fish may have passed via spill. We believe that passage of overwintering juvenile fall Chinook salmon during winter is due more

  18. Heat transfer in rotating serpentine passages with selected model orientation for smooth or skewed trip walls

    NASA Technical Reports Server (NTRS)

    Johnson, B. V.; Wagner, J. H.; Steuber, G. D.; Yeh, F. C.

    1993-01-01

    Experiments were conducted to determine the effects of model orientation as well as buoyancy and Coriolis forces on heat transfer in turbine blade internal coolant passages. Turbine blades have internal coolant passage surfaces at the leading and trailing edges of the airfoil with surfaces at angles which are as large as +/- 50 to 60 degrees to the axis of rotation. Most of the previously-presented, multiple-passage, rotating heat transfer experiments have focused on radial passages aligned with the axis of rotation. Results from serpentine passages with orientations 0 and 45 degrees to the axis of rotation which simulate the coolant passages for the mid chord and trailing edge regions of the rotating airfoil are compared. The experiments were conducted with rotation in both directions to simulate serpentine coolant passages with the rearward flow of coolant or with the forward flow of coolant. The experiments were conducted for passages with smooth surfaces and with 45 degree trips adjacent to airfoil surfaces for the radial portion of the serpentine passages. At a typical flow condition, the heat transfer on the leading surfaces for flow outward in the first passage with smooth walls was twice as much for the model at 45 degrees compared to the model at 0 degrees. However, the differences for the other passages and with trips were less. In addition, the effects of buoyancy and Coriolis forces on heat transfer in the rotating passage were decreased with the model at 45 degrees, compared to the results at 0 degrees. The heat transfer in the turn regions and immediately downstream of the turns in the second passage with flow inward and in the third passage with flow outward was also a function of model orientation with differences as large as 40 to 50 percent occurring between the model orientations with forward flow and rearward flow of coolant.

  19. Effects of rotation on coolant passage heat transfer. Volume 2: Coolant passages with trips normal and skewed to the flow

    NASA Technical Reports Server (NTRS)

    Johnson, B. V.; Wagner, J. H.; Steuber, G. D.

    1993-01-01

    An experimental program was conducted to investigate heat transfer and pressure loss characteristics of rotating multipass passages, for configurations and dimensions typical of modem turbine blades. This experimental program is one part of the NASA Hot Section Technology (HOST) Initiative, which has as its overall objective the development and verification of improved analysis methods that will form the basis for a design system that will produce turbine components with improved durability. The objective of this program was the generation of a data base of heat transfer and pressure loss data required to develop heat transfer correlations and to assess computational fluid dynamic techniques for rotating coolant passages. The experimental work was broken down into two phases. Phase 1 consists of experiments conducted in a smooth wall large scale heat transfer model. A detailed discussion of these results was presented in volume 1 of a NASA Report. In Phase 2 the large scale model was modified to investigate the effects of skewed and normal passage turbulators. The results of Phase 2 along with comparison to Phase 1 is the subject of this Volume 2 NASA Report.

  20. Kinetic energy equations for the average-passage equation system

    NASA Technical Reports Server (NTRS)

    Johnson, Richard W.; Adamczyk, John J.

    1989-01-01

    Important kinetic energy equations derived from the average-passage equation sets are documented, with a view to their interrelationships. These kinetic equations may be used for closing the average-passage equations. The turbulent kinetic energy transport equation used is formed by subtracting the mean kinetic energy equation from the averaged total instantaneous kinetic energy equation. The aperiodic kinetic energy equation, averaged steady kinetic energy equation, averaged unsteady kinetic energy equation, and periodic kinetic energy equation, are also treated.

  1. Rho kinase inhibitor Y-27632 and Accutase dramatically increase mouse embryonic stem cell derivation.

    PubMed

    Zhang, Peng; Wu, Xinglong; Hu, Chunchao; Wang, Pengbo; Li, Xiangyun

    2012-01-01

    Although it has been 30 yr since the development of derivation methods for mouse embryonic stem (ES) cells, the biology of derivation of ES cells is poorly understood and the efficiency varies dramatically between cell lines. Recently, the Rho kinase inhibitor Y-27632 and the cell dissociation reagent Accutase were reported to significantly inhibit apoptosis of human ES cells during passaging. Therefore, in the current study, C57BL/6×129/Sv mouse blastocysts were used to evaluate the effect of the combination of the two reagents instead of using the conventional 129 line in mouse ES cell derivation. The data presented in this study suggests that the combination of Y-27632 and Accutase significantly increases the efficiency of mouse ES cell derivation; furthermore, no negative side effects were observed with Y-27632 and Accutase treatment. The newly established ES cell lines retain stable karyotype, surface markers expression, formed teratomas, and contributed to viable chimeras and germline transmission by tetraploid complementation assay. In addition, Y-27632 improved embryoid body formation of ES cells. During ES cell microinjection, Y-27632 prevented the formation of dissociation-induced cell blebs and facilitates the selection and the capture of intact cells. The methods presented in this study clearly demonstrate that inhibition of Rho kinase with Y-27632 and Accutase dissociation improve the derivation efficiently and reproducibility of mouse ES cell generation which is essential for reducing variability in the results obtained from different cell lines.

  2. Federal interagency nature‐like fishway passage design guidelines for Atlantic coast diadromous fishes

    USGS Publications Warehouse

    Turek, James; Haro, Alexander J.; Towler, Brett

    2016-01-01

    The National Marine Fisheries Service (NMFS), the U.S. Geological Survey (USGS) and the U.S. Fish and Wildlife Service (USFWS) have collaborated to develop passage design guidance for use by engineers and other restoration practitioners considering and designing nature‐like fishways (NLFs). The primary purpose of these guidelines is to provide a summary of existing fish swimming and leaping performance data and the best available scientific information on safe, timely and effective passage for 14 diadromous fish species using Atlantic Coast rivers and streams. These guidelines apply to passage sites where complete barrier removal is not possible. This technical memorandum presents seven key physical design parameters based on the biometrics and swimming mode and performance of each target fishes for application in the design of NLFs addressing passage of a species or an assemblage of these species. The passage parameters include six dimensional guidelines recommended for minimum weir opening width and depth, minimum pool length, width and depth, and maximum channel slope, along with a maximum flow velocity guideline for each species. While these guidelines are targeted for the design of step‐pool NLFs, the information may also have application in the design of other NLF types being considered at passage restoration sites and grade control necessary for infrastructure protection upstream of some dam removals, and in considering passage performance at sites such as natural bedrock features.

  3. Vitrification of mouse embryo-derived ICM cells: a tool for preserving embryonic stem cell potential?

    PubMed

    Desai, Nina; Xu, Jing; Tsulaia, Tamara; Szeptycki-Lawson, Julia; AbdelHafez, Faten; Goldfarb, James; Falcone, Tommaso

    2011-02-01

    Vitrification technology presents new opportunities for preservation of embryo derived stem cells without first establishing a viable ESC line. This study tests the feasibility of cryopreserving ICM cells using vitrification. ICMs from mouse embryos were isolated and vitrified in HSV straws or on cryoloops. Upon warming, the vitrified ICMs were cultured and observed for attachment and morphology. Colonies were passaged every 3-6 days. ICMs and ICM-derived ESC colonies were tested for expression of stem cell specific markers. ICMs vitrified on both the cryoloop and the HSV straw had high survival rates. ICM derived ESCs remained undifferentiated for several passages and demonstrated expression of typical stem cell markers; SSEA-1, Sox-2, Oct 4 and alkaline phosphatase. This is the first report on successful vitrification of isolated ICMs and the subsequent derivation of ESC colonies. Vitrification of isolated ICMs is a novel approach for preservation of the "stem cell source" material.

  4. Migrations and swimming capabilities of endangered pallid sturgeon (Scaphirhynchus albus) to guide passage designs in the fragmented Yellowstone River

    USGS Publications Warehouse

    Braaten, P. J.; Elliott, Caroline M.; Rhoten, Jason C.; Fuller, D. B.; McElroy, Brandon J.

    2015-01-01

    Fragmentation of the Yellowstone River is hypothesized to preclude recruitment of endangered Scaphirhynchus albus (pallid sturgeon) by impeding upstream spawning migrations and access to upstream spawning areas, thereby limiting the length of free-flowing river required for survival of early life stages. Building on this hypothesis, the reach of the Yellowstone River affected by Intake Diversion Dam (IDD) is targeted for modification. Structures including a rock ramp and by-pass channel have been proposed as restoration alternatives to facilitate passage. Limited information on migrations and swimming capabilities of pallid sturgeon is available to guide engineering design specifications for the proposed structures. Migration behavior, pathways (channel routes used during migrations), and swimming capabilities of free-ranging wild adult pallid sturgeon were examined using radiotelemetry, and complemented with hydraulic data obtained along the migration pathways. Migrations of 12–26% of the telemetered pallid sturgeon population persisted to IDD, but upstream passage over the dam was not detected. Observed migration pathways occurred primarily through main channel habitats; however, migrations through side channels up to 3.9 km in length were documented. The majority of pallid sturgeon used depths of 2.2–3.4 m and mean water velocities of 0.89–1.83 m/s while migrating. Results provide inferences on depths, velocities, and habitat heterogeneity of reaches successfully negotiated by pallid sturgeon that may be used to guide designs for structures facilitating passage at IDD. Passage will provide connectivity to potential upstream spawning areas on the Yellowstone River, thereby increasing the likelihood of recruitment for this endangered species.

  5. Metabolic and mitochondrial dysfunction in early mouse embryos following maternal dietary protein intervention.

    PubMed

    Mitchell, Megan; Schulz, Samantha L; Armstrong, David T; Lane, Michelle

    2009-04-01

    Dietary supply of nutrients, both periconception and during pregnancy, influence the growth and development of the fetus and offspring and their health into adult life. Despite the importance of research efforts surrounding the developmental origins of health and disease hypothesis, the biological mechanisms involved remain elusive. Mitochondria are of major importance in the oocyte and early embryo, particularly as a source of ATP generation, and perturbations in their function have been related to reduced embryo quality. The present study examined embryo development following periconception exposure of females to a high-protein diet (HPD) or a low-protein diet (LPD) relative to a medium-protein diet (MPD; control), and we hypothesized that perturbed mitochondrial metabolism in the mouse embryo may be responsible for the impaired embryo and fetal development reported by others. Although the rate of development to the blastocyst stage did not differ between diets, both the HPD and LPD reduced the number of inner cell mass cells in the blastocyst-stage embryo. Furthermore, mitochondrial membrane potential was reduced and mitochondrial calcium levels increased in the 2-cell embryo. Embryos from HPD females had elevated levels of reactive oxygen species and ADP concentrations, indicative of metabolic stress and, potentially, the uncoupling of oxidative phosphorylation, whereas embryos from LPD females had reduced mitochondrial clustering around the nucleus, suggestive of an overall quietening of metabolism. Thus, although periconception dietary supply of different levels of protein is permissive of development, mitochondrial metabolism is altered in the early embryo, and the nature of the perturbation differs between HPD and LPD exposure.

  6. Walla Walla River Fish Passage Operations Program, 2004-2005 Annual Report.

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

    Bronson, James P.; Duke, Bill B.

    2006-02-01

    In the late 1990s, the Confederated Tribes of the Umatilla Indian Reservation, Oregon Department of Fish and Wildlife, and Washington Department of Fish and Wildlife, along with many other agencies, began implementing fisheries restoration activities in the Walla Walla Basin. An integral part of these efforts is to alleviate the inadequate fish migration conditions in the basin. The migration concerns are being addressed by removing diversion structures, constructing fish passage facilities, implementing minimum instream flow requirements, and providing trap and haul efforts when needed. The objective of the Walla Walla River Fish Passage Operations Project is to increase the survivalmore » of migrating adult and juvenile salmonids in the Walla Walla River basin. The project is responsible for coordinating operation and maintenance of ladders, screen sites, bypasses, trap facilities, and transportation equipment. In addition, the project provides technical input on passage criteria and passage and trapping facility design and operation. Operation of the various passage facilities and passage criteria guidelines are outlined in an annual operations plan that the project develops. During the 2004-2005 project year, there were 590 adult summer steelhead, 31 summer steelhead kelts (Oncorhynchus mykiss), 70 adult bull trout (Salvelinus confluentus); 80 adult and 1 jack spring Chinook (O. tshawytscha) enumerated at the Nursery Bridge Dam fishway video counting window between December 13, 2004, and June 16, 2005. Summer steelhead and spring chinook were observed moving upstream while bull trout were observed moving both upstream and downstream of the facility. In addition, the old ladder trap was operated by ODFW in order to enumerate fish passage. Of the total, 143 adult summer steelhead and 15 summer steelhead kelts were enumerated at the west ladder at Nursery Bridge Dam during the video efforts between February 4 and May 23, 2005. Operation of the Little Walla Walla

  7. Maternal Education, Early Child Care and the Reproduction of Advantage

    ERIC Educational Resources Information Center

    Augustine, Jennifer March; Cavanagh, Shannon E.; Crosnoe, Robert

    2009-01-01

    The social and human capital that educational attainment provides women enables them to better navigate their children's passages through school. In this study, we examine a key mechanism in this intergenerational process: mothers' selection of early child care. Analyses of the NICHD Study of Early Child Care and Youth Development revealed that…

  8. Influence of the random walk finite step on the first-passage probability

    NASA Astrophysics Data System (ADS)

    Klimenkova, Olga; Menshutin, Anton; Shchur, Lev

    2018-01-01

    A well known connection between first-passage probability of random walk and distribution of electrical potential described by Laplace equation is studied. We simulate random walk in the plane numerically as a discrete time process with fixed step length. We measure first-passage probability to touch the absorbing sphere of radius R in 2D. We found a regular deviation of the first-passage probability from the exact function, which we attribute to the finiteness of the random walk step.

  9. 77 FR 28253 - Safety Zone; America's Cup World Series, East Passage, Narragansett Bay, RI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-14

    ...-AA00 Safety Zone; America's Cup World Series, East Passage, Narragansett Bay, RI AGENCY: Coast Guard... navigable waters of the East Passage, Narragansett Bay, Rhode Island, during the America's Cup World Series... rulemaking (NPRM) entitled ``Safety Zones; America's Cup World Series, East Passage, Narragansett Bay, RI...

  10. New phenotypic aspects of the decidual spiral artery wall during early post-implantation mouse pregnancy

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

    Elia, Artemis; Charalambous, Fotini; Georgiades, Pantelis, E-mail: pgeor@ucy.ac.cy

    Highlights: Black-Right-Pointing-Pointer Spiral artery (SA) wall remodeling (SAR) is ill-defined and clinically important. Black-Right-Pointing-Pointer SA muscular phenotype prior to and during SAR in mice is underexplored. Black-Right-Pointing-Pointer SA muscular wall consists of contractile and non-contractile components. Black-Right-Pointing-Pointer SA wall non-contractile component may be synthetic smooth muscle. Black-Right-Pointing-Pointer Timing and extent of SA wall contractile component loss is revealed. -- Abstract: During pregnancy the walls of decidual spiral arteries (SAs) undergo clinically important structural modifications crucial for embryo survival/growth and maternal health. However, the mechanisms of SA remodeling (SAR) are poorly understood. Although an important prerequisite to this understanding is knowledgemore » about the phenotype of SA muscular wall prior to and during the beginning of mouse SAR, this remains largely unexplored and was the main aim of this work. Using histological and immunohistochemical techniques, this study shows for the first time that during early mouse gestation, from embryonic day 7.5 (E7.5) to E10.5, the decidual SA muscular coat is not a homogeneous structure, but consists of two concentric layers. The first is a largely one cell-thick sub-endothelial layer of contractile mural cells (positive for {alpha}-smooth muscle actin, calponin and SM22{alpha}) with pericyte characteristics (NG2 positive). The second layer is thicker, and evidence is presented that it may be of the synthetic/proliferative smooth muscle phenotype, based on absence ({alpha}-smooth muscle actin and calponin) or weak (SM22{alpha}) expression of contractile mural cell markers, and presence of synthetic smooth muscle characteristics (expression of non-muscle Myosin heavy chain-IIA and of the cell proliferation marker PCNA). Importantly, immunohistochemistry and morphometrics showed that the contractile mural cell layer although prominent at E7

  11. First passage analysis of the folding of a β-sheet miniprotein: is it more realistic than the standard equilibrium approach?

    PubMed

    Kalgin, Igor V; Chekmarev, Sergei F; Karplus, Martin

    2014-04-24

    Simulations of first-passage folding of the antiparallel β-sheet miniprotein beta3s, which has been intensively studied under equilibrium conditions by A. Caflisch and co-workers, show that the kinetics and dynamics are significantly different from those for equilibrium folding. Because the folding of a protein in a living system generally corresponds to the former (i.e., the folded protein is stable and unfolding is a rare event), the difference is of interest. In contrast to equilibrium folding, the Ch-curl conformations become very rare because they contain unfavorable parallel β-strand arrangements, which are difficult to form dynamically due to the distant N- and C-terminal strands. At the same time, the formation of helical conformations becomes much easier (particularly in the early stage of folding) due to short-range contacts. The hydrodynamic descriptions of the folding reaction have also revealed that while the equilibrium flow field presented a collection of local vortices with closed "streamlines", the first-passage folding is characterized by a pronounced overall flow from the unfolded states to the native state. The flows through the locally stable structures Cs-or and Ns-or, which are conformationally close to the native state, are negligible due to detailed balance established between these structures and the native state. Although there are significant differences in the general picture of the folding process from the equilibrium and first-passage folding simulations, some aspects of the two are in agreement. The rate of transitions between the clusters of characteristic protein conformations in both cases decreases approximately exponentially with the distance between the clusters in the hydrogen bond distance space of collective variables, and the folding time distribution in the first-passage segments of the equilibrium trajectory is in good agreement with that for the first-passage folding simulations.

  12. First Passage Analysis of the Folding of a β-Sheet Miniprotein: Is it More Realistic Than the Standard Equilibrium Approach?

    PubMed Central

    2015-01-01

    Simulations of first-passage folding of the antiparallel β-sheet miniprotein beta3s, which has been intensively studied under equilibrium conditions by A. Caflisch and co-workers, show that the kinetics and dynamics are significantly different from those for equilibrium folding. Because the folding of a protein in a living system generally corresponds to the former (i.e., the folded protein is stable and unfolding is a rare event), the difference is of interest. In contrast to equilibrium folding, the Ch-curl conformations become very rare because they contain unfavorable parallel β-strand arrangements, which are difficult to form dynamically due to the distant N- and C-terminal strands. At the same time, the formation of helical conformations becomes much easier (particularly in the early stage of folding) due to short-range contacts. The hydrodynamic descriptions of the folding reaction have also revealed that while the equilibrium flow field presented a collection of local vortices with closed ”streamlines”, the first-passage folding is characterized by a pronounced overall flow from the unfolded states to the native state. The flows through the locally stable structures Cs-or and Ns-or, which are conformationally close to the native state, are negligible due to detailed balance established between these structures and the native state. Although there are significant differences in the general picture of the folding process from the equilibrium and first-passage folding simulations, some aspects of the two are in agreement. The rate of transitions between the clusters of characteristic protein conformations in both cases decreases approximately exponentially with the distance between the clusters in the hydrogen bond distance space of collective variables, and the folding time distribution in the first-passage segments of the equilibrium trajectory is in good agreement with that for the first-passage folding simulations. PMID:24669953

  13. Hydrologic and hydraulic factors affecting passage of paddlefish through dams in the Upper Mississippi River

    USGS Publications Warehouse

    Zigler, S.J.; Dewey, M.R.; Knights, B.C.; Runstrom, A.L.; Steingraeber, M.T.

    2004-01-01

    Populations of paddlefish Polyodon spathula have been adversely affected by dams that can block their movements. Unlike high-head dams that preclude fish passage (unless they are equipped with fishways), the dams on the upper Mississippi River are typically low-head dams with bottom release gates that may allow fish passage under certain conditions. We evaluated the relation of dam head and river discharge to the passage of radio-tagged paddlefish through dams in the upper Mississippi River. Radio transmitters were surgically implanted into 71 paddlefish from Navigation Pools 5A and 8 of the upper Mississippi River and from two tributary rivers during fall 1994 through fall 1996. We tracked paddlefish through September 1997 and documented 53 passages through dams, 20 upstream and 33 downstream. Passages occurred mostly during spring (71%) but also occurred sporadically during summer and fall (29%). Spring passages varied among years in response to hydrologic conditions. We evaluated patterns in upstream and downstream passages with Cox proportional hazard regression models. Model results indicated that dam head height strongly affected the upstream passage of paddlefish but not the downstream passage. Several paddlefish, however, passed upstream through a dam during periods when the minimum head at the dam was substantial ( greater than or equal to 1m). In these cases, we hypothesize that paddlefish moved upstream through the lock chamber.

  14. 'Safe passage': pregnant Iranian Kurdish women's choice of childbirth method.

    PubMed

    Shahoei, Roonak; Riji, Haliza Mohd; Saeedi, Zhila Abed

    2011-10-01

    This article is a report of a grounded theory study of the influence of emotions on women's selection of a method of childbirth. There is substantial evidence to indicate that a pregnant woman's emotions play an important role in the decision-making process of selecting a child delivery method. Despite this, however, there is a notable lack of research about the relationship between pregnant women's emotions and their choice of a childbirth method in developing countries. A qualitative study using the grounded theory approach was conducted. The data were collected from 22 Iranian Kurdish pregnant women in their third trimester using semi-structured interviews. Concurrent data collection and analysis took place between 2008 and 2009. A cumulative process of theoretical sampling and constant comparison was used to identify concepts and then expand, validate, and clarify them. The substantive grounded theory that was identified from data analysis was 'safe passage'. 'Safe passage' involved five phases that were not mutually exclusive in their occurrence. The five phases of the 'safe passage' theory that were identified from the data analysis were: 'safety of baby', 'fear', 'previous experience', 'social support' and 'faith'. The goal of 'safe passage' was to achieve a healthy delivery and to ensure the health of the newborn. 'Safe passage' was a process used to determine how the emotions of pregnant Iranian Kurdish women influenced their choice of the mode of child delivery. More research is needed in this field to develop a body of knowledge beneficial to midwifery education and practice. © 2011 Blackwell Publishing Ltd.

  15. Walla Walla River Fish Passage Operations Program, 2000-2001 Annual Report.

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

    Zimmerman, Brian C.; Duke, Bill B.

    2004-02-01

    In the late 1990's, the Confederated Tribes of the Umatilla Indian Reservation, Oregon Department of Fish and Wildlife, and Washington Department of Fish and Wildlife, along with many other agencies, began implementing fisheries restoration activities in the Walla Walla Basin. An integral part of these efforts is to alleviate the inadequate migration conditions in the basin. The migration concerns are being addressed by removing diversion structures, constructing fish passage facilities, implementing minimum instream flow measures, and initiating trap and haul efforts. The objective of the Walla Walla River Fish Passage Operations Project is to increase the survival of migrating adultmore » and juvenile salmonids in the basin. The project is responsible for coordinating operation and maintenance of ladders, screen sites, bypasses, trap facilities, and transportation equipment. In addition, the project provides technical input on passage criteria and passage and trapping facility design and operation. Operation of the various passage facilities and passage criteria guidelines are outlined in an annual operations plan that the project develops. During the 2000-2001 project year, there were 624 summer steelhead (Oncorhynchus mykiss), 24 bull trout (Salvelinus confluentus), and 47 spring chinook (O. tshawytscha) counted at the Nursery Bridge Dam adult trap between December 27, 2000 and June 7, 2001. The Little Walla Walla River juvenile trap was not operated this year. The project transported 1600 adult spring chinook from Ringold Springs Hatchery to the South Fork Walla Walla Brood Holding Facility and outplanted 1156 for natural spawning in the basin. The project also provided equipment for transportation of juveniles captured during the construction fish salvage at Nursery Bridge Dam.« less

  16. Performance of fish passage structures at upstream barriers to migration

    USGS Publications Warehouse

    Bunt, C.M.; Castro-Santos, T.; Haro, A.

    2012-01-01

    Attraction and passage efficiency were reviewed and compared from 19 monitoring studies that produced data for evaluations of pool-and-weir, Denil, vertical-slot and nature-like fishways. Data from 26 species of anadromous and potamodromous fishes from six countries were separated by year and taxonomic family into a matrix with 101 records. Attraction performance was highly variable for the following fishway structures: pool-and-weir (attraction range = 29–100%, mean = 77%, median = 81%), vertical-slot (attraction range = 0–100%, mean = 63%, median = 80%), Denil (attraction range = 21–100%, mean = 61%, median = 57%) and nature-like (attraction range = 0–100%, mean = 48%, median = 50%). Mean passage efficiency was inversely related to mean attraction efficiency by fishway structure type, with the highest passage for nature-like fishways (range = 0–100%, mean = 70%, median = 86%), followed by Denil (range = 0–97%, mean = 51%, median = 38%), vertical-slot (range = 0–100%, mean = 45%, median = 43%) and pool-and-weir (range = 0–100%, mean = 40%, median = 34%). Principal components analysis and logistic regression modelling indicated that variation in fish attraction was driven by biological characteristics of the fish that were studied, whereas variation in fish passage was related to fishway type, slope and elevation change. This meta-analysis revealed that the species of fish monitored and structural design of the fishways have strong implications for both attraction and passage performance, and in most cases, existing data are not sufficient to support design recommendations. Many more fishway evaluations are needed over a range of species, fishway types and configurations to characterize, to optimize and to design new fishways. Furthermore, these studies must be performed in a consistent manner to identify the relative contributions of fish attraction and

  17. Conditionally Immortal Slc4a11-/- Mouse Corneal Endothelial Cell Line Recapitulates Disrupted Glutaminolysis Seen in Slc4a11-/- Mouse Model.

    PubMed

    Zhang, Wenlin; Ogando, Diego G; Kim, Edward T; Choi, Moon-Jung; Li, Hongde; Tenessen, Jason M; Bonanno, Joseph A

    2017-07-01

    To establish conditionally immortal mouse corneal endothelial cell lines with genetically matched Slc4a11+/+ and Slc4a11-/- mice as a model for investigating pathology and therapies for SLC4A11 associated congenital hereditary endothelial dystrophy (CHED) and Fuchs' endothelial corneal dystrophy. We intercrossed H-2Kb-tsA58 mice (Immortomouse) expressing an IFN-γ dependent and temperature-sensitive mutant of the SV40 large T antigen (tsTAg) with Slc4a11+/+ and Slc4a11-/- C57BL/6 mice. The growth characteristics of the cell lines was assessed by doubling time. Ion transport activities (Na+/H+ exchange, bicarbonate, lactate, and Slc4a11 ammonia transport) were analyzed by intracellular pH measurement. The metabolic status of the cell lines was assessed by analyzing TCA cycle intermediates via gas chromatography mass spectrometry (GC-MS). The immortalized Slc4a11+/+ and Slc4a11-/- mouse corneal endothelial cells (MCECs) remained proliferative through passage 49 and maintained similar active ion transport activity. As expected, proliferation was temperature sensitive and IFN-γ dependent. Slc4a11-/- MCECs exhibited decreased proliferative capacity, reduced NH3:H+ transport, altered expression of glutaminolysis enzymes similar to the Slc4a11-/- mouse, and reduced proportion of TCA cycle intermediates derived from glutamine with compensatory increases in glucose flux compared with Slc4a11+/+ MCECs. This is the first report of the immortalization of MCECs. Ion transport of the immortalized endothelial cells remains active, except for NH3:H+ transporter activity in Slc4a11-/- MCECs. Furthermore, Slc4a11-/- MCECs recapitulate the glutaminolysis defects observed in Slc4a11-/- mouse corneal endothelium, providing an excellent tool to study the pathogenesis of SLC4A11 mutations associated with corneal endothelial dystrophies and to screen potential therapeutic agents.

  18. Facilitating fish passage at ultra low head dams: An alternative to dam removal

    USGS Publications Warehouse

    Odeh, M.

    2004-01-01

    Ecosystem sustainability and returning the biological integrity to rivers continue to change the landscape of fish passage technology. Installing a conventional fishways has a limited degree of success in accommodating fish passage needs. Recently, the option of total dam removal has been gaining momentum among resource managers, conservationists, and even engineers. Certain dams, however, cannot be removed, and conventional fishways are either too expensive to build or the real estate is simply not available; yet freedom of passage must be attained. At the Little Falls Dam on the Potomac River a notch in the crest of the dam was installed to accommodate passage of fish. The notch has three labyrinth weirs used for energy dissipation. Water velocities are maintained at less than about 4 m/s anywhere within the passage structure during migratory season of the target species (American shad). Construction of this novel design was recently completed (March 2000) and future biological evaluations are ongoing. Copyright ASCE 2004.

  19. Effect of recombinant-LH and hCG in the absence of FSH on in vitro maturation (IVM) fertilization and early embryonic development of mouse germinal vesicle (GV)-stage oocytes.

    PubMed

    Dinopoulou, Vasiliki; Drakakis, Peter; Kefala, Stella; Kiapekou, Erasmia; Bletsa, Ritsa; Anagnostou, Elli; Kallianidis, Konstantinos; Loutradis, Dimitrios

    2016-06-01

    During in vitro maturation (IVM), intrinsic and extrinsic factors must co-operate properly in order to ensure cytoplasmic and nuclear maturation. We examined the possible effect of LH/hCG in the process of oocyte maturation in mice with the addition of recombinant LH (r-LH) and hCG in our IVM cultures of mouse germinal vesicle (GV)-stage oocytes. Moreover, the effects of these hormones on fertilization, early embryonic development and the expression of LH/hCG receptor were examined. Nuclear maturation of GV-stage oocytes was evaluated after culture in the presence of r-LH or hCG. Fertilization rates and embryonic development were assessed after 24h. Total RNA was isolated from oocytes of different stages of maturation and from zygotes and embryos of different stages of development in order to examine the expression of LH/hCG receptor, using RT-PCR. The in vitro nuclear maturation rate of GV-stage oocytes that received hCG was significantly higher compared to the control group. Early embryonic development was increased in the hCG and LH cultures of GV oocytes when LH was further added. The LH/hCG receptor was expressed in all stages of in vitro matured mouse oocytes and in every stage of early embryonic development. Addition of hCG in IVM cultures of mouse GV oocytes increased maturation rates significantly. LH, however, was more beneficial to early embryonic development than hCG. This suggests a promising new technique in basic science research or in clinical reproductive medicine. Copyright © 2016 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  20. Early social enrichment rescues adult behavioral and brain abnormalities in a mouse model of fragile X syndrome.

    PubMed

    Oddi, Diego; Subashi, Enejda; Middei, Silvia; Bellocchio, Luigi; Lemaire-Mayo, Valerie; Guzmán, Manuel; Crusio, Wim E; D'Amato, Francesca R; Pietropaolo, Susanna

    2015-03-13

    Converging lines of evidence support the use of environmental stimulation to ameliorate the symptoms of a variety of neurodevelopmental disorders. Applying these interventions at very early ages is critical to achieve a marked reduction of the pathological phenotypes. Here we evaluated the impact of early social enrichment in Fmr1-KO mice, a genetic mouse model of fragile X syndrome (FXS), a major developmental disorder and the most frequent monogenic cause of autism. Enrichment was achieved by providing male KO pups and their WT littermates with enhanced social stimulation, housing them from birth until weaning with the mother and an additional nonlactating female. At adulthood they were tested for locomotor, social, and cognitive abilities; furthermore, dendritic alterations were assessed in the hippocampus and amygdala, two brain regions known to be involved in the control of the examined behaviors and affected by spine pathology in Fmr1-KOs. Enrichment rescued the behavioral FXS-like deficits displayed in adulthood by Fmr1-KO mice, that is, hyperactivity, reduced social interactions, and cognitive deficits. Early social enrichment also eliminated the abnormalities shown by adult KO mice in the morphology of hippocampal and amygdala dendritic spines, namely an enhanced density of immature vs mature types. Importantly, enrichment did not induce neurobehavioral changes in WT mice, thus supporting specific effects on FXS-like pathology. These findings show that early environmental stimulation has profound and long-term beneficial effects on the pathological FXS phenotype, thereby encouraging the use of nonpharmacological interventions for the treatment of this and perhaps other neurodevelopmental diseases.

  1. Sensitivity of early mouse embryos to (/sup 3/H)thymidine

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

    Spindle, A.; Wu, K.; Pedersen, R.A.

    1982-12-01

    Effects of intranuclear radiation on the developmental capacity of early mouse embryos were studied by exposing embryos to (/sup 3/H)thymidine and counting the number of embryos forming blastocysts, trophoblast outgrowths, inner cell masses (ICMs), and two-layer ICMs (differentiated into primary endoderm and ectoderm). When embryos were cultured from the 2-cell stage for 8 days in the continuous presence of (/sup 3/H)thymidine, concentrations as low as 0.2 nCi/ml reduced the number of embryos forming two-layer ICMs. At 1 nCi/ml, the number of both ICMs and two-layer ICMs were reduced, and at 10 nCi/ml the number of embryos developing to all threemore » post-blastocyst endpoints was reduced. Blastocyst formation was not affected even at the highst concentration (/sup 3/H)thymidine and then cultured further in unlabelled medium, the effects were similar to those of 8-day exposure. When embryos were exposed to (/sup 3/H)thymidine for 24 h at various developmental stages, effects were less severe than when they were exposed continuously for 3 or 8 days, and the sensitivity of embryos differed between stages. The 24-h exposure of immunosurgically isolated ICMS to (/sup 3/H)thymidine revealed that the high sensitivity of the ICM to (/sup 3/H)thymidine persists through the late blastocyst stage and declines progressively thereafter. Autoradiography indicated that the change in radiosensitivity of embryos or ICMs is generally related to their ability to incorporate (/sup 3/H)thymidine into the DNA.« less

  2. Differentiation potential of STRO-1+ dental pulp stem cells changes during cell passaging.

    PubMed

    Yu, Jinhua; He, Huixia; Tang, Chunbo; Zhang, Guangdong; Li, Yuanfei; Wang, Ruoning; Shi, Junnan; Jin, Yan

    2010-05-08

    Dental pulp stem cells (DPSCs) can be driven into odontoblast, osteoblast, and chondrocyte lineages in different inductive media. However, the differentiation potential of naive DPSCs after serial passaging in the routine culture system has not been fully elucidated. DPSCs were isolated from human/rat dental pulps by the magnetic activated cell sorting based on STRO-1 expression, cultured and passaged in the conventional culture media. The biological features of STRO-1+ DPSCs at the 1st and 9th passages were investigated. During the long-term passage, the proliferation ability of human STRO-1+ DPSCs was downregulated as indicated by the growth kinetics. When compared with STRO-1+ DPSCs at the 1st passage (DPSC-P1), the expression of mature osteoblast-specific genes/proteins (alkaline phosphatase, bone sialoprotein, osterix, and osteopontin), odontoblast-specific gene/protein (dentin sialophosphoprotein and dentin sialoprotein), and chondrocyte-specific gene/protein (type II collagen) was significantly upregulated in human STRO-1+ DPSCs at the 9th passage (DPSC-P9). Furthermore, human DPSC-P9 cells in the mineralization-inducing media presented higher levels of alkaline phosphatase at day 3 and day 7 respectively, and produced more mineralized matrix than DPSC-P9 cells at day 14. In vivo transplantation results showed that rat DPSC-P1 cell pellets developed into dentin, bone and cartilage structures respectively, while DPSC-P9 cells can only generate bone tissues. These findings suggest that STRO-1+ DPSCs consist of several interrelated subpopulations which can spontaneously differentiate into odontoblasts, osteoblasts, and chondrocytes. The differentiation capacity of these DPSCs changes during cell passaging, and DPSCs at the 9th passage restrict their differentiation potential to the osteoblast lineage in vivo.

  3. Nonstructural Protein L* Species Specificity Supports a Mouse Origin for Vilyuisk Human Encephalitis Virus.

    PubMed

    Drappier, Melissa; Opperdoes, Fred R; Michiels, Thomas

    2017-07-15

    Vilyuisk human encephalitis virus (VHEV) is a picornavirus related to Theiler's murine encephalomyelitis virus (TMEV). VHEV was isolated from human material passaged in mice. Whether this VHEV is of human or mouse origin is therefore unclear. We took advantage of the species-specific activity of the nonstructural L* protein of theiloviruses to track the origin of TMEV isolates. TMEV L* inhibits RNase L, the effector enzyme of the interferon pathway. By using coimmunoprecipitation and functional RNase L assays, the species specificity of RNase L antagonism was tested for L* from mouse (DA) and rat (RTV-1) TMEV strains as well as for VHEV. Coimmunoprecipitation and functional assay data confirmed the species specificity of L* activity and showed that L* from rat strain RTV-1 inhibited rat but not mouse or human RNase L. Next, we showed that the VHEV L* protein was phylogenetically related to L* of mouse viruses and that it failed to inhibit human RNase L but readily antagonized mouse RNase L, unambiguously showing the mouse origin of VHEV. IMPORTANCE Defining the natural host of a virus can be a thorny issue, especially when the virus was isolated only once or when the isolation story is complex. The species Theilovirus includes Theiler's murine encephalomyelitis virus (TMEV), infecting mice and rats, and Saffold virus (SAFV), infecting humans. One TMEV strain, Vilyuisk human encephalitis virus (VHEV), however, was isolated from mice that were inoculated with cerebrospinal fluid of a patient presenting with chronic encephalitis. It is therefore unclear whether VHEV was derived from the human sample or from the inoculated mouse. The L* protein encoded by TMEV inhibits RNase L, a cellular enzyme involved in innate immunity, in a species-specific manner. Using binding and functional assays, we show that this species specificity even allows discrimination between TMEV strains of mouse and of rat origins. The VHEV L* protein clearly inhibited mouse but not human RNase L

  4. Heart valve cardiomyocytes of mouse embryos express the serotonin transporter SERT

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

    Pavone, Luigi Michele; Department of Biochemistry and Medical Biotechnologies, University of Naples Federico II, Naples; Spina, Anna

    2008-12-12

    Multiple evidence demonstrate a role for serotonin and its transporter SERT in heart valve development and disease. By utilizing a Cre/loxP system driven by SERT gene expression, we recently demonstrated a regionally restricted distribution of SERT-expressing cells in developing mouse heart. In order to characterize the cell types exhibiting SERT expression within the mouse heart valves at early developmental stages, in this study we performed immunohistochemistry for Islet1 (Isl1) and connexin-43 (Cx-43) on heart sections from SERT{sup Cre/+};ROSA26R embryos previously stained with X-gal. We observed the co-localization of LacZ staining with Isl1 labelling in the outflow tract, the right ventriclemore » and the conal region of E11.5 mouse heart. Cx-43 labelled cells co-localized with LacZ stained cells in the forming atrioventricular valves. These results demonstrate the cardiomyocyte phenotype of SERT-expressing cells in heart valves of the developing mouse heart, thus suggesting an active role of SERT in early heart valve development.« less

  5. "The caterpillar": a novel reading passage for assessment of motor speech disorders.

    PubMed

    Patel, Rupal; Connaghan, Kathryn; Franco, Diana; Edsall, Erika; Forgit, Dory; Olsen, Laura; Ramage, Lianna; Tyler, Emily; Russell, Scott

    2013-02-01

    A review of the salient characteristics of motor speech disorders and common assessment protocols revealed the need for a novel reading passage tailored specifically to differentiate between and among the dysarthrias (DYSs) and apraxia of speech (AOS). "The Caterpillar" passage was designed to provide a contemporary, easily read, contextual speech sample with specific tasks (e.g., prosodic contrasts, words of increasing length and complexity) targeted to inform the assessment of motor speech disorders. Twenty-two adults, 15 with DYS or AOS and 7 healthy controls (HC), were recorded reading "The Caterpillar" passage to demonstrate its utility in examining motor speech performance. Analysis of performance across a subset of segmental and prosodic variables illustrated that "The Caterpillar" passage showed promise for extracting individual profiles of impairment that could augment current assessment protocols and inform treatment planning in motor speech disorders.

  6. Enrichment of Female Germline Stem Cells from Mouse Ovaries Using the Differential Adhesion Method.

    PubMed

    Wu, Meng; Xiong, Jiaqiang; Ma, Lingwei; Lu, Zhiyong; Qin, Xian; Luo, Aiyue; Zhang, Jinjin; Xie, Huan; Shen, Wei; Wang, Shixuan

    2018-04-28

    The isolation and establishment of female germline stem cells (FGSCs) is controversial because of questions regarding the reliability and stability of the isolation method using antibody targeting mouse vasa homologue (MVH), and the molecular mechanism of FGSCs self-renewal remains unclear. Thus, there needs to be a simple and reliable method for sorting FGSCs to study them. We applied the differential adhesion method to enrich FGSCs (DA-FGSCs) from mouse ovaries. Through four rounds of purification and 7-9 subsequent passages, DA-FGSC lines were established. In addition, we assessed the role of the phosphoinositide-3 kinase (PI3K)-AKT pathway in regulating FGSC self-renewal. The obtained DA-FGSCs spontaneously differentiated into oocyte-like cells in vitro and formed functional eggs in vivo that were fertilized and produced healthy offspring. AKT was rapidly phosphorylated when the proliferation rate of FGSCs increased after 10 passages, and the addition of a chemical PI3K inhibitor prevented FGSCs self-renewal. Furthermore, over-expression of AKT-induced proliferation and differentiation of FGSCs, c-Myc, Oct-4 and Gdf-9 levels were increased. The differential adhesion method provides a more feasible approach and is an easier procedure to establish FGSC lines than traditional methods. The AKT pathway plays an important role in regulation of the proliferation and maintenance of FGSCs. These findings could help promote stem cell studies and provide a better understanding of causes of ovarian infertility, thereby providing potential treatments for infertility. © 2018 The Author(s). Published by S. Karger AG, Basel.

  7. Selective loss of mouse embryos due to the expression of transgenic major histocompatibility class I molecules early in embryogenesis.

    PubMed

    Aït-Azzouzene, D; Langkopf, A; Cohen, J; Bleux, C; Gendron, M C; Kanellopoulos-Langevin, C

    1998-05-01

    Among the numerous hypotheses proposed to explain the absence of fetal rejection by the mother in mammals, it has been suggested that regulation of expression of the polymorphic major histocompatibility complex (MHC) at the fetal-maternal interface plays a major role. In addition to a lack of MHC gene expression in the placenta throughout gestation, the absence of polymorphic MHC molecules on the early embryo, as well as their low level of expression after midgestation, could contribute to this important biologic phenomenon. In order to test this hypothesis, we have produced transgenic mice able to express polymorphic MHC class I molecules early in embryogenesis. We have placed the MHC class la gene H-2Kb under the control of a housekeeping gene promoter, the hydroxy-methyl-glutaryl coenzyme A reductase (HMG) gene minimal promoter. This construct has been tested for functionality after transfection into mouse fibroblast L cells. The analysis of three founder transgenic mice and their progeny suggested that fetoplacental units that could express the H-2Kb heavy chains are unable to survive in utero beyond midgestation. We have shown further that a much higher resorption rate, on days 11 to 13 of embryonic development, is observed among transgenic embryos developing from eggs microinjected at the one-cell stage with the pHMG-Kb construct than in control embryos. This lethality is not due to immune phenomena, since it is observed in histocompatible combinations between mother and fetus. These results are discussed in the context of what is currently known about the regulation of MHC expression at the fetal-maternal interface and in various transgenic mouse models.

  8. Mouse IDGenes: a reference database for genetic interactions in the developing mouse brain

    PubMed Central

    Matthes, Michaela; Preusse, Martin; Zhang, Jingzhong; Schechter, Julia; Mayer, Daniela; Lentes, Bernd; Theis, Fabian; Prakash, Nilima; Wurst, Wolfgang; Trümbach, Dietrich

    2014-01-01

    The study of developmental processes in the mouse and other vertebrates includes the understanding of patterning along the anterior–posterior, dorsal–ventral and medial– lateral axis. Specifically, neural development is also of great clinical relevance because several human neuropsychiatric disorders such as schizophrenia, autism disorders or drug addiction and also brain malformations are thought to have neurodevelopmental origins, i.e. pathogenesis initiates during childhood and adolescence. Impacts during early neurodevelopment might also predispose to late-onset neurodegenerative disorders, such as Parkinson’s disease. The neural tube develops from its precursor tissue, the neural plate, in a patterning process that is determined by compartmentalization into morphogenetic units, the action of local signaling centers and a well-defined and locally restricted expression of genes and their interactions. While public databases provide gene expression data with spatio-temporal resolution, they usually neglect the genetic interactions that govern neural development. Here, we introduce Mouse IDGenes, a reference database for genetic interactions in the developing mouse brain. The database is highly curated and offers detailed information about gene expressions and the genetic interactions at the developing mid-/hindbrain boundary. To showcase the predictive power of interaction data, we infer new Wnt/β-catenin target genes by machine learning and validate one of them experimentally. The database is updated regularly. Moreover, it can easily be extended by the research community. Mouse IDGenes will contribute as an important resource to the research on mouse brain development, not exclusively by offering data retrieval, but also by allowing data input. Database URL: http://mouseidgenes.helmholtz-muenchen.de. PMID:25145340

  9. Numerical Assessment of Four-Port Through-Flow Wave Rotor Cycles with Passage Height Variation

    NASA Technical Reports Server (NTRS)

    Paxson, D. E.; Lindau, Jules W.

    1997-01-01

    The potential for improved performance of wave rotor cycles through the use of passage height variation is examined. A Quasi-one-dimensional CFD code with experimentally validated loss models is used to determine the flowfield in the wave rotor passages. Results indicate that a carefully chosen passage height profile can produce substantial performance gains. Numerical performance data are presented for a specific profile, in a four-port, through-flow cycle design which yielded a computed 4.6% increase in design point pressure ratio over a comparably sized rotor with constant passage height. In a small gas turbine topping cycle application, this increased pressure ratio would reduce specific fuel consumption to 22% below the un-topped engine; a significant improvement over the already impressive 18% reductions predicted for the constant passage height rotor. The simulation code is briefly described. The method used to obtain rotor passage height profiles with enhanced performance is presented. Design and off-design results are shown using two different computational techniques. The paper concludes with some recommendations for further work.

  10. Animal models for studying neural crest development: is the mouse different?

    PubMed

    Barriga, Elias H; Trainor, Paul A; Bronner, Marianne; Mayor, Roberto

    2015-05-01

    The neural crest is a uniquely vertebrate cell type and has been well studied in a number of model systems. Zebrafish, Xenopus and chick embryos largely show consistent requirements for specific genes in early steps of neural crest development. By contrast, knockouts of homologous genes in the mouse often do not exhibit comparable early neural crest phenotypes. In this Spotlight article, we discuss these species-specific differences, suggest possible explanations for the divergent phenotypes in mouse and urge the community to consider these issues and the need for further research in complementary systems. © 2015. Published by The Company of Biologists Ltd.

  11. Mean first-passage times of non-Markovian random walkers in confinement.

    PubMed

    Guérin, T; Levernier, N; Bénichou, O; Voituriez, R

    2016-06-16

    The first-passage time, defined as the time a random walker takes to reach a target point in a confining domain, is a key quantity in the theory of stochastic processes. Its importance comes from its crucial role in quantifying the efficiency of processes as varied as diffusion-limited reactions, target search processes or the spread of diseases. Most methods of determining the properties of first-passage time in confined domains have been limited to Markovian (memoryless) processes. However, as soon as the random walker interacts with its environment, memory effects cannot be neglected: that is, the future motion of the random walker does not depend only on its current position, but also on its past trajectory. Examples of non-Markovian dynamics include single-file diffusion in narrow channels, or the motion of a tracer particle either attached to a polymeric chain or diffusing in simple or complex fluids such as nematics, dense soft colloids or viscoelastic solutions. Here we introduce an analytical approach to calculate, in the limit of a large confining volume, the mean first-passage time of a Gaussian non-Markovian random walker to a target. The non-Markovian features of the dynamics are encompassed by determining the statistical properties of the fictitious trajectory that the random walker would follow after the first-passage event takes place, which are shown to govern the first-passage time kinetics. This analysis is applicable to a broad range of stochastic processes, which may be correlated at long times. Our theoretical predictions are confirmed by numerical simulations for several examples of non-Markovian processes, including the case of fractional Brownian motion in one and higher dimensions. These results reveal, on the basis of Gaussian processes, the importance of memory effects in first-passage statistics of non-Markovian random walkers in confinement.

  12. Mean first-passage times of non-Markovian random walkers in confinement

    NASA Astrophysics Data System (ADS)

    Guérin, T.; Levernier, N.; Bénichou, O.; Voituriez, R.

    2016-06-01

    The first-passage time, defined as the time a random walker takes to reach a target point in a confining domain, is a key quantity in the theory of stochastic processes. Its importance comes from its crucial role in quantifying the efficiency of processes as varied as diffusion-limited reactions, target search processes or the spread of diseases. Most methods of determining the properties of first-passage time in confined domains have been limited to Markovian (memoryless) processes. However, as soon as the random walker interacts with its environment, memory effects cannot be neglected: that is, the future motion of the random walker does not depend only on its current position, but also on its past trajectory. Examples of non-Markovian dynamics include single-file diffusion in narrow channels, or the motion of a tracer particle either attached to a polymeric chain or diffusing in simple or complex fluids such as nematics, dense soft colloids or viscoelastic solutions. Here we introduce an analytical approach to calculate, in the limit of a large confining volume, the mean first-passage time of a Gaussian non-Markovian random walker to a target. The non-Markovian features of the dynamics are encompassed by determining the statistical properties of the fictitious trajectory that the random walker would follow after the first-passage event takes place, which are shown to govern the first-passage time kinetics. This analysis is applicable to a broad range of stochastic processes, which may be correlated at long times. Our theoretical predictions are confirmed by numerical simulations for several examples of non-Markovian processes, including the case of fractional Brownian motion in one and higher dimensions. These results reveal, on the basis of Gaussian processes, the importance of memory effects in first-passage statistics of non-Markovian random walkers in confinement.

  13. Factors for improved fish passage waterway construction.

    DOT National Transportation Integrated Search

    2011-06-01

    Streambeds are important fish passageways in Oregon; they provide for the necessary habitats and spawning cycles of a healthy fish population. Oregon state law requires that hydraulic structures located in water properly provide fish passage. Increas...

  14. Live dynamic imaging and analysis of developmental cardiac defects in mouse models with optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Lopez, Andrew L.; Wang, Shang; Garcia, Monica; Valladolid, Christian; Larin, Kirill V.; Larina, Irina V.

    2015-03-01

    Understanding mouse embryonic development is an invaluable resource for our interpretation of normal human embryology and congenital defects. Our research focuses on developing methods for live imaging and dynamic characterization of early embryonic development in mouse models of human diseases. Using multidisciplinary methods: optical coherence tomography (OCT), live mouse embryo manipulations and static embryo culture, molecular biology, advanced image processing and computational modeling we aim to understand developmental processes. We have developed an OCT based approach to image live early mouse embryos (E8.5 - E9.5) cultured on an imaging stage and visualize developmental events with a spatial resolution of a few micrometers (less than the size of an individual cell) and a frame rate of up to hundreds of frames per second and reconstruct cardiodynamics in 4D (3D+time). We are now using these methods to study how specific embryonic lethal mutations affect cardiac morphology and function during early development.

  15. Formation of Hyaline Cartilage Tissue by Passaged Human Osteoarthritic Chondrocytes.

    PubMed

    Bianchi, Vanessa J; Weber, Joanna F; Waldman, Stephen D; Backstein, David; Kandel, Rita A

    2017-02-01

    When serially passaged in standard monolayer culture to expand cell number, articular chondrocytes lose their phenotype. This results in the formation of fibrocartilage when they are used clinically, thus limiting their use for cartilage repair therapies. Identifying a way to redifferentiate these cells in vitro is critical if they are to be used successfully. Transforming growth factor beta (TGFβ) family members are known to be crucial for regulating differentiation of fetal limb mesenchymal cells and mesenchymal stromal cells to chondrocytes. As passaged chondrocytes acquire a progenitor-like phenotype, the hypothesis of this study was that TGFβ supplementation will stimulate chondrocyte redifferentiation in vitro in serum-free three-dimensional (3D) culture. Human articular chondrocytes were serially passaged twice (P2) in monolayer culture. P2 cells were then placed in high-density (3D) culture on top of membranes (Millipore) and cultured for up to 6 weeks in chemically defined serum-free redifferentiation media (SFRM) in the presence or absence of TGFβ. The tissues were evaluated histologically, biochemically, by immunohistochemical staining, and biomechanically. Passaged human chondrocytes cultured in SFRM supplemented with 10 ng/mL TGFβ3 consistently formed a continuous layer of articular-like cartilage tissue rich in collagen type 2 and aggrecan and lacking collagen type 1 and X in the absence of a scaffold. The tissue developed a superficial zone characterized by expression of lubricin and clusterin with horizontally aligned collagen fibers. This study suggests that passaged human chondrocytes can be used to bioengineer a continuous layer of articular cartilage-like tissue in vitro scaffold free. Further study is required to evaluate their ability to repair cartilage defects in vivo.

  16. [Hematological and immunological parameters during Ebola virus passages in guinea-pigs].

    PubMed

    Dadaeva, A A; Sizikova, L P; Subbotina, E L; Chepurnov, A A

    2006-01-01

    The trend in hematological and immunological parameters during Ebola virus passages in guinea-pigs indicated that pathophysiological changes occurred just during the second passage and further became stronger. The increase of some parameters and their correlation with the occurrence of fatal outcomes allowed the authors to reveal the most significant changes as increased juvenile platelets, whole blood virus appearance, higher echinocytes, a rise in the pro mil of blast cells and megakaryocytes in the bone marrow, and decreased neutrophilic phagocytic activity. Viral acquisition of the properties of lethality to guinea-pigs depends on the fine mechanisms responsible for viral interaction with host cells, which may lead to viral genetic changes during passages.

  17. Effect of Culture Conditions on Viability of Mouse and Rat Embryos Developed in Vitro

    PubMed Central

    Popova, Elena; Bader, Michael; Krivokharchenko, Alexander

    2011-01-01

    Currently in vitro culture of mouse preimplantation embryos has become a very important technique to investigate different mechanisms of early embryogenesis. However, there is a big difference in the preimplantation development between mammalian species. Despite close relatedness to mice, in vitro cultivation of rat preimplantation embryos is still delicate and needs further investigation and optimizations. In this study we have compared the in vitro developmental potential of mouse and rat embryos cultured at different culture conditions in parallel experiments. Interestingly, mouse zygotes developed in vitro until blastocyst stage even in inadequate medium without any phosphates and with low osmolarity which was formulated especially for cultivation of rat embryos. Rat parthenotes and zygotes developed in M16 medium formulated for mouse embryos only till 2-cell stage and further development is blocked completely at this stage. Moreover, developmental ability of rat embryos in vitro was significantly lower in comparison with mouse even in special rat mR1ECM medium. Mouse and rat embryos at 2-cell stage obtained in vivo developed until blastocyst stages significantly more efficiently compared to zygotes. Culture of mouse zygotes in glass capillaries resulted in a significantly higher rate of morula and blastocyst development compared with dishes. The Well-of-the-Well system resulted in a significant improvement when compared with dishes for the culture of rat zygotes only until morula stage. Reduced oxygen tension increased the developmental rate of rat but not mouse zygotes until blastocyst stage. This study demonstrates that development of early preimplantation embryos is altered by different culture conditions and show strong differences even between two related species such as mice and rats. Therefore, for understanding the fundamental mechanisms of early mammalian development it is very important to use embryos of various species. PMID:24710194

  18. Selection of attenuated dengue 4 viruses by serial passage in primary kidney cells. II. Attributes of virus cloned at different dog kidney passage levels.

    PubMed

    Halstead, S B; Marchette, N J; Diwan, A R; Palumbo, N E; Putvatana, R

    1984-07-01

    Uncloned dengue (DEN) 4 (H-241) which had been passaged 15, 30 and 50 times in primary dog kidney (PDK) cells were subjected to two successive terminal dilution procedures. In the first (3Cl), virus was diluted in 10-fold steps in 10 replicate tubes. An infected tube from a dilution row with three or fewer virus-infected tubes was selected for two further passages. In the second (TD3), virus was triple terminal diluted using 2-fold dilution steps and selecting one positive tube out of 10. Both procedures selected virus population which differed from antecedents. Plaque size of PDK 15 was medium, PDK 30, small and PDK 50, pin-point. PDK 19-3Cl were medium and 56-3Cl, 24-TD3, 35-TD3 and 61-TD3 were all small. All cloned virus replication was completely shut-off at 38.5 degrees C; PDK 15 and 30 continued to replicate at this temperature. Uncloned viruses showed a graduated decrease in monkey virulence with PDK passage; cloned viruses were either avirulent for monkeys (19-3Cl, 56-31Cl, 24-TD3 and 35-TD3) or produced revertant large plaque parental-type viremia (35-3Cl and 61-TD3). Those cloned viruses which exhibited temperature sensitivity, reduced monkey virulence and stability after monkey passage may be suitable as vaccine candidates for evaluation in human beings.

  19. Migratory delay leads to reduced passage success of Atlantic salmon smolts at a hydroelectric dam

    USGS Publications Warehouse

    Nyqvist, Daniel; Greenberg, L.; Goerig, E.; Calles, O.; Bergman, E.; Ardren, William R.; Castro-Santos, Theodore R.

    2017-01-01

    Passage of fish through hydropower dams is associated with mortality, delay, increased energy expenditure and migratory failure for migrating fish and the need for remedial measures for both upstream and downstream migration is widely recognised. A functional fish passage must ensure safe and timely passage routes that a substantial portion of migrating fish will use. Passage solutions must address not only the number or percentage of fish that successfully pass a barrier, but also the time it takes to pass. Here, we used radiotelemetry to study the functionality of a fish bypass for downstream-migrating wild-caught and hatchery-released Atlantic salmon smolts. We used time-to-event analysis to model the influence of fish characteristics and environmental variables on the rates of a series of events associated with dam passage. Among the modelled events were approach rate to the bypass entry zone, retention rates in both the forebay and the entry zone and passage rates. Despite repeated attempts, only 65% of the tagged fish present in the forebay passed the dam. Fish passed via the bypass (33%), via spill (18%) and via turbines (15%). Discharge was positively related to approach, passage and retention rates. We did not detect any differences between wild and hatchery fish. Even though individual fish visited the forebay and the entry zone on multiple occasions, most fish passed during the first exposures to these zones. This study underscores the importance of timeliness to passage success and the usefulness of time-to-event analysis for understanding factors governing passage performance.

  20. Computer mouse movement patterns: A potential marker of mild cognitive impairment.

    PubMed

    Seelye, Adriana; Hagler, Stuart; Mattek, Nora; Howieson, Diane B; Wild, Katherine; Dodge, Hiroko H; Kaye, Jeffrey A

    2015-12-01

    Subtle changes in cognitively demanding activities occur in MCI but are difficult to assess with conventional methods. In an exploratory study, we examined whether patterns of computer mouse movements obtained from routine home computer use discriminated between older adults with and without MCI. Participants were 42 cognitively intact and 20 older adults with MCI enrolled in a longitudinal study of in-home monitoring technologies. Mouse pointer movement variables were computed during one week of routine home computer use using algorithms that identified and characterized mouse movements within each computer use session. MCI was associated with making significantly fewer total mouse moves ( p <.01), and making mouse movements that were more variable, less efficient, and with longer pauses between movements ( p <.05). Mouse movement measures were significantly associated with several cognitive domains ( p 's<.01-.05). Remotely monitored computer mouse movement patterns are a potential early marker of real-world cognitive changes in MCI.

  1. mRNA expression pattern of selected candidate genes differs in bovine oviductal epithelial cells in vitro compared with the in vivo state and during cell culture passages.

    PubMed

    Danesh Mesgaran, Sadjad; Sharbati, Jutta; Einspanier, Ralf; Gabler, Christoph

    2016-08-15

    The mammalian oviduct provides the optimal environment for gamete maturation including sperm capacitation, fertilization, and development of the early embryo. Various cell culture models for primary bovine oviductal epithelial cells (BOEC) were established to reveal such physiological events. The aim of this study was to evaluate 17 candidate mRNA expression patterns in oviductal epithelial cells (1) in transition from in vivo cells to in vitro cells; (2) during three consecutive cell culture passages; (3) affected by the impact of LOW or HIGH glucose content media; and (4) influenced by different phases of the estrous cycle in vivo and in vitro. In addition, the release of a metabolite and proteins from BOEC at two distinct cell culture passage numbers was estimated to monitor the functionality. BOEC from 8 animals were isolated and cultured for three consecutive passages. Total RNA was extracted from in vivo and in vitro samples and subjected to reverse transcription quantitative polymerase chain reaction to reveal mRNA expression of selected candidate genes. The release of prostaglandin E2 (PGE2), oviduct-specific glycoprotein 1 (OVGP1) and interleukin 8 (IL8) by BOEC was measured by EIA or ELISA after 24 h. Almost all candidate genes (prostaglandin synthases, enzymes of cellular metabolism and mucins) mRNA expression pattern differed compared in vivo with in vitro state. In addition, transcription of most candidate genes was influenced by the number of cell culture passages. Different glucose medium content did not affect mRNA expression of most candidate genes. The phase of the estrous cycle altered some candidate mRNA expression in BOEC in vitro at later passages. The release of PGE2 and OVGP1 between passages did not differ. However, BOEC in passage 3 released significantly higher amount of IL8 compared with cells in passage 0. This study supports the hypothesis that candidate mRNA expression in BOEC was influenced by transition from the in vivo situation

  2. Crossing the Threshold Mindfully: Exploring Rites of Passage Models in Adventure Therapy

    ERIC Educational Resources Information Center

    Norris, Julian

    2011-01-01

    Rites of passage models, drawing from ethnographic descriptions of ritualized transition, are widespread in adventure therapy programmes. However, critical literature suggests that: (a) contemporary rites of passage models derive from a selective and sometimes misleading use of ethnographic materials, and (b) the appropriation of initiatory…

  3. Position- and Hippo signaling-dependent plasticity during lineage segregation in the early mouse embryo

    PubMed Central

    Posfai, Eszter; Petropoulos, Sophie; de Barros, Flavia Regina Oliveira; Schell, John Paul; Jurisica, Igor; Sandberg, Rickard; Lanner, Fredrik; Rossant, Janet

    2017-01-01

    The segregation of the trophectoderm (TE) from the inner cell mass (ICM) in the mouse blastocyst is determined by position-dependent Hippo signaling. However, the window of responsiveness to Hippo signaling, the exact timing of lineage commitment and the overall relationship between cell commitment and global gene expression changes are still unclear. Single-cell RNA sequencing during lineage segregation revealed that the TE transcriptional profile stabilizes earlier than the ICM and prior to blastocyst formation. Using quantitative Cdx2-eGFP expression as a readout of Hippo signaling activity, we assessed the experimental potential of individual blastomeres based on their level of Cdx2-eGFP expression and correlated potential with gene expression dynamics. We find that TE specification and commitment coincide and occur at the time of transcriptional stabilization, whereas ICM cells still retain the ability to regenerate TE up to the early blastocyst stage. Plasticity of both lineages is coincident with their window of sensitivity to Hippo signaling. DOI: http://dx.doi.org/10.7554/eLife.22906.001 PMID:28226240

  4. Is motivation important to brook trout passage through culverts?

    USGS Publications Warehouse

    Goerig, Elsa; Castro-Santos, Theodore R.

    2017-01-01

    Culverts can restrict movement of stream-dwelling fish. Motivation to enter and ascend these structures is an essential precursor for successful passage. However, motivation is challenging to quantify. Here, we use attempt rate to assess motivation of 447 brook trout (Salvelinus fontinalis) entering three culverts under a range of hydraulic, environmental, and biological conditions. A passive integrated transponder system allowed for the identification of passage attempts and success of individual fish. Attempt rate was quantified using time-to-event analysis allowing for time-varying covariates and recurrent events. Attempt rate was greatest during the spawning period, at elevated discharge, at dusk, and for longer fish. It decreased during the day and with increasing number of conspecifics downstream of the culvert. Results also show a positive correlation between elevated motivation and successful passage. This study enhances understanding of factors influencing brook trout motivation to ascend culverts and shows that attempt rate is a dynamic phenomenon, variable over time and among individuals. It also presents methods that could be used to investigate other species’ motivation to pass natural or anthropogenic barriers.

  5. Fish passage through retrofitted culverts : final report.

    DOT National Transportation Integrated Search

    2004-11-01

    Long term and short term studies of fish movement were conducted at several retrofitted culverts within Oregon. This was done to assess the effectiveness of retrofitting culverts with baffles to improve fish passage. The long term results showed that...

  6. Characterisation of the dynamic behaviour of lipid droplets in the early mouse embryo using adaptive harmonic generation microscopy.

    PubMed

    Watanabe, Tomoko; Thayil, Anisha; Jesacher, Alexander; Grieve, Kate; Debarre, Delphine; Wilson, Tony; Booth, Martin; Srinivas, Shankar

    2010-06-03

    Lipid droplets (LD) are organelles with an important role in normal metabolism and disease. The lipid content of embryos has a major impact on viability and development. LD in Drosophila embryos and cultured cell lines have been shown to move and fuse in a microtubule dependent manner. Due to limitations in current imaging technology, little is known about the behaviour of LD in the mammalian embryo. Harmonic generation microscopy (HGM) allows one to image LD without the use of exogenous labels. Adaptive optics can be used to correct aberrations that would otherwise degrade the quality and information content of images. We have built a harmonic generation microscope with adaptive optics to characterise early mouse embryogenesis. At fertilization, LD are small and uniformly distributed, but in the implanting blastocyst, LD are larger and enriched in the invading giant cells of the trophectoderm. Time-lapse studies reveal that LD move continuously and collide but do not fuse, instead forming aggregates that subsequently behave as single units. Using specific inhibitors, we show that the velocity and dynamic behaviour of LD is dependent not only on microtubules as in other systems, but also on microfilaments. We explore the limits within which HGM can be used to study living embryos without compromising viability and make the counterintuitive finding that 16 J of energy delivered continuously over a period of minutes can be less deleterious than an order of magnitude lower energy delivered dis-continuously over a period of hours. LD in pre-implantation mouse embryos show a previously unappreciated complexity of behaviour that is dependent not only on microtubules, but also microfilaments. Unlike LD in other systems, LD in the mouse embryo do not fuse but form aggregates. This study establishes HGM with adaptive optics as a powerful tool for the study of LD biology and provides insights into the photo-toxic effects of imaging embryos.

  7. RBP-Jkappa-dependent notch signaling is dispensable for mouse early embryonic development.

    PubMed

    Souilhol, Céline; Cormier, Sarah; Tanigaki, Kenji; Babinet, Charles; Cohen-Tannoudji, Michel

    2006-07-01

    The Notch signaling pathway is an evolutionarily conserved signaling system which has been shown to be essential in cell fate specification and in numerous aspects of embryonic development in all metazoans thus far studied. We recently demonstrated that several components of the Notch signaling pathway, including the four Notch receptors and their five ligands known in mammals, are expressed in mouse oocytes, in mouse preimplantation embryos, or both. This suggested a possible implication of the Notch pathway in the first cell fate specification of the dividing mouse embryo, which results in the formation of the blastocyst. To address this issue directly, we generated zygotes in which both the maternal and the zygotic expression of Rbpsuh, a key element of the core Notch signaling pathway, were abrogated. We find that such zygotes give rise to blastocysts which implant and develop normally. Nevertheless, after gastrulation, these embryos die around midgestation, similarly to Rbpsuh-null mutants. This demonstrates that the RBP-Jkappa-dependent pathway, otherwise called the canonical Notch pathway, is dispensable for blastocyst morphogenesis and the establishment of the three germ layers, ectoderm, endoderm, and mesoderm. These results are discussed in the light of recent observations which have challenged this conclusion.

  8. 75 FR 60804 - Nimbus Hatchery Fish Passage Project, Lower American River, California

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-01

    ... DEPARTMENT OF THE INTERIOR Bureau of Reclamation Nimbus Hatchery Fish Passage Project, Lower... Act (CEQA), the Bureau of Reclamation, the lead Federal agency, and the California Department of Fish... Draft EIS/EIR for the Nimbus Hatchery Fish Passage Project (Project). The purpose of the Project is to...

  9. Scaling properties and universality of first-passage-time probabilities in financial markets

    NASA Astrophysics Data System (ADS)

    Perelló, Josep; Gutiérrez-Roig, Mario; Masoliver, Jaume

    2011-12-01

    Financial markets provide an ideal frame for the study of crossing or first-passage time events of non-Gaussian correlated dynamics, mainly because large data sets are available. Tick-by-tick data of six futures markets are herein considered, resulting in fat-tailed first-passage time probabilities. The scaling of the return with its standard deviation collapses the probabilities of all markets examined—and also for different time horizons—into single curves, suggesting that first-passage statistics is market independent (at least for high-frequency data). On the other hand, a very closely related quantity, the survival probability, shows, away from the center and tails of the distribution, a hyperbolic t-1/2 decay typical of a Markovian dynamics, albeit the existence of memory in markets. Modifications of the Weibull and Student distributions are good candidates for the phenomenological description of first-passage time properties under certain regimes. The scaling strategies shown may be useful for risk control and algorithmic trading.

  10. Sherlock Holmes and the strange case of the missing attribution: a historical note on "The Grandfather Passage".

    PubMed

    Reilly, Jamie; Fisher, Jamie L

    2012-02-01

    In 1963, Charles Van Riper published "My Grandfather," a short reading passage that has evolved into a ubiquitous metric of reading ability and speech intelligibility. In this historical note, we describe several heretofore unacknowledged similarities between "The Grandfather Passage" (Darley, Aronson, & Brown, 1975) and a portion of The Valley of Fear (Conan Doyle, 1915/2006), the final novel of the Sherlock Holmes series. We also describe overlap between "My Grandfather" and "The Grandfather Passage." We contrasted propositions within The Valley of Fear to "My Grandfather" and "The Grandfather Passage." We also compared the respective text strings using the Turnitin antiplagiarism software application (iParadigms, 2011). "My Grandfather" and "The Grandfather Passage" are nearly identical passages with 88% string overlap. In addition, both passages show similarities with text from The Valley of Fear. Darley et al. (1975) did not acknowledge Van Riper (1963) as the original author of "The Grandfather Passage." In addition to this citation oversight, neither Darley et al. nor Van Riper attributed Conan Doyle as original source material. We describe the colorful history of this passage that has seen a remarkable breadth of utility in speech and language sciences.

  11. Northwest passage: Trade route for large air cushion vehicles

    NASA Technical Reports Server (NTRS)

    Anderson, J. L.

    1973-01-01

    A conceptual vehicle and powerplant (10,000-ton) nuclear-powered air-cushion vehicle (ACV) that could open the Northwest Passage and other Arctic passages to commercial traffic is identified. The report contains a description of the conceptual vehicle, including the powerplant and operations, an assessment of technical feasibility, estimates of capital and operating costs, and identification of eligible cargo and markets. A comparison of the nuclear ACV freighter with nuclear container ships shows that for containerized or roll-on/roll-off cargo the ACV would provide greatly reduced transit time between North Atlantic and North Pacific ports at a competitive cost.

  12. Subchronic Glucocorticoid Receptor Inhibition Rescues Early Episodic Memory and Synaptic Plasticity Deficits in a Mouse Model of Alzheimer's Disease

    PubMed Central

    Lanté, Fabien; Chafai, Magda; Raymond, Elisabeth Fabienne; Salgueiro Pereira, Ana Rita; Mouska, Xavier; Kootar, Scherazad; Barik, Jacques; Bethus, Ingrid; Marie, Hélène

    2015-01-01

    The early phase of Alzheimer's disease (AD) is characterized by hippocampus-dependent memory deficits and impaired synaptic plasticity. Increasing evidence suggests that stress and dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis, marked by the elevated circulating glucocorticoids, are risk factors for AD onset. How these changes contribute to early hippocampal dysfunction remains unclear. Using an elaborated version of the object recognition task, we carefully monitored alterations in key components of episodic memory, the first type of memory altered in AD patients, in early symptomatic Tg2576 AD mice. We also combined biochemical and ex vivo electrophysiological analyses to reveal novel cellular and molecular dysregulations underpinning the onset of the pathology. We show that HPA axis, circadian rhythm, and feedback mechanisms, as well as episodic memory, are compromised in this early symptomatic phase, reminiscent of human AD pathology. The cognitive decline could be rescued by subchronic in vivo treatment with RU486, a glucocorticoid receptor antagonist. These observed phenotypes were paralleled by a specific enhancement of N-Methyl-D-aspartic acid receptor (NMDAR)-dependent LTD in CA1 pyramidal neurons, whereas LTP and metabotropic glutamate receptor-dependent LTD remain unchanged. NMDAR transmission was also enhanced. Finally, we show that, as for the behavioral deficit, RU486 treatment rescues this abnormal synaptic phenotype. These preclinical results define glucocorticoid signaling as a contributing factor to both episodic memory loss and early synaptic failure in this AD mouse model, and suggest that glucocorticoid receptor targeting strategies could be beneficial to delay AD onset. PMID:25622751

  13. Amnesia in an actor: Learning and re-learning of play passages despite severe autobiographical amnesia.

    PubMed

    Kopelman, Michael D; Morton, John

    2015-06-01

    We describe the case of an accomplished actor, whom we term AB, who suffered severe amnesia following a cardiac arrest and hypoxic brain damage, affecting medial temporal and thalamic structures. His performance on standard episodic memory tests, and on measures of retrograde amnesia, including autobiographical memory, was severely impaired. When presented with passages from plays he had not appeared in, AB showed a severe impairment at the first learning trial, but thereafter showed a 'normal' learning curve for this semantically and syntactically complex material. On being presented with passages from plays he had performed in the past, AB did not show any recognition of them whatsoever, as one might expect from his severe episodic memory impairment. However, AB showed a striking benefit (savings score) in relearning passages he had previously performed, compared with new passages, despite not having any autobiographical recall of having performed the relearned passages before. Moreover, although his initial recall performance in learning these passages was impaired compared with healthy control actors of similar age and experience, AB demonstrated the same incremental learning rate on subsequent learning trials of the passages as did the controls. We conclude that, although severely impaired at the first learning trial (on both 'new' and 'old' passages), AB was able to employ his long-established semantic and procedural skills to attempt the task, and that thereafter he showed a 'normal' rate of incremental learning from a lower baseline. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  14. Statistical Analysis of the First Passage Path Ensemble of Jump Processes

    NASA Astrophysics Data System (ADS)

    von Kleist, Max; Schütte, Christof; Zhang, Wei

    2018-02-01

    The transition mechanism of jump processes between two different subsets in state space reveals important dynamical information of the processes and therefore has attracted considerable attention in the past years. In this paper, we study the first passage path ensemble of both discrete-time and continuous-time jump processes on a finite state space. The main approach is to divide each first passage path into nonreactive and reactive segments and to study them separately. The analysis can be applied to jump processes which are non-ergodic, as well as continuous-time jump processes where the waiting time distributions are non-exponential. In the particular case that the jump processes are both Markovian and ergodic, our analysis elucidates the relations between the study of the first passage paths and the study of the transition paths in transition path theory. We provide algorithms to numerically compute statistics of the first passage path ensemble. The computational complexity of these algorithms scales with the complexity of solving a linear system, for which efficient methods are available. Several examples demonstrate the wide applicability of the derived results across research areas.

  15. Mouse IDGenes: a reference database for genetic interactions in the developing mouse brain.

    PubMed

    Matthes, Michaela; Preusse, Martin; Zhang, Jingzhong; Schechter, Julia; Mayer, Daniela; Lentes, Bernd; Theis, Fabian; Prakash, Nilima; Wurst, Wolfgang; Trümbach, Dietrich

    2014-01-01

    The study of developmental processes in the mouse and other vertebrates includes the understanding of patterning along the anterior-posterior, dorsal-ventral and medial- lateral axis. Specifically, neural development is also of great clinical relevance because several human neuropsychiatric disorders such as schizophrenia, autism disorders or drug addiction and also brain malformations are thought to have neurodevelopmental origins, i.e. pathogenesis initiates during childhood and adolescence. Impacts during early neurodevelopment might also predispose to late-onset neurodegenerative disorders, such as Parkinson's disease. The neural tube develops from its precursor tissue, the neural plate, in a patterning process that is determined by compartmentalization into morphogenetic units, the action of local signaling centers and a well-defined and locally restricted expression of genes and their interactions. While public databases provide gene expression data with spatio-temporal resolution, they usually neglect the genetic interactions that govern neural development. Here, we introduce Mouse IDGenes, a reference database for genetic interactions in the developing mouse brain. The database is highly curated and offers detailed information about gene expressions and the genetic interactions at the developing mid-/hindbrain boundary. To showcase the predictive power of interaction data, we infer new Wnt/β-catenin target genes by machine learning and validate one of them experimentally. The database is updated regularly. Moreover, it can easily be extended by the research community. Mouse IDGenes will contribute as an important resource to the research on mouse brain development, not exclusively by offering data retrieval, but also by allowing data input. http://mouseidgenes.helmholtz-muenchen.de. © The Author(s) 2014. Published by Oxford University Press.

  16. White sturgeon (Acipenser transmontanus) passage at the Dalles Dam, Columbia River, USA

    USGS Publications Warehouse

    Parsley, M.J.; Wright, C.D.; Van Der Leeuw, B. K.; Kofoot, E.E.; Peery, C.A.; Moser, M.L.

    2007-01-01

    White sturgeon (Acipenser transmontanus) ???95 cm TL were monitored using acoustic and radio telemetry at a large hydroelectric dam (the Dalles Dam) on the Columbia River, during March 2004 through November 2005 to determine timing and routes of passage and to characterize general movements. Transmitters were surgically implanted into 148 fish during the study; 90 were released into the tailrace and 58 into the forebay. We documented 26 passage events by 19 tagged fish: eight upstream via fish ladders and 18 downstream, mostly through open spill gates. During the study 17 fish entered the two ladders one or more times; 11 entered only the east ladder, three entered only the north ladder, and three entered both ladders at sometime. Residence time within the ladders by individual fish was variable, ranging from about 1 min to nearly 6 months (median = 7.7 h). Only six fish successfully ascended the east ladder, one fish twice. We could not unequivocally determine which fish ladder one fish used to pass upstream. Differences in construction between the north and east fish ladders may account for the greater success of the east fish ladder in passing sturgeon upstream. Changes to operations at hydroelectric dams to benefit migrating anadromous salmonids may influence upstream or downstream passage by white sturgeon. Altering patterns and timing of spill discharge, altering fish ladder entrance attraction flows, and the use of lights, sound, and partial barriers to direct other species of fish to preferred passage routes have unknown effects on sturgeon passage. A better understanding of the consequences to the metapopulation of increasing or precluding upstream or downstream passage is needed. ?? 2007 The Authors.

  17. Positive and negative early life experiences differentially modulate long term survival and amyloid protein levels in a mouse model of Alzheimer's disease.

    PubMed

    Lesuis, Sylvie L; Maurin, Herve; Borghgraef, Peter; Lucassen, Paul J; Van Leuven, Fred; Krugers, Harm J

    2016-06-28

    Stress has been implicated as a risk factor for the severity and progression of sporadic Alzheimer's disease (AD). Early life experiences determine stress responsivity in later life, and modulate age-dependent cognitive decline. Therefore, we examined whether early life experiences influence AD outcome in a bigenic mouse model which progressively develops combined tau and amyloid pathology (biAT mice).Mice were subjected to either early life stress (ELS) or to 'positive' early handling (EH) postnatally (from day 2 to 9). In biAT mice, ELS significantly compromised long term survival, in contrast to EH which increased life expectancy. In 4 month old mice, ELS-reared biAT mice displayed increased hippocampal Aβ levels, while these levels were reduced in EH-reared biAT mice. No effects of ELS or EH were observed on the brain levels of APP, protein tau, or PSD-95. Dendritic morphology was moderately affected after ELS and EH in the amygdala and medial prefrontal cortex, while object recognition memory and open field performance were not affected. We conclude that despite the strong transgenic background, early life experiences significantly modulate the life expectancy of biAT mice. Parallel changes in hippocampal Aβ levels were evident, without affecting cognition of young adult biAT mice.

  18. Relation between Streamflow of Swiftcurrent Creek, Montana, and the Geometry of Passage for Bull Trout (Salvelinus confluentus)

    USGS Publications Warehouse

    Auble, Gregor T.; Holmquist-Johnson, Christopher L.; Mogen, Jim T.; Kaeding, Lynn R.; Bowen, Zachary H.

    2009-01-01

    Operation of Sherburne Dam in northcentral Montana has typically reduced winter streamflow in Swiftcurrent Creek downstream of the dam and resulted in passage limitations for bull trout (Salvelinus confluentus). We defined an empirical relation between discharge in Swiftcurrent Creek between Sherburne Dam and the downstream confluence with Boulder Creek and fish passage geometry by considering how the cross-sectional area of water changed as a function of discharge at a set of cross sections likely to limit fish passage. With a minimum passage window of 15 x 45 cm, passage at the cross sections increased strongly with discharge over the range of 1.2 to 24 cfs. Most cross sections did not satisfy the minimum criteria at 1.2 cfs, 25 percent had no passage at 12.7 cfs, whereas at 24 cfs all but one of 26 cross sections had some passage and 90 percent had more than 3 m of width satisfying the minimum criteria. Sensitivity analysis suggests that the overall results are not highly dependent on exact dimensions of the minimum passage window. Combining these results with estimates of natural streamflow in the study reach further suggests that natural streamflow provided adequate passage at some times in most months and locations in the study reach, although not for all individual days and locations. Limitations of our analysis include assumptions about minimum passage geometry, measurement error, limitations of the cross-sectional model we used to characterize passage, the relation of Sherburne Dam releases to streamflow in the downstream study reach in the presence of ephemeral accretions, and the relation of passage geometry as we have measured it to fish responses of movement, stranding, and mortality, especially in the presence of ice cover.

  19. Effects of Repeated Reading and Listening Passage Preview on Oral Reading Fluency

    ERIC Educational Resources Information Center

    Swain, Kristine D.; Leader-Janssen, Elizabeth M.; Conley, Perry

    2017-01-01

    This case study examined the effectiveness of three fluency interventions (i.e., repeated reading, audio listening passage preview and teacher modeled listening passage preview) with a fifth grade student struggling with fluency skills. When compared to baseline, each intervention increased oral reading fluency by the end of the 7 weeks of…

  20. "The Caterpillar": A Novel Reading Passage for Assessment of Motor Speech Disorders

    ERIC Educational Resources Information Center

    Patel, Rupal; Connaghan, Kathryn; Franco, Diana; Edsall, Erika; Forgit, Dory; Olsen, Laura; Ramage, Lianna; Tyler, Emily; Russell, Scott

    2013-01-01

    Purpose: A review of the salient characteristics of motor speech disorders and common assessment protocols revealed the need for a novel reading passage tailored specifically to differentiate between and among the dysarthrias (DYSs) and apraxia of speech (AOS). Method: "The Caterpillar" passage was designed to provide a contemporary, easily read,…

  1. Neutron Imaging for Selective Laser Melting Inconel Hardware with Internal Passages

    NASA Technical Reports Server (NTRS)

    Tramel, Terri L.; Norwood, Joseph K.; Bilheux, Hassina

    2014-01-01

    Additive Manufacturing is showing great promise for the development of new innovative designs and large potential life cycle cost reduction for the Aerospace Industry. However, more development work is required to move this technology into space flight hardware production. With selective laser melting (SLM), hardware that once consisted of multiple, carefully machined and inspected pieces, joined together can be made in one part. However standard inspection techniques cannot be used to verify that the internal passages are within dimensional tolerances or surface finish requirements. NASA/MSFC traveled to Oak Ridge National Lab's (ORNL) Spallation Neutron Source to perform some non-destructive, proof of concept imaging measurements to assess the capabilities to understand internal dimensional tolerances and internal passages surface roughness. This presentation will describe 1) the goals of this proof of concept testing, 2) the lessons learned when designing and building these Inconel 718 test specimens to minimize beam time, 3) the neutron imaging test setup and test procedure to get the images, 4) the initial results in images, volume and a video, 4) the assessment of using this imaging technique to gather real data for designing internal flow passages in SLM manufacturing aerospace hardware, and lastly 5) how proper cleaning of the internal passages is critically important. In summary, the initial results are very promising and continued development of a technique to assist in SLM development for aerospace components is desired by both NASA and ORNL. A plan forward that benefits both ORNL and NASA will also be presented, based on the promising initial results. The initial images and volume reconstruction showed that clean, clear images of the internal passages geometry are obtainable. These clear images of the internal passages of simple geometries will be compared to the build model to determine any differences. One surprising result was that a new cleaning

  2. Reproductive changes in fluctuating house mouse populations in southeastern Australia.

    PubMed

    Singleton, G; Krebs, C J; Davis, S; Chambers, L; Brown, P

    2001-08-22

    House mice (Mus domesticus) in the Victorian mallee region of southeastern Australia show irregular outbreaks. Changes in reproductive output that could potentially drive changes in mouse numbers were assessed from 1982 to 2000. Litter size in females is positively correlated with body size. When standardized to an average size female, litter size changes seasonally from highest in spring to lowest in autumn and winter. Litter size is depressed throughout breeding seasons that begin when the abundance of mice is high, but is similar in breeding seasons over which the abundance of mice increases rapidly or remains low. Breeding begins early and is extended on average by about five weeks during seasons when mouse abundance increases rapidly. The size at which females begin to reproduce is larger during breeding seasons that begin when mouse abundance is high. An extended breeding season that begins early in spring is necessary for the generation of a house mouse plague, but it is not in itself sufficient. Reproductive changes in outbreaks of house mice in Australia are similar but not identical to reproductive changes that accompany rodent population increases in the Northern Hemisphere. We conclude that food quality, particularly protein, is a probable mechanism driving these reproductive changes, but experimental evidence for field populations is conflicting.

  3. Stemness and angiogenic gene expression changes of serial-passage human amnion mesenchymal cells.

    PubMed

    Fatimah, Simat Siti; Tan, Geok Chin; Chua, Kienhui; Fariha, Mohd Manzor Nur; Tan, Ay Eeng; Hayati, Abdul Rahman

    2013-03-01

    Particular attention has been directed towards human amnion mesenchymal stem cells (HAMCs) due to their accessibility, availability and immunomodulatory properties. Therefore, the aim of the present study was to determine the temporal changes of stemness and angiogenic gene expressions of serial-passage HAMCs. HAMCs were isolated from human term placenta and cultured in serial passages in culture medium supplemented with 10% fetal bovine serum. Morphological analysis, growth kinetic and CFU-F assay of HAMCs were assessed. In vitro differentiation and the immunophenotype of HAMCs at P5 were also analyzed. Quantitative PCR was used to determine the stemness, angiogenic and endothelial gene expression of cultured HAMCs after serial passage. Cultured HAMCs displayed intermediate epitheloid-fibroblastoid morphology at an initial culture and the fibroblastoid features became more pronounced in later passages. They showed high clonogenic activity and faster proliferation at later passages with colony forming efficiency of 0.88%. HAMCs were successfully differentiated into adipocytes, osteocytes and neuron-like cells. Most HAMCs expressed CD9, CD44, CD73, CD90 and HLA-A,B,C but negligibly expressed CD31, CD34, CD45, CD117 and HLA-DR,DP,DQ. After serial passage, stemness genes Oct-3/4, Sox-2, Nanog3, Rex-1, FGF-4 and FZD-9 expressions significantly decreased. Of the angiogenic genes PECAM-1, bFGF, eNOS, VEGFR-2, VEGF, and vWF expressions also decreased significantly except angiopoietin-1 which significantly increased. No significant differences were observed in ABCG-2, BST-1, nestin, PGF and HGF expressions after serial passage. These results suggested that cultured HAMCs could be an alternative source of stem cells and may have the potential for angiogenesis and hence its use in stem-cell based therapy. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Vortex-generating coolant-flow-passage design for increased film-cooling effectiveness and surface coverage

    NASA Astrophysics Data System (ADS)

    Papell, S. S.

    1984-11-01

    The thermal film-cooling footprints observed by infrared imagery for three coolant-passage configurations embedded in adiabatic-test plates are discussed. The configurations included a standard round-hole cross section and two orientations of a vortex-generating flow passage. Both orientations showed up to factors of four increases in both film-cooling effectiveness and surface coverage over that obtained with the round coolant passage. The crossflow data covered a range of tunnel velocities from 15.5 to 45 m/sec with blowing rates from 0.20 to 2.05. A photographic streakline flow visualization technique supported the concept of the counterrotating apability of the flow passage design and gave visual credence to its role in inhibiting flow separation.

  5. Vortex-generating coolant-flow-passage design for increased film-cooling effectiveness and surface coverage

    NASA Technical Reports Server (NTRS)

    Papell, S. S.

    1984-01-01

    The thermal film-cooling footprints observed by infrared imagery for three coolant-passage configurations embedded in adiabatic-test plates are discussed. The configurations included a standard round-hole cross section and two orientations of a vortex-generating flow passage. Both orientations showed up to factors of four increases in both film-cooling effectiveness and surface coverage over that obtained with the round coolant passage. The crossflow data covered a range of tunnel velocities from 15.5 to 45 m/sec with blowing rates from 0.20 to 2.05. A photographic streakline flow visualization technique supported the concept of the counterrotating apability of the flow passage design and gave visual credence to its role in inhibiting flow separation.

  6. Vortex generating flow passage design for increased film-cooling effectiveness and surface coverage

    NASA Astrophysics Data System (ADS)

    Papell, S. S.

    The fluid mechanics of the basic discrete hole film cooling process is described as an inclined jet in crossflow and a cusp shaped coolant flow channel contour that increases the efficiency of the film cooling process is hypothesized. The design concept requires the channel to generate a counter rotating vortex pair secondary flow within the jet stream by virture of flow passage geometry. The interaction of the vortex structures generated by both geometry and crossflow was examined in terms of film cooling effectiveness and surface coverage. Comparative data obtained with this vortex generating coolant passage showed up to factors of four increases in both effectiveness and surface coverage over that obtained with a standard round cross section flow passage. A streakline flow visualization technique was used to support the concept of the counter rotating vortex pair generating capability of the flow passage design.

  7. Study of mean- and turbulent-velocity fields in a large-scale turbine-vane passage

    NASA Technical Reports Server (NTRS)

    Bailey, D. A.

    1979-01-01

    Laser-Doppler velocimetry, and to a lesser extent hot-wire anemometry, were employed to measure three components of the mean velocity and the six turbulent stresses at four planes within the turbine inlet-guide-vane passage. One variation in the turbulent inlet boundary layer thickness and one variation in the blade aspect ratio (span/axial chord) were studied. A longitudinal vortex (passage vortex) was clearly identified in the exit plane of the passage for the three test cases. The maximum turbulence intensities within the longitudinal vortex were found to be on the order of 2 to 4 percent, with large regions appearing nonturbulent. Because a turbulent wall boundary layer was the source of vorticity that produced the passage vortex, these low turbulence levels were not anticipated. For the three test cases studied, the lateral velocity field extended significantly beyond the region of the longitudinal velocity defect. Changing the inlet boundary layer thickness produced a difference in the location, the strength, and the extent of the passage vortex. Changing the aspect ratio of the blade passage had a measurable but less significant effect. The experiment was performed in a 210 mm pitch, 272 mm axial chord model in low speed wind tunnel at an inlet Mach number of 0.07.

  8. Time Perspective and Emotion Regulation as Predictors of Age-Related Subjective Passage of Time.

    PubMed

    Wittmann, Marc; Rudolph, Tina; Linares Gutierrez, Damisela; Winkler, Isabell

    2015-12-17

    Hardly any empirical work exists concerning the relationship between the intra-individually stable time perspective relating to the past, present, and future and the subjective speed of time passing in everyday life. Moreover, studies consistently show that the subjective passage of time over the period of the last ten years speeds up as we get older. Modulating variables influencing this phenomenon are still unknown. To investigate these two unresolved issues, we conducted an online survey with n = 423 participants ranging in age between 17 and 81 assessing trait time perspective of the past, present, and future, and relating these subscales with a battery of measures pertaining to the subjective passage of time. Moreover, the subjective passage of time as an age-dependent variable was probed in relationship to emotion awareness, appraisal and regulation. Results show how present hedonism is linked with having fewer routines in life and a faster passage of the last week; the past negative perspective is related to time pressure, time expansion and more routine; a pronounced future perspective is related to a general faster passage of time. Importantly, increased emotion regulation and a balanced time perspective are related to a slower passage of the last ten years. These novel findings are discussed within models of time perception and the time perspective.

  9. RBP-Jκ-Dependent Notch Signaling Is Dispensable for Mouse Early Embryonic Development

    PubMed Central

    Souilhol, Céline; Cormier, Sarah; Tanigaki, Kenji; Babinet, Charles; Cohen-Tannoudji, Michel

    2006-01-01

    The Notch signaling pathway is an evolutionarily conserved signaling system which has been shown to be essential in cell fate specification and in numerous aspects of embryonic development in all metazoans thus far studied. We recently demonstrated that several components of the Notch signaling pathway, including the four Notch receptors and their five ligands known in mammals, are expressed in mouse oocytes, in mouse preimplantation embryos, or both. This suggested a possible implication of the Notch pathway in the first cell fate specification of the dividing mouse embryo, which results in the formation of the blastocyst. To address this issue directly, we generated zygotes in which both the maternal and the zygotic expression of Rbpsuh, a key element of the core Notch signaling pathway, were abrogated. We find that such zygotes give rise to blastocysts which implant and develop normally. Nevertheless, after gastrulation, these embryos die around midgestation, similarly to Rbpsuh-null mutants. This demonstrates that the RBP-Jκ-dependent pathway, otherwise called the canonical Notch pathway, is dispensable for blastocyst morphogenesis and the establishment of the three germ layers, ectoderm, endoderm, and mesoderm. These results are discussed in the light of recent observations which have challenged this conclusion. PMID:16782866

  10. Inverted light-sheet microscope for imaging mouse pre-implantation development.

    PubMed

    Strnad, Petr; Gunther, Stefan; Reichmann, Judith; Krzic, Uros; Balazs, Balint; de Medeiros, Gustavo; Norlin, Nils; Hiiragi, Takashi; Hufnagel, Lars; Ellenberg, Jan

    2016-02-01

    Despite its importance for understanding human infertility and congenital diseases, early mammalian development has remained inaccessible to in toto imaging. We developed an inverted light-sheet microscope that enabled us to image mouse embryos from zygote to blastocyst, computationally track all cells and reconstruct a complete lineage tree of mouse pre-implantation development. We used this unique data set to show that the first cell fate specification occurs at the 16-cell stage.

  11. View of FE Fossum working on the ESA PASSAGES Experiment

    NASA Image and Video Library

    2011-06-16

    ISS028-E-008393 (16 June 2011) --- NASA astronaut Mike Fossum, Expedition 28 flight engineer, uses Neurospat hardware to perform a science session with the European Space Agency PASSAGES experiment in the Columbus laboratory of the International Space Station. PASSAGES is designed to test how astronauts interpret visual information in weightlessness. It aims at studying the effects of microgravity on the use of the 'Eye-Height' strategy for estimating allowed actions in an environment, and whether this could possibly decrease after a long exposure to weightlessness.

  12. A high-temperature passaging attenuated Pseudorabies vaccine protects piglets completely against emerging PRV variant.

    PubMed

    Liang, Chao; Tong, Wu; Zheng, Hao; Liu, Fei; Wu, Jiqiang; Li, Guoxin; Zhou, En-Min; Tong, Guangzhi

    2017-06-01

    Emerging variant of pseudorabies virus (PRV) have evaded the antiviral immunity of commercially available PRV vaccine and have led to PRV outbreaks in Chinese pig farms. Here, we attenuated a PRV variant strain by serial passages in vitro and evaluate the protective efficacy of the attenuated strain as a vaccine candidate. The virulent PRV variant strain JS-2012 was continuously passaged in Vero cells at 40°C and attenuated rapidly. After 90 passages in Vero cells, the passaged virus lost its ability to cause death in 2-week-old piglets. The 120th passage virus was avirulent in the sucking piglets. An attenuated strain, JS-2012-F120 derived from the 120th passage virus by three rounds of plaque cloning grew better than its parent strain JS-2012 in Vero cells and showed notably different cytopathic effects and plaque morphology from JS-2012. PCR combined with sequence analysis showed that JS-2012-F120 contained a 2307-bp deletion covering nucleotide 487 of gE gene to 531 of US2 gene. After inoculation with JS-2012-F120, young piglets were completely protected from challenge with the classical and emerging virulent PRVs. Moreover, the piglets did not develop specific gE antibodies. Thus, JS-2012-F120 appears to be a promising marker vaccine to control PRV variant circulating in Chinese pig farms, and the high-temperature passaging in vitro was an efficient method to attenuated alphaherpesvirus. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Abnormal neural precursor cell regulation in the early postnatal Fragile X mouse hippocampus.

    PubMed

    Sourial, Mary; Doering, Laurie C

    2017-07-01

    The regulation of neural precursor cells (NPCs) is indispensable for a properly functioning brain. Abnormalities in NPC proliferation, differentiation, survival, or integration have been linked to various neurological diseases including Fragile X syndrome. Yet, no studies have examined NPCs from the early postnatal Fragile X mouse hippocampus despite the importance of this developmental time point, which marks the highest expression level of FMRP, the protein missing in Fragile X, in the rodent hippocampus and is when hippocampal NPCs have migrated to the dentate gyrus (DG) to give rise to lifelong neurogenesis. In this study, we examined NPCs from the early postnatal hippocampus and DG of Fragile X mice (Fmr1-KO). Immunocytochemistry on neurospheres showed increased Nestin expression and decreased Ki67 expression, which collectively indicated aberrant NPC biology. Intriguingly, flow cytometric analysis of the expression of the antigens CD15, CD24, CD133, GLAST, and PSA-NCAM showed a decreased proportion of neural stem cells (GLAST + CD15 + CD133 + ) and an increased proportion of neuroblasts (PSA-NCAM + CD15 + ) in the DG of P7 Fmr1-KO mice. This was mirrored by lower expression levels of Nestin and the mitotic marker phospho-histone H3 in vivo in the P9 hippocampus, as well as a decreased proportion of cells in the G 2 /M phases of the P7 DG. Thus, the absence of FMRP leads to fewer actively cycling NPCs, coinciding with a decrease in neural stem cells and an increase in neuroblasts. Together, these results show the importance of FMRP in the developing hippocampal formation and suggest abnormalities in cell cycle regulation in Fragile X. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  14. Passage Key Inlet, Florida; CMS Modeling and Borrow Site Impact Analysis

    DTIC Science & Technology

    2016-06-01

    Impact Analysis by Kelly R. Legault and Sirisha Rayaprolu PURPOSE: This Coastal and Hydraulics Engineering Technical Note (CHETN) describes the...use of a nested Coastal Modeling System (CMS) model for Passage Key Inlet, which is one of the connections between the Gulf of Mexico and Tampa Bay...driven sediment transport at Passage Key Inlet. This analysis resulted in issuing a new Florida Department of Environmental Protection (FDEP) permit to

  15. Examining the Effect of Computer-Based Passage Presentation on Reading Test Performance

    ERIC Educational Resources Information Center

    Higgins, Jennifer; Russell, Michael; Hoffmann, Thomas

    2005-01-01

    To examine the impact of transitioning 4th grade reading comprehension assessments to the computer, 219 fourth graders were randomly assigned to take a one-hour reading comprehension assessment on paper, on a computer using scrolling text to navigate through passages, or on a computer using paging text to navigate through passages. This study…

  16. Effect of Fin Passage Length on Optimization of Cylinder Head Cooling Fins

    NASA Technical Reports Server (NTRS)

    Siegel, R.; Graham, R. W.

    1977-01-01

    The heat transfer performance of baffled cooling fins on cylinder heads of small, air-cooled, general-aviation aircraft engines was analyzed to determine the potential for improving cooling fin design. Flow baffles were assumed to be installed tightly against the fin end edges, an ideal baffle configuration for guiding all flow between the fins. A rectangular flow passage is thereby formed between each set of two adjacent fins, the fin base surface, and the baffle. These passages extend around each side of the cylinder head, and the cooling air absorbs heat as it flows within them. For each flow passage length, the analysis was concerned with optimizing fin spacing and thickness to achieve the best heat transfer for each fin width. Previous literature has been concerned mainly with maximizing the local fin conductance and has not considered the heating of the gas in the flow direction, which leads to higher wall temperatures at the fin passage exits. If the fins are close together, there is a large surface area, but the airflow is restricted.

  17. Zeb1-Hdac2-eNOS circuitry identifies early cardiovascular precursors in naive mouse embryonic stem cells.

    PubMed

    Cencioni, Chiara; Spallotta, Francesco; Savoia, Matteo; Kuenne, Carsten; Guenther, Stefan; Re, Agnese; Wingert, Susanne; Rehage, Maike; Sürün, Duran; Siragusa, Mauro; Smith, Jacob G; Schnütgen, Frank; von Melchner, Harald; Rieger, Michael A; Martelli, Fabio; Riccio, Antonella; Fleming, Ingrid; Braun, Thomas; Zeiher, Andreas M; Farsetti, Antonella; Gaetano, Carlo

    2018-03-29

    Nitric oxide (NO) synthesis is a late event during differentiation of mouse embryonic stem cells (mESC) and occurs after release from serum and leukemia inhibitory factor (LIF). Here we show that after release from pluripotency, a subpopulation of mESC, kept in the naive state by 2i/LIF, expresses endothelial nitric oxide synthase (eNOS) and endogenously synthesizes NO. This eNOS/NO-positive subpopulation (ESNO+) expresses mesendodermal markers and is more efficient in the generation of cardiovascular precursors than eNOS/NO-negative cells. Mechanistically, production of endogenous NO triggers rapid Hdac2 S-nitrosylation, which reduces association of Hdac2 with the transcriptional repression factor Zeb1, allowing mesendodermal gene expression. In conclusion, our results suggest that the interaction between Zeb1, Hdac2, and eNOS is required for early mesendodermal differentiation of naive mESC.

  18. Spin-Label CW Microwave Power Saturation and Rapid Passage with Triangular Non-Adiabatic Rapid Sweep (NARS) and Adiabatic Rapid Passage (ARP) EPR Spectroscopy

    PubMed Central

    Kittell, Aaron W.; Hyde, James S.

    2015-01-01

    Non-adiabatic rapid passage (NARS) electron paramagnetic resonance (EPR) spectroscopy was introduced by Kittell, A.W., Camenisch, T.G., Ratke, J.J. Sidabras, J.W., Hyde, J.S., 2011 as a general purpose technique to collect the pure absorption response. The technique has been used to improve sensitivity relative to sinusoidal magnetic field modulation, increase the range of inter-spin distances that can be measured under near physiological conditions, and enhance spectral resolution in copper (II) spectra. In the present work, the method is extended to CW microwave power saturation of spin-labeled T4 Lysozyme (T4L). As in the cited papers, rapid triangular sweep of the polarizing magnetic field was superimposed on slow sweep across the spectrum. Adiabatic rapid passage (ARP) effects were encountered in samples undergoing very slow rotational diffusion as the triangular magnetic field sweep rate was increased. The paper reports results of variation of experimental parameters at the interface of adiabatic and non-adiabatic rapid sweep conditions. Comparison of the forward (up) and reverse (down) triangular sweeps is shown to be a good indicator of the presence of rapid passage effects. Spectral turning points can be distinguished from spectral regions between turning points in two ways: differential microwave power saturation and differential passage effects. Oxygen accessibility data are shown under NARS conditions that appear similar to conventional field modulation data. However, the sensitivity is much higher, permitting, in principle, experiments at substantially lower protein concentrations. Spectral displays were obtained that appear sensitive to rotational diffusion in the range of rotational correlation times of 10−3 to 10−7 s in a manner that is analogous to saturation transfer spectroscopy. PMID:25917132

  19. Cognitive flexibility predicts early reading skills

    PubMed Central

    Colé, Pascale; Duncan, Lynne G.; Blaye, Agnès

    2014-01-01

    An important aspect of learning to read is efficiency in accessing different kinds of linguistic information (orthographic, phonological, and semantic) about written words. The present study investigates whether, in addition to the integrity of such linguistic skills, early progress in reading may require a degree of cognitive flexibility in order to manage the coordination of this information effectively. Our study will look for evidence of a link between flexibility and both word reading and passage reading comprehension, and examine whether any such link involves domain-general or reading-specific flexibility. As the only previous support for a predictive relationship between flexibility and early reading comes from studies of reading comprehension in the opaque English orthography, another possibility is that this relationship may be largely orthography-dependent, only coming into play when mappings between representations are complex and polyvalent. To investigate these questions, 60 second-graders learning to read the more transparent French orthography were presented with two multiple classification tasks involving reading-specific cognitive flexibility (based on words) and non-specific flexibility (based on pictures). Reading skills were assessed by word reading, pseudo-word decoding, and passage reading comprehension measures. Flexibility was found to contribute significant unique variance to passage reading comprehension even in the less opaque French orthography. More interestingly, the data also show that flexibility is critical in accounting for one of the core components of reading comprehension, namely, the reading of words in isolation. Finally, the results constrain the debate over whether flexibility has to be reading-specific to be critically involved in reading. PMID:24966842

  20. A mouse model for MERS coronavirus-induced acute respiratory distress syndrome.

    PubMed

    Cockrell, Adam S; Yount, Boyd L; Scobey, Trevor; Jensen, Kara; Douglas, Madeline; Beall, Anne; Tang, Xian-Chun; Marasco, Wayne A; Heise, Mark T; Baric, Ralph S

    2016-11-28

    Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that emerged in 2012, causing acute respiratory distress syndrome (ARDS), severe pneumonia-like symptoms and multi-organ failure, with a case fatality rate of ∼36%. Limited clinical studies indicate that humans infected with MERS-CoV exhibit pathology consistent with the late stages of ARDS, which is reminiscent of the disease observed in patients infected with severe acute respiratory syndrome coronavirus. Models of MERS-CoV-induced severe respiratory disease have been difficult to achieve, and small-animal models traditionally used to investigate viral pathogenesis (mouse, hamster, guinea-pig and ferret) are naturally resistant to MERS-CoV. Therefore, we used CRISPR-Cas9 gene editing to modify the mouse genome to encode two amino acids (positions 288 and 330) that match the human sequence in the dipeptidyl peptidase 4 receptor, making mice susceptible to MERS-CoV infection and replication. Serial MERS-CoV passage in these engineered mice was then used to generate a mouse-adapted virus that replicated efficiently within the lungs and evoked symptoms indicative of severe ARDS, including decreased survival, extreme weight loss, decreased pulmonary function, pulmonary haemorrhage and pathological signs indicative of end-stage lung disease. Importantly, therapeutic countermeasures comprising MERS-CoV neutralizing antibody treatment or a MERS-CoV spike protein vaccine protected the engineered mice against MERS-CoV-induced ARDS.

  1. Investigations into Retinal Pathology in the Early Stages of a Mouse Model of Alzheimer’s Disease

    PubMed Central

    Chidlow, Glyn; Wood, John P.M.; Manavis, Jim; Finnie, John; Casson, Robert J.

    2016-01-01

    There is increasing recognition that visual performance is impaired in early stages of Alzheimer’s disease (AD); however, no consensus exists as to the mechanisms underlying this visual dysfunction, in particular regarding the timing, nature, and extent of retinal versus cortical pathology. If retinal pathology presents sufficiently early, it offers great potential as a source of novel biomarkers for disease diagnosis. The current project utilized an array of immunochemical and molecular tools to perform a characterization of retinal pathology in the early stages of disease progression using a well-validated mouse model of AD (APPSWE/PS1ΔE9). Analytical endpoints included examination of aberrant amyloid and tau in the retina, quantification of any neuronal degeneration, delineation of cellular stress responses of neurons and particularly glial cells, and investigation of oxidative stress. Brain, eyes, and optic nerves were taken from transgenic and wild-type mice of 3 to 12 months of age and processed for immunohistochemistry, qPCR, or western immunoblotting. The results revealed robust expression of the human APP transgene in the retinas of transgenic mice, but a lack of identifiable retinal pathology during the period when amyloid deposits were dramatically escalating in the brain. We were unable to demonstrate the presence of amyloid plaques, dystrophic neurites, neuronal loss, macro- or micro-gliosis, aberrant cell cycle re-entry, oxidative stress, tau hyperphosphorylation, or upregulations of proinflammatory cytokines or stress signaling molecules in the retina. The overall results do not support the hypothesis that detectable retinal pathology occurs concurrently with escalating amyloid deposition in the brains of APPSWE/PS1ΔE9 mice. PMID:28035930

  2. In Vivo Hyperthermic Stress Model: An Easy Tool to Study the Effects of Oxidative Stress on Neuronal Tau Functionality in Mouse Brain.

    PubMed

    Chauderlier, Alban; Delattre, Lucie; Buée, Luc; Galas, Marie-Christine

    2017-01-01

    Oxidative damage is an early event in neurodegenerative disorders such as Alzheimer disease. To increase oxidative stress in AD-related mouse models is essential to study early mechanisms involved in the physiopathology of these diseases. In this chapter, we describe an experimental mouse model of transient and acute hyperthermic stress to induce in vivo an increase of oxidative stress in the brain of any kind of wild-type or transgenic mouse.

  3. Film-cooling effectiveness with developing coolant flow through straight and curved tubular passages

    NASA Technical Reports Server (NTRS)

    Papell, S. S.; Wang, C. R.; Graham, R. W.

    1982-01-01

    The data were obtained with an apparatus designed to determine the influence of tubular coolant passage curvature on film-cooling performance while simulating the developing flow entrance conditions more representative of cooled turbine blade. Data comparisons were made between straight and curved single tubular passages embedded in the wall and discharging at 30 deg angle in line with the tunnel flow. The results showed an influence of curvature on film-cooling effectiveness that was inversely proportional to the blowing rate. At the lowest blowing rate of 0.18, curvature increased the effectiveness of film cooling by 35 percent; but at a blowing rate of 0.76, the improvement was only 10 percent. In addition, the increase in film-cooling area coverage ranged from 100 percent down to 25 percent over the same blowing rates. A data trend reversal at a blowing rate of 1.5 showed the straight tubular passage's film-cooling effectiveness to be 20 percent greater than that of the curved passage with about 80 percent more area coverage. An analysis of turbulence intensity detain the mixing layer in terms of the position of the mixing interface relative to the wall supported the concept that passage curvature tends to reduce the diffusion of the coolant jet into the main stream at blowing rates below about. Explanations for the film-cooling performance of both test sections were made in terms differences in turbulences structure and in secondary flow patterns within the coolant jets as influenced by flow passage geometry.

  4. Film-cooling effectiveness with developing coolant flow through straight and curved tubular passages

    NASA Astrophysics Data System (ADS)

    Papell, S. S.; Wang, C. R.; Graham, R. W.

    1982-11-01

    The data were obtained with an apparatus designed to determine the influence of tubular coolant passage curvature on film-cooling performance while simulating the developing flow entrance conditions more representative of cooled turbine blade. Data comparisons were made between straight and curved single tubular passages embedded in the wall and discharging at 30 deg angle in line with the tunnel flow. The results showed an influence of curvature on film-cooling effectiveness that was inversely proportional to the blowing rate. At the lowest blowing rate of 0.18, curvature increased the effectiveness of film cooling by 35 percent; but at a blowing rate of 0.76, the improvement was only 10 percent. In addition, the increase in film-cooling area coverage ranged from 100 percent down to 25 percent over the same blowing rates. A data trend reversal at a blowing rate of 1.5 showed the straight tubular passage's film-cooling effectiveness to be 20 percent greater than that of the curved passage with about 80 percent more area coverage. An analysis of turbulence intensity detain the mixing layer in terms of the position of the mixing interface relative to the wall supported the concept that passage curvature tends to reduce the diffusion of the coolant jet into the main stream at blowing rates below about. Explanations for the film-cooling performance of both test sections were made in terms differences in turbulences structure and in secondary flow patterns within the coolant jets as influenced by flow passage geometry.

  5. Establishment of an attenuated strain of porcine parvovirus by serial passage at low temperature.

    PubMed

    Fujisaki, Y; Murakami, Y; Suzuki, H

    1982-01-01

    To prepare a live virus vaccine strain for the prevention of porcine parvovirus infection, the 90HS strain, isolated from the brain of a stillborn porcine fetus, was subjected to the first 45 serial passages in swine kidney established (ESK) cells of porcine kidney origin at 30-35 degrees C and to the 46th and later serial passages in the same cells as these at 32 degrees C. When swine were inoculated with the strain at the 38th passage level possessing such properties as expressed with rct/37+ and rct/40-, they presented viremia, virus discharge, and the transmission of virus to other swine. When swine were inoculated with the strain at the 54th and 55th passage level possessing such properties as expressed with rct/37- and rct/40-, they failed to exhibit viremia, virus discharge, and the transmission of virus to other swine, but retained for a long time hemagglutination-inhibiting antibody which had been produced after inoculation. A low virulent variant strain was obtained after 54 serial passages at low temperature. It was called the HT- strain.

  6. First-passage problems: A probabilistic dynamic analysis for degraded structures

    NASA Technical Reports Server (NTRS)

    Shiao, Michael C.; Chamis, Christos C.

    1990-01-01

    Structures subjected to random excitations with uncertain system parameters degraded by surrounding environments (a random time history) are studied. Methods are developed to determine the statistics of dynamic responses, such as the time-varying mean, the standard deviation, the autocorrelation functions, and the joint probability density function of any response and its derivative. Moreover, the first-passage problems with deterministic and stationary/evolutionary random barriers are evaluated. The time-varying (joint) mean crossing rate and the probability density function of the first-passage time for various random barriers are derived.

  7. Flexible and experimentally feasible shortcut to quantum Zeno dynamic passage

    NASA Astrophysics Data System (ADS)

    Li, Wenlin; Zhang, Fengyang; Jiang, Yunfeng; Li, Chong; Song, Heshan

    2016-10-01

    We propose and discuss a theoretical scheme to speed up Zeno dynamic passage by an external acceleration Hamiltonian. This scheme is a flexible and experimentally feasible acceleration because the acceleration Hamiltonian does not adhere rigidly to an invariant relationship, whereas it can be a more general form ∑uj (t)Hcj. Here Hcj can be arbitrarily selected without any limitation, and therefore one can always construct an acceleration Hamiltonian by only using realizable Hcj. Applying our scheme, we finally design an experimentally feasible Hamiltonian as an example to speed up an entanglement preparation passage.

  8. Using Necessary Information to Identify Item Dependence in Passage-Based Reading Comprehension Tests

    ERIC Educational Resources Information Center

    Baldonado, Angela Argo; Svetina, Dubravka; Gorin, Joanna

    2015-01-01

    Applications of traditional unidimensional item response theory models to passage-based reading comprehension assessment data have been criticized based on potential violations of local independence. However, simple rules for determining dependency, such as including all items associated with a particular passage, may overestimate the dependency…

  9. 75 FR 61479 - Western Passage OCGenTM

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 12680-004] Western Passage...' express permission. The proposed project would consist of: (1) 2 OCGen\\TM\\ hydrokinetic tidal devices each... turbine-generating units of each device to a shore station; (5) a 2,800-foot-long, 34.5-kilovolt...

  10. Time Perspective and Emotion Regulation as Predictors of Age-Related Subjective Passage of Time

    PubMed Central

    Wittmann, Marc; Rudolph, Tina; Linares Gutierrez, Damisela; Winkler, Isabell

    2015-01-01

    Hardly any empirical work exists concerning the relationship between the intra-individually stable time perspective relating to the past, present, and future and the subjective speed of time passing in everyday life. Moreover, studies consistently show that the subjective passage of time over the period of the last ten years speeds up as we get older. Modulating variables influencing this phenomenon are still unknown. To investigate these two unresolved issues, we conducted an online survey with n = 423 participants ranging in age between 17 and 81 assessing trait time perspective of the past, present, and future, and relating these subscales with a battery of measures pertaining to the subjective passage of time. Moreover, the subjective passage of time as an age-dependent variable was probed in relationship to emotion awareness, appraisal and regulation. Results show how present hedonism is linked with having fewer routines in life and a faster passage of the last week; the past negative perspective is related to time pressure, time expansion and more routine; a pronounced future perspective is related to a general faster passage of time. Importantly, increased emotion regulation and a balanced time perspective are related to a slower passage of the last ten years. These novel findings are discussed within models of time perception and the time perspective. PMID:26694439

  11. A semi-automated method of monitoring dam passage of American Eels Anguilla rostrata

    USGS Publications Warehouse

    Welsh, Stuart A.; Aldinger, Joni L.

    2014-01-01

    Fish passage facilities at dams have become an important focus of fishery management in riverine systems. Given the personnel and travel costs associated with physical monitoring programs, automated or semi-automated systems are an attractive alternative for monitoring fish passage facilities. We designed and tested a semi-automated system for eel ladder monitoring at Millville Dam on the lower Shenandoah River, West Virginia. A motion-activated eel ladder camera (ELC) photographed each yellow-phase American Eel Anguilla rostrata that passed through the ladder. Digital images (with date and time stamps) of American Eels allowed for total daily counts and measurements of eel TL using photogrammetric methods with digital imaging software. We compared physical counts of American Eels with camera-based counts; TLs obtained with a measuring board were compared with TLs derived from photogrammetric methods. Data from the ELC were consistent with data obtained by physical methods, thus supporting the semi-automated camera system as a viable option for monitoring American Eel passage. Time stamps on digital images allowed for the documentation of eel passage time—data that were not obtainable from physical monitoring efforts. The ELC has application to eel ladder facilities but can also be used to monitor dam passage of other taxa, such as crayfishes, lampreys, and water snakes.

  12. Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum

    PubMed Central

    Maltese, Marta; Stanic, Jennifer; Tassone, Annalisa; Sciamanna, Giuseppe; Ponterio, Giulia; Vanni, Valentina; Martella, Giuseppina; Imbriani, Paola; Bonsi, Paola; Mercuri, Nicola Biagio

    2018-01-01

    The onset of abnormal movements in DYT1 dystonia is between childhood and adolescence, although it is unclear why clinical manifestations appear during this developmental period. Plasticity at corticostriatal synapses is critically involved in motor memory. In the Tor1a+/Δgag DYT1 dystonia mouse model, long-term potentiation (LTP) appeared prematurely in a critical developmental window in striatal spiny neurons (SPNs), while long-term depression (LTD) was never recorded. Analysis of dendritic spines showed an increase of both spine width and mature mushroom spines in Tor1a+/Δgag neurons, paralleled by an enhanced AMPA receptor (AMPAR) accumulation. BDNF regulates AMPAR expression during development. Accordingly, both proBDNF and BDNF levels were significantly higher in Tor1a+/Δgag mice. Consistently, antagonism of BDNF rescued synaptic plasticity deficits and AMPA currents. Our findings demonstrate that early loss of functional and structural synaptic homeostasis represents a unique endophenotypic trait during striatal maturation, promoting the appearance of clinical manifestations in mutation carriers. PMID:29504938

  13. The chromosomal mapping of four genes encoding winged helix proteins expressed early in mouse development

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

    Labosky, P.A.; Sakaki, Hiroshi; Hogan, B.L.M.

    1996-06-01

    Members of the winged helix family of transcription factors are required for the normal embryonic development of the mouse. Using the interspecific backcross panel from The Jackson Laboratory, we have determined the chromosomal locations of four genes that encode winged helix containing proteins. Mf1 was assigned to mouse Chromosome 8, Mf2 to Chromosome 4, Mf3 to Chromosome 9, and Mf4 to Chromosome 13. Since Mf3 is located in a region of Chromosome 9 containing many well-characterized mouse mutations such as short ear (se), ashen (ash), and dilute (d), we have analyzed deletion mutants to determine the location of Mf3 moremore » precisely. 14 refs., 3 figs.« less

  14. Passage Independence within Standardized Reading Comprehension Tests

    ERIC Educational Resources Information Center

    Roy-Charland, Annie; Colangelo, Gabrielle; Foglia, Victoria; Reguigui, Leïla

    2017-01-01

    In tests used to measure reading comprehension, validity is important in obtaining accurate results. Unfortunately, studies have shown that people can correctly answer some questions of these tests without reading the related passage. These findings bring forth the need to address whether this phenomenon is observed in multiple-choice only tests…

  15. Walla Walla River Fish Passage Operations Program, 2003-2004 Annual Report.

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

    Bronson, James P.

    2004-12-01

    In the late 1990s, the Confederated Tribes of the Umatilla Indian Reservation, Oregon Department of Fish and Wildlife, and Washington Department of Fish and Wildlife, along with many other agencies, began implementing fisheries restoration activities in the Walla Walla Basin. An integral part of these efforts is to alleviate the inadequate fish migration conditions in the basin. The migration concerns are being addressed by removing diversion structures, constructing fish passage facilities, implementing minimum instream flow requirements, and providing trap and haul efforts when needed. The objective of the Walla Walla River Fish Passage Operations Project is to increase the survivalmore » of migrating adult and juvenile salmonids in the Walla Walla River basin. The project is responsible for coordinating operation and maintenance of ladders, screen sites, bypasses, trap facilities, and transportation equipment. In addition, the project provides technical input on passage criteria and passage and trapping facility design and operation. Operation of the various passage facilities and passage criteria guidelines are outlined in an annual operations plan that the project develops. During the 2003-2004 project year, there were 379 adult summer steelhead (Oncorhynchus mykiss), 36 adult bull trout (Salvelinus confluentus); 108 adult and 3 jack spring chinook (O. tshawytscha) enumerated at the Nursery Bridge Dam fishway video counting window between December 21, 2003, and June 30, 2004. Summer steelhead and spring chinook were observed moving upstream while bull trout were observed moving both upstream and downstream of the facility. In addition, the old ladder trap was operated by the WWBNPME project in order to radio tag spring chinook adults. A total of 2 adult summer steelhead, 4 bull trout, and 23 adult spring chinook were enumerated at the west ladder at Nursery Bridge Dam during the trapping operations between May 6 and May 23, 2004. Operation of the Little

  16. Two Pore Channel 2 Differentially Modulates Neural Differentiation of Mouse Embryonic Stem Cells

    PubMed Central

    Zhang, Zhe-Hao; Lu, Ying-Ying; Yue, Jianbo

    2013-01-01

    Nicotinic acid adenine dinucleotide phosphate (NAADP) is an endogenous Ca2+ mobilizing nucleotide presented in various species. NAADP mobilizes Ca2+ from acidic organelles through two pore channel 2 (TPC2) in many cell types and it has been previously shown that NAADP can potently induce neuronal differentiation in PC12 cells. Here we examined the role of TPC2 signaling in the neural differentiation of mouse embryonic stem (ES) cells. We found that the expression of TPC2 was markedly decreased during the initial ES cell entry into neural progenitors, and the levels of TPC2 gradually rebounded during the late stages of neurogenesis. Correspondingly, TPC2 knockdown accelerated mouse ES cell differentiation into neural progenitors but inhibited these neural progenitors from committing to neurons. Overexpression of TPC2, on the other hand, inhibited mouse ES cell from entering the early neural lineage. Interestingly, TPC2 knockdown had no effect on the differentiation of astrocytes and oligodendrocytes of mouse ES cells. Taken together, our data indicate that TPC2 signaling plays a temporal and differential role in modulating the neural lineage entry of mouse ES cells, in that TPC2 signaling inhibits ES cell entry to early neural progenitors, but is required for late neuronal differentiation. PMID:23776607

  17. A Novel Use of Three-dimensional High-frequency Ultrasonography for Early Pregnancy Characterization in the Mouse.

    PubMed

    Peavey, Mary C; Reynolds, Corey L; Szwarc, Maria M; Gibbons, William E; Valdes, Cecilia T; DeMayo, Francesco J; Lydon, John P

    2017-10-24

    High-frequency ultrasonography (HFUS) is a common method to non-invasively monitor the real-time development of the human fetus in utero. The mouse is routinely used as an in vivo model to study embryo implantation and pregnancy progression. Unfortunately, such murine studies require pregnancy interruption to enable follow-up phenotypic analysis. To address this issue, we used three-dimensional (3-D) reconstruction of HFUS imaging data for early detection and characterization of murine embryo implantation sites and their individual developmental progression in utero. Combining HFUS imaging with 3-D reconstruction and modeling, we were able to accurately quantify embryo implantation site number as well as monitor developmental progression in pregnant C57BL6J/129S mice from 5.5 days post coitus (d.p.c.) through to 9.5 d.p.c. with the use of a transducer. Measurements included: number, location, and volume of implantation sites as well as inter-implantation site spacing; embryo viability was assessed by cardiac activity monitoring. In the immediate post-implantation period (5.5 to 8.5 d.p.c.), 3-D reconstruction of the gravid uterus in both mesh and solid overlay format enabled visual representation of the developing pregnancies within each uterine horn. As genetically engineered mice continue to be used to characterize female reproductive phenotypes derived from uterine dysfunction, this method offers a new approach to detect, quantify, and characterize early implantation events in vivo. This novel use of 3-D HFUS imaging demonstrates the ability to successfully detect, visualize, and characterize embryo-implantation sites during early murine pregnancy in a non-invasive manner. The technology offers a significant improvement over current methods, which rely on the interruption of pregnancies for gross tissue and histopathologic characterization. Here we use a video and text format to describe how to successfully perform ultrasounds of early murine pregnancy to

  18. Evaluation of Fish Passage Conditions for Juvenile Salmonids Using Sensor Fish at Detroit Dam, Oregon

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

    Duncan, Joanne P.

    2010-01-29

    Fish passage conditions through two spillways at Detroit Dam on the North Santiam River in Oregon were evaluated by Pacific Northwest National Laboratory for the U.S. Army Corps of Engineers (USACE), Portland District, using Sensor Fish devices. The objective of the study was to describe and compare passage exposure conditions through Spillbay 3 and Spillbay 6 at 1.5- and 3.5-ft gate openings, identifying potential fish injury regions of the routes. The study was performed in July 2009, concurrent with HI-Z balloon-tag studies by Normandeau Associates, Inc. Sensor Fish and live fish were deployed at elevations approximately 3 ft above structuremore » at depths determined using a computational fluid dynamics model. Data collected were analyzed to estimate 1) exposure conditions, particularly exposure to severe collision and shear events by passage route sub-regions; 2) differences in passage conditions between passage routes; and 3) relationships to live-fish injury and mortality data estimates.« less

  19. Early fear memory defects are associated with altered synaptic plasticity and molecular architecture in the TgCRND8 Alzheimer's disease mouse model.

    PubMed

    Steele, John W; Brautigam, Hannah; Short, Jennifer A; Sowa, Allison; Shi, Mengxi; Yadav, Aniruddha; Weaver, Christina M; Westaway, David; Fraser, Paul E; St George-Hyslop, Peter H; Gandy, Sam; Hof, Patrick R; Dickstein, Dara L

    2014-07-01

    Alzheimer's disease (AD) is a complex and slowly progressing dementing disorder that results in neuronal and synaptic loss, deposition in brain of aberrantly folded proteins, and impairment of spatial and episodic memory. Most studies of mouse models of AD have employed analyses of cognitive status and assessment of amyloid burden, gliosis, and molecular pathology during disease progression. Here we sought to understand the behavioral, cellular, ultrastructural, and molecular changes that occur at a pathological stage equivalent to the early stages of human AD. We studied the TgCRND8 mouse, a model of aggressive AD amyloidosis, at an early stage of plaque pathology (3 months of age) in comparison to their wildtype littermates and assessed changes in cognition, neuron and spine structure, and expression of synaptic glutamate receptor proteins. We found that, at this age, TgCRND8 mice display substantial plaque deposition in the neocortex and hippocampus and impairment on cued and contextual memory tasks. Of particular interest, we also observed a significant decrease in the number of neurons in the hippocampus. Furthermore, analysis of CA1 neurons revealed significant changes in apical and basal dendritic spine types, as well as altered expression of GluN1 and GluA2 receptors. This change in molecular architecture within the hippocampus may reflect a rising representation of inherently less stable thin spine populations, which can cause cognitive decline. These changes, taken together with toxic insults from amyloid-β protein, may underlie the observed neuronal loss. Copyright © 2014 Wiley Periodicals, Inc.

  20. Hyperconnectivity and slow synapses during early development of medial prefrontal cortex in a mouse model for mental retardation and autism.

    PubMed

    Testa-Silva, Guilherme; Loebel, Alex; Giugliano, Michele; de Kock, Christiaan P J; Mansvelder, Huibert D; Meredith, Rhiannon M

    2012-06-01

    Neuronal theories of neurodevelopmental disorders (NDDs) of autism and mental retardation propose that abnormal connectivity underlies deficits in attentional processing. We tested this theory by studying unitary synaptic connections between layer 5 pyramidal neurons within medial prefrontal cortex (mPFC) networks in the Fmr1-KO mouse model for mental retardation and autism. In line with predictions from neurocognitive theory, we found that neighboring pyramidal neurons were hyperconnected during a critical period in early mPFC development. Surprisingly, excitatory synaptic connections between Fmr1-KO pyramidal neurons were significantly slower and failed to recover from short-term depression as quickly as wild type (WT) synapses. By 4-5 weeks of mPFC development, connectivity rates were identical for both KO and WT pyramidal neurons and synapse dynamics changed from depressing to facilitating responses with similar properties in both groups. We propose that the early alteration in connectivity and synaptic recovery are tightly linked: using a network model, we show that slower synapses are essential to counterbalance hyperconnectivity in order to maintain a dynamic range of excitatory activity. However, the slow synaptic time constants induce decreased responsiveness to low-frequency stimulation, which may explain deficits in integration and early information processing in attentional neuronal networks in NDDs.

  1. Hyperconnectivity and Slow Synapses during Early Development of Medial Prefrontal Cortex in a Mouse Model for Mental Retardation and Autism

    PubMed Central

    Testa-Silva, Guilherme; Loebel, Alex; Giugliano, Michele; de Kock, Christiaan P.J.; Mansvelder, Huibert D.; Meredith, Rhiannon M.

    2013-01-01

    Neuronal theories of neurodevelopmental disorders (NDDs) of autism and mental retardation propose that abnormal connectivity underlies deficits in attentional processing. We tested this theory by studying unitary synaptic connections between layer 5 pyramidal neurons within medial prefrontal cortex (mPFC) networks in the Fmr1-KO mouse model for mental retardation and autism. In line with predictions from neurocognitive theory, we found that neighboring pyramidal neurons were hyperconnected during a critical period in early mPFC development. Surprisingly, excitatory synaptic connections between Fmr1-KO pyramidal neurons were significantly slower and failed to recover from short-term depression as quickly as wild type (WT) synapses. By 4--5 weeks of mPFC development, connectivity rates were identical for both KO and WT pyramidal neurons and synapse dynamics changed from depressing to facilitating responses with similar properties in both groups. We propose that the early alteration in connectivity and synaptic recovery are tightly linked: using a network model, we show that slower synapses are essential to counterbalance hyperconnectivity in order to maintain a dynamic range of excitatory activity. However, the slow synaptic time constants induce decreased responsiveness to low-frequency stimulation, which may explain deficits in integration and early information processing in attentional neuronal networks in NDDs. PMID:21856714

  2. Experimental study of the influence of flow passage subtle variation on mixed-flow pump performance

    NASA Astrophysics Data System (ADS)

    Bing, Hao; Cao, Shuliang

    2014-05-01

    In the mixed-flow pump design, the shape of the flow passage can directly affect the flow capacity and the internal flow, thus influencing hydraulic performance, cavitation performance and operation stability of the mixed-flow pump. However, there is currently a lack of experimental research on the influence mechanism. Therefore, in order to analyze the effects of subtle variations of the flow passage on the mixed-flow pump performance, the frustum cone surface of the end part of inlet contraction flow passage of the mixed-flow pump is processed into a cylindrical surface and a test rig is built to carry out the hydraulic performance experiment. In this experiment, parameters, such as the head, the efficiency, and the shaft power, are measured, and the pressure fluctuation and the noise signal are also collected. The research results suggest that after processing the inlet flow passage, the head of the mixed-flow pump significantly goes down; the best efficiency of the mixed-flow pump drops by approximately 1.5%, the efficiency decreases more significantly under the large flow rate; the shaft power slightly increases under the large flow rate, slightly decreases under the small flow rate. In addition, the pressure fluctuation amplitudes on both the impeller inlet and the diffuser outlet increase significantly with more drastic pressure fluctuations and significantly lower stability of the internal flow of the mixed-flow pump. At the same time, the noise dramatically increases. Overall speaking, the subtle variation of the inlet flow passage leads to a significant change of the mixed-flow pump performance, thus suggesting a special attention to the optimization of flow passage. This paper investigates the influence of the flow passage variation on the mixed-flow pump performance by experiment, which will benefit the optimal design of the flow passage of the mixed-flow pump.

  3. First-passage and risk evaluation under stochastic volatility

    NASA Astrophysics Data System (ADS)

    Masoliver, Jaume; Perelló, Josep

    2009-07-01

    We solve the first-passage problem for the Heston random diffusion model. We obtain exact analytical expressions for the survival and the hitting probabilities to a given level of return. We study several asymptotic behaviors and obtain approximate forms of these probabilities which prove, among other interesting properties, the nonexistence of a mean-first-passage time. One significant result is the evidence of extreme deviations—which implies a high risk of default—when certain dimensionless parameter, related to the strength of the volatility fluctuations, increases. We confront the model with empirical daily data and we observe that it is able to capture a very broad domain of the hitting probability. We believe that this may provide an effective tool for risk control which can be readily applicable to real markets both for portfolio management and trading strategies.

  4. Mule deer passage beneath an overland coal conveyor

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

    Greenwood, C.L.; Dalton, L.B.

    1984-07-31

    Presently, information pertaining to migration and daily movement patterns of big game in relation to overland conveyors or large diameter pipelines is sparse. A literature review showed that moose, caribou, reindeer, and dall sheep will pass beneath or over large diameter pipeline systems. But no information was found relative to big game crossing coal conveyor systems. Mule deer passage beneath an overland coal conveyor in Carbon County, Utah, was studied during spring 1981. Deer avoided crossing at underpass opportunities where the clearance was less than 50 cm. Clearances between 50 and 90 cm were selected for crossing. Deer passed beneathmore » the conveyor during day and nighttime conditions and while the conveyor was either operating or idle. Recommendations are discussed for designing conveyors and pipelines to facilitate big game passage. 13 references, 2 tables.« less

  5. Compliance Monitoring of Subyearling Chinook Salmon Survival and Passage at The Dalles Dam, Summer 2012

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

    Skalski, J. R.; Townsend, Richard L.; Seaburg, Adam

    2013-05-01

    The purpose of this compliance study was to estimate dam passage survival of subyearling Chinook salmon at The Dalles Dam during summer 2012. Under the 2008 Federal Columbia River Power System Biological Opinion, dam passage survival is required to be greater than or equal to 0.93 and estimated with a standard error (SE) less than or equal to 0.015. The study also estimated survival from the forebay 2 km upstream of the dam and through the tailrace to 2 km downstream of the dam, forebay residence time, tailrace egress time, spill passage efficiency (SPE), and fish passage efficiency (FPE), asmore » required by the 2008 Columbia Basin Fish Accords.« less

  6. Synergistic and singular effects of river discharge and lunar illumination on dam passage of upstream migrant yellow-phase American eels

    USGS Publications Warehouse

    Welsh, Stuart A.; Aldinger, Joni L.; Braham, Melissa A.; Zimmerman, Jennifer L.

    2016-01-01

    Monitoring of dam passage can be useful for management and conservation assessments of American eel, particularly if passage counts can be examined over multiple years. During a 7-year study (2007–2013) of upstream migration of American eels within the lower Shenandoah River (Potomac River drainage), we counted and measured American eels at the Millville Dam eel pass, where annual study periods were determined by the timing of the eel pass installation during spring or summer and removal during fall. Daily American eel counts were analysed with negative binomial regression models, with and without a year (YR) effect, and with the following time-varying environmental covariates: river discharge of the Shenandoah River at Millville (RDM) and of the Potomac River at Point of Rocks, lunar illumination (LI), water temperature, and cloud cover. A total of 17 161 yellow-phase American eels used the pass during the seven annual periods, and length measurements were obtained from 9213 individuals (mean = 294 mm TL, s.e. = 0.49, range 183–594 mm). Data on passage counts of American eels supported an additive-effects model (YR + LI + RDM) where parameter estimates were positive for river discharge (β = 7.3, s.e. = 0.01) and negative for LI (β = −1.9, s.e. = 0.34). Interestingly, RDM and LI acted synergistically and singularly as correlates of upstream migration of American eels, but the highest daily counts and multiple-day passage events were associated with increased RDM. Annual installation of the eel pass during late spring or summer prevented an early spring assessment, a period with higher RDM relative to those values obtained during sampling periods. Because increases in river discharge are climatically controlled events, upstream migration events of American eels within the Potomac River drainage are likely linked to the influence of climate variability on flow regime.

  7. [Effect of human oviductal embryotrophic factors on gene expression of mouse preimplantation embryos].

    PubMed

    Yao, Yuan-Qing; Lee, Kai-Fai; Xu, Jia-Seng; Ho, Pak-Chung; Yeung, Shu-Biu

    2007-09-01

    To investigate the effect of embryotrophic factors (ETF) from human oviductal cells on gene expression of mouse early developmental embryos and discuss the role of fallopian tube in early development of embryos. ETF was isolated from conditioned medium of human oviductal cell line by sequential liquid chromatographic systems. Mouse embryos were treated by ETF in vitro. Using differential display RT-PCR, the gene expression of embryos treated by ETF was compared with embryos without ETF treatment. The differentially expressed genes were separated, re-amplified, cloned and sequenced. Gene expression profiles of embryos with ETF treatment was different from embryos without this treatment. Eight differentially expressed genes were cloned and sequenced. These genes functioned in RNA degradation, synthesis, splicing, protein trafficking, cellular differentiation and embryo development. Embryotrophic factors from human oviductal cells affect gene expression of early developmental embryos. The human oviductal cells play wide roles in early developmental stages of embryos.

  8. TGF-β mediates early angiogenesis and latent fibrosis in an Emilin1-deficient mouse model of aortic valve disease

    PubMed Central

    Munjal, Charu; Opoka, Amy M.; Osinska, Hanna; James, Jeanne F.; Bressan, Giorgio M.; Hinton, Robert B.

    2014-01-01

    Aortic valve disease (AVD) is characterized by elastic fiber fragmentation (EFF), fibrosis and aberrant angiogenesis. Emilin1 is an elastin-binding glycoprotein that regulates elastogenesis and inhibits TGF-β signaling, but the role of Emilin1 in valve tissue is unknown. We tested the hypothesis that Emilin1 deficiency results in AVD, mediated by non-canonical (MAPK/phosphorylated Erk1 and Erk2) TGF-β dysregulation. Using histology, immunohistochemistry, electron microscopy, quantitative gene expression analysis, immunoblotting and echocardiography, we examined the effects of Emilin1 deficiency (Emilin1−/−) in mouse aortic valve tissue. Emilin1 deficiency results in early postnatal cell-matrix defects in aortic valve tissue, including EFF, that progress to latent AVD and premature death. The Emilin1−/− aortic valve displays early aberrant provisional angiogenesis and late neovascularization. In addition, Emilin1−/− aortic valves are characterized by early valve interstitial cell activation and proliferation and late myofibroblast-like cell activation and fibrosis. Interestingly, canonical TGF-β signaling (phosphorylated Smad2 and Smad3) is upregulated constitutively from birth to senescence, whereas non-canonical TGF-β signaling (phosphorylated Erk1 and Erk2) progressively increases over time. Emilin1 deficiency recapitulates human fibrotic AVD, and advanced disease is mediated by non-canonical (MAPK/phosphorylated Erk1 and Erk2) TGF-β activation. The early manifestation of EFF and aberrant angiogenesis suggests that these processes are crucial intermediate factors involved in disease progression and therefore might provide new therapeutic targets for human AVD. PMID:25056700

  9. Schooling as a Rational Rite of Passage

    ERIC Educational Resources Information Center

    Dimitrijevic, Ivan

    2017-01-01

    Starting from Illich's identification of the compulsory schooling process with the rational initiation rite to the modern, free-market, society, the paper aims to detach the philosophical premises this expensive and unequal ritual is grounded in. After having referred to Van Gennep's conception of the rites of passage, we shall show that the…

  10. A multi-year analysis of passage and survival at McNary Dam, 2004-09

    USGS Publications Warehouse

    Adams, Noah S.; Walker, C.E.; Perry, R.W.

    2011-01-01

    We analyzed 6 years (2004–09) of passage and survival data collected at McNary Dam to determine how dam operations and environmental conditions affect passage and survival of juvenile salmonids. A multinomial logistic regression was used to examine how environmental variables and dam operations relate to passage behavior of juvenile salmonids at McNary Dam. We used the Cormack-Jolly-Seber release-recapture model to determine how the survival of juvenile salmonids passing through McNary Dam relates to environmental variables and dam operations. Total project discharge and the proportion of flow passing the spillway typically had a positive effect on survival for all species and routes. As the proportion of water through the spillway increased, the number of fish passing the spillway increased, as did overall survival. Additionally, survival generally was higher at night. There was no meaningful difference in survival for fish that passed through the north or south portions of the spillway or powerhouse. Similarly, there was no difference in survival for fish released in the north, middle, or south portions of the tailrace. For subyearling Chinook salmon migrating during the summer season, increased temperatures had a drastic effect on passage and survival. As temperature increased, survival of subyearling Chinook salmon decreased through all passage routes and the number of fish that passed through the turbines increased. During years when the temporary spillway weirs (TSWs) were installed, passage through the spillway increased for spring migrants. However, due to the changes made in the location of the TSW between years and the potential effect of other confounding environmental conditions, it is not certain if the increase in spillway passage was due solely to the presence of the TSWs. The TSWs appeared to improve forebay survival during years when they were operated.

  11. Inhibition of Cell Division and DNA Replication Impair Mouse-Naïve Pluripotency Exit.

    PubMed

    Waisman, Ariel; Vazquez Echegaray, Camila; Solari, Claudia; Cosentino, María Soledad; Martyn, Iain; Deglincerti, Alessia; Ozair, Mohammad Zeeshan; Ruzo, Albert; Barañao, Lino; Miriuka, Santiago; Brivanlou, Ali; Guberman, Alejandra

    2017-09-01

    The cell cycle has gained attention as a key determinant for cell fate decisions, but the contribution of DNA replication and mitosis in stem cell differentiation has not been extensively studied. To understand if these processes act as "windows of opportunity" for changes in cell identity, we established synchronized cultures of mouse embryonic stem cells as they exit the ground state of pluripotency. We show that initial transcriptional changes in this transition do not require passage through mitosis and that conversion to primed pluripotency is linked to lineage priming in the G1 phase. Importantly, we demonstrate that impairment of DNA replication severely blocks transcriptional switch to primed pluripotency, even in the absence of p53 activity induced by the DNA damage response. Our data suggest an important role for DNA replication during mouse embryonic stem cell differentiation, which could shed light on why pluripotent cells are only receptive to differentiation signals during G1, that is, before the S phase. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Effect of electric barrier on passage and physical condition of juvenile and adult rainbow trout

    USGS Publications Warehouse

    Layhee, Megan J.; Sepulveda, Adam; Shaw, Amy; Smuckall, Matthew; Kapperman, Kevin; Reyes, Alejandro

    2016-01-01

    Electric barriers can inhibit passage and injure fish. Few data exist on electric barrier parameters that minimize these impacts and on how body size affects susceptibility, especially to nontarget fish species. The goal of this study was to determine electric barrier voltage and pulse-width settings that inhibit passage of larger bodied rainbow trout Oncorhynchus mykiss (215–410 mm fork length) while allowing passage of smaller bodied juvenile rainbow trout (52–126 mm) in a static laboratory setting. We exposed rainbow trout to 30-Hz pulsed-direct current voltage gradients (0.00–0.45 V cm−1) and pulse widths (0.0–0.7 ms) and recorded their movement, injury incidence, and mortality. No settings tested allowed all juveniles to pass while impeding all adult passage. Juvenile and adult rainbow trout avoided the barrier at higher pulse widths, and fewer rainbow trout passed the barrier at 0.7-ms pulse width compared to 0.1 ms and when the barrier was turned off. We found no effect of voltage gradient on fish passage. No mortality occurred, and we observed external bruising in 5 (7%) juvenile rainbow trout and 15 (21%) adult rainbow trout. This study may aid managers in selecting barrier settings that allow for increased juvenile passage.

  13. Stable isotope-labelled feed nutrients to assess nutrient-specific feed passage kinetics in ruminants.

    PubMed

    Warner, Daniel; Dijkstra, Jan; Hendriks, Wouter H; Pellikaan, Wilbert F

    2014-03-30

    Knowledge of digesta passage kinetics in ruminants is essential to predict nutrient supply to the animal in relation to optimal animal performance, environmental pollution and animal health. Fractional passage rates (FPR) of feed are widely used in modern feed evaluation systems and mechanistic rumen models, but data on nutrient-specific FPR are scarce. Such models generally rely on conventional external marker techniques, which do not always describe digesta passage kinetics in a satisfactory manner. Here the use of stable isotope-labelled dietary nutrients as a promising novel tool to assess nutrient-specific passage kinetics is discussed. Some major limitations of this technique include a potential marker migration, a poor isotope distribution in the labelled feed and a differential disappearance rate of isotopes upon microbial fermentation in non-steady state conditions. Such limitations can often be circumvented by using intrinsically stable isotope-labelled plant material. Data are limited but indicate that external particulate markers overestimate rumen FPR of plant fibre compared with the internal stable isotope markers. Stable isotopes undergo the same digestive mechanism as the labelled feed components and are thus of particular interest to specifically measure passage kinetics of digestible dietary nutrients. © 2013 Society of Chemical Industry.

  14. Size illusion, distance illusion, and terrestrial passage: comment on reed.

    PubMed

    Loftus, G R

    1985-03-01

    Two assumptions of Reed's (1984) terrestrial passage theory are questioned. First, Reed assumes that the moon's failure to increase in visual subtense while elevating is accounted for strictly by perceptual distancing. This allows a formal account of the moon distance illusion, but at the expense of a compelling explanation of the moon size illusion. Second, in order to explain the distance illusion, Reed assumes that all objects, regardless of their perceived altitude, are perceived to start from a common point at the horizon. Several alternative application of Reed's terrestrial-passage foundation to the actual illusions are suggested.

  15. FUNCTIONS OF VATA (BASED ON CHARAKA) A Passage from Vaatkalaakaleeyam.

    PubMed

    Trivedi, A R

    1982-04-01

    The author has chosen 12(th) Chapter from the Sutra Sthana of this great epic containing 12,000 verses and passages which is replete with materials to revive the whole art of healing even if the whole medical literatures is lost. The passage puts in a nutshell the key role played by Vayu / Vata in the working of the tantra and yantra of the body. Though exploration of the humours is yet to be done by modern physiologists to explain the Ayurvedic Vata which is responsible to no less than 18 functions of the normal body mechanism.

  16. Chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis

    PubMed Central

    Perry, Meghan R.; Wyllie, Susan; Raab, Andrea; Feldmann, Joerg; Fairlamb, Alan H.

    2013-01-01

    The Indian subcontinent is the only region where arsenic contamination of drinking water coexists with widespread resistance to antimonial drugs that are used to treat the parasitic disease visceral leishmaniasis. We have previously proposed that selection for parasite resistance within visceral leishmaniasis patients who have been exposed to trivalent arsenic results in cross-resistance to the related metalloid antimony, present in the pentavalent state as a complex in drugs such as sodium stibogluconate (Pentostam) and meglumine antimonate (Glucantime). To test this hypothesis, Leishmania donovani was serially passaged in mice exposed to arsenic in drinking water at environmentally relevant levels (10 or 100 ppm). Arsenic accumulation in organs and other tissues was proportional to the level of exposure and similar to that previously reported in human liver biopsies. After five monthly passages in mice exposed to arsenic, isolated parasites were found to be completely refractory to 500 μg⋅mL−1 Pentostam compared with the control passage group (38.5 μg⋅mL−1) cultured in vitro in mouse peritoneal macrophages. Reassessment of resistant parasites following further passage for 4 mo in mice without arsenic exposure showed that resistance was stable. Treatment of infected mice with Pentostam confirmed that resistance observed in vitro also occurred in vivo. We conclude that arsenic contamination may have played a significant role in the development of Leishmania antimonial resistance in Bihar because inadequate treatment with antimonial drugs is not exclusive to India, whereas widespread antimonial resistance is. PMID:24167266

  17. Chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis.

    PubMed

    Perry, Meghan R; Wyllie, Susan; Raab, Andrea; Feldmann, Joerg; Fairlamb, Alan H

    2013-12-03

    The Indian subcontinent is the only region where arsenic contamination of drinking water coexists with widespread resistance to antimonial drugs that are used to treat the parasitic disease visceral leishmaniasis. We have previously proposed that selection for parasite resistance within visceral leishmaniasis patients who have been exposed to trivalent arsenic results in cross-resistance to the related metalloid antimony, present in the pentavalent state as a complex in drugs such as sodium stibogluconate (Pentostam) and meglumine antimonate (Glucantime). To test this hypothesis, Leishmania donovani was serially passaged in mice exposed to arsenic in drinking water at environmentally relevant levels (10 or 100 ppm). Arsenic accumulation in organs and other tissues was proportional to the level of exposure and similar to that previously reported in human liver biopsies. After five monthly passages in mice exposed to arsenic, isolated parasites were found to be completely refractory to 500 μg · mL(-1) Pentostam compared with the control passage group (38.5 μg · mL(-1)) cultured in vitro in mouse peritoneal macrophages. Reassessment of resistant parasites following further passage for 4 mo in mice without arsenic exposure showed that resistance was stable. Treatment of infected mice with Pentostam confirmed that resistance observed in vitro also occurred in vivo. We conclude that arsenic contamination may have played a significant role in the development of Leishmania antimonial resistance in Bihar because inadequate treatment with antimonial drugs is not exclusive to India, whereas widespread antimonial resistance is.

  18. A passage retrieval method based on probabilistic information retrieval model and UMLS concepts in biomedical question answering.

    PubMed

    Sarrouti, Mourad; Ouatik El Alaoui, Said

    2017-04-01

    Passage retrieval, the identification of top-ranked passages that may contain the answer for a given biomedical question, is a crucial component for any biomedical question answering (QA) system. Passage retrieval in open-domain QA is a longstanding challenge widely studied over the last decades. However, it still requires further efforts in biomedical QA. In this paper, we present a new biomedical passage retrieval method based on Stanford CoreNLP sentence/passage length, probabilistic information retrieval (IR) model and UMLS concepts. In the proposed method, we first use our document retrieval system based on PubMed search engine and UMLS similarity to retrieve relevant documents to a given biomedical question. We then take the abstracts from the retrieved documents and use Stanford CoreNLP for sentence splitter to make a set of sentences, i.e., candidate passages. Using stemmed words and UMLS concepts as features for the BM25 model, we finally compute the similarity scores between the biomedical question and each of the candidate passages and keep the N top-ranked ones. Experimental evaluations performed on large standard datasets, provided by the BioASQ challenge, show that the proposed method achieves good performances compared with the current state-of-the-art methods. The proposed method significantly outperforms the current state-of-the-art methods by an average of 6.84% in terms of mean average precision (MAP). We have proposed an efficient passage retrieval method which can be used to retrieve relevant passages in biomedical QA systems with high mean average precision. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. 17β-Estradiol Promotes Schwann Cell Proliferation and Differentiation, Accelerating Early Remyelination in a Mouse Peripheral Nerve Injury Model

    PubMed Central

    Chen, Yan; Guo, Wenjie; Li, Wenjuan; Cheng, Meng; Hu, Ying; Xu, Wenming

    2016-01-01

    Estrogen induces oligodendrocyte remyelination in response to demyelination in the central nervous system. Our objective was to determine the effects of 17β-estradiol (E2) on Schwann cell function and peripheral nerve remyelination after injury. Adult male C57BL/6J mice were used to prepare the sciatic nerve transection injury model and were randomly categorized into control and E2 groups. To study myelination in vitro, dorsal root ganglion (DRG) explant culture was prepared using 13.5-day-old mouse embryos. Primary Schwann cells were isolated from the sciatic nerves of 1- to 3-day-old Sprague–Dawley rats. Immunostaining for myelin basic protein (MBP) expression and toluidine blue staining for myelin sheaths demonstrated that E2 treatment accelerates early remyelination in the “nerve bridge” region between the proximal and distal stumps of the transection injury site in the mouse sciatic nerve. The 5-bromo-2′-deoxyuridine incorporation assay revealed that E2 promotes Schwann cell proliferation in the bridge region and in the primary culture, which is blocked using AKT inhibitor MK2206. The in vitro myelination in the DRG explant culture determined showed that the MBP expression in the E2-treated group is higher than that in the control group. These results show that E2 promotes Schwann cell proliferation and myelination depending on AKT activation. PMID:27872858

  20. Complementary velocity and heat transfer measurements in a rotating turbine cooling passage

    NASA Astrophysics Data System (ADS)

    Bons, Jeffrey Peter

    An experimental investigation was conducted on the internal flowfield of a simulated turbine blade cooling passage. The passage is of a square cross-section and was manufactured from quartz for optical accessibility. Velocity measurements were taken using Particle Image Velocimetry for both heated and non-heated cases. Thin film resistive heaters on the four passage walls allow heat to be added to the coolant flow without obstructing laser access. Under the same conditions, an infrared detector with associated optics collected wall temperature data for use in calculating local Nusselt number. The test section was operated with radial outward flow and at values of Reynolds number, Rotation number, and density ratio typical of applications. Velocity data for the non-heated case document the evolution of the Coriolis-induced double vortex. The vortex has the effect of increasing the leading side boundary layer thickness while decreasing the trailing side boundary layer thickness. Also, the streamwise component of the Coriolis acceleration creates a thinned side wall boundary layer. These data reveal an unsteady, turbulent flowfield in the cooling passage. Velocity data for the heated case show a strongly distorted streamwise profile indicative of a buoyancy effect on the leading side. The Coriolis vortex is the mechanism for the accumulation of stagnant flow on the leading side of the passage. Heat transfer data show a maximum factor of two difference in the Nusselt number from trailing side to leading side. An estimate of this heat transfer disparity based on the measured boundary layer edge velocity yields approximately the same factor of two. A momentum integral model was developed for data interpretation which accounts for Coriolis and buoyancy effects. Calculated streamwise profiles and secondary flows match the experimental data well. The model, the velocity data, and the heat transfer data combine to suggest the presence of separated flow on the leading wall

  1. Three Dimensional Viscous Flow Field in an Axial Flow Turbine Nozzle Passage

    NASA Technical Reports Server (NTRS)

    Ristic, D.; Lakshminarayana, B.

    1997-01-01

    The objective of this investigation is experimental and computational study of three dimensional viscous flow field in the nozzle passage of an axial flow turbine stage. The nozzle passage flow field has been measured using a two sensor hot-wire probe at various axial and radial stations. In addition, two component LDV measurements at one axial station (x/c(sum m) = 0.56) were performed to measure the velocity field. Static pressure measurements and flow visualization, using a fluorescent oil technique, were also performed to obtain the location of transition and the endwall limiting streamlines. A three dimensional boundary layer code, with a simple intermittency transition model, was used to predict the viscous layers along the blade and endwall surfaces. The boundary layers on the blade surface were found to be very thin and mostly laminar, except on the suction surface downstream of 70% axial chord. Strong radial pressure gradient, especially close to the suction surface, induces strong cross flow components in the trailing edge regions of the blade. On the end-walls the boundary layers were much thicker, especially near the suction corner of the casing surface, caused by secondary flow. The secondary flow region near the suction-casing surface corner indicates the presence of the passage vortex detached from the blade surface. The corner vortex is found to be very weak. The presence of a closely spaced rotor downstream (20% of the nozzle vane chord) introduces unsteadiness in the blade passage. The measured instantaneous velocity signal was filtered using FFT square window to remove the periodic unsteadiness introduced by the downstream rotor and fans. The filtering decreased the free stream turbulence level from 2.1% to 0.9% but had no influence on the computed turbulence length scale. The computation of the three dimensional boundary layers is found to be accurate on the nozzle passage blade surfaces, away from the end-walls and the secondary flow region. On

  2. Senescence of nickel-transformed cells by an X chromosome: Possible epigenetic control

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

    Klein, C.B.; Xin Wei Wang; Bhamra, R.K.

    1991-02-15

    Transfer of a normal Chinese hamster X chromosome (carried in a mouse A9 donor cell line) to a nickel-transformed Chinese hamster cell line with an Xq chromosome deletion resulted in senescense of these previously immortal cells. At early passages of the A9/CX donor cells, the hamster X chromosome was highly active, inducing senescence in 100% of the colonies obtained after its transfer into the nickel-transformed cells. However, senescence was reduced to 50% when Chinese hamster X chromosomes were transferred from later passage A9 cells. Full senescing activity of the intact hamster X chromosome was restored by treatment of the donormore » mouse cells with 5-azacytidine, which induced demethylation of DMA. These results suggest that a senescence gene or genes, which may be located on the Chinese hamster X chromosome, can be regulated by DNA methylation, and that escape from senescence and possibly loss of tumor suppressor gene activity can occur by epigenetic mechanisms.« less

  3. Aquatic organism passage at road-stream crossings—synthesis and guidelines for effectiveness monitoring

    Treesearch

    Robert L. Hoffman; Jason B. Dunham; Bruce P. Hansen

    2012-01-01

    Restoration and maintenance of passage for aquatic organisms at road-stream crossings represents a major management priority, involving an investment of hundreds of millions of dollars. This report has been written, in part, for field biologists who will be undertaking and evaluating the effectiveness of aquatic organism passage restoration projects at road-stream...

  4. Pathogenicity, sequence and phylogenetic analysis of Malaysian Chicken anaemia virus obtained after low and high passages in MSB-1 cells.

    PubMed

    Chowdhury, S M Z H; Omar, A R; Aini, I; Hair-Bejo, M; Jamaluddin, A A; Md-Zain, B M; Kono, Y

    2003-12-01

    Specific-pathogen-free (SPF) chickens inoculated with low passage Chicken anaemia virus (CAV), SMSC-1 and 3-1 isolates produced lesions suggestive of CAV infection. Repeated passages of the isolates in cell culture until passage 60 (P60) and passage 123 produced viruses that showed a significantly reduced level of pathogenicity in SPF chickens compared to the low passage isolates. Sequence comparison indicated that nucleotide changes in only the coding region of the P60 passage isolates were thought to contribute to virus attenuation. Phylogenetic analysis indicated that SMSC-1 and 3-1 were highly divergent, but their P60 passage derivatives shared significant homology to a Japanese isolate A2.

  5. Heat transfer and pressure drop for air flow through enhanced passages

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

    Obot, N.T.; Esen, E.B.

    1992-06-01

    An extensive experimental investigation was carried out to determine the pressure drop and heat transfer characteristics for laminar, transitional and turbulent flow of air through a smooth passage and twenty-three enhanced passages. The internal surfaces of all enhanced passages had spirally shaped geometries; these included fluted, finned/ribbed and indented surfaces. The Reynolds number (Re) was varied between 400 and 50000. The effect of heat transfer (wall cooling or fluid heating) on pressure drop is most significant within the transition region; the recorded pressure drop with heat transfer is much higher than that without heat transfer. The magnitude of this effectmore » depends markedly on the average surface temperature and, to a lesser extent, on the geometric characteristics of the enhanced surfaces. When the pressure drop data are reduced as values of the Fanning friction factor(f), the results are about the same with and without heat transfer for turbulent flow, with moderate differences in the laminar and transition regions.« less

  6. A multi-scale GIS and hydrodynamic modelling approach to fish passage assessment: Clarence and Shoalhaven Rivers, NSW Australia

    NASA Astrophysics Data System (ADS)

    Bonetti, Rita M.; Reinfelds, Ivars V.; Butler, Gavin L.; Walsh, Chris T.; Broderick, Tony J.; Chisholm, Laurie A.

    2016-05-01

    Natural barriers such as waterfalls, cascades, rapids and riffles limit the dispersal and in-stream range of migratory fish, yet little is known of the interplay between these gradient dependent landforms, their hydraulic characteristics and flow rates that facilitate fish passage. The resurgence of dam construction in numerous river basins world-wide provides impetus to the development of robust techniques for assessment of the effects of downstream flow regime changes on natural fish passage barriers and associated consequences as to the length of rivers available to migratory species. This paper outlines a multi-scale technique for quantifying the relative magnitude of natural fish passage barriers in river systems and flow rates that facilitate passage by fish. First, a GIS-based approach is used to quantify channel gradients for the length of river or reach under investigation from a high resolution DEM, setting the magnitude of identified passage barriers in a longer context (tens to hundreds of km). Second, LiDAR, topographic and bathymetric survey-based hydrodynamic modelling is used to assess flow rates that can be regarded as facilitating passage across specific barriers identified by the river to reach scale gradient analysis. Examples of multi-scale approaches to fish passage assessment for flood-flow and low-flow passage issues are provided from the Clarence and Shoalhaven Rivers, NSW, Australia. In these river systems, passive acoustic telemetry data on actual movements and migrations by Australian bass (Macquaria novemaculeata) provide a means of validating modelled assessments of flow rates associated with successful fish passage across natural barriers. Analysis of actual fish movements across passage barriers in these river systems indicates that two dimensional hydraulic modelling can usefully quantify flow rates associated with the facilitation of fish passage across natural barriers by a majority of individual fishes for use in management

  7. Novel mouse models of oculopharyngeal muscular dystrophy (OPMD) reveal early onset mitochondrial defects and suggest loss of PABPN1 may contribute to pathology.

    PubMed

    Vest, Katherine E; Phillips, Brittany L; Banerjee, Ayan; Apponi, Luciano H; Dammer, Eric B; Xu, Weiting; Zheng, Dinghai; Yu, Julia; Tian, Bin; Pavlath, Grace K; Corbett, Anita H

    2017-09-01

    Oculopharyngeal muscular dystrophy (OPMD) is a late onset disease caused by polyalanine expansion in the poly(A) binding protein nuclear 1 (PABPN1). Several mouse models have been generated to study OPMD; however, most of these models have employed transgenic overexpression of alanine-expanded PABPN1. These models do not recapitulate the OPMD patient genotype and PABPN1 overexpression could confound molecular phenotypes. We have developed a knock-in mouse model of OPMD (Pabpn1+/A17) that contains one alanine-expanded Pabpn1 allele under the control of the native promoter and one wild-type Pabpn1 allele. This mouse is the closest available genocopy of OPMD patients. We show that Pabpn1+/A17 mice have a mild myopathic phenotype in adult and aged animals. We examined early molecular and biochemical phenotypes associated with expressing native levels of A17-PABPN1 and detected shorter poly(A) tails, modest changes in poly(A) signal (PAS) usage, and evidence of mitochondrial damage in these mice. Recent studies have suggested that a loss of PABPN1 function could contribute to muscle pathology in OPMD. To investigate a loss of function model of pathology, we generated a heterozygous Pabpn1 knock-out mouse model (Pabpn1+/Δ). Like the Pabpn1+/A17 mice, Pabpn1+/Δ mice have mild histologic defects, shorter poly(A) tails, and evidence of mitochondrial damage. However, the phenotypes detected in Pabpn1+/Δ mice only partially overlap with those detected in Pabpn1+/A17 mice. These results suggest that loss of PABPN1 function could contribute to but may not completely explain the pathology detected in Pabpn1+/A17 mice. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Compliance Monitoring of Subyearling Chinook Salmon Smolt Survival and Passage at Bonneville Dam, Summer 2012

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

    Skalski, J. R.; Townsend, Richard L.; Seaburg, Adam

    2013-05-01

    The purpose of this compliance study was to estimate dam passage survival of subyearling Chinook salmon at Bonneville Dam during summer 2012, as required by the 2008 Federal Columbia River Power System Biological Opinion. The study also estimated smolt passage survival from the forebay 2 km upstream of the dam to the tailrace 1 km below the dam, as well as forebay residence time, tailrace egress, and spill passage efficiency, as required in the 2008 Columbia Basin Fish Accords.

  9. Red Blood Cell Passage of Small Capillaries Is Associated with Transient Ca2+-mediated Adaptations.

    PubMed

    Danielczok, Jens G; Terriac, Emmanuel; Hertz, Laura; Petkova-Kirova, Polina; Lautenschläger, Franziska; Laschke, Matthias W; Kaestner, Lars

    2017-01-01

    When red blood cells (RBCs) pass constrictions or small capillaries they need to pass apertures falling well below their own cross section size. We used different means of mechanical stimulations (hypoosmotic swelling, local mechanical stimulation, passing through microfluidic constrictions) to observe cellular responses of human RBCs in terms of intracellular Ca 2+ -signaling by confocal microscopy of Fluo-4 loaded RBCs. We were able to confirm our in vitro results in a mouse dorsal skinfold chamber model showing a transiently increased intracellular Ca 2+ when RBCs were passing through small capillaries in vivo . Furthermore, we performed the above-mentioned in vitro experiments as well as measurements of RBCs filterability under various pharmacological manipulations (GsMTx-4, TRAM-34) to explore the molecular mechanism of the Ca 2+ -signaling. Based on these experiments we conclude that mechanical stimulation of RBCs activates mechano-sensitive channels most likely Piezo1. This channel activity allows Ca 2+ to enter the cell, leading to a transient activation of the Gardos-channel associated with K + , Cl - , and water loss, i.e., with a transient volume adaptation facilitating the passage of the RBCs through the constriction.

  10. Red Blood Cell Passage of Small Capillaries Is Associated with Transient Ca2+-mediated Adaptations

    PubMed Central

    Danielczok, Jens G.; Terriac, Emmanuel; Hertz, Laura; Petkova-Kirova, Polina; Lautenschläger, Franziska; Laschke, Matthias W.; Kaestner, Lars

    2017-01-01

    When red blood cells (RBCs) pass constrictions or small capillaries they need to pass apertures falling well below their own cross section size. We used different means of mechanical stimulations (hypoosmotic swelling, local mechanical stimulation, passing through microfluidic constrictions) to observe cellular responses of human RBCs in terms of intracellular Ca2+-signaling by confocal microscopy of Fluo-4 loaded RBCs. We were able to confirm our in vitro results in a mouse dorsal skinfold chamber model showing a transiently increased intracellular Ca2+ when RBCs were passing through small capillaries in vivo. Furthermore, we performed the above-mentioned in vitro experiments as well as measurements of RBCs filterability under various pharmacological manipulations (GsMTx-4, TRAM-34) to explore the molecular mechanism of the Ca2+-signaling. Based on these experiments we conclude that mechanical stimulation of RBCs activates mechano-sensitive channels most likely Piezo1. This channel activity allows Ca2+ to enter the cell, leading to a transient activation of the Gardos-channel associated with K+, Cl−, and water loss, i.e., with a transient volume adaptation facilitating the passage of the RBCs through the constriction. PMID:29259557

  11. Effect of spiral outlet hydraulic passage geometrics on the radial thrust

    NASA Astrophysics Data System (ADS)

    Lugova, S. O.; Ignateva, P. I.

    2017-08-01

    The article presents the results of investigation of the effect of geometrics of a double-volute outlet hydraulic passage on the magnitude and direction of acting of the radial reaction forces in a between-bearings single-stage centrifugal pump with a double entry impeller. The investigation has been performed with the use of a computing experiment. Characteristic curves as well as values and directions of the radial thrust have been compared for three variants of outlet hydraulic passages differing in the width at their entrance.

  12. Lipopolysaccharide reduces food passage rate from the crop by a prostaglandin-independent mechanism in chickens

    PubMed Central

    Tachibana, T.; Ogino, M.; Makino, R.; Khan, M. S. I.; Cline, M. A.

    2017-01-01

    ABSTRACT 1. We examined the effect of lipopolysaccharide (LPS), a component of Gram-negative bacteria, on food passage in the digestive tract of chickens (Gallus gallus) in order to clarify whether bacterial infection affects food passage in birds. 2. Food passage in the crop was significantly reduced by intraperitoneal (IP) injection of LPS while it did not affect the number of defecations, suggesting that LPS may affect food passage only in the upper digestive tract. 3. Similar to LPS, prostaglandin E2 (PGE2), one of the mediators of LPS, also reduced crop-emptying rate in chickens while it had no effect on the number of defecations. 4. Pretreatment with indomethacin, which is an inhibitor of cyclooxygenase (COX), a prostaglandin synthase, had no effect on LPS-induced inhibition of crop emptying. 5. IP injection of LPS did not affect the mRNA expression of COX2 in the upper digestive tract of chickens. 6. It is therefore likely that LPS and PGE2 reduced food passage rate in the crop by a prostaglandin-independent pathway in chickens. PMID:27871194

  13. Lipopolysaccharide reduces food passage rate from the crop by a prostaglandin-independent mechanism in chickens.

    PubMed

    Tachibana, T; Ogino, M; Makino, R; Khan, M S I; Cline, M A

    2017-02-01

    1. We examined the effect of lipopolysaccharide (LPS), a component of Gram-negative bacteria, on food passage in the digestive tract of chickens (Gallus gallus) in order to clarify whether bacterial infection affects food passage in birds. 2. Food passage in the crop was significantly reduced by intraperitoneal (IP) injection of LPS while it did not affect the number of defecations, suggesting that LPS may affect food passage only in the upper digestive tract. 3. Similar to LPS, prostaglandin E2 (PGE2), one of the mediators of LPS, also reduced crop-emptying rate in chickens while it had no effect on the number of defecations. 4. Pretreatment with indomethacin, which is an inhibitor of cyclooxygenase (COX), a prostaglandin synthase, had no effect on LPS-induced inhibition of crop emptying. 5. IP injection of LPS did not affect the mRNA expression of COX2 in the upper digestive tract of chickens. 6. It is therefore likely that LPS and PGE2 reduced food passage rate in the crop by a prostaglandin-independent pathway in chickens.

  14. Walla Walla River Fish Passage Operations Project : Annual Progress Report October 2007 - September 2008.

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

    Bronson, James P.; Duke, Bill; Loffink, Ken

    2008-12-30

    In the late 1990s, the Confederated Tribes of the Umatilla Indian Reservation, Oregon Department of Fish and Wildlife, and Washington Department of Fish and Wildlife, along with many other agencies, began implementing fisheries restoration activities in the Walla Walla Basin. An integral part of these efforts is to alleviate the inadequate fish migration conditions in the basin. Migration concerns are being addressed by removing diversion structures, constructing fish passage facilities, implementing minimum instream flow requirements, and providing trap and haul efforts when needed. The objective of the Walla Walla River Fish Passage Operations Project is to increase the survival ofmore » migrating adult and juvenile salmonids in the Walla Walla River basin. The project is responsible for coordinating operation and maintenance of ladders, screen sites, bypasses, trap facilities, and transportation equipment. In addition, the project provides technical input on passage and trapping facility design, operation, and criteria. Operation of the various passage facilities and passage criteria guidelines are outlined in an annual operations plan that the project develops. Beginning in March of 2007, two work elements from the Walla Walla Fish Passage Operations Project were transferred to other projects. The work element Enumeration of Adult Migration at Nursery Bridge Dam is now conducted under the Walla Walla Basin Natural Production Monitoring and Evaluation Project and the work element Provide Transportation Assistance is conducted under the Umatilla Satellite Facilities Operation and Maintenance Project. Details of these activities can be found in those project's respective annual reports.« less

  15. Heat Transfer Experiments in the Internal Cooling Passages of a Cooled Radial Turbine Rotor

    NASA Technical Reports Server (NTRS)

    Johnson, B. V.; Wagner, J. H.

    1996-01-01

    An experimental study was conducted (1) to experimentally measure, assess and analyze the heat transfer within the internal cooling configuration of a radial turbine rotor blade and (2) to obtain heat transfer data to evaluate and improve computational fluid dynamics (CFD) procedures and turbulent transport models of internal coolant flows. A 1.15 times scale model of the coolant passages within the NASA LERC High Temperature Radial Turbine was designed, fabricated of Lucite and instrumented for transient beat transfer tests using thin film surface thermocouples and liquid crystals to indicate temperatures. Transient heat transfer tests were conducted for Reynolds numbers of one-fourth, one-half, and equal to the operating Reynolds number for the NASA Turbine. Tests were conducted for stationary and rotating conditions with rotation numbers in the range occurring in the NASA Turbine. Results from the experiments showed the heat transfer characteristics within the coolant passage were affected by rotation. In general, the heat transfer increased and decreased on the sides of the straight radial passages with rotation as previously reported from NASA-HOST-sponsored experiments. The heat transfer in the tri-passage axial flow region adjacent to the blade exit was relatively unaffected by rotation. However, the heat transfer on one surface, in the transitional region between the radial inflow passage and axial, constant radius passages, decreased to approximately 20 percent of the values without rotation. Comparisons with previous 3-D numerical studies indicated regions where the heat transfer characteristics agreed and disagreed with the present experiment.

  16. [Observation of animal behavior by revolving activity cage method: A new automatic measuring and recording system of motor activity of a mouse by means of revolving activity cage is presented (author's transl)].

    PubMed

    Nakamura, K

    1978-09-01

    With this system, several parameters can be recorded continuously over several months without exterior stimuli. Time per revolution is counted and punched into the paper tape as binary coded numbers, and the number of revolutions and the frequency of "passage" in a given time are printed out on a rolled paper by a digital recorder. "Passage" is defined as one revolving trial without a pause over a fixed time (criterion time) and used as a behavioral unit of "stop and go". The raw data on the paper tape are processed and analyzed with a general-purpose computer. It was confirmed that when a mouse became well accustomed to the revolving activity cage, the time per revolution followed the law of exponential distribution probability, while the length of passage (i.e. the number of revolutions per revolving trial) followed that of geometrical distribution probability. The revolving activity of mice treated with single subcutaneous injection of methamphetamine was examined using these parameters.

  17. The Effect of Connecting-passage Diameter on the Performance of a Compression-ignition Engine with a Precombustion Chamber

    NASA Technical Reports Server (NTRS)

    Moore, C S; Collins, J H

    1932-01-01

    Results of motoring tests are presented showing the effect of passage diameter on chamber and cylinder compression pressures, maximum pressure differences, and f.m.e.p. over a speed range from 300 to 1,750 r.p.m. Results of engine performance tests are presented which show the effect of passage diameter on m.e.p., explosion pressures, specific fuel consumption, and rates of pressure rise for a range of engine speeds from 500 to 1,500 r.p.m. The cylinder compression pressure, the maximum pressure difference, and the f.m.e.p. decreased rapidly as the passage diameter increased to 29/64 inch, whereas further increase in passage diameter effected only a slight change. The most suitable passage diameter for good engine performance and operating characteristics was 29/64 inch. Passage diameter became less critical with a decrease in engine speed. Therefore, the design should be based on maximum operating speed. Optimum performance and satisfactory combustion control could not be obtained by means of any single diameter of the connecting passage.

  18. Migration depth and residence time of juvenile salmonids in the forebays of hydropower dams prior to passage through turbines or juvenile bypass systems: implications for turbine-passage survival.

    PubMed

    Li, Xinya; Deng, Zhiqun D; Brown, Richard S; Fu, Tao; Martinez, Jayson J; McMichael, Geoffrey A; Skalski, John R; Townsend, Richard L; Trumbo, Bradly A; Ahmann, Martin L; Renholds, Jon F

    2015-01-01

    Little is known about the three-dimensional depth distributions in rivers of individually marked fish that are in close proximity to hydropower facilities. Knowledge of the depth distributions of fish approaching dams can be used to understand how vulnerable fish are to injuries such as barotrauma as they pass through dams. To predict the possibility of barotrauma injury caused by pressure changes during turbine passage, it is necessary to understand fish behaviour relative to acclimation depth in dam forebays as they approach turbines. A guiding study was conducted using high-resolution three-dimensional tracking results of salmonids implanted with Juvenile Salmon Acoustic Telemetry System transmitters to investigate the depth distributions of subyearling and yearling Chinook salmon (Oncorhynchus tshawytscha) and juvenile steelhead (Oncorhynchus mykiss) passing two dams on the Snake River in Washington State. Multiple approaches were evaluated to describe the depth at which fish were acclimated, and statistical analyses were performed on large data sets extracted from ∼28 000 individually tagged fish during 2012 and 2013. Our study identified patterns of depth distributions of juvenile salmonids in forebays prior to passage through turbines or juvenile bypass systems. This research indicates that the median depth at which juvenile salmonids approached turbines ranged from 2.8 to 12.2 m, with the depths varying by species/life history, year, location (which dam) and diel period (between day and night). One of the most enlightening findings was the difference in dam passage associated with the diel period. The amount of time that turbine-passed fish spent in the immediate forebay prior to entering the powerhouse was much lower during the night than during the day. This research will allow scientists to understand turbine-passage survival better and enable them to assess more accurately the effects of dam passage on juvenile salmon survival.

  19. Migration depth and residence time of juvenile salmonids in the forebays of hydropower dams prior to passage through turbines or juvenile bypass systems: implications for turbine-passage survival

    PubMed Central

    Li, Xinya; Deng, Zhiqun D.; Brown, Richard S.; Fu, Tao; Martinez, Jayson J.; McMichael, Geoffrey A.; Skalski, John R.; Townsend, Richard L.; Trumbo, Bradly A.; Ahmann, Martin L.; Renholds, Jon F.

    2015-01-01

    Little is known about the three-dimensional depth distributions in rivers of individually marked fish that are in close proximity to hydropower facilities. Knowledge of the depth distributions of fish approaching dams can be used to understand how vulnerable fish are to injuries such as barotrauma as they pass through dams. To predict the possibility of barotrauma injury caused by pressure changes during turbine passage, it is necessary to understand fish behaviour relative to acclimation depth in dam forebays as they approach turbines. A guiding study was conducted using high-resolution three-dimensional tracking results of salmonids implanted with Juvenile Salmon Acoustic Telemetry System transmitters to investigate the depth distributions of subyearling and yearling Chinook salmon (Oncorhynchus tshawytscha) and juvenile steelhead (Oncorhynchus mykiss) passing two dams on the Snake River in Washington State. Multiple approaches were evaluated to describe the depth at which fish were acclimated, and statistical analyses were performed on large data sets extracted from ∼28 000 individually tagged fish during 2012 and 2013. Our study identified patterns of depth distributions of juvenile salmonids in forebays prior to passage through turbines or juvenile bypass systems. This research indicates that the median depth at which juvenile salmonids approached turbines ranged from 2.8 to 12.2 m, with the depths varying by species/life history, year, location (which dam) and diel period (between day and night). One of the most enlightening findings was the difference in dam passage associated with the diel period. The amount of time that turbine-passed fish spent in the immediate forebay prior to entering the powerhouse was much lower during the night than during the day. This research will allow scientists to understand turbine-passage survival better and enable them to assess more accurately the effects of dam passage on juvenile salmon survival. PMID:27293685

  20. The circadian clock controls sunburn apoptosis and erythema in mouse skin.

    PubMed

    Gaddameedhi, Shobhan; Selby, Christopher P; Kemp, Michael G; Ye, Rui; Sancar, Aziz

    2015-04-01

    Epidemiological studies of humans and experimental studies with mouse models suggest that sunburn resulting from exposure to excessive UV light and damage to DNA confers an increased risk for melanoma and non-melanoma skin cancer. Previous reports have shown that both nucleotide excision repair, which is the sole pathway in humans for removing UV photoproducts, and DNA replication are regulated by the circadian clock in mouse skin. Furthermore, the timing of UV exposure during the circadian cycle has been shown to affect skin carcinogenesis in mice. Because sunburn and skin cancer are causally related, we investigated UV-induced sunburn apoptosis and erythema in mouse skin as a function of circadian time. Interestingly, we observed that sunburn apoptosis, inflammatory cytokine induction, and erythema were maximal following an acute early-morning exposure to UV and minimal following an afternoon exposure. Early-morning exposure to UV also produced maximal activation of ataxia telangiectasia mutated and Rad3-related (Atr)-mediated DNA damage checkpoint signaling, including activation of the tumor suppressor p53, which is known to control the process of sunburn apoptosis. These data provide early evidence that the circadian clock has an important role in the erythemal response in UV-irradiated skin. The early morning is when DNA repair is at a minimum, and thus the acute responses likely are associated with unrepaired DNA damage. The prior report that mice are more susceptible to skin cancer induction following chronic irradiation in the AM, when p53 levels are maximally induced, is discussed in terms of the mutational inactivation of p53 during chronic irradiation.

  1. Centrifugation assay for measuring adhesion of serially passaged bovine chondrocytes to polystyrene surfaces.

    PubMed

    Kaplan, David S; Hitchins, Victoria M; Vegella, Thomas J; Malinauskas, Richard A; Ferlin, Kimberly M; Fisher, John P; Frondoza, Carmelita G

    2012-07-01

    A major obstacle in chondrocyte-based therapy for cartilage repair is the limited availability of cells that maintain their original phenotype. Propagation of chondrocytes as monolayer cultures on polystyrene surfaces is used extensively for amplifying cell numbers. However, chondrocytes undergo a phenotypic shift when propagated in this manner and display characteristics of more adherent fibroblastic cells. Little information is available about the effect of this phenotypic shift on cellular adhesion properties. We evaluated changes in adhesion property as bovine chondrocytes were serially propagated up to five passages in monolayer culture using a centrifugation cell adhesion assay, which was based on counting of cells before and after being exposed to centrifugal dislodgement forces of 120 and 350 g. Chondrocytes proliferated well in a monolayer culture with doubling times of 2-3 days, but they appeared more fibroblastic and exhibited elongated cell morphology with continued passage. The centrifugation cell adhesion assay showed that chondrocytes became more adhesive with passage as the percentage of adherent cells after centrifugation increased and was not statistically different from the adhesion of the fibroblast cell line, L929, starting at passage 3. This increased adhesiveness correlated with a shift to a fibroblastic morphology and increased collagen I mRNA expression starting at passage 2. Our findings indicate that the centrifugation cell adhesion assay may serve as a reproducible tool to track alterations in chondrocyte phenotype during their extended propagation in culture.

  2. 49 CFR 192.150 - Passage of internal inspection devices.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... devices; or (ii) If the design includes taps for lateral connections, the operator can demonstrate, based... circumstances to the use of a tap that will obstruct the passage of instrumented internal inspection devices...

  3. 4D MEMRI atlas of neonatal FVB/N mouse brain development.

    PubMed

    Szulc, Kamila U; Lerch, Jason P; Nieman, Brian J; Bartelle, Benjamin B; Friedel, Miriam; Suero-Abreu, Giselle A; Watson, Charles; Joyner, Alexandra L; Turnbull, Daniel H

    2015-09-01

    The widespread use of the mouse as a model system to study brain development has created the need for noninvasive neuroimaging methods that can be applied to early postnatal mice. The goal of this study was to optimize in vivo three- (3D) and four-dimensional (4D) manganese (Mn)-enhanced MRI (MEMRI) approaches for acquiring and analyzing data from the developing mouse brain. The combination of custom, stage-dependent holders and self-gated (motion-correcting) 3D MRI sequences enabled the acquisition of high-resolution (100-μm isotropic), motion artifact-free brain images with a high level of contrast due to Mn-enhancement of numerous brain regions and nuclei. We acquired high-quality longitudinal brain images from two groups of FVB/N strain mice, six mice per group, each mouse imaged on alternate odd or even days (6 3D MEMRI images at each day) covering the developmental stages between postnatal days 1 to 11. The effects of Mn-exposure, anesthesia and MRI were assessed, showing small but significant transient effects on body weight and brain volume, which recovered with time and did not result in significant morphological differences when compared to controls. Metrics derived from deformation-based morphometry (DBM) were used for quantitative analysis of changes in volume and position of a number of brain regions. The cerebellum, a brain region undergoing significant changes in size and patterning at early postnatal stages, was analyzed in detail to demonstrate the spatiotemporal characterization made possible by this new atlas of mouse brain development. These results show that MEMRI is a powerful tool for quantitative analysis of mouse brain development, with great potential for in vivo phenotype analysis in mouse models of neurodevelopmental diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Spontaneous passage of long, sharp gastrointestinal foreign body in a child.

    PubMed

    Karthikeyan, Vilvapathy Senguttuvan; Ansari, Mohammed Gaffoor; Suresh, Ramasamy; Easwaran, Bettaiyagowder

    2015-01-19

    Foreign body (FB) ingestion is a common problem in children. Up to 90% of these FBs pass spontaneously. FBs reaching the stomach usually pass out spontaneously. Exceptions to this spontaneous passage include a long FB that cannot cross the pylorus, duodenum or ileocaecal junction. We present a case of a 9-year boy who accidentally ingested a long paper pin, which spontaneously passed in 26 h. This case is being reported to highlight the successful spontaneous passage of a 4 cm long sharp foreign body in a child. 2015 BMJ Publishing Group Ltd.

  5. The development of inter-strain variation in cortical and trabecular traits during growth of the mouse lumbar vertebral body.

    PubMed

    Ramcharan, M A; Faillace, M E; Guengerich, Z; Williams, V A; Jepsen, K J

    2017-03-01

    How cortical and trabecular bone co-develop to establish a mechanically functional structure is not well understood. Comparing early postnatal differences in morphology of lumbar vertebral bodies for three inbred mouse strains identified coordinated changes within and between cortical and trabecular traits. These early coordinate changes defined the phenotypic differences among the inbred mouse strains. Age-related changes in cortical and trabecular traits have been well studied; however, very little is known about how these bone tissues co-develop from day 1 of postnatal growth to establish functional structures by adulthood. In this study, we aimed to establish how cortical and trabecular tissues within the lumbar vertebral body change during growth for three inbred mouse strains that express wide variation in adult bone structure and function. Bone traits were quantified for lumbar vertebral bodies of female A/J, C57BL/6J (B6), and C3H/HeJ (C3H) inbred mouse strains from 1 to 105 days of age (n = 6-10 mice/age/strain). Inter-strain differences in external bone size were observed as early as 1 day of age. Reciprocal and rapid changes in the trabecular bone volume fraction and alignment in the direction of axial compression were observed by 7 days of age. Importantly, the inter-strain difference in adult trabecular bone volume fraction was established by 7 days of age. Early variation in external bone size and trabecular architecture was followed by progressive increases in cortical area between 28 and 105 days of age, with the greatest increases in cortical area seen in the mouse strain with the lowest trabecular mass. Establishing the temporal changes in bone morphology for three inbred mouse strains revealed that genetic variation in adult trabecular traits were established early in postnatal development. Early variation in trabecular architecture preceded strain-specific increases in cortical area and changes in cortical thickness. This study

  6. Influence of long-term equine herpesvirus type 1 (EHV-1) infection on primary murine neurons-the possible effects of the multiple passages of EHV-1 on its neurovirulence.

    PubMed

    Cymerys, Joanna; Słońska, A; Tucholska, A; Golke, A; Chmielewska, A; Bańbura, M W

    2018-01-01

    Equine herpesvirus 1 (EHV-1), like other members of the Alphaherpesvirinae subfamily, is a neurotropic virus causing latent infections in the nervous system of the natural host. In the present study, we have investigated EHV-1 replication (wild-type Jan-E strain and Rac-H laboratory strain) during long-term infection and during the passages of the virus in cultured neurons. The studies were performed on primary murine neurons, which are an excellent in vitro model for studying neurotropism and neurovirulence of EHV-1. Using real-time cell growth analysis, we have demonstrated for the first time that primary murine neurons are able to survive long-term EHV-1 infection. Positive results of real-time PCR test indicated a high level of virus DNA in cultured neurons, and during long-term infection, these neurons were still able to transmit the virus to the other cells. We also compared the neurovirulence of Rac-H and Jan-E EHV-1 strains after multiple passages of these strains in neuron cell culture. The results showed that multiple passages of EHV-1 in neurons lead to the inhibition of viral replication as early as in the third passage. Interestingly, the inhibition of the EHV-1 replication occurred exclusively in neurons, because the equine dermal (ED) cells co-cultivated with neuroculture medium from the third passage showed the presence of large amount of viral DNA. In conclusion, our results showed that certain balance between EHV-1 and neurons has been established during in vitro infection allowing neurons to survive long-term infection.

  7. California's tobacco tax initiative: the development and passage of Proposition 99.

    PubMed

    Traynor, M P; Glantz, S A

    1996-01-01

    In this case study, we describe and analyze the development and passage of California's tobacco tax initiative, Proposition 99, the Tobacco Tax and Health Promotion Act of 1988. We gathered information from published reports, public documents, personal correspondence, internal memorandums, polling data, and interviews with representatives from organizations that participated in the Proposition 99 campaign. Proposition 99 passed as a result of the efforts of a coalition of voluntary health agencies, medical organizations, and environmental groups. They organized a long-term effort by conducting essential polling, planning strategies, gaining media exposure, developing a coalition, and running a successful campaign to enact the tax by shifting the venue from legislative to initiative politics. To build the coalition that was needed to pass Proposition 99, public health proponents enlisted the help of medical organizations in exchange for additional revenue to be allocated to medical services. By shifting the venue from the legislature to the general public, advocates capitalized on public concern about tobacco and for youth and took advantage of the tobacco industry's low credibility. The passage of Proposition 99, despite a massive campaign against it by the tobacco industry, represents a milestone in the tobacco control and public health fields. From its passage in 1988 through 1993, tobacco use in California declined by 27 percent, which is three times faster than the United States average. As a result, Proposition 99 has served as a national model for other states and the federal government. Although allocation of tobacco tax revenues specifically to health education and prevention was a primary goal during the development and passage of Proposition 99, when the venue shifted back to the legislature for implementation, medical organizations successfully advocated illegal diversions of Proposition 99 tobacco control and research funds to medical services

  8. Characterization of Fish Passage Conditions through a Francis Turbine, Spillway, and Regulating Outlet at Detroit Dam, Oregon, Using Sensor Fish, 2009

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

    Duncan, Joanne P.; Carlson, Thomas J.

    2011-05-06

    Fish passage conditions through two spillways, a Francis turbine, and a regulating outlet (RO) at Detroit Dam on the North Santiam River in Oregon were evaluated by Pacific Northwest National Laboratory for the U.S. Army Corps of Engineers (USACE), Portland District, using Sensor Fish devices. The objective of the study was to describe and compare passage exposure conditions, identifying potential fish injury regions within the routes. The study was performed in July, October, and December 2009 concurrent with HI-Z balloon-tag studies by Normandeau Associates, Inc. Sensor Fish data were analyzed to estimate 1) exposure conditions, particularly exposure to severe strike,more » collision, and shear events by passage route sub-regions; 2) differences in passage conditions between passage routes; and 3) relationships to live-fish injury and mortality data estimates. Comparison of the three passage routes evaluated at Detroit Dam indicates that the RO passage route through the 5-ft gate opening was relatively the safest route for fish passage under the operating conditions tested; turbine passage was the most deleterious. These observations were supported also by the survival and malady estimates obtained from live-fish testing. Injury rates were highest for turbine and spillway passage. However, none of the passage routes tested is safe for juvenile salmonid passage.« less

  9. First passage properties of a generalized Pólya urn

    NASA Astrophysics Data System (ADS)

    Kearney, Michael J.; Martin, Richard J.

    2016-12-01

    A generalized two-component Pólya urn process, parameterized by a variable α , is studied in terms of the likelihood that due to fluctuations the initially smaller population in a scenario of competing population growth eventually becomes the larger, or is the larger after a certain passage of time. By casting the problem as an inhomogeneous directed random walk we quantify this role-reversal phenomenon through the first passage probability that equality in size is first reached at a given time, and the related exit probability that equality in size is reached no later than a given time. Using an embedding technique, exact results are obtained which complement existing results and provide new insights into behavioural changes (akin to phase transitions) which occur at defined values of α .

  10. Mouse vocal communication system: are ultrasounds learned or innate?

    PubMed Central

    Arriaga, Gustavo; Jarvis, Erich D.

    2013-01-01

    Mouse ultrasonic vocalizations (USVs) are often used as behavioral readouts of internal states, to measure effects of social and pharmacological manipulations, and for behavioral phenotyping of mouse models for neuropsychiatric and neurodegenerative disorders. However, little is known about the neurobiological mechanisms of rodent USV production. Here we discuss the available data to assess whether male mouse song behavior and the supporting brain circuits resemble those of known vocal non-learning or vocal learning species. Recent neurobiology studies have demonstrated that the mouse USV brain system includes motor cortex and striatal regions, and that the vocal motor cortex sends a direct sparse projection to the brainstem vocal motor nucleus ambiguous, a projection thought be unique to humans among mammals. Recent behavioral studies have reported opposing conclusions on mouse vocal plasticity, including vocal ontogeny changes in USVs over early development that might not be explained by innate maturation processes, evidence for and against a role for auditory feedback in developing and maintaining normal mouse USVs, and evidence for and against limited vocal imitation of song pitch. To reconcile these findings, we suggest that the trait of vocal learning may not be dichotomous but encompass a broad set of behavioral and neural traits we call the continuum hypothesis, and that mice possess some of the traits associated with a capacity for limited vocal learning. PMID:23295209

  11. Analysis of conditions favourable for small vertical axis wind turbines between building passages in urban areas of Sweden

    NASA Astrophysics Data System (ADS)

    Awan, Muhammad Rizwan; Riaz, Fahid; Nabi, Zahid

    2017-05-01

    This paper presents the analysis of installing the vertical axis wind turbines between the building passages on an island in Stockholm, Sweden. Based on the idea of wind speed amplification due to the venture effect in passages, practical measurements were carried out to study the wind profile for a range of passage widths in parallel building passages. Highest increment in wind speed was observed in building passages located on the periphery of sland as wind enters from free field. Wind mapping was performed in the island to choose the most favourable location to install the vertical axis wind turbines (VAWT). Using the annual wind speed data for location and measured amplification factor, energy potential of the street was calculated. This analysis verified that small vertical axis wind turbines can be installed in the passage centre line provided that enough space is provided for traffic and passengers.

  12. Female Listeners' Autonomic Responses to Dramatic Shifts Between Loud and Soft Music/Sound Passages: A Study of Heavy Metal Songs.

    PubMed

    Cheng, Tzu-Han; Tsai, Chen-Gia

    2016-01-01

    Although music and the emotion it conveys unfold over time, little is known about how listeners respond to shifts in musical emotions. A special technique in heavy metal music utilizes dramatic shifts between loud and soft passages. Loud passages are penetrated by distorted sounds conveying aggression, whereas soft passages are often characterized by a clean, calm singing voice and light accompaniment. The present study used heavy metal songs and soft sea sounds to examine how female listeners' respiration rates and heart rates responded to the arousal changes associated with auditory stimuli. The high-frequency power of heart rate variability (HF-HRV) was used to assess cardiac parasympathetic activity. The results showed that the soft passages of heavy metal songs and soft sea sounds expressed lower arousal and induced significantly higher HF-HRVs than the loud passages of heavy metal songs. Listeners' respiration rate was determined by the arousal level of the present music passage, whereas the heart rate was dependent on both the present and preceding passages. Compared with soft sea sounds, the loud music passage led to greater deceleration of the heart rate at the beginning of the following soft music passage. The sea sounds delayed the heart rate acceleration evoked by the following loud music passage. The data provide evidence that sound-induced parasympathetic activity affects listeners' heart rate in response to the following music passage. These findings have potential implications for future research on the temporal dynamics of musical emotions.

  13. Female Listeners’ Autonomic Responses to Dramatic Shifts Between Loud and Soft Music/Sound Passages: A Study of Heavy Metal Songs

    PubMed Central

    Cheng, Tzu-Han; Tsai, Chen-Gia

    2016-01-01

    Although music and the emotion it conveys unfold over time, little is known about how listeners respond to shifts in musical emotions. A special technique in heavy metal music utilizes dramatic shifts between loud and soft passages. Loud passages are penetrated by distorted sounds conveying aggression, whereas soft passages are often characterized by a clean, calm singing voice and light accompaniment. The present study used heavy metal songs and soft sea sounds to examine how female listeners’ respiration rates and heart rates responded to the arousal changes associated with auditory stimuli. The high-frequency power of heart rate variability (HF-HRV) was used to assess cardiac parasympathetic activity. The results showed that the soft passages of heavy metal songs and soft sea sounds expressed lower arousal and induced significantly higher HF-HRVs than the loud passages of heavy metal songs. Listeners’ respiration rate was determined by the arousal level of the present music passage, whereas the heart rate was dependent on both the present and preceding passages. Compared with soft sea sounds, the loud music passage led to greater deceleration of the heart rate at the beginning of the following soft music passage. The sea sounds delayed the heart rate acceleration evoked by the following loud music passage. The data provide evidence that sound-induced parasympathetic activity affects listeners’ heart rate in response to the following music passage. These findings have potential implications for future research on the temporal dynamics of musical emotions. PMID:26925009

  14. Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum.

    PubMed

    Maltese, Marta; Stanic, Jennifer; Tassone, Annalisa; Sciamanna, Giuseppe; Ponterio, Giulia; Vanni, Valentina; Martella, Giuseppina; Imbriani, Paola; Bonsi, Paola; Mercuri, Nicola Biagio; Gardoni, Fabrizio; Pisani, Antonio

    2018-03-05

    The onset of abnormal movements in DYT1 dystonia is between childhood and adolescence, although it is unclear why clinical manifestations appear during this developmental period. Plasticity at corticostriatal synapses is critically involved in motor memory. In the Tor1a +/Δgag DYT1 dystonia mouse model, long-term potentiation (LTP) appeared prematurely in a critical developmental window in striatal spiny neurons (SPNs), while long-term depression (LTD) was never recorded. Analysis of dendritic spines showed an increase of both spine width and mature mushroom spines in Tor1a +/Δgag neurons, paralleled by an enhanced AMPA receptor (AMPAR) accumulation. BDNF regulates AMPAR expression during development. Accordingly, both proBDNF and BDNF levels were significantly higher in Tor1a +/Δgag mice. Consistently, antagonism of BDNF rescued synaptic plasticity deficits and AMPA currents. Our findings demonstrate that early loss of functional and structural synaptic homeostasis represents a unique endophenotypic trait during striatal maturation, promoting the appearance of clinical manifestations in mutation carriers. © 2018, Maltese et al.

  15. Vision-related quality of life in patients undergoing silicone tube intubation for lacrimal passage obstructions.

    PubMed

    Kabata, Yoshiaki; Goto, Satoshi; Takahashi, Genichiro; Tsuneoka, Hiroshi

    2011-07-01

    To evaluate the changes in vision-related quality of life in patients with lacrimal passage obstructions undergoing silicone tube intubations. Prospective, consecutive, comparative, interventional case series. Forty-five patients with the chief complaint of epiphora diagnosed with complete and unilateral lacrimal passage obstructions were enrolled. Exclusion criteria included history of congenital nasolacrimal stenosis; lacrimal passage obstructions resulting from trauma, tumor, or chemotherapy; previous lacrimal passage surgery; and partial and functional nasolacrimal duct obstructions. Silicone tube intubation using a Nunchaku-style tube was performed under direct visualization with dacryoendoscope in all patients. Operations were considered as successful when the irrigating fluid could pass through the lacrimal passage and the disappearance of dye was observed in dye disappearance test and the patients' epiphora symptoms improved 3 months postoperatively. The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was self-administered in all patients preoperatively and 3 months postoperatively. Patients' preoperative and 3-months-postoperative NEI VFQ-25 scores were compared. Operations were successful in 40 patients (89%). Fully completed questionnaires were received from 32 patients (80%). Silicone tube intubation using a Nunchaku-style tube was associated with a significant improvement of the NEI VFQ-25 composite score (P = .0001), ocular pain score (P < .0001), and mental health score (P = .0003). Relief of epiphora by silicone tube intubation using a Nunchaku-style tube treatment significantly improved the vision-related quality of life in patients with lacrimal passage obstructions. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Phase Variation Analysis of Coxiella burnetii during Serial Passage in Cell Culture by Use of Monoclonal Antibodies

    PubMed Central

    Hotta, Akitoyo; Kawamura, Midori; To, Ho; Andoh, Masako; Yamaguchi, Tsuyoshi; Fukushi, Hideto; Hirai, Katsuya

    2002-01-01

    Antigenic changes in Coxiella burnetii Nine Mile strain phase I during serial passages in cell culture were analyzed with three groups of monoclonal antibodies (MAbs) against lipopolysaccharide. The MAbs of group 1 did not react with organisms that were passaged over five times, and the MAbs of group 2 did not react with organisms that were passaged over eight times. The MAbs of group 3 reacted with organisms passaged up to 15 times but did not react with phase II cells. These results suggest that C. burnetii could be differentiated into four phase states during phase variation. PMID:12117996

  17. High-fat, high-calorie diet promotes early pancreatic neoplasia in the conditional KrasG12D mouse model.

    PubMed

    Dawson, David W; Hertzer, Kathleen; Moro, Aune; Donald, Graham; Chang, Hui-Hua; Go, Vay Liang; Pandol, Steven J; Lugea, Aurelia; Gukovskaya, Anna S; Li, Gang; Hines, Oscar J; Rozengurt, Enrique; Eibl, Guido

    2013-10-01

    There is epidemiologic evidence that obesity increases the risk of cancers. Several underlying mechanisms, including inflammation and insulin resistance, are proposed. However, the driving mechanisms in pancreatic cancer are poorly understood. The goal of the present study was to develop a model of diet-induced obesity and pancreatic cancer development in a state-of-the-art mouse model, which resembles important clinical features of human obesity, for example, weight gain and metabolic disturbances. Offspring of Pdx-1-Cre and LSL-KrasG12D mice were allocated to either a high-fat, high-calorie diet (HFCD; ∼4,535 kcal/kg; 40% of calories from fats) or control diet (∼3,725 kcal/kg; 12% of calories from fats) for 3 months. Compared with control animals, mice fed with the HFCD significantly gained more weight and developed hyperinsulinemia, hyperglycemia, hyperleptinemia, and elevated levels of insulin-like growth factor I (IGF-I). The pancreas of HFCD-fed animals showed robust signs of inflammation with increased numbers of infiltrating inflammatory cells (macrophages and T cells), elevated levels of several cytokines and chemokines, increased stromal fibrosis, and more advanced PanIN lesions. Our results show that a diet high in fats and calories leads to obesity and metabolic disturbances similar to humans and accelerates early pancreatic neoplasia in the conditional KrasG12D mouse model. This model and findings will provide the basis for more robust studies attempting to unravel the mechanisms underlying the cancer-promoting properties of obesity, as well as to evaluate dietary- and chemopreventive strategies targeting obesity-associated pancreatic cancer development.

  18. Validation of a Functional Pyelocalyceal Renal Model for the Evaluation of Renal Calculi Passage While Riding a Roller Coaster.

    PubMed

    Mitchell, Marc A; Wartinger, David D

    2016-10-01

    The identification and evaluation of activities capable of dislodging calyceal renal calculi require a patient surrogate or validated functional pyelocalyceal renal model. To evaluate roller coaster facilitation of calyceal renal calculi passage using a functional pyelocalyceal renal model. A previously described adult ureteroscopy and renoscopy simulator (Ideal Anatomic) was modified and remolded to function as a patient surrogate. Three renal calculi of different sizes from the patient who provided the original computed tomographic urograph on which the simulator was based were used. The renal calculi were suspended in urine in the model and taken for 20 rides on the Big Thunder Mountain Railroad roller coaster at Walt Disney World in Orlando, Florida. The roller coaster rides were analyzed using variables of renal calculi volume, calyceal location, model position on the roller coaster, and renal calculi passage. Sixty renal calculi rides were analyzed. Independent of renal calculi volume and calyceal location, front seating on the roller coaster resulted in a passage rate of 4 of 24. Independent of renal calculi volume and calyceal location, rear seating on the roller coaster resulted in a passage rate of 23 of 36. Independent of renal calculi volume in rear seating, calyceal location differed in passage rates, with an upper calyceal calculi passage rate of 100%; a middle calyceal passage rate of 55.6%; and a lower calyceal passage rate of 40.0%. The functional pyelocalyceal renal model serves as a functional patient surrogate to evaluate activities that facilitate calyceal renal calculi passage. The rear seating position on the roller coaster led to the most renal calculi passages.

  19. Characterization of Fish Passage Conditions through a Francis Turbine and Regulating Outlet at Cougar Dam, Oregon, Using Sensor Fish, 2009–2010

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

    Duncan, Joanne P.

    2011-05-23

    Fish passage conditions through a Francis turbine and a regulating outlet (RO) at Cougar Dam on the south fork of the McKenzie River in Oregon were evaluated by Pacific Northwest National Laboratory for the U.S. Army Corps of Engineers, Portland District, using Sensor Fish devices. The objective of the study was to describe and compare passage exposure conditions, identifying potential fish injury regions encountered during passage via specific routes. The RO investigation was performed in December 2009 and the turbine evaluation in January 2010, concurrent with HI-Z balloon-tag studies by Normandeau Associates, Inc. Sensor Fish data were analyzed to estimatemore » 1) exposure conditions, particularly exposure to severe collision, strike, and shear events by passage route sub-regions; 2) differences in passage conditions between passage routes; and 3) relationships to live-fish injury and mortality data estimates. Comparison of the three passage routes evaluated at Cougar Dam indicates that the RO passage route through the 3.7-ft gate opening was relatively the safest route for fish passage under the operating conditions tested; turbine passage was the most deleterious. These observations were supported also by the survival and malady estimates obtained from live-fish testing. Injury rates were highest for turbine passage. Compared to mainstem Columbia River passage routes, none of the Cougar Dam passage routes as tested are safe for juvenile salmonid passage.« less

  20. Investigating passage of ESA-listed juvenile fall Chinook salmon at Lower Granite Dam during winter when the fish bypass system is not operated. 2006 Annual Report

    USGS Publications Warehouse

    Tiffan, Kenneth F.; Kock, Tobias J.; Connor, William P.

    2007-01-01

    During the winter of 2005-06, we radio and PIT tagged and released 48 juvenile fall Chinook salmon to evaluate over-wintering behavior and dam passage in the lower Snake River, Washington. Fish were released at the upstream end of the Lower Granite Dam forebay in November and December 2005. Fixed radio telemetry detection sites located in forebay and tailrace areas of Lower Granite, Little Goose, Lower Monumental and Ice Harbor dams were used to monitor fish movements and dam passage through early-May 2006. Of the 48 fish released during our study, 39 (81 %) passed Lower Granite Dam and were detected at downstream detection sites, 29 (60%) passed Little Goose Dam, 25 (52%) passed Lower Monumental Dam, and 15 (31%) passed Ice Harbor Dam. Thirty-seven (95%), 23 (79%), 16 (64%), and 9 (60%) of the fish that passed Lower Granite, Little Goose, Lower Monumental, and Ice Harbor dams respectively, did so when the fish bypass system was not operated. Passage of tagged fish past lower Snake River dams generally declined during the winter, but increased again after bypass began in April. Fish residence times in reservoirs and forebays was lengthy during the winter (up to 118 d), and varied by reservoir and time of year. We observed no diel passage trends. Only 15 of the 48 fish were subsequently detected at a PIT-tag interrogation site the following spring. We believe that passage of overwintering juvenile fall Chinook salmon during winter is due more to chance than directed downstream movement. Since the primary route of passage during the winter is through powerhouse turbines, the potential exists for increased mortality for over-wintering juvenile fall Chinook salmon in the Snake River. Our findings also have implications for transportation studies of subyearling fall Chinook salmon in the Snake River. Specifically, the finding that some fish can pass undetected during the winter may bias smolt-to-adult return rate calculations that are typically used to measure the

  1. 33 CFR 110.245 - Vieques Passage and Vieques Sound, near Vieques Island, P.R.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Vieques Passage and Vieques Sound, near Vieques Island, P.R. 110.245 Section 110.245 Navigation and Navigable Waters COAST GUARD... and Vieques Sound, near Vieques Island, P.R. (a) The anchorage grounds—(1) Vieques Passage explosives...

  2. 33 CFR 110.245 - Vieques Passage and Vieques Sound, near Vieques Island, P.R.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Vieques Passage and Vieques Sound, near Vieques Island, P.R. 110.245 Section 110.245 Navigation and Navigable Waters COAST GUARD... and Vieques Sound, near Vieques Island, P.R. (a) The anchorage grounds—(1) Vieques Passage explosives...

  3. 33 CFR 110.245 - Vieques Passage and Vieques Sound, near Vieques Island, P.R.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Vieques Passage and Vieques Sound, near Vieques Island, P.R. 110.245 Section 110.245 Navigation and Navigable Waters COAST GUARD... and Vieques Sound, near Vieques Island, P.R. (a) The anchorage grounds—(1) Vieques Passage explosives...

  4. Comparison of Methods for Demonstrating Passage of Time When Using Computer-Based Video Prompting

    ERIC Educational Resources Information Center

    Mechling, Linda C.; Bryant, Kathryn J.; Spencer, Galen P.; Ayres, Kevin M.

    2015-01-01

    Two different video-based procedures for presenting the passage of time (how long a step lasts) were examined. The two procedures were presented within the framework of video prompting to promote independent multi-step task completion across four young adults with moderate intellectual disability. The two procedures demonstrating passage of the…

  5. Review and status of heat-transfer technology for internal passages of air-cooled turbine blades

    NASA Technical Reports Server (NTRS)

    Yeh, F. C.; Stepka, F. S.

    1984-01-01

    Selected literature on heat-transfer and pressure losses for airflow through passages for several cooling methods generally applicable to gas turbine blades is reviewed. Some useful correlating equations are highlighted. The status of turbine-blade internal air-cooling technology for both nonrotating and rotating blades is discussed and the areas where further research is needed are indicated. The cooling methods considered include convection cooling in passages, impingement cooling at the leading edge and at the midchord, and convection cooling in passages, augmented by pin fins and the use of roughened internal walls.

  6. Amino Acid Residue at Position 79 of Marburg Virus VP40 Confers Interferon Antagonism in Mouse Cells.

    PubMed

    Feagins, Alicia R; Basler, Christopher F

    2015-10-01

    Marburg viruses (MARVs) cause highly lethal infections in humans and nonhuman primates. Mice are not generally susceptible to MARV infection; however, if the strain is first adapted to mice through serial passaging, it becomes able to cause disease in this animal. A previous study correlated changes accrued during mouse adaptation in the VP40 gene of a MARV strain known as Ravn virus (RAVV) with an increased capacity to inhibit interferon (IFN) signaling in mouse cell lines. The MARV strain Ci67, which belongs to a different phylogenetic clade than RAVV, has also been adapted to mice and in the process the Ci67 VP40 acquired a different collection of genetic changes than did RAVV VP40. Here, we demonstrate that the mouse-adapted Ci67 VP40 more potently antagonizes IFN-α/β-induced STAT1 and STAT2 tyrosine phosphorylation, gene expression, and antiviral activity in both mouse and human cell lines, compared with the parental Ci67 VP40. Ci67 VP40 is also demonstrated to target the activation of kinase Jak1. A single change at VP40 residue 79 was found to be sufficient for the increased VP40 IFN antagonism. These data argue that VP40 IFN-antagonist activity plays a key role in MARV pathogenesis in mice. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Performance of the SERI parallel-passage dehumidifer

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

    Schlepp, D.; Barlow, R.

    1984-09-01

    The key component in improving the performance of solar desiccant cooling systems is the dehumidifier. A parallel-passage geometry for the desiccant dehumidifier has been identified as meeting key criteria of low pressure drop, high mass transfer efficiency, and compact size. An experimental program to build and test a small-scale prototype of this design was undertaken in FY 1982, and the results are presented in this report. Computer models to predict the adsorption/desorption behavior of desiccant dehumidifiers were updated to take into account the geometry of the bed and predict potential system performance using the new component design. The parallel-passage designmore » proved to have high mass transfer effectiveness and low pressure drop over a wide range of test conditions typical of desiccant cooling system operation. The prototype dehumidifier averaged 93% effectiveness at pressure drops of less than 50 Pa at design point conditions. Predictions of system performance using models validated with the experimental data indicate that system thermal coefficients of performance (COPs) of 1.0 to 1.2 and electrical COPs above 8.5 are possible using this design.« less

  8. Bathymetry and oceanic flow structure at two deep passages crossing the Lomonosov Ridge

    NASA Astrophysics Data System (ADS)

    Björk, Göran; Jakobsson, Martin; Assmann, Karen; Andersson, Leif G.; Nilsson, Johan; Stranne, Christian; Mayer, Larry

    2018-01-01

    The Lomonosov Ridge represents a major topographical feature in the Arctic Ocean which has a large effect on the water circulation and the distribution of water properties. This study presents detailed bathymetric survey data along with hydrographic data at two deep passages across the ridge: a southern passage (80-81° N), where the ridge crest meets the Siberian continental slope, and a northern passage around 84.5° N. The southern channel is characterized by smooth and flat bathymetry around 1600-1700 m with a sill depth slightly shallower than 1700 m. A hydrographic section across the channel reveals an eastward flow with Amundsen Basin properties in the southern part and a westward flow of Makarov Basin properties in the northern part. The northern passage includes an approximately 72 km long and 33 km wide trough which forms an intra-basin in the Lomonosov Ridge morphology (the Oden Trough). The eastern side of the Oden Trough is enclosed by a narrow and steep ridge rising 500-600 m above a generally 1600 m deep trough bottom. The deepest passage (the sill) is 1470 m deep and located on this ridge. Hydrographic data show irregular temperature and salinity profiles indicating that water exchange occurs as midwater intrusions bringing water properties from each side of the ridge in well-defined but irregular layers. There is also morphological evidence that some rather energetic flows may occur in the vicinity of the sill. A well expressed deepening near the sill may be the result of seabed erosion by bottom currents.

  9. Meridional contrasts in productivity changes driven by the Cenozoic opening of Drake Passage

    NASA Astrophysics Data System (ADS)

    Donnadieu, Y.; Ladant, J. B.; Bopp, L.; Wilson, P. A.; Lear, C. H.

    2017-12-01

    The progressive opening of Drake Passage across the Eocene and the Oligocene occurs contemporaneously to the long-term global cooling of the late Eocene, which culminated with the Eocene-Oligocene glaciation of Antarctica. Atmospheric pCO2 decline during the late Eocene is thought to have played a major role in the climatic shifts of the Eocene-Oligocene boundary, yet reasons behind CO2 variations remain obscure. Changes in marine productivity affecting the biological oceanic carbon pump represent a possible cause. Here, we explore whether and how the opening of Drake Passage may have affected the marine biogeochemistry, and in particular paleoproductivity changes, with the use of a fully coupled atmosphere-ocean-biogeochemical model (IPSL-CM5A). We find that the simulated changes to Drake Passage opening exhibit a uniform decrease in the low latitudes while the high latitude response is more spatially heterogeneous. Mechanistically, the low latitude productivity decrease is a consequence of the dramatic reorganization of the ocean circulation when Drake Passage opens, as the shift from a well ventilated to a swampier ocean drives nutrient depletion in the low latitudes. In the high latitudes, the onset of the Antarctic Circumpolar Current in the model exerts a strong control both on nutrient availability but also on regions of deep water formation, which results in non-uniform patterns of productivity change in the Southern Ocean. The qualitative agreement between geographically diverse long-term paleoproductivity records and the simulated variations suggests that the opening of Drake Passage may contribute to part of the long-term paleoproductivity signal recorded in the data.

  10. Juvenile and resident salmonid movement and passage through culverts

    DOT National Transportation Integrated Search

    1998-07-01

    An outcome of the Washington State Department of Transportation's Juvenile Fish Passage Workshop on September 24, 1997, was agreement that a literature review was necessary to determine the state of knowledge about juvenile salmonid movement and pass...

  11. Can Ureteral Jet Flow Measurement Predict Spontaneous Passage of Distal Ureteral Stones?

    PubMed

    Ongun, Sakir; Teken, Abdurrazak; Yılmaz, Orkun; Süleyman, Sakir

    2018-06-27

    The study aimed to investigate the relationship between the spontaneous passage of distal ureteral stones and ureteral jet flow measurement. The study included 74 patients with acute renal colic between June 2015 and June 2016, and distal ureteral stones of 10 mm or less in a non-contrast CT were comprised in a prospective study. The ureteral jet was measured by Doppler ultrasonography. At the fourth week follow-up, kidney-ureter-bladder radiography was taken and the patients who no longer had a stone were considered to have spontaneously passed it. The average stone size of the patients was 5.6 ± 2.0 mm. After 4 weeks of follow-up, 55 patients (74.3%) had passed the stone spontaneously whereas 19 (25.6%) had not. The patients in the former group were found to have a higher peak flow velocity of ureteral jet on the stone side than those in the latter group. In regression analysis ureteral jet on the stone side was independently associated with spontaneous passage (p = 0.027). For the spontaneous passage, a ureteral jet flow peak velocity above 15.25 cm/s had an 85.4% sensitivity and 63.1% specificity. Measurement of the ureteral jet flow peak velocity can be beneficial in predicting the potential spontaneous passage of distal ureteral stones. © 2018 S. Karger AG, Basel.

  12. Dosimetric characteristics of PASSAG as a new polymer gel dosimeter with negligible toxicity

    NASA Astrophysics Data System (ADS)

    Farhood, Bagher; Abtahi, Seyed Mohammad Mahdi; Geraily, Ghazale; Ghorbani, Mehdi; Mahdavi, Seied Rabi; Zahmatkesh, Mohammad Hasan

    2018-06-01

    Despite many advantages of polymer gel dosimeters, their clinical use is only not realized now. Toxicity of polymer gel dosimeters can be considered as one of their main limitations for use in routine clinical applications. In the current study, a new polymer gel dosimeter is introduced with negligible toxicity. For this purpose, 2-Acrylamido-2-Methy-1-PropaneSulfonic acid (AMPS) sodium salt monomer was replaced instead of acrylamide monomer used in PAGAT gel dosimeter by using %6 T and %50 C to the gel formula and the new formulation is called PASSAG (Poly AMPS Sodium Salt and Gelatin) polymer gel dosimeter. The irradiation of gel dosimeters was carried out using a Co-60 therapy machine. MRI technique was used to quantify the dose responses of the PASSAG gel dosimeter. Then, the MRI responses (R2) of the gel dosimeter was analyzed at different dose values, post-irradiation times, and scanning temperatures. The results showed that the new gel formulation has a negligible toxicity and it is also eco-friendly. In addition, carcinogenicity and genetic toxicity tests are negative for the monomer used in PASSAG. The radiological properties of PASSAG gel dosimeter showed that this substance can be considered as a soft tissue/water equivalent material. Furthermore, dosimetric evaluation of the new polymer gel dosimeter revealed an excellent linear R2-dose response in the evaluated dose range (0-15 Gy). The R2-dose sensitivity and dose resolution of PASSAG gel dosimeter were 0.081 s-1Gy-1 (in 0-15 Gy dose range) and 1 Gy (in 0-10 Gy dose range), respectively. Moreover, it was shown that the R2-dose sensitivity and dose resolution of the new gel dosimeter improves over time after irradiation. It was also found that the R2 response of the PASSAG gel dosimeter has less dependency to the 18, 20, and 24 °C scanning temperature in comparison to that of room temperature (22 °C).

  13. Targeting early PKCθ-dependent T-cell infiltration of dystrophic muscle reduces disease severity in a mouse model of muscular dystrophy.

    PubMed

    Lozanoska-Ochser, Biliana; Benedetti, Anna; Rizzo, Giuseppe; Marrocco, Valeria; Di Maggio, Rosanna; Fiore, Piera; Bouche, Marina

    2018-03-01

    Chronic muscle inflammation is a critical feature of Duchenne muscular dystrophy and contributes to muscle fibre injury and disease progression. Although previous studies have implicated T cells in the development of muscle fibrosis, little is known about their role during the early stages of muscular dystrophy. Here, we show that T cells are among the first cells to infiltrate mdx mouse dystrophic muscle, prior to the onset of necrosis, suggesting an important role in early disease pathogenesis. Based on our comprehensive analysis of the kinetics of the immune response, we further identify the early pre-necrotic stage of muscular dystrophy as the relevant time frame for T-cell-based interventions. We focused on protein kinase C θ (PKCθ, encoded by Prkcq), a critical regulator of effector T-cell activation, as a potential target to inhibit T-cell activity in dystrophic muscle. Lack of PKCθ not only reduced the frequency and number of infiltrating T cells but also led to quantitative and qualitative changes in the innate immune cell infiltrate in mdx/Prkcq -/- muscle. These changes were due to the inhibition of T cells, since PKCθ was necessary for T-cell but not for myeloid cell infiltration of acutely injured muscle. Targeting T cells with a PKCθ inhibitor early in the disease process markedly diminished the size of the inflammatory cell infiltrate and resulted in reduced muscle damage. Moreover, diaphragm necrosis and fibrosis were also reduced following treatment. Overall, our findings identify the early T-cell infiltrate as a therapeutic target and highlight the potential of PKCθ inhibition as a therapeutic approach to muscular dystrophy. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  14. "Forward To the Past": Africentric Rites of Passage.

    ERIC Educational Resources Information Center

    Hill, Paul, Jr.

    No ceremony or rite exists to usher the African American male youth into proper manhood. Such ceremonies, referred to as rites of passage, mark commonly agreed-upon standards, activities, tasks, and trials that each youth must master to achieve the community-sanctioned title "man." The clear articulation and subsequent implementation of…

  15. An Incidence Loss Model for Wave Rotors with Axially Aligned Passages

    NASA Technical Reports Server (NTRS)

    Paxson, Daniel E.

    1998-01-01

    A simple mathematical model is described to account for the losses incurred when the flow in the duct (port) of a wave rotor is not aligned with the passages. The model, specifically for wave rotors with axially aligned passages, describes a loss mechanism which is sensitive to incident flow angle and Mach number. Implementation of the model in a one-dimensional CFD based wave rotor simulation is presented. Comparisons with limited experimental results are consistent with the model. Sensitivity studies are presented which highlight the significance of the incidence loss relative to other loss mechanisms in the wave rotor.

  16. Anesthetic Sevoflurane Causes Rho-Dependent Filopodial Shortening in Mouse Neurons.

    PubMed

    Zimering, Jeffrey H; Dong, Yuanlin; Fang, Fang; Huang, Lining; Zhang, Yiying; Xie, Zhongcong

    2016-01-01

    Early postnatal anesthesia causes long-lasting learning and memory impairment in rodents, however, evidence for a specific neurotoxic effect on early synaptogenesis has not been demonstrated. Drebrin A is an actin binding protein whose localization in dendritic protrusions serves an important role in dendritic spine morphogenesis, and is a marker for early synaptogenesis. We therefore set out to investigate whether clinically-relevant concentrations of anesthetic sevoflurane, widely- used in infants and children, alters dendritic morphology in cultured fetal day 16 mouse hippocampal neurons. After 7 days in vitro, mouse hippocampal neurons were exposed to four hours of 3% sevoflurane in 95% air/5% CO2 or control condition (95% air/5% CO2). Neurons were fixed in 4% paraformaldehyde and stained with Alexa Fluor555-Phalloidin, and/or rabbit anti-mouse drebrin A/E antibodies which permitted subcellular localization of filamentous (F)-actin and/or drebrin immunoreactivity, respectively. Sevoflurane caused acute significant length-shortening in filopodia and thin dendritic spines in days-in-vitro 7 neurons, an effect which was completely rescued by co-incubating neurons with ten micromolar concentrations of the selective Rho kinase inhibitor Y27632. Filopodia and thin spine recovered in length two days after sevoflurane exposure. Yet cluster-type filopodia (a precursor to synaptic filopodia) were persistently significantly decreased in number on day-in-vitro 9, in part owing to preferential localization of drebrin immunoreactivity to dendritic shafts versus filopodial stalks. These data suggest that sevoflurane induces F-actin depolymerization leading to acute, reversible length-shortening in dendritic protrusions through a mechanism involving (in part) activation of RhoA/Rho kinase signaling and impairs localization of drebrin A to filopodia required for early excitatory synapse formation.

  17. Pipette-based Method to Study Embryoid Body Formation Derived from Mouse and Human Pluripotent Stem Cells Partially Recapitulating Early Embryonic Development Under Simulated Microgravity Conditions

    NASA Astrophysics Data System (ADS)

    Shinde, Vaibhav; Brungs, Sonja; Hescheler, Jürgen; Hemmersbach, Ruth; Sachinidis, Agapios

    2016-06-01

    The in vitro differentiation of pluripotent stem cells partially recapitulates early in vivo embryonic development. More recently, embryonic development under the influence of microgravity has become a primary focus of space life sciences. In order to integrate the technique of pluripotent stem cell differentiation with simulated microgravity approaches, the 2-D clinostat compatible pipette-based method was experimentally investigated and adapted for investigating stem cell differentiation processes under simulated microgravity conditions. In order to keep residual accelerations as low as possible during clinorotation, while also guaranteeing enough material for further analysis, stem cells were exposed in 1-mL pipettes with a diameter of 3.5 mm. The differentiation of mouse and human pluripotent stem cells inside the pipettes resulted in the formation of embryoid bodies at normal gravity (1 g) after 24 h and 3 days. Differentiation of the mouse pluripotent stem cells on a 2-D pipette-clinostat for 3 days also resulted in the formation of embryoid bodies. Interestingly, the expression of myosin heavy chain was downregulated when cultivation was continued for an additional 7 days at normal gravity. This paper describes the techniques for culturing and differentiation of pluripotent stem cells and exposure to simulated microgravity during culturing or differentiation on a 2-D pipette clinostat. The implementation of these methodologies along with -omics technologies will contribute to understand the mechanisms regulating how microgravity influences early embryonic development.

  18. Mean first passage time for random walk on dual structure of dendrimer

    NASA Astrophysics Data System (ADS)

    Li, Ling; Guan, Jihong; Zhou, Shuigeng

    2014-12-01

    The random walk approach has recently been widely employed to study the relations between the underlying structure and dynamic of complex systems. The mean first-passage time (MFPT) for random walks is a key index to evaluate the transport efficiency in a given system. In this paper we study analytically the MFPT in a dual structure of dendrimer network, Husimi cactus, which has different application background and different structure (contains loops) from dendrimer. By making use of the iterative construction, we explicitly determine both the partial mean first-passage time (PMFT, the average of MFPTs to a given target) and the global mean first-passage time (GMFT, the average of MFPTs over all couples of nodes) on Husimi cactus. The obtained closed-form results show that PMFPT and EMFPT follow different scaling with the network order, suggesting that the target location has essential influence on the transport efficiency. Finally, the impact that loop structure could bring is analyzed and discussed.

  19. Understanding the Microstructure and Macrostructure of Passages Among Chinese Elementary School Children.

    PubMed

    Lo, Lap-Yan; Ho, Connie Suk-Han; Wong, Yau-Kai; Chan, David Wai-Ock; Chung, Kevin Kien-Hoa

    2016-12-01

    Understanding the microstructure and macrostructure of passages is important for reading comprehension. What cognitive-linguistic skills may contribute to understanding these two levels of structures has rarely been investigated. The present study examined whether some word-level and text-level cognitive-linguistic skills may contribute differently to the understanding of microstructure and macrostructure respectively. Seventy-nine Chinese elementary school children were tested on some cognitive-linguistic skills and literacy skills. It was found that word reading fluency and syntactic skills predicted significantly the understanding of microstructure of passages after controlling for age and IQ; while morphological awareness, syntactic skills, and discourse skills contributed significantly to understanding of macrostructure. These findings suggest that syntactic skills facilitate children's access of meaning from grammatical structures, which is a fundamental process in gaining text meaning at any level of reading comprehension. Discourse skills also allow readers to understand the cohesive interlinks within and between sentences and is important for a macro level of passage understanding.

  20. Evolutionary characteristics of morbilliviruses during serial passages in vitro: Gradual attenuation of virus virulence.

    PubMed

    Liu, Fuxiao; Wu, Xiaodong; Li, Lin; Zou, Yanli; Liu, Shan; Wang, Zhiliang

    2016-08-01

    The genus Morbillivirus is classified into the family Paramyxoviridae, and is composed of 6 members, namely measles virus (MV), rinderpest virus (RPV), peste-des-petits-ruminants virus (PPRV), canine distemper virus (CDV), phocine distemper virus (PDV) and cetacean morbillivirus (CeMV). The MV, RPV, PPRV and CDV have been successfully attenuated through their serial passages in vitro for the production of live vaccines. It has been demonstrated that the morbilliviral virulence in animals was progressively attenuated with their consecutive passages in vitro. However, only a few reports were involved in explanation of an attenuation-related mechanism on them until many years after the establishment of a quasispecies theory. RNA virus quasispecies arise from rapid evolution of viruses with high mutation rate during genomic replication, and play an important role in gradual loss of viral virulence by serial passages. Here, we overviewed the development of live-attenuated vaccine strains against morbilliviruses by consecutive passages in vitro, and further discussed a related mechanism concerning the relationship between virulence attenuation and viral evolution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Mouse Mix gene is activated early during differentiation of ES and F9 stem cells and induces endoderm in frog embryos.

    PubMed

    Mohn, Deanna; Chen, Siming W; Dias, Dora Campos; Weinstein, Daniel C; Dyer, Michael A; Sahr, Kenneth; Ducker, Charles E; Zahradka, Elizabeth; Keller, Gordon; Zaret, Kenneth S; Gudas, Lorraine J; Baron, Margaret H

    2003-03-01

    In frog and zebrafish, the Mix/Bix family of paired type homeodomain proteins play key roles in specification and differentiation of mesendoderm. However, in mouse, only a single Mix gene (mMix) has been identified to date and its function is unknown. We have analyzed the expression of mouse Mix RNA and protein in embryos, embryoid bodies formed from embryonic stem cells and F9 teratocarcinoma cells, as well as several differentiated cell types. Expression in embryoid bodies in culture mirrors that in embryos, where Mix is transcribed transiently in primitive (visceral) endoderm (VE) and in nascent mesoderm. In F9 cells induced by retinoic acid to differentiate to VE, mMix is coordinately expressed with three other endodermal transcription factors, well before AFP, and its protein product is localized to the nucleus. In a subpopulation of nascent mesodermal cells from embryonic stem cell embryoid bodies, mMix is coexpressed with Brachyury. Intriguingly, mMix mRNA is detected in a population (T+Flk1+) of cells which may contain hemangioblasts, before the onset of hematopoiesis and activation of hematopoietic markers. In vitro and in vivo, mMix expression in nascent mesoderm is rapidly down-regulated and becomes undetectable in differentiated cell types. In the region of the developing gut, mMix expression is confined to the mesoderm of mid- and hindgut but is absent from definitive endoderm. Injection of mouse mMix RNA into early frog embryos results in axial truncation of developing tadpoles and, in animal cap assays, mMix alone is sufficient to activate expression of several endodermal (but not mesodermal) markers. Although these observations do not exclude a possible cell-autonomous function for mMix in mesendodermal progenitor cells, they do suggest an additional, non-cell autonomous role in nascent mesoderm in the formation and/or patterning of adjacent definitive endoderm. Copyright 2003 Wiley-Liss, Inc.

  2. Identification of an epigenetic signature of early mouse liver regeneration that is disrupted by Zn-HDAC inhibition.

    PubMed

    Huang, Jiansheng; Schriefer, Andrew E; Yang, Wei; Cliften, Paul F; Rudnick, David A

    2014-11-01

    Liver regeneration has been well studied with hope of discovering strategies to improve liver disease outcomes. Nevertheless, the signals that initiate such regeneration remain incompletely defined, and translation of mechanism-based pro-regenerative interventions into new treatments for hepatic diseases has not yet been achieved. We previously reported the isoform-specific regulation and essential function of zinc-dependent histone deacetylases (Zn-HDACs) during mouse liver regeneration. Those data suggest that epigenetically regulated anti-proliferative genes are deacetylated and transcriptionally suppressed by Zn-HDAC activity or that pro-regenerative factors are acetylated and induced by such activity in response to partial hepatectomy (PH). To investigate these possibilities, we conducted genome-wide interrogation of the liver histone acetylome during early PH-induced liver regeneration in mice using acetyL-histone chromatin immunoprecipitation and next generation DNA sequencing. We also compared the findings of that study to those seen during the impaired regenerative response that occurs with Zn-HDAC inhibition. The results reveal an epigenetic signature of early liver regeneration that includes both hyperacetylation of pro-regenerative factors and deacetylation of anti-proliferative and pro-apoptotic genes. Our data also show that administration of an anti-regenerative regimen of the Zn-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) not only disrupts gene-specific pro-regenerative changes in liver histone deacetylation but also reverses PH-induced effects on histone hyperacetylation. Taken together, these studies offer new insight into and suggest novel hypotheses about the epigenetic mechanisms that regulate liver regeneration.

  3. Identification of an epigenetic signature of early mouse liver regeneration that is disrupted by Zn-HDAC inhibition

    PubMed Central

    Huang, Jiansheng; Schriefer, Andrew E; Yang, Wei; Cliften, Paul F; Rudnick, David A

    2014-01-01

    Liver regeneration has been well studied with hope of discovering strategies to improve liver disease outcomes. Nevertheless, the signals that initiate such regeneration remain incompletely defined, and translation of mechanism-based pro-regenerative interventions into new treatments for hepatic diseases has not yet been achieved. We previously reported the isoform-specific regulation and essential function of zinc-dependent histone deacetylases (Zn-HDACs) during mouse liver regeneration. Those data suggest that epigenetically regulated anti-proliferative genes are deacetylated and transcriptionally suppressed by Zn-HDAC activity or that pro-regenerative factors are acetylated and induced by such activity in response to partial hepatectomy (PH). To investigate these possibilities, we conducted genome-wide interrogation of the liver histone acetylome during early PH-induced liver regeneration in mice using acetyL-histone chromatin immunoprecipitation and next generation DNA sequencing. We also compared the findings of that study to those seen during the impaired regenerative response that occurs with Zn-HDAC inhibition. The results reveal an epigenetic signature of early liver regeneration that includes both hyperacetylation of pro-regenerative factors and deacetylation of anti-proliferative and pro-apoptotic genes. Our data also show that administration of an anti-regenerative regimen of the Zn-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) not only disrupts gene-specific pro-regenerative changes in liver histone deacetylation but also reverses PH-induced effects on histone hyperacetylation. Taken together, these studies offer new insight into and suggest novel hypotheses about the epigenetic mechanisms that regulate liver regeneration. PMID:25482284

  4. Highly efficient methods to obtain homogeneous dorsal neural progenitor cells from human and mouse embryonic stem cells and induced pluripotent stem cells.

    PubMed

    Zhang, Meixiang; Ngo, Justine; Pirozzi, Filomena; Sun, Ying-Pu; Wynshaw-Boris, Anthony

    2018-03-15

    Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been widely used to generate cellular models harboring specific disease-related genotypes. Of particular importance are ESC and iPSC applications capable of producing dorsal telencephalic neural progenitor cells (NPCs) that are representative of the cerebral cortex and overcome the challenges of maintaining a homogeneous population of cortical progenitors over several passages in vitro. While previous studies were able to derive NPCs from pluripotent cell types, the fraction of dorsal NPCs in this population is small and decreases over several passages. Here, we present three protocols that are highly efficient in differentiating mouse and human ESCs, as well as human iPSCs, into a homogeneous and stable population of dorsal NPCs. These protocols will be useful for modeling cerebral cortical neurological and neurodegenerative disorders in both mouse and human as well as for high-throughput drug screening for therapeutic development. We optimized three different strategies for generating dorsal telencephalic NPCs from mouse and human pluripotent cell types through single or double inhibition of bone morphogenetic protein (BMP) and/or SMAD pathways. Mouse and human pluripotent cells were aggregated to form embryoid bodies in suspension and were treated with dorsomorphin alone (BMP inhibition) or combined with SB431542 (double BMP/SMAD inhibition) during neural induction. Neural rosettes were then selected from plated embryoid bodies to purify the population of dorsal NPCs. We tested the expression of key dorsal NPC markers as well as nonectodermal markers to confirm the efficiency of our three methods in comparison to published and commercial protocols. Single and double inhibition of BMP and/or SMAD during neural induction led to the efficient differentiation of dorsal NPCs, based on the high percentage of PAX6-positive cells and the NPC gene expression profile. There were no statistically

  5. 33 CFR 110.245 - Vieques Passage and Vieques Sound, near Vieques Island, P.R.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Vieques Passage and Vieques Sound... and Vieques Sound, near Vieques Island, P.R. (a) The anchorage grounds—(1) Vieques Passage explosives... center at latitude 18°09′00″ N., longitude 65°32′40″ W. (2) Vieques Sound explosives anchorage and...

  6. 33 CFR 110.245 - Vieques Passage and Vieques Sound, near Vieques Island, P.R.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Vieques Passage and Vieques Sound... and Vieques Sound, near Vieques Island, P.R. (a) The anchorage grounds—(1) Vieques Passage explosives... center at latitude 18°09′00″ N., longitude 65°32′40″ W. (2) Vieques Sound explosives anchorage and...

  7. Tobacco Smoke Pollution in Hospitality Venues Before and After Passage of Statewide Smoke-Free Legislation.

    PubMed

    Buettner-Schmidt, Kelly; Boursaw, Blake; Lobo, Marie L; Travers, Mark J

    2017-03-01

    In 2012, North Dakota enacted a comprehensive statewide law prohibiting smoking in enclosed public places. Disparities in tobacco control exist in rural areas. This study's objective was to determine the extent to which the passage of a comprehensive, statewide, smoke-free law in a predominantly rural state influenced tobacco smoke pollution in rural and nonrural venues. A longitudinal cohort design study comparing the levels of tobacco smoke pollution before and after passage of the statewide smoke-free law was conducted in 64 restaurants and bars statewide in North Dakota. Particulate matter with a median aerodynamic diameter of <2.5 μm (a valid atmospheric marker of tobacco smoke pollution) was assessed. A significant 83% reduction in tobacco smoke pollution levels occurred after passage of the law. Significant reductions in tobacco smoke pollution levels occurred in each of the rural categories; however, no difference by rurality was noted in the analysis after passage of the law, in contrast to the study before passage. To our knowledge, this was the largest, single, rural postlaw study globally. A comprehensive statewide smoke-free law implemented in North Dakota dramatically decreased the level of tobacco smoke pollution in bars and restaurants. © 2016 The Authors. Public Health Nursing Published by Wiley Periodicals, Inc.

  8. Mentoring staff members as patient safety leaders: the Clarian Safe Passage Program.

    PubMed

    Rapala, Kathryn

    2005-06-01

    This article describes a second element of the Synergy Model of Patient Care implemented by Clarian Health Partners of Indiana. The Clarian Safe Passage Program is a unique approach to the promotion of patient safety. In this program, frontline staff nurses are trained to serve as Safe Passage nurses, who are unit-based safety experts. These nurses mentor each other and their peers in acquiring patient safety expertise and promoting a free flow of information to avert actual and potential errors in health care delivery.

  9. Selection against BALB/c strain cells in mouse chimaeras

    PubMed Central

    Tang, Pin-Chi; MacKay, Gillian E.; Flockhart, Jean H.; Keighren, Margaret A.; Kopakaki, Anna

    2018-01-01

    ABSTRACT It has been shown previously that BALB/c strain embryos tend to contribute poorly to mouse aggregation chimaeras. In the present study we showed that BALB/c cells were not preferentially allocated to any extraembryonic lineages of mouse aggregation chimaeras, but their contribution decreased during the early postimplantation period and they were significantly depleted by E8.5. The development of BALB/c strain preimplantation embryos lagged behind embryos from some other strains and the contribution that BALB/c and other embryos made to chimaeras correlated with their developmental stage at E2.5. This relationship suggests that the poor contribution of BALB/c embryos to aggregation chimaeras is at least partly a consequence of generalised selection related to slow or delayed preimplantation development. The suitability of BALB/c embryos for maximising the ES cell contribution to mouse ES cell chimaeras is also discussed. PMID:29330350

  10. Pro-inflammatory Cytokine Expression of Spleen Dendritic Cells in Mouse Toxoplasmosis

    PubMed Central

    Nam, Ho-Woo; Ahn, Hye-Jin

    2011-01-01

    Dendritic cells have been known as a member of strong innate immune cells against infectious organelles. In this study, we evaluated the cytokine expression of splenic dendritic cells in chronic mouse toxoplasmosis by tissue cyst-forming Me49 strain and demonstrated the distribution of lymphoid dendritic cells by fluorescence-activated cell sorter (FACS). Pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-6, and IL-10 increased rapidly at week 1 post-infection (PI) and peaked at week 3 PI. Serum IL-10 level followed the similar patterns. FACS analysis showed that the number of CD8α+/CD11c+ splenic dendritic cells increased at week 1 and peaked at week 3 PI. In conclusion, mouse splenic dendritic cells showed early and rapid cytokine changes and may have important protective roles in early phases of murine toxoplasmosis. PMID:21738265

  11. Delayed Release from Proactive Interference with Meaningful Material: How Much Do We Remember After Reading Brief Prose Passages?

    ERIC Educational Resources Information Center

    Blumenthal, Gary B.; Robbins, Donald

    1977-01-01

    Three experiments were conducted, investigating the buildup of and the release from proactive interference, in which the stimulus materials were brief prose passages about specific topics. Each passage was followed by a multiple-choice test, and then a final test on all the passages read was given. Implications of the data for standardized tests…

  12. Role of Abcg2 During Mouse Embroyonic Stem Cell Diffferentiation

    EPA Science Inventory

    Role of Abcg2 During Mouse Embryonic Stem Cell Differentiation. Abcg2 is a multidrug resistance ATP-binding cassette (ABC) transporter whose activity may be considered a hallmark of stem cell plasticity. The role of Abcg2 during early embryogenesis, however, is unclear. Studies...

  13. In vivo time-serial multi-modality optical imaging in a mouse model of ovarian tumorigenesis

    PubMed Central

    Watson, Jennifer M; Marion, Samuel L; Rice, Photini F; Bentley, David L; Besselsen, David G; Utzinger, Urs; Hoyer, Patricia B; Barton, Jennifer K

    2014-01-01

    Identification of the early microscopic changes associated with ovarian cancer may lead to development of a diagnostic test for high-risk women. In this study we use optical coherence tomography (OCT) and multiphoton microscopy (MPM) (collecting both two photon excited fluorescence [TPEF] and second harmonic generation [SHG]) to image mouse ovaries in vivo at multiple time points. We demonstrate the feasibility of imaging mouse ovaries in vivo during a long-term survival study and identify microscopic changes associated with early tumor development. These changes include alterations in tissue microstructure, as seen by OCT, alterations in cellular fluorescence and morphology, as seen by TPEF, and remodeling of collagen structure, as seen by SHG. These results suggest that a combined OCT-MPM system may be useful for early detection of ovarian cancer. PMID:24145178

  14. Local Neighbourhoods for First-Passage Percolation on the Configuration Model

    NASA Astrophysics Data System (ADS)

    Dereich, Steffen; Ortgiese, Marcel

    2018-04-01

    We consider first-passage percolation on the configuration model. Once the network has been generated each edge is assigned an i.i.d. weight modeling the passage time of a message along this edge. Then independently two vertices are chosen uniformly at random, a sender and a recipient, and all edges along the geodesic connecting the two vertices are coloured in red (in the case that both vertices are in the same component). In this article we prove local limit theorems for the coloured graph around the recipient in the spirit of Benjamini and Schramm. We consider the explosive regime, in which case the random distances are of finite order, and the Malthusian regime, in which case the random distances are of logarithmic order.

  15. Conditionally Immortal Slc4a11−/− Mouse Corneal Endothelial Cell Line Recapitulates Disrupted Glutaminolysis Seen in Slc4a11−/− Mouse Model

    PubMed Central

    Zhang, Wenlin; Ogando, Diego G.; Kim, Edward T.; Choi, Moon-Jung; Li, Hongde; Tenessen, Jason M.; Bonanno, Joseph A.

    2017-01-01

    Purpose To establish conditionally immortal mouse corneal endothelial cell lines with genetically matched Slc4a11+/+ and Slc4a11−/− mice as a model for investigating pathology and therapies for SLC4A11 associated congenital hereditary endothelial dystrophy (CHED) and Fuchs' endothelial corneal dystrophy. Methods We intercrossed H-2Kb-tsA58 mice (Immortomouse) expressing an IFN-γ dependent and temperature-sensitive mutant of the SV40 large T antigen (tsTAg) with Slc4a11+/+ and Slc4a11−/− C57BL/6 mice. The growth characteristics of the cell lines was assessed by doubling time. Ion transport activities (Na+/H+ exchange, bicarbonate, lactate, and Slc4a11 ammonia transport) were analyzed by intracellular pH measurement. The metabolic status of the cell lines was assessed by analyzing TCA cycle intermediates via gas chromatography mass spectrometry (GC-MS). Results The immortalized Slc4a11+/+ and Slc4a11−/− mouse corneal endothelial cells (MCECs) remained proliferative through passage 49 and maintained similar active ion transport activity. As expected, proliferation was temperature sensitive and IFN-γ dependent. Slc4a11−/− MCECs exhibited decreased proliferative capacity, reduced NH3:H+ transport, altered expression of glutaminolysis enzymes similar to the Slc4a11−/− mouse, and reduced proportion of TCA cycle intermediates derived from glutamine with compensatory increases in glucose flux compared with Slc4a11+/+ MCECs. Conclusions This is the first report of the immortalization of MCECs. Ion transport of the immortalized endothelial cells remains active, except for NH3:H+ transporter activity in Slc4a11−/− MCECs. Furthermore, Slc4a11−/− MCECs recapitulate the glutaminolysis defects observed in Slc4a11−/− mouse corneal endothelium, providing an excellent tool to study the pathogenesis of SLC4A11 mutations associated with corneal endothelial dystrophies and to screen potential therapeutic agents. PMID:28738416

  16. Passages: Helping College Students Matriculate through Outdoor Adventure.

    ERIC Educational Resources Information Center

    Stremba, Bob

    Since 1985, freshman entering the University of Puget Sound in Tacoma, Washington, have embarked on a 3-day outdoor adventure program as part of their orientation experience prior to their first semester. Most of the 700-800 freshmen entering the university participate in the program titled "Passages." While half of the group is on…

  17. The emotion potential of words and passages in reading Harry Potter--an fMRI study.

    PubMed

    Hsu, Chun-Ting; Jacobs, Arthur M; Citron, Francesca M M; Conrad, Markus

    2015-03-01

    Previous studies suggested that the emotional connotation of single words automatically recruits attention. We investigated the potential of words to induce emotional engagement when reading texts. In an fMRI experiment, we presented 120 text passages from the Harry Potter book series. Results showed significant correlations between affective word (lexical) ratings and passage ratings. Furthermore, affective lexical ratings correlated with activity in regions associated with emotion, situation model building, multi-modal semantic integration, and Theory of Mind. We distinguished differential influences of affective lexical, inter-lexical, and supra-lexical variables: differential effects of lexical valence were significant in the left amygdala, while effects of arousal-span (the dynamic range of arousal across a passage) were significant in the left amygdala and insula. However, we found no differential effect of passage ratings in emotion-associated regions. Our results support the hypothesis that the emotion potential of short texts can be predicted by lexical and inter-lexical affective variables. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Cell block four exercise yard with original passage to cell ...

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

    Cell block four exercise yard with original passage to cell re-exposed, looking from the baseball field, facing west, with scale - Eastern State Penitentiary, 2125 Fairmount Avenue, Philadelphia, Philadelphia County, PA

  19. Attenuation of an original US porcine epidemic diarrhea virus strain PC22A via serial cell culture passage.

    PubMed

    Lin, Chun-Ming; Hou, Yixuan; Marthaler, Douglas G; Gao, Xiang; Liu, Xinsheng; Zheng, Lanlan; Saif, Linda J; Wang, Qiuhong

    2017-03-01

    Although porcine epidemic diarrhea (PED) has caused huge economic losses in the pork industry worldwide, an effective live, attenuated vaccine is lacking. In this study, an original US, highly virulent PED virus (PEDV) strain PC22A was serially passaged in Vero CCL81 and Vero BI cells. The virus growth kinetics in cell culture, virulence in neonatal pigs and the whole genomic sequences of selected passages were examined. Increased virus titers and sizes of syncytia were observed at the 65th passage level (P65) and P120, respectively. Based on the severity of clinical signs, histopathological lesions and the distribution of PEDV antigens in the gut, the virulence of P100 and above, but not P95C13 (CCL81), was markedly reduced in 4-day-old, caesarian-derived, colostrum-deprived piglets. Subsequently, the attenuation of P120 and P160 was confirmed in 4-day-old, conventional suckling piglets. Compared with P120, P160 replicated less efficiently in the intestine of pigs and induced a lower rate of protection after challenge. Sequence analysis revealed that the virulent viruses [P3 and P95C13 (CCL81)] had one, one, sixteen (including an early termination of nine amino acids) and two amino acid differences in non-structure protein 1 (nsp1), nsp4, spike and membrane proteins, respectively, from the fully attenuated P160. However, the overall pattern of attenuation-related genetic changes in PC22A differed from those of the other four pairs of PEDV wild type strains and their attenuated derivatives. These results suggest that PEDV attenuation can occur through multiple molecular mechanisms. The knowledge provides insights into potential molecular mechanisms of PEDV attenuation. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. 35. Basement, passage beneath main entrance porch, showing circular skylight ...

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

    35. Basement, passage beneath main entrance porch, showing circular skylight opening, view to northwest - Portsmouth Naval Hospital, Hospital Building, Rixey Place, bounded by Williamson Drive, Holcomb Road, & The Circle, Portsmouth, Portsmouth, VA

  1. BLDG 101, CENTRAL ENTRY/ PASSAGE SHOWING LEAD FLOOR, STEEL WALLS ...

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

    BLDG 101, CENTRAL ENTRY/ PASSAGE SHOWING LEAD FLOOR, STEEL WALLS AND ASBESTOS CEILING - Naval Magazine Lualualei, Headquarters Branch, Operational Storage Building, Fifteenth Street near Kolekole Road intersection, Pearl City, Honolulu County, HI

  2. Connection between optimal control theory and adiabatic-passage techniques in quantum systems

    NASA Astrophysics Data System (ADS)

    Assémat, E.; Sugny, D.

    2012-08-01

    This work explores the relationship between optimal control theory and adiabatic passage techniques in quantum systems. The study is based on a geometric analysis of the Hamiltonian dynamics constructed from Pontryagin's maximum principle. In a three-level quantum system, we show that the stimulated Raman adiabatic passage technique can be associated to a peculiar Hamiltonian singularity. One deduces that the adiabatic pulse is solution of the optimal control problem only for a specific cost functional. This analysis is extended to the case of a four-level quantum system.

  3. Early Onset Intrauterine Growth Restriction in a Mouse Model of Gestational Hypercholesterolemia and Atherosclerosis

    PubMed Central

    Busso, Dolores; Mascareño, Lilian; Salas, Francisca; Berkowitz, Loni; Santander, Nicolás; Quiroz, Alonso; Amigo, Ludwig; Valdés, Gloria; Rigotti, Attilio

    2014-01-01

    The susceptibility to develop atherosclerosis is increased by intrauterine growth restriction and prenatal exposure to maternal hypercholesterolemia. Here, we studied whether mouse gestational hypercholesterolemia and atherosclerosis affected fetal development and growth at different stages of gestation. Female LDLR KO mice fed a proatherogenic, high cholesterol (HC) diet for 3 weeks before conception and during pregnancy exhibited a significant increase in non-HDL cholesterol and developed atherosclerosis. At embryonic days 12.5 (E12.5), E15.5, and E18.5, maternal gestational hypercholesterolemia and atherosclerosis were associated to a 22–24% reduction in male and female fetal weight without alterations in fetal number/litter or morphology nor placental weight or structure. Feeding the HC diet exclusively at the periconceptional period did not alter fetal growth, suggesting that maternal hypercholesterolemia affected fetal weight only after implantation. Vitamin E supplementation (1,000 UI of α-tocopherol/kg) of HC-fed females did not change the mean weight of E18.5 fetuses but reduced the percentage of fetuses exhibiting body weights below the 10th percentile of weight (HC: 90% vs. HC/VitE: 68%). In conclusion, our results showed that maternal gestational hypercholesterolemia and atherosclerosis in mice were associated to early onset fetal growth restriction and that dietary vitamin E supplementation had a beneficial impact on this condition. PMID:25295255

  4. Characterization of Mouse Models of Early Pancreatic Lesions Induced by Alcohol and Chronic Pancreatitis.

    PubMed

    Xu, Shiping; Chheda, Chintan; Ouhaddi, Yassine; Benhaddou, Hajar; Bourhim, Mouloud; Grippo, Paul J; Principe, Daniel R; Mascariñas, Emman; DeCant, Brian; Tsukamoto, Hidekazu; Pandol, Stephen J; Edderkaoui, Mouad

    2015-08-01

    We describe the first mouse model of pancreatic intraepithelial neoplasia (PanIN) lesions induced by alcohol in the presence and absence of chronic pancreatitis. Pdx1-Cre;LSL-K-ras mice were exposed to Lieber-DeCarli alcohol diet for 6 weeks with cerulein injections. The PanIN lesions and markers of fibrosis, inflammation, histone deacetylation, epithelial-to-mesenchymal transition (EMT), and cancer stemness were measured by immunohistochemistry and Western. Exposure of Pdx1-Cre;LSL-K-ras mice to an alcohol diet significantly stimulated fibrosis and slightly but not significantly increased the level of PanIN lesions associated with an increase in tumor-promoting M2 macrophages. Importantly, the alcohol diet did not increase activation of stellate cells. Alcohol diet and cerulein injections resulted in synergistic and additive effects on PanIN lesion and M2 macrophage phenotype induction, respectively. Cerulein pancreatitis caused stellate cell activation, EMT, and cancer stemness in the pancreas. Pancreatitis caused histone deacetylation, which was promoted by the alcohol diet. Pancreatitis increased EMT and cancer stemness markers, which were not further affected by the alcohol diet. The results suggest that alcohol has independent effects on promotion of PDAC associated with fibrosis formed through a stellate cell-independent mechanism and that it further promotes early PDAC and M2 macrophage induction in the context of chronic pancreatitis.

  5. Making lineage decisions with biological noise: Lessons from the early mouse embryo.

    PubMed

    Simon, Claire S; Hadjantonakis, Anna-Katerina; Schröter, Christian

    2018-04-30

    Understanding how individual cells make fate decisions that lead to the faithful formation and homeostatic maintenance of tissues is a fundamental goal of contemporary developmental and stem cell biology. Seemingly uniform populations of stem cells and multipotent progenitors display a surprising degree of heterogeneity, primarily originating from the inherent stochastic nature of molecular processes underlying gene expression. Despite this heterogeneity, lineage decisions result in tissues of a defined size and with consistent proportions of differentiated cell types. Using the early mouse embryo as a model we review recent developments that have allowed the quantification of molecular intercellular heterogeneity during cell differentiation. We first discuss the relationship between these heterogeneities and developmental cellular potential. We then review recent theoretical approaches that formalize the mechanisms underlying fate decisions in the inner cell mass of the blastocyst stage embryo. These models build on our extensive knowledge of the genetic control of fate decisions in this system and will become essential tools for a rigorous understanding of the connection between noisy molecular processes and reproducible outcomes at the multicellular level. We conclude by suggesting that cell-to-cell communication provides a mechanism to exploit and buffer intercellular variability in a self-organized process that culminates in the reproducible formation of the mature mammalian blastocyst stage embryo that is ready for implantation into the maternal uterus. This article is categorized under: Gene Expression and Transcriptional Hierarchies > Cellular Differentiation Establishment of Spatial and Temporal Patterns > Regulation of Size, Proportion, and Timing Gene Expression and Transcriptional Hierarchies > Gene Networks and Genomics Gene Expression and Transcriptional Hierarchies > Quantitative Methods and Models. © 2018 Wiley Periodicals, Inc.

  6. The polyphased tectonic evolution of the Anegada Passage in the northern Lesser Antilles subduction zone

    NASA Astrophysics Data System (ADS)

    Laurencin, M.; Marcaillou, B.; Graindorge, D.; Klingelhoefer, F.; Lallemand, S.; Laigle, M.; Lebrun, J.-F.

    2017-05-01

    The influence of the highly oblique plate convergence at the northern Lesser Antilles onto the margin strain partitioning and deformation pattern, although frequently invoked, has never been clearly imaged. The Anegada Passage is a set of basins and deep valleys, regularly related to the southern boundary of the Puerto Rico-Virgin Islands (PRVI) microplate. Despite the publications of various tectonic models mostly based on bathymetric data, the tectonic origin and deformation of this Passage remains unconstrained in the absence of deep structure imaging. During cruises Antithesis 1 and 3 (2013-2016), we recorded the first deep multichannel seismic images and new multibeam data in the northern Lesser Antilles margin segment in order to shed a new light on the structure and tectonic pattern of the Anegada Passage. We image the northeastern extent of the Anegada Passage, from the Sombrero Basin to the Lesser Antilles margin front. Our results reveal that this northeastern segment is an EW trending left-stepping en échelon strike-slip system that consists of the Sombrero and Malliwana pull-apart basins, the Malliwana and Anguilla left-lateral faults, and the NE-SW compressional restraining bend at the Malliwana Hill. Reviewing the structure of the Anegada Passage, from the south of Puerto Rico to the Lesser Antilles margin front, reveals a polyphased tectonic history. The Anegada Passage is formed by a NW-SE extension, possibly related to the rotation or escape of PRVI block due to collision of the Bahamas Bank. Currently, it is deformed by an active WNW-ESE strike-slip deformation associated to the shear component of the strain partitioning resulting from the subduction obliquity.

  7. Effect of Altered Prior Knowledge on Passage Recall.

    ERIC Educational Resources Information Center

    Langer, Judith A.; Nicolich, Mark

    A study was conducted to determine: (1) the relationships between prior knowledge and passage recall; (2) the effect of a prereading activity (PReP) on available knowledge; and (3) the effect of the PReP activity on total comprehension scores. The subjects were 161 sixth grade students from a middle class suburban Long Island, New York, public…

  8. Transcriptional and epigenetic control in mouse pluripotency: lessons from in vivo and in vitro studies.

    PubMed

    Habibi, Ehsan; Stunnenberg, Hendrik G

    2017-10-01

    Pluripotent cells were first derived from mouse blastocysts several decades ago. Since then, our knowledge of the molecular events that occur in the pre-implantation embryo has been vastly progressing. The emergence of epigenetics has revolutionized stem cell and developmental biology and further deepened our understanding of the underlying molecular mechanisms controlling the early embryo development. In particular, the emergence of massive parallel sequencing technologies has opened new avenues and became indispensable tools in modern biology. Additionally, development of new and exciting techniques for genome manipulation (TALEN and CRISPR/Cas9) and in vivo imaging provide unique opportunities to perturb and trace biological systems at very high resolution. Finally, recent single-cell - omics combined with sophisticated computational methodologies allow accurate, quantitative measurements for deconvolution of cellular variation in complex cell populations. Collectively, these achievements enabled the detailed characterization and monitoring of various cell states and trajectories during early stages of embryonic development. Here we review recent studies of the transcriptional and epigenetic changes during very early stages of mouse embryo development and compare these with pluripotent cells grown in vitro under different culture conditions. We discuss whether the in vitro cell states have an 'epi-phenocopy' in the embryo and refine our understanding of the circuitries controlling pluripotency and lineage commitment during early stages of mouse development. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Data of piezoelectric vibration energy harvesting of a bridge undergoing vibration testing and train passage.

    PubMed

    Cahill, Paul; Hazra, Budhaditya; Karoumi, Raid; Mathewson, Alan; Pakrashi, Vikram

    2018-04-01

    The data presented in this article is in relation to the research article "Vibration energy harvesting based monitoring of an operational bridge undergoing forced vibration and train passage" Cahill et al. (2018) [1]. The article provides data on the full-scale bridge testing using piezoelectric vibration energy harvesters on Pershagen Bridge, Sweden. The bridge is actively excited via a swept sinusoidal input. During the testing, the bridge remains operational and train passages continue. The test recordings include the voltage responses obtained from the vibration energy harvesters during these tests and train passages. The original dataset is made available to encourage the use of energy harvesting for Structural Health Monitoring.

  10. The Development of SAH Reading Passage Compendium: A Tool for the Assessment of Reading Performance Related to Visual Function

    ERIC Educational Resources Information Center

    Chen, Ai-Hong; Buari, Noor Halilah; Jufri, Shauqiah

    2017-01-01

    Passages with continuous sentences are commonly used for the assessment of reading performance related to visual function, and rehabilitation in optometric practices. Passages created in native languages are crucial for a reliable interpretation in a real scenario. This study aimed to report the development of SAH Reading Passage Compendium…

  11. An Ancient Transcription Factor Initiates the Burst of piRNA Production During Early Meiosis in Mouse Testes

    PubMed Central

    Li, Xin Zhiguo; Roy, Christian K.; Dong, Xianjun; Bolcun-Filas, Ewelina; Wang, Jie; Han, Bo W.; Xu, Jia; Moore, Melissa J.; Schimenti, John C.; Weng, Zhiping; Zamore, Phillip D.

    2013-01-01

    SUMMARY Animal germ cells produce PIWI-interacting RNAs (piRNAs), small silencing RNAs that suppress transposons and enable gamete maturation. Mammalian transposon-silencing piRNAs accumulate early in spermatogenesis, whereas pachytene piRNAs are produced later during post-natal spermatogenesis and account for >95% of all piRNAs in the adult mouse testis. Mutants defective for pachytene piRNA pathway proteins fail to produce mature sperm, but neither the piRNA precursor transcripts nor the trigger for pachytene piRNA production is known. Here, we show that the transcription factor A-MYB initiates pachytene piRNA production. A-MYB drives transcription of both pachytene piRNA precursor RNAs and the mRNAs for core piRNA biogenesis factors, including MIWI, the protein through which pachytene piRNAs function. A-MYB regulation of piRNA pathway proteins and piRNA genes creates a coherent feed-forward loop that ensures the robust accumulation of pachytene piRNAs. This regulatory circuit, which can be detected in rooster testes, likely predates the divergence of birds and mammals. PMID:23523368

  12. First passage time: Connecting random walks to functional responses in heterogeneous environments (Invited)

    NASA Astrophysics Data System (ADS)

    Lewis, M. A.; McKenzie, H.; Merrill, E.

    2010-12-01

    In this talk I will outline first passage time analysis for animals undertaking complex movement patterns, and will demonstrate how first passage time can be used to derive functional responses in predator prey systems. The result is a new approach to understanding type III functional responses based on a random walk model. I will extend the analysis to heterogeneous environments to assess the effects of linear features on functional responses in wolves and elk using GPS tracking data.

  13. 76 FR 20707 - Cle Elum Dam Fish Passage Facilities and Fish Reintroduction Project; Kittitas County, WA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-13

    ... DEPARTMENT OF THE INTERIOR Bureau of Reclamation [INT-FES 11-02] Cle Elum Dam Fish Passage Facilities and Fish Reintroduction Project; Kittitas County, WA AGENCY: Bureau of Reclamation, Interior... Fish Passage Facilities and Fish Reintroduction Project. SUMMARY: The Bureau of Reclamation...

  14. Culvert roughness elements for native Utah fish passage : phase II.

    DOT National Transportation Integrated Search

    2012-04-01

    Native fishes have become an increasingly important concern when designing fish passable culverts. Many operational culverts constrict waterways which increase velocities and prevent upstream passage of small fish species. The current method to ensur...

  15. Detail view of keystone sculpted head in the arched passage ...

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

    Detail view of keystone sculpted head in the arched passage to the lobby vestibule - United States Department of Commerce, Bounded by Fourteenth, Fifteenth, and E streets and Constitution Avenue, Washington, District of Columbia, DC

  16. The Mouse House: a brief history of the ORNL mouse-genetics program, 1947-2009.

    PubMed

    Russell, Liane B

    2013-01-01

    The large mouse genetics program at the Oak Ridge National Laboratory (ORNL) is often remembered chiefly for the germ-cell mutation-rate data it generated and their uses in estimating the risk of heritable radiation damage. In fact, it soon became a multi-faceted research effort that, over a period of almost 60 years, generated a wealth of information in the areas of mammalian mutagenesis, basic genetics (later enriched by molecular techniques), cytogenetics, reproductive biology, biochemistry of germ cells, and teratology. Research in the area of germ-cell mutagenesis explored the important physical and biological factors that affect the frequency and nature of induced mutations and made several unexpected discoveries, such as the major importance of the perigametic interval (the zygote stage) for the origin of spontaneous mutations and for the sensitivity to induced genetic change. Of practical value was the discovery that ethylnitrosourea was a supermutagen for point mutations, making high-efficiency mutagenesis in the mouse feasible worldwide. Teratogenesis findings resulted in recommendations still generally accepted in radiological practice. Studies supporting the mutagenesis research added whole bodies of information about mammalian germ-cell development and about molecular targets in germ cells. The early decision to not merely count but propagate genetic variants of all sorts made possible further discoveries, such as the Y-chromosome's importance in mammalian sex determination and the identification of rare X-autosome translocations, which, in turn, led to the formulation of the single-active-X hypothesis and provided tools for studies of functional mosaicism for autosomal genes, male sterility, and chromosome-pairing mechanism. Extensive genetic and then molecular analyses of large numbers of induced specific-locus mutants resulted in fine-structure physical and correlated functional mapping of significant portions of the mouse genome and constituted a

  17. Observed and Simulated Eddy Diffusivity Upstream of the Drake Passage

    NASA Astrophysics Data System (ADS)

    Tulloch, R.; Ferrari, R. M.; Marshall, J.

    2012-12-01

    Estimates of eddy diffusivity in the Southern Ocean are poorly constrained due to lack of observations. We compare the first direct estimate of isopycnal eddy diffusivity upstream of the Drake Passage (from Ledwell et al. 2011) with a numerical simulation. The estimate is computed from a point tracer release as part of the Diapycnal and Isopycnal Mixing Experiment in the Southern Ocean (DIMES). We find that the observational diffusivity estimate of about 500m^2/s at 1500m depth is close to that computed in a data-constrained, 1/20th of a degree simulation of the Drake Passage region. This tracer estimate also agrees with Lagrangian float calculations in the model. The role of mean flow suppression of eddy diffusivity at shallower depths will also be discussed.

  18. Molecular Indicators of Stress-Induced Neuroinflammation in a Mouse Model Simulating Features of Post-Traumatic Stress Disorder (Open Access)

    DTIC Science & Technology

    2017-05-23

    OPEN ORIGINAL ARTICLE Molecular indicators of stress-induced neuroinflammation in a mouse model simulating features of post -traumatic stress disorder... post -traumatic stress disorder (PTSD). The model involved exposure of an intruder (male C57BL/6) mouse to a resident aggressor (male SJL) mouse for 5...revealed that neurogenesis and synaptic plasticity pathways were activated during the early responses but were inhibited after the later post -trauma

  19. An Analysis of the Text Complexity of Leveled Passages in Four Popular Classroom Reading Assessments

    ERIC Educational Resources Information Center

    Toyama, Yukie; Hiebert, Elfrieda H.; Pearson, P. David

    2017-01-01

    This study investigated the complexity of leveled passages used in four classroom reading assessments. A total of 167 passages leveled for Grades 1-6 from these assessments were analyzed using four analytical tools of text complexity. More traditional, two-factor measures of text complexity found a general trend of fairly consistent across-grade…

  20. Introducing Intertextuality-Aware Instruction as a Novel Approach of Teaching Reading Passages in EFL Context

    ERIC Educational Resources Information Center

    Khaghaninejad, Mohammad Saber

    2014-01-01

    This study was an attempt to investigate the possible effect of intertextuality-aware instruction of reading passages on a sample of intermediate EFL learners of both genders. First, the intertextuality deployed through the reading passages of the study's course-book was focused inspired by Fairclough's (192) framework in terms of genre, text…

  1. Teaching Students with Moderate Intellectual Disability Who Are Emergent Readers to Comprehend Passages of Text

    ERIC Educational Resources Information Center

    Browder, Diane M.; Hudson, Melissa E.; Wood, Alyson Leah

    2013-01-01

    A modified system of least intrusive prompting was used to teach middle school students with moderate intellectual disability who were emergent readers to comprehend short passages of text. Text passages were summaries of the chapters of age-appropriate novels rewritten for a beginning reading level. Time delay was used to teach the participants…

  2. A tetravalent alphavirus-vector based Dengue vaccine provides effective immunity in an early life mouse model

    PubMed Central

    Khalil, Syed Muaz; Tonkin, Daniel R.; Mattocks, Melissa D.; Snead, Andrew T.; Johnston, Robert E.; White, Laura J.

    2014-01-01

    Dengue viruses (DENV1-4) cause 390 million clinical infections every year, several hundred thousand of which progress to severe hemorrhagic and shock syndromes. Preexisting immunity resulting from a previous DENV infection is the major risk factor for severe dengue during secondary heterologous infections. During primary infections in infants, maternal antibodies pose an analogous risk. At the same time, maternal antibodies are likely to prevent induction of endogenous anti-DENV antibodies in response to current live, attenuated virus (LAV) vaccine candidates. Any effective early life dengue vaccine has to overcome maternal antibody interference (leading to ineffective vaccination) and poor induction of antibody responses (increasing the risk of severe dengue disease upon primary infection). In a previous study, we demonstrated that a non-propagating Venezuelan equine encephalitis virus replicon expression vector (VRP), expressing the ectodomain of DENV E protein (E85), overcomes maternal interference in a BALB/c mouse model. We report here that a single immunization with a tetravalent VRP vaccine induced NAb and T-cell responses to each serotype at a level equivalent to the monovalent vaccine components, suggesting that this vaccine modality can overcome serotype interference. Furthermore, neonatal immunization was durable and could be boosted later in life to further increase NAb and T-cell responses. Although the neonatal immune response was lower in magnitude than responses in adult BALB/c mice, we demonstrate that VRP vaccines generated protective immunity from a lethal challenge after a single neonatal immunization. In summary, VRP vaccines expressing DENV antigens were immunogenic and protective in neonates, and hence are promising candidates for safe and effective vaccination in early life. PMID:24882043

  3. Hydroacoustic Evaluation of Juvenile Salmonid Passage at The Dalles Dam Sluiceway, 2005

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

    Johnson, Gary E.; Khan, Fenton; Hedgepeth, J

    2006-06-01

    The U.S. Army Corps of Engineers Portland District engaged the Pacific Northwest National Laboratory to evaluate fish passage at The Dalles Dam powerhouse in 2005. The goal of the study was to provide information on smolt passage that will inform decisions on long-term measures and operations to enhance sluiceway passage and reduce turbine passage to improve smolt survival at the dam. The study addressed one of the main programs dedicated to improving juvenile salmonid survival at The Dalles Dam: Surface Flow Bypass. The study objectives (see below) were met using a combination of hydroacoustic and hydraulic data. The study incorporatedmore » fixed-location hydroacoustic methods across the entire powerhouse, with especially intense sampling using multiple split-beam transducers at all sluiceway portals. We did not sample fish passage at the spillway in 2005. In the sluiceway nearfield, we used an acoustic camera to track fish movements. The fish data were interpreted with hydraulic data from a computational fluid dynamics (CFD) model. Fish passage data were collected in the framework of an “experiment” using a randomized block design (3-day treatments; two treatments) to compare two sluiceway operational configurations: Sluice 2+5 and Sluice 2+19 (six gates open for each configuration). Total project outflow was 76% of the 10-year average for spring and 71% of the 10-year average for summer. Based on these findings, we make the following recommendations: 1) The sluice should be operated 24 h/d from April until November. 2) Open six rather than three sluice gates to take advantage of the maximum hydraulic capacity of the sluiceway. 3) Open the three gates above the western-most operating main turbine unit and the three gates at MU 8 where turbine passage rates are relatively high. 4) Operate the turbine units below open sluice gates as a standard fish operations procedure. 5) Develop hydraulic and entrance enhancements to the sluiceway to tap the potential of

  4. ZINC INFLUENCES THE IN VITRO DEVELOPMENT OF PERI-IMPLANTATION MOUSE EMBRYOS

    EPA Science Inventory

    Background: For humans, it is estimated that over 70% of concepti are lost during early development. In culture, mouse peri-implantation embryos can mimic development from the blastocyst to the egg cylinder stage of development, a period during which implantation occurs in viv...

  5. Major mutation events in structural genes of peste des petits ruminants virus through serial passages in vitro.

    PubMed

    Wu, Xiaodong; Liu, Fuxiao; Li, Lin; Zou, Yanli; Liu, Shan; Wang, Zhiliang

    2016-06-01

    Peste des petits ruminants (PPR) is an highly contagious disease of small ruminants, and caused by peste des petits ruminants virus (PPRV), a member of the genus Morbillivirus in the family Paramyxoviridae. The first outbreak of PPR in China was officially reported in July 2007, when a PPRV strain was successfully isolated from a sick goat in Tibet, followed by sequencing at a full-genome level (China/Tibet/Geg/07-30, GenBank: FJ905304.1). To date, this isolate has been virulently attenuated by more than 90 serial passages in Vero-Dog-SLAM cells at our laboratory. In this study, a total of nine strains by serial passages (namely the 10th, 20th, 30th, 40th, 50th, 60th, 70th, 80th, and 90th passages) were chosen for sequencing of six structural genes in PPRV. The sequence analysis showed that mutation rates in all viral genes were relatively low, and only a few identical mutations within certain genes were stably maintained after an earlier passage, perhaps indicating a predominance of mutants after such a passage.

  6. 49 CFR 192.150 - Passage of internal inspection devices.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) of this section, each new transmission line and each replacement of line pipe, valve, fitting, or other line component in a transmission line must be designed and constructed to accommodate the passage... TRANSPORTATION OF NATURAL AND OTHER GAS BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Design of Pipeline...

  7. 49 CFR 192.150 - Passage of internal inspection devices.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) of this section, each new transmission line and each replacement of line pipe, valve, fitting, or other line component in a transmission line must be designed and constructed to accommodate the passage... TRANSPORTATION OF NATURAL AND OTHER GAS BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Design of Pipeline...

  8. 49 CFR 192.150 - Passage of internal inspection devices.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) of this section, each new transmission line and each replacement of line pipe, valve, fitting, or other line component in a transmission line must be designed and constructed to accommodate the passage... TRANSPORTATION OF NATURAL AND OTHER GAS BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Design of Pipeline...

  9. 49 CFR 192.150 - Passage of internal inspection devices.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...) of this section, each new transmission line and each replacement of line pipe, valve, fitting, or other line component in a transmission line must be designed and constructed to accommodate the passage... TRANSPORTATION OF NATURAL AND OTHER GAS BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Design of Pipeline...

  10. Upper York Creek Dam Removal, Fish Passage, and Ecosystem Restoration

    EPA Pesticide Factsheets

    Information about the Upper York Creek Dam Removal, Fish Passage, and Ecosystem Restoration part of an EPA competitive grant program to improve SF Bay water quality focused on restoring impaired waters and enhancing aquatic resources.

  11. Summary of juvenile salmonid passage and survival at McNary Dam-Acoustic survival studies, 2006-09

    USGS Publications Warehouse

    Adams, Noah S.; Evans, Scott D.

    2011-01-01

    Passage and survival data were collected at McNary Dam between 2006 and 2009. These data have provided critical information for resource managers to implement structural and operational changes designed to improve the survival of juvenile salmonids as they migrate past the dam. Given the importance of these annual studies, the primary objectives of this report were to summarize the findings of these annual studies to ensure that passage and survival metrics are consistently calculated and reported across all years and to consolidate this information in a single document, thereby making it easier to reference. It is worth noting that this report does not contain all the information from all the annual reports. The intent of this report was to summarize the key findings from multiple years of research. The reader is encouraged to reference the annual reports if more detailed information is needed. Chapter 1 summarizes existing behavior, passage, and survival results for fish released 10 rkm upstream of McNary Dam and from the McNary Dam tailrace during 2006-09. Chapter 2 summarizes existing behavior, passage, and survival results for fish released in the mid-Columbia River and detected at McNary Dam during 2006-09. Results from 2006 indicated that higher spill discharge generally resulted in higher fish passage through spill, and in turn, higher fish survival through the entire dam. Within the spillway, passage effectiveness was highest for the south spill bays, adjacent to the powerhouse. Increased passage in this area, combined with detailed 3-dimensional approach paths, aided in the design and location of the temporary spillway weirs (TSWs) at McNary Dam prior to the 2007 migration of juvenile salmonids. During the 2007 study, the TSWs were tested under two spill treatments during the spring and summer: a "2006 Modified spill," and a "2007 test spill." In the spring, slightly higher discharge through spill bays 14-17 was the primary difference between the spill

  12. Transport, dam passage, and size selection of adult Atlantic Salmon in the Penobscot River, Maine

    USGS Publications Warehouse

    Sigourney, Douglas B.; Zydlewski, Joseph D.; Hughes, Edward; Cox, Oliver

    2015-01-01

    Prior to 2012, returning adult Atlantic Salmon Salmo salar had to pass through fishways at three dams in the lower section of the Penobscot River, Maine: Veazie Dam (river kilometer [rkm] 48; removed in 2013), Great Works Dam (rkm 60; removed in 2012), and Milford Dam (rkm 62). To facilitate better passage through the lower river, a fish transport program was implemented in 2010 and 2011. Fish were captured at Veazie Dam and were either transported by truck above Milford Dam (TRKD group) or released into the head pond above Veazie Dam (run-of-the-river [ROR] group). To assess the efficacy of transport, we used PIT telemetry to compare the performance and passage of TRKD and ROR fish based on their (1) success in reaching one of the three dams upstream of Milford Dam, (2) time taken to reach an upstream dam (transit time), and (3) success in passing that upstream dam. In both years, the percentage of fish detected at upstream dams was higher for the TRKD group (82.4% in 2010; 78.6% in 2011) than for the ROR group (41.3% in 2010; 22.4% in 2011). In addition, median transit time was faster for TRKD fish (7 d in 2010; 5 d in 2011) than for ROR fish (23 d in 2010; 25 d in 2011). However, passage success through the upstream dams did not differ between the two release groups. Our analysis also revealed a strong, negative size-selective force on dam passage: larger fish were consistently less likely to successfully pass dams than smaller fish. Finally, environmental conditions also influenced passage success. Our analysis shows that the transport of adult Atlantic Salmon can be an effective means by which to increase migration success in systems where upstream passage is poor.

  13. Comparison of two culture approaches, blind passage and dual observation, for detecting Chlamydia trachomatis in various prevalence populations.

    PubMed Central

    Zimmerman, S J; Moses, E; Sofat, N; Bartholomew, W R; Amsterdam, D

    1992-01-01

    Chlamydia trachomatis diagnosis in our laboratory consisted of dual inoculation of shell vials and detection of inclusions by using fluorescein-conjugated monoclonal antiserum; the second culture vial was conventionally used for blind passage when the first vial was negative. We compared the increase in positivity using blind passage with that of a strategy utilizing observation of two stained monolayers (dual observation) without blind passage, in an effort to reduce the reporting time and labor associated with the conventional approach. A total of 4,329 specimens were obtained from an obstetrics and gynecology (OB-GYN) clinic (2,563 specimens) and the sexually transmitted disease clinic (1,766 specimens). These specimens were used to compare the two strategies. Blind passage of 1,269 initially culture-negative specimens from the OB-GYN clinic resulted in an additional 6 positive chlamydial diagnoses. In comparison, a similar number of specimens (1,294) from the OB-GYN clinic collected subsequently to the first group were tested by dual observation. There were five additional positive findings. A similar evaluation of specimens from the sexually transmitted disease clinic was performed. Blind passage of 313 initially culture-negative specimens yielded 3 additional positive diagnoses, whereas dual observation of 1,435 similar specimens resulted in 9 positive diagnoses. On the basis of analysis of 4,332 specimens, sensitivity of dual observation is comparable to that of blind passage; labor, cost, and reporting time of dual observation are reduced in comparison to those of blind passage. PMID:1452664

  14. Identification of disease specific pathways using in vivo SILAC proteomics in dystrophin deficient mdx mouse.

    PubMed

    Rayavarapu, Sree; Coley, William; Cakir, Erdinc; Jahnke, Vanessa; Takeda, Shin'ichi; Aoki, Yoshitsugu; Grodish-Dressman, Heather; Jaiswal, Jyoti K; Hoffman, Eric P; Brown, Kristy J; Hathout, Yetrib; Nagaraju, Kanneboyina

    2013-05-01

    Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder caused by a mutation in the dystrophin gene. DMD is characterized by progressive weakness of skeletal, cardiac, and respiratory muscles. The molecular mechanisms underlying dystrophy-associated muscle weakness and damage are not well understood. Quantitative proteomics techniques could help to identify disease-specific pathways. Recent advances in the in vivo labeling strategies such as stable isotope labeling in mouse (SILAC mouse) with (13)C6-lysine or stable isotope labeling in mammals (SILAM) with (15)N have enabled accurate quantitative analysis of the proteomes of whole organs and tissues as a function of disease. Here we describe the use of the SILAC mouse strategy to define the underlying pathological mechanisms in dystrophin-deficient skeletal muscle. Differential SILAC proteome profiling was performed on the gastrocnemius muscles of 3-week-old (early stage) dystrophin-deficient mdx mice and wild-type (normal) mice. The generated data were further confirmed in an independent set of mdx and normal mice using a SILAC spike-in strategy. A total of 789 proteins were quantified; of these, 73 were found to be significantly altered between mdx and normal mice (p < 0.05). Bioinformatics analyses using Ingenuity Pathway software established that the integrin-linked kinase pathway, actin cytoskeleton signaling, mitochondrial energy metabolism, and calcium homeostasis are the pathways initially affected in dystrophin-deficient muscle at early stages of pathogenesis. The key proteins involved in these pathways were validated by means of immunoblotting and immunohistochemistry in independent sets of mdx mice and in human DMD muscle biopsies. The specific involvement of these molecular networks early in dystrophic pathology makes them potential therapeutic targets. In sum, our findings indicate that SILAC mouse strategy has uncovered previously unidentified pathological pathways in mouse models of

  15. Identification of Disease Specific Pathways Using in Vivo SILAC Proteomics in Dystrophin Deficient mdx Mouse*

    PubMed Central

    Rayavarapu, Sree; Coley, William; Cakir, Erdinc; Jahnke, Vanessa; Takeda, Shin'ichi; Aoki, Yoshitsugu; Grodish-Dressman, Heather; Jaiswal, Jyoti K.; Hoffman, Eric P.; Brown, Kristy J.; Hathout, Yetrib; Nagaraju, Kanneboyina

    2013-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder caused by a mutation in the dystrophin gene. DMD is characterized by progressive weakness of skeletal, cardiac, and respiratory muscles. The molecular mechanisms underlying dystrophy-associated muscle weakness and damage are not well understood. Quantitative proteomics techniques could help to identify disease-specific pathways. Recent advances in the in vivo labeling strategies such as stable isotope labeling in mouse (SILAC mouse) with 13C6-lysine or stable isotope labeling in mammals (SILAM) with 15N have enabled accurate quantitative analysis of the proteomes of whole organs and tissues as a function of disease. Here we describe the use of the SILAC mouse strategy to define the underlying pathological mechanisms in dystrophin-deficient skeletal muscle. Differential SILAC proteome profiling was performed on the gastrocnemius muscles of 3-week-old (early stage) dystrophin-deficient mdx mice and wild-type (normal) mice. The generated data were further confirmed in an independent set of mdx and normal mice using a SILAC spike-in strategy. A total of 789 proteins were quantified; of these, 73 were found to be significantly altered between mdx and normal mice (p < 0.05). Bioinformatics analyses using Ingenuity Pathway software established that the integrin-linked kinase pathway, actin cytoskeleton signaling, mitochondrial energy metabolism, and calcium homeostasis are the pathways initially affected in dystrophin-deficient muscle at early stages of pathogenesis. The key proteins involved in these pathways were validated by means of immunoblotting and immunohistochemistry in independent sets of mdx mice and in human DMD muscle biopsies. The specific involvement of these molecular networks early in dystrophic pathology makes them potential therapeutic targets. In sum, our findings indicate that SILAC mouse strategy has uncovered previously unidentified pathological pathways in mouse models of human

  16. Bladed disc crack diagnostics using blade passage signals

    NASA Astrophysics Data System (ADS)

    Hanachi, Houman; Liu, Jie; Banerjee, Avisekh; Koul, Ashok; Liang, Ming; Alavi, Elham

    2012-12-01

    One of the major potential faults in a turbo fan engine is the crack initiation and propagation in bladed discs under cyclic loads that could result in the breakdown of the engines if not detected at an early stage. Reliable fault detection techniques are therefore in demand to reduce maintenance cost and prevent catastrophic failures. Although a number of approaches have been reported in the literature, it remains very challenging to develop a reliable technique to accurately estimate the health condition of a rotating bladed disc. Correspondingly, this paper presents a novel technique for bladed disc crack detection through two sequential signal processing stages: (1) signal preprocessing that aims to eliminate the noises in the blade passage signals; (2) signal postprocessing that intends to identify the crack location. In the first stage, physics-based modeling and interpretation are established to help characterize the noises. The crack initiation can be determined based on the calculated health monitoring index derived from the sinusoidal effects. In the second stage, the crack is located through advanced detrended fluctuation analysis of the preprocessed data. The proposed technique is validated using a set of spin rig test data (i.e. tip clearance and time of arrival) that was acquired during a test conducted on a bladed military engine fan disc. The test results have demonstrated that the developed technique is an effective approach for identifying and locating the incipient crack that occurs at the root of a bladed disc.

  17. Investigation of boundary layer and turbulence characteristics inside the passages of an axial flow inducer

    NASA Technical Reports Server (NTRS)

    Anand, A.; Gorton, C.; Lakshminarayana, B.; Yamaoka, H.

    1973-01-01

    A study of the boundary layer and turbulence characteristics inside the passages of an axial flow inducer is reported. The first part deals with the analytical and experimental investigation of the boundary layer characteristics in a four bladed flat plate inducer passage operated with no throttle. An approximate analysis for the prediction of radial and chordwise velocity profiles across the passage is carried out. The momentum integral technique is used to predict the gross properties of the boundary layer. Equations are given for the exact analysis of the turbulent boundary layer characteristics using the turbulent field method. Detailed measurement of boundary layer profiles, limiting streamline angle and skin friction stress on the rotating blade is also reported. Part two of this report deals with the prediction of the flow as well as blade static pressure measurements in a three bladed inducer with cambered blades operated at a flow coefficient of 0.065. In addition, the mean velocity and turbulence measurements carried out inside the passage using a rotating triaxial probe is reported.

  18. Isolation and characterization of progenitor cells from surgically created - early healing alveolar defects in humans. A preliminary study.

    PubMed

    Sant'Ana, Adriana Campos Passanezi; Damante, Carla Andreotti; Martinez, Maria Alejandra Frias; Valdivia, Maria Alejandra Medina; Karam, Paula Stefânia Hage; de Oliveira, Flavia Amadeu; de Oliveira, Rodrigo Cardoso; Gasparoto, Thais Helena; Campanelli, Ana Paula; Zangrando, Mariana Schutzer Ragghianti; de Rezende, Maria Lúcia Rubo; Greghi, Sebastião Luiz Aguiar; Passanezi, Euloir

    2018-05-30

    The granulation tissue (GT) present in surgically-created early healing sockets has been considered as a possible source of osteoprogenitor cells for periodontal regeneration, as demonstrated in animal studies. However, the in vitro osteogenic properties of tissue removed from human surgically-created early healing alveolar defects (SC-EHAD) remains to be established, being that the aim of this study. Surgical defects were created in the edentulous ridge of two systemically healthy adults. The healing tissue present in these defects was removed 21 days later for the establishment of primary culture. The in vitro characteristics of the cultured cells were determined by Armelin method, MTT assay, immunohistochemistry, alkaline phosphatase (ALP) activity, mineralization assay and flow cytometry for detection of stem cells/osteoprogenitor cell markers. Cells were able to adhere to the plastic and assumed spindle-shaped morphology at earlier passages, changing to a cuboidal one with increasing passages. Differences in the proliferation rate were observed with increasing passages, suggesting osteogenic differentiation. ALP and mineralization activities were detected in conventional and osteogenic medium. Fresh samples of SC-EHAD tissue exhibited CD34 - and CD45 - phenotypes. Cells at later passages (14 th ) exhibited CD34 - , CD45 - , CD105 - , CD166 - and collagen type I + phenotype. Tissue removed from SC-EHAD is a possible source of progenitor cells. This article is protected by copyright. All rights reserved. © 2018 American Academy of Periodontology.

  19. The Circadian Clock Controls Sunburn Apoptosis and Erythema in Mouse Skin

    PubMed Central

    Gaddameedhi, Shobhan; Selby, Christopher P.; Kemp, Michael G.; Ye, Rui; Sancar, Aziz

    2014-01-01

    Epidemiological studies of humans and experimental studies with mouse models suggest that sunburn resulting from exposure to excessive UV light and damage to DNA confers an increased risk for melanoma and non-melanoma skin cancer. Previous reports have shown that both nucleotide excision repair, which is the sole pathway in humans for removing UV photoproducts, and DNA replication, are regulated by the circadian clock in mouse skin. Furthermore, the timing of UV exposure during the circadian cycle has been shown to affect skin carcinogenesis in mice. Because sunburn and skin cancer are causally related, we investigated UV-induced sunburn apoptosis and erythema in mouse skin as a function of circadian time. Interestingly, we observed that sunburn apoptosis, inflammatory cytokine induction, and erythema were maximal following an acute early morning exposure to UV and minimal following an afternoon exposure. Early morning exposure to UV also produced maximal activation of Atr-mediated DNA damage checkpoint signaling including activation of the tumor suppressor p53, which is known to control the process of sunburn apoptosis. To our knowledge these data provide the first evidence that the circadian clock plays an important role in the erythemal response in UV-irradiated skin. The early morning is when DNA repair is at a minimum, thus the acute responses likely are associated with unrepaired DNA damage. The prior report that mice are more susceptible to skin cancer induction following chronic irradiation in the AM, when p53 levels are maximally induced, is discussed in terms of the mutational inactivation of p53 during chronic irradiation. PMID:25431853

  20. Strong-field adiabatic passage in the continuum: Electromagnetically induced transparency and stimulated Raman adiabatic passage

    NASA Astrophysics Data System (ADS)

    Eilam, A.; Shapiro, M.

    2012-01-01

    We present a fully quantum-mechanical theory of the mutual light-matter effects when two laser pulses interact with three discrete states coupled to a (quasi)continuum. Our formulation uses a single set of equations to describe the time dependence of the discrete and continuum populations, as well as pulse propagation in electromagnetically induced transparency (EIT) and stimulated Raman adiabatic passage (STIRAP) situations, for both weak and strong laser pulses. The theory gives a mechanistic picture of the “slowing down of light” and the state of spontaneously emitted photons during this process. Surprising features regarding the time dependence of material and radiative transients as well as limitations on quantum light storage and retrieval are unraveled.

  1. Parapatric Speciation in the Evolution of Early Intervention for Infants and Toddlers with Disabilities and Their Families

    ERIC Educational Resources Information Center

    Dunst, Carl J.

    2012-01-01

    The term parapatric speciation, borrowed from biogeography, is used as a metaphor for describing and illustrating a little acknowledged change in the field of early intervention that occurred at the time of the passage of the Education of the Handicapped Act Part H early intervention legislation. The term refers to the formation of a new species…

  2. Formation of Fenestrae in Murine Liver Sinusoids Depends on Plasmalemma Vesicle-Associated Protein and Is Required for Lipoprotein Passage

    PubMed Central

    Herrnberger, Leonie; Hennig, Robert; Kremer, Werner; Hellerbrand, Claus; Goepferich, Achim; Kalbitzer, Hans Robert; Tamm, Ernst R.

    2014-01-01

    Liver sinusoidal endothelial cells (LSEC) are characterized by the presence of fenestrations that are not bridged by a diaphragm. The molecular mechanisms that control the formation of the fenestrations are largely unclear. Here we report that mice, which are deficient in plasmalemma vesicle-associated protein (PLVAP), develop a distinct phenotype that is caused by the lack of sinusoidal fenestrations. Fenestrations with a diaphragm were not observed in mouse LSEC at three weeks of age, but were present during embryonic life starting from embryonic day 12.5. PLVAP was expressed in LSEC of wild-type mice, but not in that of Plvap-deficient littermates. Plvap-/- LSEC showed a pronounced and highly significant reduction in the number of fenestrations, a finding, which was seen both by transmission and scanning electron microscopy. The lack of fenestrations was associated with an impaired passage of macromolecules such as FITC-dextran and quantum dot nanoparticles from the sinusoidal lumen into Disse's space. Plvap-deficient mice suffered from a pronounced hyperlipoproteinemia as evidenced by milky plasma and the presence of lipid granules that occluded kidney and liver capillaries. By NMR spectroscopy of plasma, the nature of hyperlipoproteinemia was identified as massive accumulation of chylomicron remnants. Plasma levels of low density lipoproteins (LDL) were also significantly increased as were those of cholesterol and triglycerides. In contrast, plasma levels of high density lipoproteins (HDL), albumin and total protein were reduced. At around three weeks of life, Plvap-deficient livers developed extensive multivesicular steatosis, steatohepatitis, and fibrosis. PLVAP is critically required for the formation of fenestrations in LSEC. Lack of fenestrations caused by PLVAP deficiency substantially impairs the passage of chylomicron remnants between liver sinusoids and hepatocytes, and finally leads to liver damage. PMID:25541982

  3. Dynamic Convergent Evolution Drives the Passage Adaptation across 48 Years' History of H3N2 Influenza Evolution.

    PubMed

    Chen, Hui; Deng, Qiang; Ng, Sock Hoon; Lee, Raphael Tze Chuen; Maurer-Stroh, Sebastian; Zhai, Weiwei

    2016-12-01

    Influenza viruses are often propagated in a diverse set of culturing media and additional substitutions known as passage adaptation can cause extra evolution in the target strain, leading to ineffective vaccines. Using 25,482 H3N2 HA1 sequences curated from Global Initiative on Sharing All Influenza Data and National Center for Biotechnology Information databases, we found that passage adaptation is a very dynamic process that changes over time and evolves in a seesaw like pattern. After crossing the species boundary from bird to human in 1968, the influenza H3N2 virus evolves to be better adapted to the human environment and passaging them in embryonated eggs (i.e., an avian environment) leads to increasingly stronger positive selection. On the contrary, passage adaptation to the mammalian cell lines changes from positive selection to negative selection. Using two statistical tests, we identified 19 codon positions around the receptor binding domain strongly contributing to passage adaptation in the embryonated egg. These sites show strong convergent evolution and overlap extensively with positively selected sites identified in humans, suggesting that passage adaptation can confound many of the earlier studies on influenza evolution. Interestingly, passage adaptation in recent years seems to target a few codon positions in antigenic surface epitopes, which makes it difficult to produce antigenically unaltered vaccines using embryonic eggs. Our study outlines another interesting scenario whereby both convergent and adaptive evolution are working in synchrony driving viral adaptation. Future studies from sequence analysis to vaccine production need to take careful consideration of passage adaptation. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Heat transfer and pressure drop for air flow through enhanced passages. Final report

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

    Obot, N.T.; Esen, E.B.

    1992-06-01

    An extensive experimental investigation was carried out to determine the pressure drop and heat transfer characteristics for laminar, transitional and turbulent flow of air through a smooth passage and twenty-three enhanced passages. The internal surfaces of all enhanced passages had spirally shaped geometries; these included fluted, finned/ribbed and indented surfaces. The Reynolds number (Re) was varied between 400 and 50000. The effect of heat transfer (wall cooling or fluid heating) on pressure drop is most significant within the transition region; the recorded pressure drop with heat transfer is much higher than that without heat transfer. The magnitude of this effectmore » depends markedly on the average surface temperature and, to a lesser extent, on the geometric characteristics of the enhanced surfaces. When the pressure drop data are reduced as values of the Fanning friction factor(f), the results are about the same with and without heat transfer for turbulent flow, with moderate differences in the laminar and transition regions.« less

  5. 77 FR 35368 - Inside Passage Electric Cooperative; Notice of Application Tendered for Filing With the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-13

    ..., 16 U.S.C. 791(a)-825(r). h. Applicant Contact: Mr. Peter A. Bibb, Operations Manager, Inside Passage... No.: P-14066-002. c. Date filed: May 25, 2012. d. Applicant: Inside Passage Electric Cooperative. e..., [email protected] . i. FERC Contact: Ryan Hansen, 888 1st St. NE., Washington, DC 20426, (202) 502-8074, ryan...

  6. Atlantic Sturgeon Spatial and Temporal Distribution in Minas Passage, Nova Scotia, Canada, a Region of Future Tidal Energy Extraction

    PubMed Central

    Stokesbury, Michael J. W.; Logan-Chesney, Laura M.; McLean, Montana F.; Buhariwalla, Colin F.; Redden, Anna M.; Beardsall, Jeffrey W.; Broome, Jeremy E.; Dadswell, Michael J.

    2016-01-01

    In the Bay of Fundy, Atlantic sturgeon from endangered and threatened populations in the USA and Canada migrate through Minas Passage to enter and leave Minas Basin. A total of 132 sub-adult and adult Atlantic sturgeon were tagged in Minas Basin during the summers of 2010–2014 using pressure measuring, uniquely coded, acoustic transmitters with a four or eight year life span. The aim of this study was to examine spatial and seasonal distribution of sturgeon in Minas Passage during 2010–2014 and test the hypothesis that, when present, Atlantic sturgeon were evenly distributed from north to south across Minas Passage. This information is important as tidal energy extraction using in-stream, hydrokinetic turbines is planned for only the northern portion of Minas Passage. Electronic tracking data from a total of 740 sturgeon days over four years demonstrated that Atlantic sturgeon used the southern portion of Minas Passage significantly more than the northern portion. Sturgeon moved through Minas Passage at depths mostly between 15 and 45 m (n = 10,116; mean = 31.47 m; SD = 14.88). Sturgeon mean swimming depth was not significantly related to bottom depth and in deeper regions they swam pelagically. Sturgeon predominately migrated inward through Minas Passage during spring, and outward during late summer-autumn. Sturgeon were not observed in Minas Passage during winter 2012–2013 when monitoring receivers were present. This information will enable the estimation of encounters of Atlantic sturgeon with in-stream hydrokinetic turbines. PMID:27383274

  7. Development of a Nebraska culvert aquatic organism passage screening tool.

    DOT National Transportation Integrated Search

    2012-12-01

    Culverts channelize water relative to natural stream reaches, which can increase the velocity of water passing through them. Increased water velocities can alter stream morphology and create a possible barrier or obstacle to fish passage, which may a...

  8. Culvert Length and Interior Lighting Impacts to Topeka Shiner Passage

    DOT National Transportation Integrated Search

    2017-11-01

    Culverts can act as barriers to fish passage for a number of reasons including insufficient water depth or excess velocity. In addition, concern is being raised over behavioral barriers where culvert conditions elicit an avoidance response that deter...

  9. Drake passage and central american seaway controls on the distribution of the oceanic carbon reservoir

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

    Fyke, Jeremy G.; D'Orgeville, Marc; Weaver, Andrew J.

    2015-05-01

    A coupled carbon/climate model is used to explore the impact of Drake Passage opening and Central American Seaway closure on the distribution of carbon in the global oceans. We find that gateway evolution likely played an important role in setting the modern day distribution of oceanic dissolved inorganic carbon (DIC), which is currently characterized by relatively low concentrations in the Atlantic ocean, and high concentrations in the Southern, Indian, and Pacific oceans. In agreement with previous studies, we find a closed Drake Passage in the presence of an open Central American Seaway results in suppressed Atlantic meridional overturning and enhancedmore » southern hemispheric deep convection. Opening of the Drake Passage triggers Antarctic Circumpolar Current flow and a weak Atlantic meridional overturning circulation (AMOC). Subsequent Central American Seaway closure reinforces the AMOC while also stagnating equatorial Pacific subsurface waters. These gateway-derived oceanographic changes are reflected in large shifts to the global distribution of DIC. An initially closed Drake Passage results in high DIC concentrations in the Atlantic and Arctic oceans, and lower DIC concentrations in the Pacific/Indian/Southern oceans. Opening Drake Passage reverses this gradient by lowering mid-depth Atlantic and Arctic DIC concentrations and raising deep Pacific/Indian/Southern Ocean DIC concentrations. Central American Seaway closure further reinforces this trend through additional Atlantic mid-depth DIC decreases, as well as Pacific mid-depth DIC concentration increases, with the net effect being a transition to a modern distribution of oceanic DIC.« less

  10. Compliance Monitoring of Juvenile Subyearling Chinook Salmon Survival and Passage at The Dalles Dam, Summer 2010

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

    Johnson, Gary E.; Carlson, Thomas J.; Skalski, John R.

    2010-12-21

    The purpose of this compliance study was to estimate dam passage survival of subyearling Chinook salmon smolts at The Dalles Dam during summer 2010. Under the 2008 Federal Columbia River Power System (FCRPS) Biological Opinion (BiOp), dam passage survival should be greater than or equal to 0.93 and estimated with a standard error (SE) less than or equal 0.015. The study also estimated smolt passage survival from the forebay 2 km upstream of the dam to the tailrace 2 km below the dam The forebay-to-tailrace survival estimate satisfies the “BRZ-to-BRZ” survival estimate called for in the Fish Accords. , asmore » well as the forebay residence time, tailrace egress time, and spill passage efficiency, as required in the Columbia Basin Fish Accords. The estimate of dam survival for subyearling Chinook salmon at The Dalles in 2010 was 0.9404 with an associated standard error of 0.0091.« less

  11. Centralized mouse repositories.

    PubMed

    Donahue, Leah Rae; Hrabe de Angelis, Martin; Hagn, Michael; Franklin, Craig; Lloyd, K C Kent; Magnuson, Terry; McKerlie, Colin; Nakagata, Naomi; Obata, Yuichi; Read, Stuart; Wurst, Wolfgang; Hörlein, Andreas; Davisson, Muriel T

    2012-10-01

    Because the mouse is used so widely for biomedical research and the number of mouse models being generated is increasing rapidly, centralized repositories are essential if the valuable mouse strains and models that have been developed are to be securely preserved and fully exploited. Ensuring the ongoing availability of these mouse strains preserves the investment made in creating and characterizing them and creates a global resource of enormous value. The establishment of centralized mouse repositories around the world for distributing and archiving these resources has provided critical access to and preservation of these strains. This article describes the common and specialized activities provided by major mouse repositories around the world.

  12. Stimulated Raman adiabatic passage in physics, chemistry, and beyond

    NASA Astrophysics Data System (ADS)

    Vitanov, Nikolay V.; Rangelov, Andon A.; Shore, Bruce W.; Bergmann, Klaas

    2017-01-01

    The technique of stimulated Raman adiabatic passage (STIRAP), which allows efficient and selective population transfer between quantum states without suffering loss due to spontaneous emission, was introduced in 1990 by Gaubatz et al.. Since then STIRAP has emerged as an enabling methodology with widespread successful applications in many fields of physics, chemistry, and beyond. This article reviews the many applications of STIRAP emphasizing the developments since 2001, the time when the last major review on the topic was written (Vitanov, Fleischhauer et al.). A brief introduction into the theory of STIRAP and the early applications for population transfer within three-level systems is followed by the discussion of several extensions to multilevel systems, including multistate chains and tripod systems. The main emphasis is on the wide range of applications in atomic and molecular physics (including atom optics, cavity quantum electrodynamics, formation of ultracold molecules, etc.), quantum information (including single- and two-qubit gates, entangled-state preparation, etc.), solid-state physics (including processes in doped crystals, nitrogen-vacancy centers, superconducting circuits, semiconductor quantum dots and wells), and even some applications in classical physics (including waveguide optics, polarization optics, frequency conversion, etc.). Promising new prospects for STIRAP are also presented (including processes in optomechanics, precision experiments, detection of parity violation in molecules, spectroscopy of core-nonpenetrating Rydberg states, population transfer with x-ray pulses, etc.).

  13. Early Transition and Adjustment and Children's Adjustment after Six Years of Schooling

    ERIC Educational Resources Information Center

    Margetts, Kay

    2009-01-01

    Researchers have made convincing arguments for the benefits of a smooth transition to school. The passage through this significant social change may have a lasting influence on children's progress. For example, social, emotional and academic difficulties in the early years of schooling have been shown to persist through school and into…

  14. Parameters estimation using the first passage times method in a jump-diffusion model

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

    Khaldi, K., E-mail: kkhaldi@umbb.dz; LIMOSE Laboratory, Boumerdes University, 35000; Meddahi, S., E-mail: samia.meddahi@gmail.com

    2016-06-02

    The main purposes of this paper are two contributions: (1) it presents a new method, which is the first passage time (FPT method) generalized for all passage times (GPT method), in order to estimate the parameters of stochastic Jump-Diffusion process. (2) it compares in a time series model, share price of gold, the empirical results of the estimation and forecasts obtained with the GPT method and those obtained by the moments method and the FPT method applied to the Merton Jump-Diffusion (MJD) model.

  15. Parallel Passages: Contrasting Views from U.S. and Japan.

    ERIC Educational Resources Information Center

    Becker, James; Wojtan, Linda

    Using selected passages from Japanese and U.S. social studies textbooks, this booklet presents contrasting views and interpretations of historical events or circumstances. The textbooks, review, and supplementary materials collected or developed in conjunction with the Japan/U.S. Textbook Study Project provides much of the basic material for the…

  16. Planning Guide for Fish Passage at Pittsburgh District Dams

    DTIC Science & Technology

    2013-08-01

    attracted to a downstream flow at the entrance gate of the lift. 2) Immigrants pass around a moveable crowder that, when engaged, forces fish into the...might influence fish passage over a large number of sites. REFERENCES Bailey, M. M., J. J. Isely, and W. C. Bridges , Jr. 2004. Movement and

  17. Survival and Passage of Juvenile Chinook Salmon and Steelhead Passing through Bonneville Dam, 2011

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

    Ploskey, Gene R.; Batten, G.; Cushing, Aaron W.

    Pacific Northwest National Laboratory (PNNL) and subcontractors conducted an acoustic-telemetry study of juvenile salmonid fish passage and survival at Bonneville Dam in 2011. The study was conducted to assess the readiness of the monitoring system for official compliance studies under the 2008 Biological Opinion and Fish Accords and to assess performance measures including route-specific fish passage proportions, travel times, and survival based upon a virtual/paired-release model. The study relied on releases of live Juvenile Salmon Acoustic Telemetry System tagged smolts in the Columbia River and used acoustic telemetry to evaluate the approach, passage, and survival of passing juvenile salmon usingmore » a virtual release, paired reference release survival model. This study supports the U.S. Army Corps of Engineers’ continual effort to improve conditions for juvenile anadromous fish passing through Columbia River dams.« less

  18. Is Early Enteral Nutrition Better for Postoperative Course in Esophageal Cancer Patients?

    PubMed Central

    Kobayashi, Kazuaki; Koyama, Yu; Kosugi, Shin-ichi; Ishikawa, Takashi; Sakamoto, Kaoru; Ichikawa, Hiroshi; Wakai, Toshifumi

    2013-01-01

    We retrospectively examined esophageal cancer patients who received enteral nutrition (EN) to clarify the validity of early EN compared with delayed EN. A total of 103 patients who underwent transthoracic esophagectomy with three-field lymphadenectomy for esophageal cancer were entered. Patients were divided into two groups; Group E received EN within postoperative day 3, and Group L received EN after postoperative day 3. The clinical factors such as days for first fecal passage, the dose of postoperative albumin infusion, differences of serum albumin value between pre- and postoperation, duration of systematic inflammatory response syndrome (SIRS), incidence of postoperative infectious complication, and use of total parenteral nutrition (TPN) were compared between the groups. The statistical analyses were performed using Mann-Whitney U test and Chi square test. The statistical significance was defined as p < 0.05. Group E showed fewer days for the first fecal passage (p < 0.01), lesser dose of postoperative albumin infusion (p < 0.01), less use of TPN (p < 0.01), and shorter duration of SIRS (p < 0.01). However, there was no significant difference in postoperative complications between the two groups. Early EN started within 3 days after esophagectomy. It is safe and valid for reduction of albumin infusion and TPN, for promoting early recovery of intestinal movement, and for early recovery from systemic inflammation. PMID:24067386

  19. Generation and characterization of Dyt1 DeltaGAG knock-in mouse as a model for early-onset dystonia.

    PubMed

    Dang, Mai T; Yokoi, Fumiaki; McNaught, Kevin St P; Jengelley, Toni-Ann; Jackson, Tehone; Li, Jianyong; Li, Yuqing

    2005-12-01

    A trinucleotide deletion of GAG in the DYT1 gene that encodes torsinA protein is implicated in the neurological movement disorder of Oppenheim's early-onset dystonia. The mutation removes a glutamic acid in the carboxy region of torsinA, a member of the Clp protease/heat shock protein family. The function of torsinA and the role of the mutation in causing dystonia are largely unknown. To gain insight into these unknowns, we made a gene-targeted mouse model of Dyt1 DeltaGAG to mimic the mutation found in DYT1 dystonic patients. The mutated heterozygous mice had deficient performance on the beam-walking test, a measure of fine motor coordination and balance. In addition, they exhibited hyperactivity in the open-field test. Mutant mice also showed a gait abnormality of increased overlap. Mice at 3 months of age did not display deficits in beam-walking and gait, while 6-month mutant mice did, indicating an age factor in phenotypic expression as well. While striatal dopamine and 4-dihydroxyphenylacetic acid (DOPAC) levels in Dyt1 DeltaGAG mice were similar to that of wild-type mice, a 27% decrease in 4-hydroxy, 3-methoxyphenacetic acid (homovanillic acid) was detected in mutant mice. Dyt1 DeltaGAG tissues also have ubiquitin- and torsinA-containing aggregates in neurons of the pontine nuclei. A sex difference was noticed in the mutant mice with female mutant mice exhibiting fewer alterations in behavioral, neurochemical, and cellular changes. Our results show that knocking in a Dyt1 DeltaGAG allele in mouse alters their motor behavior and recapitulates the production of protein aggregates that are seen in dystonic patients. Our data further support alterations in the dopaminergic system as a part of dystonia's neuropathology.

  20. Dam operations affect route-specific passage and survival of juvenile Chinook salmon at a main-stem diversion dam

    USGS Publications Warehouse

    Perry, Russell W.; Kock, Tobias J.; Couter, Ian I; Garrison, Thomas M; Hubble, Joel D; Child, David B

    2016-01-01

    Diversion dams can negatively affect emigrating juvenile salmon populations because fish must pass through the impounded river created by the dam, negotiate a passage route at the dam and then emigrate through a riverine reach that has been affected by reduced river discharge. To quantify the effects of a main-stem diversion dam on juvenile Chinook salmon in the Yakima River, Washington, USA, we used radio telemetry to understand how dam operations and river discharge in the 18-km reach downstream of the dam affected route-specific passage and survival. We found evidence of direct mortality associated with dam passage and indirect mortality associated with migration through the reach below the dam. Survival of fish passing over a surface spill gate (the west gate) was positively related to river discharge, and survival was similar for fish released below the dam, suggesting that passage via this route caused little additional mortality. However, survival of fish that passed under a sub-surface spill gate (the east gate) was considerably lower than survival of fish released downstream of the dam, with the difference in survival decreasing as river discharge increased. The probability of fish passing the dam via three available routes was strongly influenced by dam operations, with passage through the juvenile fish bypass and the east gate increasing with discharge through those routes. By simulating daily passage and route-specific survival, we show that variation in total survival is driven by river discharge and moderated by the proportion of fish passing through low-survival or high-survival passage routes.

  1. Influence of Prior Knowledge and Interest on Fourth- and Fifth-Grade Passage Comprehension on the Qualitative Reading Inventory-4

    ERIC Educational Resources Information Center

    Clark, Mary Kristen; Kamhi, Alan G.

    2014-01-01

    Purpose: In 2 experiments, we examined the influence of prior knowledge and interest on 4th- and 5th-grade students' passage comprehension scores on the Qualitative Reading Inventory-4 (QRI-4) and 2 experimenter constructed passages. Method: In Experiment 1, 4th- and 5th-grade students were administered 4 Level 4 passages or 4 Level 5…

  2. The Mouse House: A brief history of the ORNL mouse-genetics program, 1947–2009

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

    Russell, Liane B.

    The large mouse genetics program at the Oak Ridge National Lab is often re-membered chiefly for the germ-cell mutation-rate data it generated and their uses in estimating the risk of heritable radiation damage. In fact, it soon became a multi-faceted research effort that, over a period of almost 60 years, generated a wealth of information in the areas of mammalian mutagenesis, basic genetics (later enriched by molecular techniques), cytogenetics, reproductive biology, biochemistry of germ cells, and teratology. Research in the area of germ-cell mutagenesis explored the important physical and biological factors that affect the frequency and nature of induced mutationsmore » and made several unexpected discoveries, such as the major importance of the perigametic interval (the zygote stage) for the origin of spontaneous mutations and for the sensitivity to induced genetic change. Of practical value was the discovery that ethylnitrosourea was a supermutagen for point mutations, making high-efficiency mutagenesis in the mouse feasible worldwide. Teratogenesis findings resulted in recommendations still generally accepted in radiological practice. Studies supporting the mutagenesis research added whole bodies of information about mammalian germ-cell development and about molecular targets in germ cells. The early decision to not merely count but propagate genetic variants of all sorts made possible further discoveries, such as the Y-Chromosome s importance in mammalian sex determination and the identification of rare X-autosome translocations, which, in turn, led to the formulation of the single-active-X hypothesis and provided tools for studies of functional mosaicism for autosomal genes, male sterility, and chromosome-pairing mechanism. Extensive genetic and then molecular analyses of large numbers of induced specific-locus mutants resulted in fine-structure physical and correlated functional mapping of significant portions of the mouse genome and constituted a

  3. Vortex generating flow passage design for increased film-cooling effectiveness and surface coverage. [aircraft engine blade cooling

    NASA Technical Reports Server (NTRS)

    Papell, S. S.

    1984-01-01

    The fluid mechanics of the basic discrete hole film cooling process is described as an inclined jet in crossflow and a cusp shaped coolant flow channel contour that increases the efficiency of the film cooling process is hypothesized. The design concept requires the channel to generate a counter rotating vortex pair secondary flow within the jet stream by virture of flow passage geometry. The interaction of the vortex structures generated by both geometry and crossflow was examined in terms of film cooling effectiveness and surface coverage. Comparative data obtained with this vortex generating coolant passage showed up to factors of four increases in both effectiveness and surface coverage over that obtained with a standard round cross section flow passage. A streakline flow visualization technique was used to support the concept of the counter rotating vortex pair generating capability of the flow passage design.

  4. INTERIOR VIEW, PASSAGE EXTENDING FROM AN EXTERIOR DOOR TO THE ...

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

    INTERIOR VIEW, PASSAGE EXTENDING FROM AN EXTERIOR DOOR TO THE KITCHEN, WITH THE OFFICE TO THE RIGHT. THIS VIEW CLEARLY DEMONSTRATES THE UTILIZATION AND FUNCTION OF BORROWED LIGHT THROUGHOUT THE HOUSE - The Woodlands, 4000 Woodlands Avenue, Philadelphia, Philadelphia County, PA

  5. Quantifying mortal injury of juvenile Chinook salmon exposed to simulated hydro-turbine passage

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

    Brown, Richard S.; Carlson, Thomas J.; Gingerich, Andrew J.

    A proportion of juvenile Chinook salmon and other salmonids travel through one or more turbines during seaward migration in the Columbia and Snake River every year. Despite this understanding, limited information exists on how these fish respond to hydraulic pressures found during turbine passage events. In this study we exposed juvenile Chinook salmon to varied acclimation pressures and subsequent exposure pressures (nadir) to mimic the hydraulic pressures of large Kaplan turbines (ratio of pressure change). Additionally, we varied abiotic (total dissolved gas, rate of pressure change) and biotic (condition factor, fish length, fish weight) factors that may contribute to themore » incidence of mortal injury associated with fish passing through hydro-turbines. We determined that the main factor associated with mortal injury of juvenile Chinook salmon during simulated turbine passage was the ratio between acclimation and nadir pressures. Condition factor, total dissolved gas, and the rate of pressure change were found to only slightly increase the predictive power of equations relating probability of mortal injury to conditions of exposure or characteristics of test fish during simulated turbine passage. This research will assist engineers and fisheries managers in operating and improving hydroelectric facility efficiency while minimizing mortality and injury of turbine-passed juvenile Chinook salmon. The results are discussed in the context of turbine development and the necessity of understanding how different species of fish will respond to the hydraulic pressures of turbine passage.« less

  6. Tight junction protein expression and barrier properties of immortalized mouse brain microvessel endothelial cells.

    PubMed

    Brown, Rachel C; Morris, Andrew P; O'Neil, Roger G

    2007-01-26

    Understanding the molecular and biochemical mechanisms regulating the blood-brain barrier is aided by in vitro model systems. Many studies have used primary cultures of brain microvessel endothelial cells for this purpose. However, primary cultures limit the generation of material for molecular and biochemical assays since cells grow slowly, are prone to contamination by other neurovascular unit cells, and lose blood-brain barrier characteristics when passaged. To address these issues, immortalized cell lines have been generated. In these studies, we assessed the suitability of the immortalized mouse brain endothelial cell line, bEnd3, as a blood-brain barrier model. RT-PCR and immunofluorescence indicated expression of multiple tight junction proteins. bEnd3 cells formed barriers to radiolabeled sucrose, and responded like primary cultures to disrupting stimuli. Exposing cells to serum-free media on their basolateral side significantly decreased paracellular permeability; astrocyte-conditioned media did not enhance barrier properties. The serum-free media-induced decrease in permeability was correlated with an increase in claudin-5 and zonula occludens-1 immunofluorescence at cell-cell contracts. We conclude that bEnd3 cells are an attractive candidate as a model of the blood-brain barrier due to their rapid growth, maintenance of blood-brain barrier characteristics over repeated passages, formation of functional barriers and amenability to numerous molecular interventions.

  7. TIGHT JUNCTION PROTEIN EXPRESSION AND BARRIER PROPERTIES OF IMMORTALIZED MOUSE BRAIN MICROVESSEL ENDOTHELIAL CELLS

    PubMed Central

    Brown, Rachel C.; Morris, Andrew P.; O’Neil, Roger G.

    2007-01-01

    Understanding the molecular and biochemical mechanisms regulating the blood-brain barrier is aided by in vitro model systems. Many studies have used primary cultures of brain microvessel endothelial cells for this purpose. However, primary cultures limit the generation of material for molecular and biochemical assays since cells grow slowly, are prone to contamination by other neurovascular unit cells, and lose blood-brain barrier characteristics when passaged. To address these issues, immortalized cell lines have been generated. In these studies, we assessed the suitability of the immortalized mouse brain endothelial cell line, bEnd3, as a blood-brain barrier model. RT-PCR and immunofluorescence indicated expression of multiple tight junction proteins. bEnd3 cells formed barriers to radiolabeled sucrose, and responded like primary cultures to disrupting stimuli. Exposing cells to serum-free media on their basolateral side significantly decreased paracellular permeability; astrocyte-conditioned media did not enhance barrier properties. The serum-free media-induced decrease in permeability was correlated with an increase in claudin-5 and zonula occludens-1 immunofluorescence at cell-cell contracts. We conclude that bEnd3 cells are an attractive candidate as a model of the blood-brain barrier due to their rapid growth, maintenance of blood-brain barrier characteristics over repeated passages, formation of functional barriers and amenability to numerous molecular interventions. PMID:17169347

  8. Centralized Mouse Repositories

    PubMed Central

    Donahue, Leah Rae; de Angelis, Martin Hrabe; Hagn, Michael; Franklin, Craig; Lloyd, K. C. Kent; Magnuson, Terry; McKerlie, Colin; Nakagata, Naomi; Obata, Yuichi; Read, Stuart; Wurst, Wolfgang; Hörlein, Andreas; Davisson, Muriel T.

    2013-01-01

    Because the mouse is used so widely for biomedical research and the number of mouse models being generated is increasing rapidly, centralized repositories are essential if the valuable mouse strains and models that have been developed are to be securely preserved and fully exploited. Ensuring the ongoing availability of these mouse strains preserves the investment made in creating and characterizing them and creates a global resource of enormous value. The establishment of centralized mouse repositories around the world for distributing and archiving these resources has provided critical access to and preservation of these strains. This article describes the common and specialized activities provided by major mouse repositories around the world. PMID:22945696

  9. Mean first passage times of Brownian rotators from differential recurrence relations

    NASA Astrophysics Data System (ADS)

    Coffey, W. T.

    1999-11-01

    An exact method of calculation of mean first passage times (analogous to that previously used [W. T. Coffey, Yu. P. Kalmykov, E. S. Massawe, and J. T. Waldron, J. Chem. Phys. 99, 4011 (1993)] for the correlation time) is developed in terms of continued fractions from the zero frequency limit of the Laplace transform of the set of differential recurrence relations generated by the Fokker-Planck or Langevin equations. The method because it is based on a Floquet representation avoids the use of quadratures and so may be easily generalized to multidegree of freedom systems by the use of matrix continued fractions. The procedure is illustrated by considering the mean first passage time of a fixed axis rotator with two equivalent sites.

  10. First passage times for multiple particles with reversible target-binding kinetics

    NASA Astrophysics Data System (ADS)

    Grebenkov, Denis S.

    2017-10-01

    We investigate the first passage problem for multiple particles that diffuse towards a target, partially adsorb there, and then desorb after a finite exponentially distributed residence time. We search for the first time when m particles undergoing such reversible target-binding kinetics are found simultaneously on the target that may trigger an irreversible chemical reaction or a biophysical event. Even if the particles are independent, the finite residence time on the target yields an intricate temporal coupling between particles. We compute analytically the mean first passage time (MFPT) for two independent particles by mapping the original problem to higher-dimensional surface-mediated diffusion and solving the coupled partial differential equations. The respective effects of the adsorption and desorption rates on the MFPT are revealed and discussed.

  11. Effect of serial pig passages on the adaptation of an avian H9N2 influenza virus to swine.

    PubMed

    Mancera Gracia, Jose Carlos; Van den Hoecke, Silvie; Saelens, Xavier; Van Reeth, Kristien

    2017-01-01

    H9N2 avian influenza viruses are endemic in poultry in Asia and the Middle East. These viruses sporadically cause dead-end infections in pigs and humans raising concerns about their potential to adapt to mammals or reassort with human or swine influenza viruses. We performed ten serial passages with an avian H9N2 virus (A/quail/Hong Kong/G1/1997) in influenza naïve pigs to assess the potential of this virus to adapt to swine. Virus replication in the entire respiratory tract and nasal virus excretion were examined after each passage and we deep sequenced viral genomic RNA of the parental and passage four H9N2 virus isolated from the nasal mucosa and lung. The parental H9N2 virus caused a productive infection in pigs with a predominant tropism for the nasal mucosa, whereas only 50% lung samples were virus-positive. In contrast, inoculation of pigs with passage four virus resulted in viral replication in the entire respiratory tract. Subsequent passages were associated with reduced virus replication in the lungs and infectious virus was no longer detectable in the upper and lower respiratory tract of inoculated pigs at passage ten. The broader tissue tropism after four passages was associated with an amino acid residue substitution at position 225, within the receptor-binding site of the hemagglutinin. We also compared the parental H9N2, passage four H9N2 and the 2009 pandemic H1N1 (pH1N1) virus in a direct contact transmission experiment. Whereas only one out of six contact pigs showed nasal virus excretion of the wild-type H9N2 for more than four days, all six contact animals shed the passage four H9N2 virus. Nevertheless, the amount of excreted virus was significantly lower when compared to that of the pH1N1, which readily transmitted and replicated in all six contact animals. Our data demonstrate that serial passaging of H9N2 virus in pigs enhances its replication and transmissibility. However, full adaptation of an avian H9N2 virus to pigs likely requires an

  12. Effect of serial pig passages on the adaptation of an avian H9N2 influenza virus to swine

    PubMed Central

    Van den Hoecke, Silvie; Saelens, Xavier; Van Reeth, Kristien

    2017-01-01

    H9N2 avian influenza viruses are endemic in poultry in Asia and the Middle East. These viruses sporadically cause dead-end infections in pigs and humans raising concerns about their potential to adapt to mammals or reassort with human or swine influenza viruses. We performed ten serial passages with an avian H9N2 virus (A/quail/Hong Kong/G1/1997) in influenza naïve pigs to assess the potential of this virus to adapt to swine. Virus replication in the entire respiratory tract and nasal virus excretion were examined after each passage and we deep sequenced viral genomic RNA of the parental and passage four H9N2 virus isolated from the nasal mucosa and lung. The parental H9N2 virus caused a productive infection in pigs with a predominant tropism for the nasal mucosa, whereas only 50% lung samples were virus-positive. In contrast, inoculation of pigs with passage four virus resulted in viral replication in the entire respiratory tract. Subsequent passages were associated with reduced virus replication in the lungs and infectious virus was no longer detectable in the upper and lower respiratory tract of inoculated pigs at passage ten. The broader tissue tropism after four passages was associated with an amino acid residue substitution at position 225, within the receptor-binding site of the hemagglutinin. We also compared the parental H9N2, passage four H9N2 and the 2009 pandemic H1N1 (pH1N1) virus in a direct contact transmission experiment. Whereas only one out of six contact pigs showed nasal virus excretion of the wild-type H9N2 for more than four days, all six contact animals shed the passage four H9N2 virus. Nevertheless, the amount of excreted virus was significantly lower when compared to that of the pH1N1, which readily transmitted and replicated in all six contact animals. Our data demonstrate that serial passaging of H9N2 virus in pigs enhances its replication and transmissibility. However, full adaptation of an avian H9N2 virus to pigs likely requires an

  13. Examination of diagnostic features in multiphoton microscopy and optical coherence tomography images of ovarian tumorigenesis in a mouse model

    NASA Astrophysics Data System (ADS)

    Watson, Jennifer M.

    Ovarian cancer is a deadly disease owing to the non-specific symptoms and suspected rapid progression, leading to frequent late stage detection and poor prognosis. Medical imaging methods such as CT, MRI and ultrasound as well as serum testing for cancer markers have had extremely poor performance for early disease detection. Due to the poor performance of available screening methods, and the impracticality and ineffectiveness of taking tissue biopsies from the ovary, women at high risk for developing ovarian cancer are often advised to undergo prophylactic salpingo-oophorectomy. This surgery results in many side effects and is most often unnecessary since only a fraction of high risk women go on to develop ovarian cancer. Better understanding of the early development of ovarian cancer and characterization of morphological changes associated with early disease could lead to the development of an effective screening test for women at high risk. Optical imaging methods including optical coherence tomography (OCT) and multiphoton microscopy (MPM) are excellent tools for studying disease progression owing to the high resolution and depth sectioning capabilities. Further, these techniques are excellent for optical biopsy because they can image in situ non-destructively. In the studies described in this dissertation OCT and MPM are used to identify cellular and tissue morphological changes associated with early tumor development in a mouse model of ovarian cancer. This work is organized into three specific aims. The first aim is to use the images from the MPM phenomenon of second harmonic generation to quantitatively examine the morphological differences in collagen structure in normal mouse ovarian tissue and mouse ovarian tumors. The second aim is to examine the differences in endogenous two-photon excited fluorescence in normal mouse ovarian tissue and mouse ovarian tumors. The third and final aim is to identify changes in ovarian microstructure resulting from early

  14. Early cell lineage specification in a marsupial: a case for diverse mechanisms among mammals.

    PubMed

    Frankenberg, Stephen; Shaw, Geoff; Freyer, Claudia; Pask, Andrew J; Renfree, Marilyn B

    2013-03-01

    Early cell lineage specification in eutherian mammals results in the formation of a pluripotent inner cell mass (ICM) and trophoblast. By contrast, marsupials have no ICM. Here, we present the first molecular analysis of mechanisms of early cell lineage specification in a marsupial, the tammar wallaby. There was no overt differential localisation of key lineage-specific transcription factors in cleavage and early unilaminar blastocyst stages. Pluriblast cells (equivalent to the ICM) became distinguishable from trophoblast cells by differential expression of POU5F1 and, to a greater extent, POU2, a paralogue of POU5F1. Unlike in the mouse, pluriblast-trophoblast differentiation coincided with a global nuclear-to-cytoplasmic transition of CDX2 localisation. Also unlike in the mouse, Hippo pathway factors YAP and WWTR1 showed mutually distinct localisation patterns that suggest non-redundant roles. NANOG and GATA6 were conserved as markers of epiblast and hypoblast, respectively, but some differences to the mouse were found in their mode of differentiation. Our results suggest that there is considerable evolutionary plasticity in the mechanisms regulating early lineage specification in mammals.

  15. Reactivity of mouse antibodies against bromelain-treated mouse erythrocytes with thrombin-treated mouse platelets.

    PubMed Central

    Kawaguchi, S

    1989-01-01

    The reactivity of mouse antibodies against bromelain-treated mouse erythrocytes (BrMRBC) with mouse platelets before and after thrombin treatment was assessed by flow cytometry. Anti-BrMRBC antibodies could bind to thrombin-treated platelets, although normal platelets were also weakly reactive with the antibodies. The binding of anti-BrMRBC antibodies to platelets was confirmed by complement-dependent lysis. It is suggested that thrombin-activated platelets may be a real target for anti-BrMRBC antibodies. PMID:2467876

  16. Effective conductivity, dielectric constant, and diffusion coefficient of digitized composite media via first-passage-time equations

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

    Torquato, S.; Kim, I.C.; Cule, D.

    1999-02-01

    We generalize the Brownian motion simulation method of Kim and Torquato [J. Appl. Phys. {bold 68}, 3892 (1990)] to compute the effective conductivity, dielectric constant and diffusion coefficient of digitized composite media. This is accomplished by first generalizing the {ital first-passage-time equations} to treat first-passage regions of arbitrary shape. We then develop the appropriate first-passage-time equations for digitized media: first-passage squares in two dimensions and first-passage cubes in three dimensions. A severe test case to prove the accuracy of the method is the two-phase periodic checkerboard in which conduction, for sufficiently large phase contrasts, is dominated by corners that joinmore » two conducting-phase pixels. Conventional numerical techniques (such as finite differences or elements) do not accurately capture the local fields here for reasonable grid resolution and hence lead to inaccurate estimates of the effective conductivity. By contrast, we show that our algorithm yields accurate estimates of the effective conductivity of the periodic checkerboard for widely different phase conductivities. Finally, we illustrate our method by computing the effective conductivity of the random checkerboard for a wide range of volume fractions and several phase contrast ratios. These results always lie within rigorous four-point bounds on the effective conductivity. {copyright} {ital 1999 American Institute of Physics.}« less

  17. Nucleostemin Delays Cellular Senescence and Negatively Regulates TRF1 Protein Stability▿ †

    PubMed Central

    Zhu, Qubo; Yasumoto, Hiroaki; Tsai, Robert Y. L.

    2006-01-01

    Nucleostemin (NS) encodes a nucleolar GTP-binding protein highly enriched in the stem cells and cancer cells. To determine its biological activity in vivo, we generated NS loss- and gain-of-function mouse models. The embryogenesis of homozygous NS-null (NS−/−) mice was aborted before the blastula stage. Although the growth and fertility of heterozygous NS-null (NS+/−) mice appeared normal, NS+/− mouse embryonic fibroblasts (MEFs) had fewer NS proteins, a lower population growth rate, and higher percentages of senescent cells from passage 5 (P5) to P7 than their wild-type littermates. Conversely, transgenic overexpression of NS could rescue the NS−/− embryo in a dose-dependent manner, increase the population growth rate, and reduce the senescent percentage of MEFs. Cell cycle analyses revealed increased pre-G1 percentages in the late-passage NS+/− MEF cultures compared to the wild-type cultures. We demonstrated that NS could interact with telomeric repeat-binding factor 1 (TRF1) and enhance the degradation but not the ubiquitination of the TRF1 protein, which negatively regulates telomere length and is essential for early embryogenesis. This work demonstrates the roles of NS in establishing early embryogenesis and delaying cellular senescence of MEFs and reveals a mechanism of a NS-regulated degradation of TRF1. PMID:17000763

  18. Africentric Youth and Family Rites of Passage Program: Promoting Resilience among At-Risk African American Youths

    ERIC Educational Resources Information Center

    Harvey, Aminifu R.; Hill, Robert B.

    2004-01-01

    This article examines the effects of an Africentric youth and family rites of passage program on at-risk African American youths and their parents. Data were obtained from a three-year evaluation of a youth rites of passage demonstration project using therapeutic interventions based on Africentric principles. At-risk African American boys between…

  19. 46 CFR 67.81 - Passage of title in conjunction with a corporate merger or similar transaction.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Passage of title in conjunction with a corporate merger or similar transaction. 67.81 Section 67.81 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY...; Waiver § 67.81 Passage of title in conjunction with a corporate merger or similar transaction. When the...

  20. 46 CFR 67.81 - Passage of title in conjunction with a corporate merger or similar transaction.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Passage of title in conjunction with a corporate merger or similar transaction. 67.81 Section 67.81 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY...; Waiver § 67.81 Passage of title in conjunction with a corporate merger or similar transaction. When the...