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Sample records for embryonic morphogen nodal

  1. The embryonic morphogen, Nodal, is associated with channel-like structures in human malignant melanoma xenografts.

    PubMed

    McAllister, Josephine C; Zhan, Qian; Weishaupt, Carsten; Hsu, Mei-Yu; Murphy, George F

    2010-04-01

    Formation of channel-like structures, also termed vasculogenic mimicry (VM), describes the ability of aggressive melanoma cells to form PAS-positive anastomosing structures that correlate with tumor virulence. This phenomenon may indicate differentiation plasticity, a feature melanoma cells may share with stem cells in the developing embryo. Recent studies have indicated that VM and tumorigenicity of human malignant melanoma may depend on the signaling pathways of an embryonic morphogen, Nodal. However, given the secretory nature of Nodal protein and melanoma cell heterogeneity, it remains unclear whether the Nodal-expressing cells participate directly or indirectly in VM that is potentially related to tumorigenic growth. We have developed a humanized murine xenograft model in which developing human melanomas may be sequentially studied during early stages of tumorigenic growth within a physiological human dermal microenvironment. Nodal protein localized diffusely to melanoma cell membranes, with occasional foci of accentuated reactivity in patterns suggestive of channel formation. Similar findings were detected in a limited number of patient-derived tumors. In situ hybridization confirmed Nodal mRNA to be restricted to tumor cells within xenografts that formed arborizing networks in patterns consistent with VM. These data indicate that Nodal gene expression is associated with formation of VM-like structures in a physiologically relevant model of human melanoma tumorigenesis, and further support a key role for Nodal expression in the formation of channel-like structures. The humanized xenograft model should be useful in future studies to define the mechanistic pathways responsible for VM and melanoma progression.

  2. Embryonic pattern scaling achieved by oppositely directed morphogen gradients.

    PubMed

    McHale, Peter; Rappel, Wouter-Jan; Levine, Herbert

    2006-05-16

    Morphogens are proteins, often produced in a localized region, whose concentrations spatially demarcate regions of differing gene expression in developing embryos. The boundaries of gene expression are typically sharp and the genes can be viewed as abruptly switching from on to off or vice versa upon crossing the boundary. To ensure the viability of the organism these boundaries must be set at certain fractional positions within the corresponding developing field. Remarkably this can be done with high precision despite the fact that the size of the developing field itself can vary widely from embryo to embryo. How this scaling is accomplished is unknown but it is clear that a single morphogen gradient is insufficient. Here we show how a pair of morphogens A and B, produced at opposite ends of a one-dimensional developing field, can solve the pattern-scaling problem. In the most promising scenario the morphogens interact via an effective annihilation reaction A + B --> slashed circle and the switch occurs according to the absolute concentration of A or B. We define a scaling criterion and show that morphogens coupled in this way can set embryonic markers across the entire developing field in proportion to the field size. This scaling occurs at developing-field sizes of a few times the morphogen decay length. The scaling criterion is not met if instead the gradients couple combinatorially such that downstream genes are regulated by the ratio A/B of the morphogen concentrations.

  3. Response to Nodal morphogen gradient is determined by the kinetics of target gene induction

    PubMed Central

    Dubrulle, Julien; Jordan, Benjamin M; Akhmetova, Laila; Farrell, Jeffrey A; Kim, Seok-Hyung; Solnica-Krezel, Lilianna; Schier, Alexander F

    2015-01-01

    Morphogen gradients expose cells to different signal concentrations and induce target genes with different ranges of expression. To determine how the Nodal morphogen gradient induces distinct gene expression patterns during zebrafish embryogenesis, we measured the activation dynamics of the signal transducer Smad2 and the expression kinetics of long- and short-range target genes. We found that threshold models based on ligand concentration are insufficient to predict the response of target genes. Instead, morphogen interpretation is shaped by the kinetics of target gene induction: the higher the rate of transcription and the earlier the onset of induction, the greater the spatial range of expression. Thus, the timing and magnitude of target gene expression can be used to modulate the range of expression and diversify the response to morphogen gradients. DOI: http://dx.doi.org/10.7554/eLife.05042.001 PMID:25869585

  4. Morphogene adsorption as a Turing instability regulator: Theoretical analysis and possible applications in multicellular embryonic systems

    PubMed Central

    Nesterenko, Alexey M.; Kuznetsov, Maxim B.; Korotkova, Daria D.; Zaraisky, Andrey G.

    2017-01-01

    The Turing instability in the reaction-diffusion system is a widely recognized mechanism of the morphogen gradient self-organization during the embryonic development. One of the essential conditions for such self-organization is sharp difference in the diffusion rates of the reacting substances (morphogens). In classical models this condition is satisfied only for significantly different values of diffusion coefficients which cannot hold for morphogens of similar molecular size. One of the most realistic explanations of the difference in diffusion rate is the difference between adsorption of morphogens to the extracellular matrix (ECM). Basing on this assumption we develop a novel mathematical model and demonstrate its effectiveness in describing several well-known examples of biological patterning. Our model consisting of three reaction-diffusion equations has the Turing-type instability and includes two elements with equal diffusivity and immobile binding sites as the third reaction substance. The model is an extension of the classical Gierer-Meinhardt two-components model and can be reduced to it under certain conditions. Incorporation of ECM in the model system allows us to validate the model for available experimental parameters. According to our model introduction of binding sites gradient, which is frequently observed in embryonic tissues, allows one to generate more types of different spatial patterns than can be obtained with two-components models. Thus, besides providing an essential condition for the Turing instability for the system of morphogen with close values of the diffusion coefficients, the morphogen adsorption on ECM may be important as a factor that increases the variability of self-organizing structures. PMID:28170437

  5. BMP4 acts as a dorsal telencephalic morphogen in a mouse embryonic stem cell culture system.

    PubMed

    Watanabe, Momoko; Fung, Ernest S; Chan, Felicia B; Wong, Jessica S; Coutts, Margaret; Monuki, Edwin S

    2016-12-15

    The concept of a morphogen - a molecule that specifies two or more cell fates in a concentration-dependent manner - is paradigmatic in developmental biology. Much remains unknown, however, about the existence of morphogens in the developing vertebrate central nervous system (CNS), including the mouse dorsal telencephalic midline (DTM). Bone morphogenetic proteins (BMPs) are candidate DTM morphogens, and our previous work demonstrated BMP4 sufficiency to induce one DTM cell fate - that of choroid plexus epithelial cells (CPECs) - in a mouse embryonic stem cell (mESC) culture system. Here we used BMP4 in a modified mESC culture system to derive a second DTM fate, the cortical hem (CH). CH and CPEC markers were induced by BMP4 in a concentration-dependent manner consistent with in vivo development. BMP4 concentrations that led to CH fate also promoted markers for Cajal-Retzius neurons, which are known CH derivatives. Interestingly, single BMP4 administrations also sufficed for appropriate temporal regulation of CH, CPEC, and cortical genes, with initially broad and overlapping dose-response profiles that sharpened over time. BMP4 concentrations that yielded CH- or CPEC-enriched populations also had different steady-state levels of phospho-SMAD1/5/8, suggesting that differences in BMP signaling intensity underlie DTM fate choice. Surprisingly, inactivation of the cortical selector gene Lhx2 did not affect DTM expression levels, dose-response profiles, or timing in response to BMP4, although neural progenitor genes were downregulated. These data indicate that BMP4 can act as a classic morphogen to orchestrate both spatial and temporal aspects of DTM fate acquisition, and can do so in the absence of Lhx2.

  6. BMP4 acts as a dorsal telencephalic morphogen in a mouse embryonic stem cell culture system

    PubMed Central

    Watanabe, Momoko; Fung, Ernest S.; Chan, Felicia B.; Wong, Jessica S.; Coutts, Margaret

    2016-01-01

    ABSTRACT The concept of a morphogen – a molecule that specifies two or more cell fates in a concentration-dependent manner – is paradigmatic in developmental biology. Much remains unknown, however, about the existence of morphogens in the developing vertebrate central nervous system (CNS), including the mouse dorsal telencephalic midline (DTM). Bone morphogenetic proteins (BMPs) are candidate DTM morphogens, and our previous work demonstrated BMP4 sufficiency to induce one DTM cell fate – that of choroid plexus epithelial cells (CPECs) – in a mouse embryonic stem cell (mESC) culture system. Here we used BMP4 in a modified mESC culture system to derive a second DTM fate, the cortical hem (CH). CH and CPEC markers were induced by BMP4 in a concentration-dependent manner consistent with in vivo development. BMP4 concentrations that led to CH fate also promoted markers for Cajal–Retzius neurons, which are known CH derivatives. Interestingly, single BMP4 administrations also sufficed for appropriate temporal regulation of CH, CPEC, and cortical genes, with initially broad and overlapping dose-response profiles that sharpened over time. BMP4 concentrations that yielded CH- or CPEC-enriched populations also had different steady-state levels of phospho-SMAD1/5/8, suggesting that differences in BMP signaling intensity underlie DTM fate choice. Surprisingly, inactivation of the cortical selector gene Lhx2 did not affect DTM expression levels, dose-response profiles, or timing in response to BMP4, although neural progenitor genes were downregulated. These data indicate that BMP4 can act as a classic morphogen to orchestrate both spatial and temporal aspects of DTM fate acquisition, and can do so in the absence of Lhx2. PMID:27815243

  7. Removal of maternal retinoic acid by embryonic CYP26 is required for correct Nodal expression during early embryonic patterning

    PubMed Central

    Uehara, Masayuki; Yashiro, Kenta; Takaoka, Katsuyoshi; Yamamoto, Masamichi; Hamada, Hiroshi

    2009-01-01

    The abundance of retinoic acid (RA) is determined by the balance between its synthesis by retinaldehyde dehydrogenase (RALDH) and its degradation by CYP26. In particular, the dynamic expression of three CYP26 genes controls the regional level of RA within the body. Pregastrulation mouse embryos express CYP26 but not RALDH. We now show that mice lacking all three CYP26 genes manifest duplication of the body axis as a result of expansion of the Nodal expression domain throughout the epiblast. Mouse Nodal was found to contain an RA-responsive element in intron 1 that is highly conserved among mammals. In the absence of CYP26, maternally derived RA activates Nodal expression in the entire epiblast of pregastrulation embryos via this element. These observations suggest that maternal RA must be removed by embryonic CYP26 for correct Nodal expression during embryonic patterning. PMID:19605690

  8. New Anti-Nodal Monoclonal Antibodies Targeting the Nodal Pre-Helix Loop Involved in Cripto-1 Binding

    PubMed Central

    Focà, Annalia; Sanguigno, Luca; Focà, Giuseppina; Strizzi, Luigi; Iannitti, Roberta; Palumbo, Rosanna; Hendrix, Mary J. C.; Leonardi, Antonio; Ruvo, Menotti; Sandomenico, Annamaria

    2015-01-01

    Nodal is a potent embryonic morphogen belonging to the TGF-β superfamily. Typically, it also binds to the ALK4/ActRIIB receptor complex in the presence of the co-receptor Cripto-1. Nodal expression is physiologically restricted to embryonic tissues and human embryonic stem cells, is absent in normal cells but re-emerges in several human cancers, including melanoma, breast, and colon cancer. Our aim was to obtain mAbs able to recognize Nodal on a major CBR (Cripto-Binding-Region) site and to block the Cripto-1-mediated signalling. To achieve this, antibodies were raised against hNodal(44–67) and mAbs generated by the hybridoma technology. We have selected one mAb, named 3D1, which strongly associates with full-length rhNodal (KD 1.4 nM) and recognizes the endogenous protein in a panel of human melanoma cell lines by western blot and FACS analyses. 3D1 inhibits the Nodal-Cripto-1 binding and blocks Smad2/3 phosphorylation. Data suggest that inhibition of the Nodal-Cripto-1 axis is a valid therapeutic approach against melanoma and 3D1 is a promising and interesting agent for blocking Nodal-Cripto mediated tumor development. These findings increase the interest for Nodal as both a diagnostic and prognostic marker and as a potential new target for therapeutic intervention. PMID:26370966

  9. Activin/Nodal signaling controls divergent transcriptional networks in human embryonic stem cells and in endoderm progenitors.

    PubMed

    Brown, Stephanie; Teo, Adrian; Pauklin, Siim; Hannan, Nicholas; Cho, Candy H-H; Lim, Bing; Vardy, Leah; Dunn, N Ray; Trotter, Matthew; Pedersen, Roger; Vallier, Ludovic

    2011-08-01

    Activin/Nodal signaling is necessary to maintain pluripotency of human embryonic stem cells (hESCs) and to induce their differentiation toward endoderm. However, the mechanisms by which Activin/Nodal signaling achieves these opposite functions remain unclear. To unravel these mechanisms, we examined the transcriptional network controlled in hESCs by Smad2 and Smad3, which represent the direct effectors of Activin/Nodal signaling. These analyses reveal that Smad2/3 participate in the control of the core transcriptional network characterizing pluripotency, which includes Oct-4, Nanog, FoxD3, Dppa4, Tert, Myc, and UTF1. In addition, similar experiments performed on endoderm cells confirm that a broad part of the transcriptional network directing differentiation is downstream of Smad2/3. Therefore, Activin/Nodal signaling appears to control divergent transcriptional networks in hESCs and in endoderm. Importantly, we observed an overlap between the transcriptional network downstream of Nanog and Smad2/3 in hESCs; whereas, functional studies showed that both factors cooperate to control the expression of pluripotency genes. Therefore, the effect of Activin/Nodal signaling on pluripotency and differentiation could be dictated by tissue specific Smad2/3 partners such as Nanog, explaining the mechanisms by which signaling pathways can orchestrate divergent cell fate decisions.

  10. Endogenous Nodal promotes melanoma undergoing epithelial-mesenchymal transition via Snail and Slug in vitro and in vivo

    PubMed Central

    Guo, Qiang; Ning, Fen; Fang, Rui; Wang, Hong-Sheng; Zhang, Ge; Quan, Mei-Yu; Cai, Shao-Hui; Du, Jun

    2015-01-01

    Nodal, an important embryonic morphogen, has been reported to modulate tumorigenesis. Epithelial-mesenchymal transition (EMT) plays an important role in cancer metastasis. We have previously reported that recombinant Nodal treatment can promote melanoma undergoing EMT, but the effects of endogenous Nodal on EMT are still unknown. Here we generated both Nodal-overexpression and -knockdown stable cell lines to investigate the in vitro and in vivo characteristics of Nodal-induced EMT in murine melanoma cells. Nodal-overexpression cells displayed increased migration ability, accompanied by typical phenotype changes of EMT. In contrast, Nodal-knockdown stable cells repressed the EMT phenotype as well as reduced cell motility. Results of animal experiments confirmed that overexpression of Nodal can promote the metastasis of melanoma tumor in vivo. Mechanistically, we found that Nodal-induced expression of Snail and Slug involves its activation of ALK/Smads and PI3k/AKT pathways, which is an important process in the Nodal-induced EMT. However, we also found that the EMT phenotype was not completely inhibited by blocking the paracrine activity of Nodal in Nodal overexpression cell line suggesting the presence of additional mechanism(s) in the Nodal-induced EMT. This study provides a better understanding of Nodal function in melanoma, and suggests targeting Nodal as a potential strategy for melanoma therapey. PMID:26269769

  11. Plasticity underlies tumor progression: Role of Nodal signaling

    PubMed Central

    Bodenstine, Thomas M.; Chandler, Grace S.; Seftor, Richard E. B.; Seftor, Elisabeth A.; Hendrix, Mary J. C.

    2016-01-01

    The transforming growth factor beta (TGFβ) superfamily member Nodal is an established regulator of early embryonic development, with primary roles in endoderm induction, left-right asymmetry and primitive streak formation. Nodal signals through TGFβ family receptors at the plasma membrane and induces signaling cascades leading to diverse transcriptional regulation. While conceptually simple, the regulation of Nodal and its molecular effects are profoundly complex and context dependent. Pioneering work by developmental biologists has characterized the signaling pathways, regulatory components, and provided detailed insight into the mechanisms by which Nodal mediates changes at the cellular and organismal levels. Nodal is also an important factor in maintaining pluripotency of embryonic stem cells through regulation of core transcriptional programs. Collectively, this work has led to an appreciation for Nodal as a powerful morphogen capable of orchestrating multiple cellular phenotypes. Although Nodal is not active in most adult tissues, its re-expression and signaling have been linked to multiple types of human cancer, and Nodal has emerged as a driver of tumor growth and cellular plasticity. In vitro and in vivo experimental evidence has demonstrated that inhibition of Nodal signaling reduces cancer cell aggressive characteristics, while clinical data have established associations with Nodal expression and patient outcomes. As a result, there is great interest in the potential targeting of Nodal activity in a therapeutic setting for cancer patients that may provide new avenues for suppressing tumor growth and metastasis. In this review, we evaluate our current understanding of the complexities of Nodal function in cancer and highlight recent experimental evidence that sheds light on the therapeutic potential of its inhibition. PMID:26951550

  12. Visualisation and Quantification of Morphogen Gradient Formation in the Zebrafish

    PubMed Central

    Harvey, Steven A; Smith, James C

    2009-01-01

    During embryonic development, signalling molecules known as morphogens act in a concentration-dependent manner to provide positional information to responding tissues. In the early zebrafish embryo, graded signalling by members of the nodal family induces the formation of mesoderm and endoderm, thereby patterning the embryo into three germ layers. Nodal signalling has also been implicated in the establishment of the dorso-ventral axis of the embryo. Although one can infer the existence of nodal gradients by comparing gene expression patterns in wild-type embryos and embryos in which nodal signalling is diminished or augmented, real understanding can only come from directly observing the gradients. One approach is to determine local ligand concentrations in the embryo, but this is technically challenging, and the presence of inhibitors might cause the effective concentration of a ligand to differ from its actual concentration. We have therefore taken two approaches to visualise a direct response to nodal signalling. In the first, we have used transgenic embryos to study the nuclear accumulation of a Smad2-Venus fusion protein, and in the second we have used bimolecular fluorescence complementation to visualise the formation of a complex between Smad2 and Smad4. This has allowed us to visualise, in living embryos, the formation of a graded distribution of nodal signalling activity. We have quantified the formation of the gradient in time and space, and our results not only confirm that nodal signalling patterns the embryo into three germ layers, but also shed light on its role in patterning the dorso-ventral axis and highlight unexpected complexities of mesodermal patterning. PMID:19419239

  13. Long non-coding RNA GAS5 controls human embryonic stem cell self-renewal by maintaining NODAL signalling

    PubMed Central

    Xu, Chen; Zhang, Yan; Wang, Qiaoling; Xu, Zhenyu; Jiang, Junfeng; Gao, Yuping; Gao, Minzhi; Kang, Jiuhong; Wu, Minjuan; Xiong, Jun; Ji, Kaihong; Yuan, Wen; Wang, Yue; Liu, Houqi

    2016-01-01

    Long non-coding RNAs (lncRNAs) are known players in the regulatory circuitry of the self-renewal in human embryonic stem cells (hESCs). However, most hESC-specific lncRNAs remain uncharacterized. Here we demonstrate that growth-arrest-specific transcript 5 (GAS5), a known tumour suppressor and growth arrest-related lncRNA, is highly expressed and directly regulated by pluripotency factors OCT4 and SOX2 in hESCs. Phenotypic analysis shows that GAS5 knockdown significantly impairs hESC self-renewal, but its overexpression significantly promotes hESC self-renewal. Using RNA sequencing and functional analysis, we demonstrate that GAS5 maintains NODAL signalling by protecting NODAL expression from miRNA-mediated degradation. Therefore, we propose that the above pluripotency factors, GAS5 and NODAL form a feed-forward signalling loop that maintains hESC self-renewal. As this regulatory function of GAS5 is stem cell specific, our findings also indicate that the functions of lncRNAs may vary in different cell types due to competing endogenous mechanisms. PMID:27811843

  14. Phosphoinositide 3-kinase alpha-dependent regulation of branching morphogenesis in murine embryonic lung: evidence for a role in determining morphogenic properties of FGF7.

    PubMed

    Carter, Edward; Miron-Buchacra, Gabriela; Goldoni, Silvia; Danahay, Henry; Westwick, John; Watson, Malcolm L; Tosh, David; Ward, Stephen G

    2014-01-01

    Branching morphogenesis is a critical step in the development of many epithelial organs. The phosphoinositide-3-kinase (PI3K) pathway has been identified as a central component of this process but the precise role has not been fully established. Herein we sought to determine the role of PI3K in murine lung branching using a series of pharmacological inhibitors directed at this pathway. The pan-class I PI3K inhibitor ZSTK474 greatly enhanced the branching potential of whole murine lung explants as measured by an increase in the number of terminal branches compared with controls over 48 hours. This enhancement of branching was also observed following inhibition of the downstream signalling components of PI3K, Akt and mTOR. Isoform selective inhibitors of PI3K identified that the alpha isoform of PI3K is a key driver in branching morphogenesis. To determine if the effect of PI3K inhibition on branching was specific to the lung epithelium or secondary to an effect on the mesenchyme we assessed the impact of PI3K inhibition in cultures of mesenchyme-free lung epithelium. Isolated lung epithelium cultured with FGF7 formed large cyst-like structures, whereas co-culture with FGF7 and ZSTK474 induced the formation of defined branches with an intact lumen. Together these data suggest a novel role for PI3K in the branching program of the murine embryonic lung contradictory to that reported in other branching organs. Our observations also point towards PI3K acting as a morphogenic switch for FGF7 signalling.

  15. Morphogen transport in epithelia

    NASA Astrophysics Data System (ADS)

    Bollenbach, T.; Kruse, K.; Pantazis, P.; González-Gaitán, M.; Jülicher, F.

    2007-01-01

    We present a general theoretical framework to discuss mechanisms of morphogen transport and gradient formation in a cell layer. Trafficking events on the cellular scale lead to transport on larger scales. We discuss in particular the case of transcytosis where morphogens undergo repeated rounds of internalization into cells and recycling. Based on a description on the cellular scale, we derive effective nonlinear transport equations in one and two dimensions which are valid on larger scales. We derive analytic expressions for the concentration dependence of the effective diffusion coefficient and the effective degradation rate. We discuss the effects of a directional bias on morphogen transport and those of the coupling of the morphogen and receptor kinetics. Furthermore, we discuss general properties of cellular transport processes such as the robustness of gradients and relate our results to recent experiments on the morphogen Decapentaplegic (Dpp) that acts in the wing disk of the fruit fly Drosophila.

  16. Conformational features and binding affinities to Cripto, ALK7 and ALK4 of Nodal synthetic fragments.

    PubMed

    Calvanese, Luisa; Sandomenico, Annamaria; Caporale, Andrea; Focà, Annalia; Focà, Giuseppina; D'Auria, Gabriella; Falcigno, Lucia; Ruvo, Menotti

    2015-04-01

    Nodal, a member of the TGF-β superfamily, is a potent embryonic morphogen also implicated in tumor progression. As for other TGF-βs, it triggers the signaling functions through the interaction with the extracellular domains of type I and type II serine/threonine kinase receptors and with the co-receptor Cripto. Recently, we reported the molecular models of Nodal in complex with its type I receptors (ALK4 and ALK7) as well as with Cripto, as obtained by homology modeling and docking simulations. From such models, potential binding epitopes have been identified. To validate such hypotheses, a series of mutated Nodal fragments have been synthesized. These peptide analogs encompass residues 44-67 of the Nodal protein, corresponding to the pre-helix loop and the H3 helix, and reproduce the wild-type sequence or bear some modifications to evaluate the hot-spot role of modified residues in the receptor binding. Here, we show the structural characterization in solution by CD and NMR of the Nodal peptides and the measurement of binding affinity toward Cripto by surface plasmon resonance. Data collected by both conformational analyses and binding measurements suggest a role for Y58 of Nodal in the recognition with Cripto and confirm that previously reported for E49 and E50. Surface plasmon resonance binding assays with recombinant proteins show that Nodal interacts in vitro also with ALK7 and ALK4 and preliminary data, generated using the Nodal synthetic fragments, suggest that Y58 of Nodal may also be involved in the recognition with these protein partners.

  17. Morphogens, Membranes and Mechanotransduction in Articular Cartilage

    NASA Astrophysics Data System (ADS)

    Motaung, Shirley; Chan, Stephanie; Reddi, A. Hari

    The three fundamentals of developmental biology are cell growth, cellular differentiation, and morphogenesis. Morphogenesis is the process of the generation of the shape of tissues, organs, and entire organisms from various cells. During embryonic development, as cells reproduce and divide, chemical and mechanical signals induce the cell to sort and differentiate into specialized cells. Morphogenesis is the process by which these cells become distributed and organized into tissues and organs. Morphogenetic responses can be stimulated in organisms by morphogenetic proteins, hormones, and environmental cues. There are different types of molecules that play an important role during morphogenesis and include the transcription factors and morphogens themselves.

  18. Interpretation of the FGF8 morphogen gradient is regulated by endocytic trafficking.

    PubMed

    Nowak, Matthias; Machate, Anja; Yu, Shuizi Rachel; Gupta, Mansi; Brand, Michael

    2011-02-01

    Forty years ago, it was proposed that during embryonic development and organogenesis, morphogen gradients provide positional information to the individual cells within a tissue leading to specific fate decisions. Recently, much insight has been gained into how such morphogen gradients are formed and maintained; however, which cellular mechanisms govern their interpretation within target tissues remains debated. Here we used in vivo fluorescence correlation spectroscopy and automated image analysis to assess the role of endocytic sorting dynamics on fibroblast growth factor 8 (Fgf8) morphogen gradient interpretation. By interfering with the function of the ubiquitin ligase Cbl, we found an expanded range of Fgf target gene expression and a delay of Fgf8 lysosomal transport. However, the extracellular Fgf8 morphogen gradient remained unchanged, indicating that the observed signalling changes are due to altered gradient interpretation. We propose that regulation of morphogen signalling activity through endocytic sorting allows fast feedback-induced changes in gradient interpretation during the establishment of complex patterns.

  19. Cytonemes and the dispersion of morphogens

    PubMed Central

    Kornberg, Thomas B.

    2014-01-01

    Filopodia are cellular protrusions that have been implicated in many types of mechanosensory activities. Morphogens are signaling proteins that regulate the patterned development of embryos and tissues. Both have long histories that date to the beginnings of cell and developmental biology in the early 20th century, but recent findings tie specialized filopodia called cytonemes to morphogen movement and morphogen signaling. This review explores the conceptual and experimental background for a model of paracrine signaling in which the exchange of morphogens between cells is directed to sites where cytonemes directly link cells that produce morphogens to cells that receive and respond to them. PMID:25186102

  20. Control of Adult Neurogenesis by Short-Range Morphogenic-Signaling Molecules.

    PubMed

    Choe, Youngshik; Pleasure, Samuel J; Mira, Helena

    2015-12-04

    Adult neurogenesis is dynamically regulated by a tangled web of local signals emanating from the neural stem cell (NSC) microenvironment. Both soluble and membrane-bound niche factors have been identified as determinants of adult neurogenesis, including morphogens. Here, we review our current understanding of the role and mechanisms of short-range morphogen ligands from the Wnt, Notch, Sonic hedgehog, and bone morphogenetic protein (BMP) families in the regulation of adult neurogenesis. These morphogens are ideally suited to fine-tune stem-cell behavior, progenitor expansion, and differentiation, thereby influencing all stages of the neurogenesis process. We discuss cross talk between their signaling pathways and highlight findings of embryonic development that provide a relevant context for understanding neurogenesis in the adult brain. We also review emerging examples showing that the web of morphogens is in fact tightly linked to the regulation of neurogenesis by diverse physiologic processes.

  1. Measurement and Perturbation of Morphogen Lifetime: Effects on Gradient Shape

    PubMed Central

    Drocco, Jeffrey A.; Grimm, Oliver; Tank, David W.; Wieschaus, Eric

    2011-01-01

    Protein lifetime is of critical importance for most biological processes and plays a central role in cell signaling and embryonic development, where it impacts the absolute concentration of signaling molecules and, potentially, the shape of morphogen gradients. Early conceptual and mathematical models of gradient formation proposed that steady-state gradients are established by an equilibration between the lifetime of a morphogen and its rates of synthesis and diffusion, though whether gradients in fact reach steady state before being read out is a matter of controversy. In any case, this class of models predicts that protein lifetime is a key determinant of both the time to steady state and the spatial extent of a gradient. Using a method that employs repeated photoswitching of a fusion of the morphogen Bicoid (Bcd) and the photoconvertible fluorescent protein Dronpa, we measure and modify the lifetime of Dronpa-Bcd in living Drosophila embryos. We find that the lifetime of Bcd is dynamic, changing from 50 min before mitotic cycle 14 to 15 min during cellularization. Moreover, by measuring total quantities of Bcd over time, we find that the gradient does not reach steady state. Finally, using a nearly continuous low-level conversion to the dark state of Dronpa-Bcd to mimic the effect of increased degradation, we demonstrate that perturbation of protein lifetime changes the characteristic length of the gradient, providing direct support for a mechanism based on synthesis, diffusion, and degradation. PMID:22004733

  2. Quantitative multivariate analysis of dynamic multicellular morphogenic trajectories.

    PubMed

    White, Douglas E; Sylvester, Jonathan B; Levario, Thomas J; Lu, Hang; Streelman, J Todd; McDevitt, Todd C; Kemp, Melissa L

    2015-07-01

    Interrogating fundamental cell biology principles that govern tissue morphogenesis is critical to better understanding of developmental biology and engineering novel multicellular systems. Recently, functional micro-tissues derived from pluripotent embryonic stem cell (ESC) aggregates have provided novel platforms for experimental investigation; however elucidating the factors directing emergent spatial phenotypic patterns remains a significant challenge. Computational modelling techniques offer a unique complementary approach to probe mechanisms regulating morphogenic processes and provide a wealth of spatio-temporal data, but quantitative analysis of simulations and comparison to experimental data is extremely difficult. Quantitative descriptions of spatial phenomena across multiple systems and scales would enable unprecedented comparisons of computational simulations with experimental systems, thereby leveraging the inherent power of computational methods to interrogate the mechanisms governing emergent properties of multicellular biology. To address these challenges, we developed a portable pattern recognition pipeline consisting of: the conversion of cellular images into networks, extraction of novel features via network analysis, and generation of morphogenic trajectories. This novel methodology enabled the quantitative description of morphogenic pattern trajectories that could be compared across diverse systems: computational modelling of multicellular structures, differentiation of stem cell aggregates, and gastrulation of cichlid fish. Moreover, this method identified novel spatio-temporal features associated with different stages of embryo gastrulation, and elucidated a complex paracrine mechanism capable of explaining spatiotemporal pattern kinetic differences in ESC aggregates of different sizes.

  3. Multiple roles of Activin/Nodal, bone morphogenetic protein, fibroblast growth factor and Wnt/β-catenin signalling in the anterior neural patterning of adherent human embryonic stem cell cultures

    PubMed Central

    Lupo, Giuseppe; Novorol, Claire; Smith, Joseph R.; Vallier, Ludovic; Miranda, Elena; Alexander, Morgan; Biagioni, Stefano; Pedersen, Roger A.; Harris, William A.

    2013-01-01

    Several studies have successfully produced a variety of neural cell types from human embryonic stem cells (hESCs), but there has been limited systematic analysis of how different regional identities are established using well-defined differentiation conditions. We have used adherent, chemically defined cultures to analyse the roles of Activin/Nodal, bone morphogenetic protein (BMP), fibroblast growth factor (FGF) and Wnt/β-catenin signalling in neural induction, anteroposterior patterning and eye field specification in hESCs. We show that either BMP inhibition or activation of FGF signalling is required for effective neural induction, but these two pathways have distinct outcomes on rostrocaudal patterning. While BMP inhibition leads to specification of forebrain/midbrain positional identities, FGF-dependent neural induction is associated with strong posteriorization towards hindbrain/spinal cord fates. We also demonstrate that Wnt/β-catenin signalling is activated during neural induction and promotes acquisition of neural fates posterior to forebrain. Therefore, inhibition of this pathway is needed for efficient forebrain specification. Finally, we provide evidence that the levels of Activin/Nodal and BMP signalling have a marked influence on further forebrain patterning and that constitutive inhibition of these pathways represses expression of eye field genes. These results show that the key mechanisms controlling neural patterning in model vertebrate species are preserved in adherent, chemically defined hESC cultures and reveal new insights into the signals regulating eye field specification. PMID:23576785

  4. Positive modulator of bone morphogenic protein-2

    DOEpatents

    Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua; Takahashi, Kazuyuki

    2009-01-27

    Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

  5. Morpheus unbound: reimagining the morphogen gradient.

    PubMed

    Lander, Arthur D

    2007-01-26

    The theory that the spatial organization of cell fate is orchestrated by gradients of diffusing molecules was a major contribution to 20th century developmental biology. Although the existence of morphogens is no longer in doubt, studies on the formation and function of their gradients have yielded far more puzzles than answers. On close inspection, every morphogen gradient seems to use a rich array of regulatory mechanisms, suggesting that the tasks carried out by such systems are far more extensive than previously thought.

  6. Nodal signaling and the evolution of deuterostome gastrulation.

    PubMed

    Chea, Helen K; Wright, Christopher V; Swalla, Billie J

    2005-10-01

    Chordates, including vertebrates, evolved within a group of animals called the deuterostomes. All holoblastic deuterostomes gastrulate at the vegetal pole and the blastopore becomes the anus, while a mouth is formed at the anterior or to the oral side. Nodal is a member of the TGF-beta superfamily of signaling molecules that are important in signaling between cells during many embryonic processes in vertebrate embryos. Nodal has also been found in other invertebrate deuterostomes, such as ascidians and sea urchins, but, so far, is missing in protostomes. Nodal has been shown to be particularly important in determining left-right asymmetries in vertebrate embryos, but less information is available for its developmental role in the invertebrate deuterostomes. We review gastrulation in the deuterostomes, then examine nodal expression early during mesoderm formation and later during the establishment of asymmetries in both vertebrates and invertebrates. Nodal is expressed asymmetrically on the left side in chordates and on the presumptive oral side of the embryo in echinoid echinoderms. The expression of nodal is in different germ layers in embryos of different phyla. Expression is in the ectoderm in most of the invertebrate deuterostomes, and in the mesoderm in vertebrates. We summarize the work that has been published to date, especially nodal expression in the invertebrate deuterostomes, and suggest future experiments to better understand the evolution of nodal signaling and deuterostome gastrulation.

  7. Bone morphogenic protein signaling is a major determinant of dentate development.

    PubMed

    Choe, Youngshik; Kozlova, Anastasiia; Graf, Daniel; Pleasure, Samuel J

    2013-04-17

    To understand life-long neurogenesis in the dentate gyrus (DG), characterizing dentate neural stem cells and the signals controlling their development are crucial. In the present study, we show that bone morphogenic protein (Bmp) signaling is a critical regulator of embryonic dentate development, required for initiating neurogenesis in embryonic DG progenitors and required for the establishment of dentate neural stem cells postnatally. We tested the hypothesis that Bmp signaling regulates dentate development in part by controlling the expression of Lef1, a Wnt responsive transcription factor expressed in dentate stem cells and absolutely required for dentate granule cell production. Bmp activation through the Acvr1 receptor induced Lef1 expression and neurogenesis in the embryonic DG. Ectopic expression of Bmp7 in the embryonic midline increased DG neurogenesis and inhibition of local Bmp signaling decreased embryonic DG neurogenesis. Mice with selective loss of Bmp expression due to defective meningeal development or with selective conditional deletion of meningeal Bmp7 also have dentate developmental defects. Conditional deletion of Activin receptor type I (Acvr1) or Smad4 (a downstream target nuclear effector of Bmp signaling) in DG neural stem cells resulted in defects in the postnatal subgranular zone and reduced neurogenesis. These results suggest that Acvr1-mediated meningeal Bmp signaling regulates Lef1 expression in the dentate, regulating embryonic DG neurogenesis, DG neural stem cell niche formation, and maintenance.

  8. Morphogenic Peptides in Regeneration of Load Bearing Tissues.

    PubMed

    Moeinzadeh, Seyedsina; Jabbari, Esmaiel

    2015-01-01

    Morphogenic proteins due to their short half-life require high doses of growth factors in regeneration of load bearing tissues which leads to undesirable side effects. These side effects include bone overgrowth, tumor formation and immune reaction. An alternative approach to reduce undesirable side effects of proteins in regenerative medicine is to use morphogenic peptides derived from the active domains of morphogenic proteins or soluble and insoluble components of the extracellular matrix of mineralized load bearing tissues to induce differentiation of progenitor cells, mineralization, maturation and bone formation. In that regard, many peptides with osteogenic activity have been discovered. These include peptides derived from bone morphogenic proteins (BMPs), those based on interaction with integrin and heparin-binding receptors, collagen derived peptides, peptides derived from other soluble ECM proteins such as bone sialoprotein and enamel matrix proteins, and those peptides derived from vasculoinductive and neuro-inductive proteins. Although these peptides show significant osteogenic activity in vitro and increase mineralization and bone formation in animal models, they are not widely used in clinical orthopedic applications as an alternative to morphogenic proteins. This is partly due to the limited availability of data on structure and function of morphogenic peptides in physiological medium, particularly in tissue engineered scaffolds. Due to their amphiphilic nature, peptides spontaneously self-assemble and aggregate into micellar structures in physiological medium. Aggregation alters the sequence of amino acids in morphogenic peptides that interact with cell surface receptors thus affecting osteogenic activity of the peptide. Aggregation and micelle formation can dramatically reduce the active concentration of morphogenic peptides with many-fold increase in peptide concentration in physiological medium. Other factors that affect bioactivity are the non

  9. Nodal-chain metals

    NASA Astrophysics Data System (ADS)

    Bzdušek, Tomáš; Wu, Quansheng; Rüegg, Andreas; Sigrist, Manfred; Soluyanov, Alexey A.

    2016-10-01

    The band theory of solids is arguably the most successful theory of condensed-matter physics, providing a description of the electronic energy levels in various materials. Electronic wavefunctions obtained from the band theory enable a topological characterization of metals for which the electronic spectrum may host robust, topologically protected, fermionic quasiparticles. Many of these quasiparticles are analogues of the elementary particles of the Standard Model, but others do not have a counterpart in relativistic high-energy theories. A complete list of possible quasiparticles in solids is lacking, even in the non-interacting case. Here we describe the possible existence of a hitherto unrecognized type of fermionic excitation in metals. This excitation forms a nodal chain—a chain of connected loops in momentum space—along which conduction and valence bands touch. We prove that the nodal chain is topologically distinct from previously reported excitations. We discuss the symmetry requirements for the appearance of this excitation and predict that it is realized in an existing material, iridium tetrafluoride (IrF4), as well as in other compounds of this class of materials. Using IrF4 as an example, we provide a discussion of the topological surface states associated with the nodal chain. We argue that the presence of the nodal-chain fermions will result in anomalous magnetotransport properties, distinct from those of materials exhibiting previously known excitations.

  10. Designer Nodal/BMP2 Chimeras Mimic Nodal Signaling, Promote Chondrogenesis, and Reveal a BMP2-like Structure

    PubMed Central

    Esquivies, Luis; Blackler, Alissa; Peran, Macarena; Rodriguez-Esteban, Concepcion; Izpisua Belmonte, Juan Carlos; Booker, Evan; Gray, Peter C.; Ahn, Chihoon; Kwiatkowski, Witek; Choe, Senyon

    2014-01-01

    Nodal, a member of the TGF-β superfamily, plays an important role in vertebrate and invertebrate early development. The biochemical study of Nodal and its signaling pathway has been a challenge, mainly because of difficulties in producing the protein in sufficient quantities. We have developed a library of stable, chemically refoldable Nodal/BMP2 chimeric ligands (NB2 library). Three chimeras, named NB250, NB260, and NB264, show Nodal-like signaling properties including dependence on the co-receptor Cripto and activation of the Smad2 pathway. NB250, like Nodal, alters heart looping during the establishment of embryonic left-right asymmetry, and both NB250 and NB260, as well as Nodal, induce chondrogenic differentiation of human adipose-derived stem cells. This Nodal-induced differentiation is shown to be more efficient than BPM2-induced differentiation. Interestingly, the crystal structure of NB250 shows a backbone scaffold similar to that of BMP2. Our results show that these chimeric ligands may have therapeutic implications in cartilage injuries. PMID:24311780

  11. Topological nodal line semimetals

    NASA Astrophysics Data System (ADS)

    Fang, Chen; Weng, Hongming; Dai, Xi; Fang, Zhong

    2016-11-01

    We review the recent, mainly theoretical, progress in the study of topological nodal line semimetals in three dimensions. In these semimetals, the conduction and the valence bands cross each other along a one-dimensional curve in the three-dimensional Brillouin zone, and any perturbation that preserves a certain symmetry group (generated by either spatial symmetries or time-reversal symmetry) cannot remove this crossing line and open a full direct gap between the two bands. The nodal line(s) is hence topologically protected by the symmetry group, and can be associated with a topological invariant. In this review, (i) we enumerate the symmetry groups that may protect a topological nodal line; (ii) we write down the explicit form of the topological invariant for each of these symmetry groups in terms of the wave functions on the Fermi surface, establishing a topological classification; (iii) for certain classes, we review the proposals for the realization of these semimetals in real materials; (iv) we discuss different scenarios that when the protecting symmetry is broken, how a topological nodal line semimetal becomes Weyl semimetals, Dirac semimetals, and other topological phases; and (v) we discuss the possible physical effects accessible to experimental probes in these materials. Project partially supported by the National Key Research and Development Program of China (Grant Nos. 2016YFA0302400 and 2016YFA0300604), partially by the National Natural Science Foundation of China (Grant Nos. 11274359 and 11422428), the National Basic Research Program of China (Grant No. 2013CB921700), and the “Strategic Priority Research Program (B)” of the Chinese Academy of Sciences (Grant No. XDB07020100).

  12. Chlorpyrifos and Chlorpyrifos-Oxon Inhibit Axonal Growth by Interfering with the Morphogenic Activity of Acetylcholinesterase

    PubMed Central

    Yang, Dongren; Howard, Angela; Bruun, Donald; Ajua-Alemanj, Mispa; Pickart, Cecile; Lein, Pamela J.

    2008-01-01

    A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) that are known to selectively bind to and inactivate the enzymatic function of AChE also interfere with its morphogenic function to perturb axonogenesis. To test this hypothesis, we exposed primary cultures of sensory neurons derived from embryonic rat dorsal root ganglia (DRG) to chlorpyrifos (CPF) or its oxon metabolite (CPFO). Both OPs significantly decreased axonal length at concentrations that had no effect on cell viability, protein synthesis or the enzymatic activity of AChE. Comparative analyses of the effects of CPF and CPFO on axonal growth in DRG neurons cultured from AChE nullizygous (AChE−/−) versus wildtype (AChE+/+) mice indicated that while these OPs inhibited axonal growth in AChE+/+ DRG neurons, they had no effect on axonal growth in AChE−/− DRG neurons. However, transfection of AChE−/− DRG neurons with cDNA encoding full-length AChE restored the wildtype response to the axon inhibitory effects of OPs. These data indicate that inhibition of axonal growth by OPs requires AChE, but the mechanism involves inhibition of the morphogenic rather than enzymatic activity of AChE. These findings suggest a novel mechanism for explaining not only the functional deficits observed in children and animals following developmental exposure to OPs, but also the increased vulnerability of the developing nervous system to OPs. PMID:18076960

  13. Chlorpyrifos and chlorpyrifos-oxon inhibit axonal growth by interfering with the morphogenic activity of acetylcholinesterase

    SciTech Connect

    Yang Dongren; Howard, Angela; Bruun, Donald; Ajua-Alemanj, Mispa; Pickart, Cecile; Lein, Pamela J.

    2008-04-01

    A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) that are known to selectively bind to and inactivate the enzymatic function of AChE also interfere with its morphogenic function to perturb axonogenesis. To test this hypothesis, we exposed primary cultures of sensory neurons derived from embryonic rat dorsal root ganglia (DRG) to chlorpyrifos (CPF) or its oxon metabolite (CPFO). Both OPs significantly decreased axonal length at concentrations that had no effect on cell viability, protein synthesis or the enzymatic activity of AChE. Comparative analyses of the effects of CPF and CPFO on axonal growth in DRG neurons cultured from AChE nullizygous (AChE{sup -/-}) versus wild type (AChE{sup +/+}) mice indicated that while these OPs inhibited axonal growth in AChE{sup +/+} DRG neurons, they had no effect on axonal growth in AChE{sup -/-} DRG neurons. However, transfection of AChE{sup -/-} DRG neurons with cDNA encoding full-length AChE restored the wild type response to the axon inhibitory effects of OPs. These data indicate that inhibition of axonal growth by OPs requires AChE, but the mechanism involves inhibition of the morphogenic rather than enzymatic activity of AChE. These findings suggest a novel mechanism for explaining not only the functional deficits observed in children and animals following developmental exposure to OPs, but also the increased vulnerability of the developing nervous system to OPs.

  14. Elsevier Trophoblast Research Award lecture: The multifaceted role of Nodal signaling during mammalian reproduction.

    PubMed

    Park, C B; Dufort, D

    2011-03-01

    Nodal, a secreted signaling protein in the transforming growth factor-beta (TGF-β) superfamily, has established roles in vertebrate development. However, components of the Nodal signaling pathway are also expressed at the maternal-fetal interface and have been implicated in many processes of mammalian reproduction. Emerging evidence indicates that Nodal and its extracellular inhibitor Lefty are expressed in the uterus and complex interactions between the two proteins mediate menstruation, decidualization and embryo implantation. Furthermore, several studies have shown that Nodal from both fetal and maternal sources may regulate trophoblast cell fate and facilitate placentation as both embryonic and uterine-specific Nodal knockout mouse strains exhibit disrupted placenta morphology. Here we review the established and prospective roles of Nodal signaling in facilitating successful pregnancy, including recent evidence supporting a potential link to parturition and preterm birth.

  15. Cripto recruits Furin and PACE4 and controls Nodal trafficking during proteolytic maturation.

    PubMed

    Blanchet, Marie-Hélène; Le Good, J Ann; Mesnard, Daniel; Oorschot, Viola; Baflast, Stéphane; Minchiotti, Gabriella; Klumperman, Judith; Constam, Daniel B

    2008-10-08

    The glycosylphosphatidylinositol (GPI)-anchored proteoglycan Cripto binds Nodal and its type I receptor Alk4 to activate Smad2,3 transcription factors, but a role during Nodal precursor processing has not been described. We show that Cripto also binds the proprotein convertases Furin and PACE4 and localizes Nodal processing at the cell surface. When coexpressed as in early embryonic cells, Cripto and uncleaved Nodal already associated during secretion, and a Cripto-interacting region in the Nodal propeptide potentiated the effect of proteolytic maturation on Nodal signalling. Disruption of the trans-Golgi network (TGN) by brefeldin A blocked secretion, but export of Cripto and Nodal to the cell surface was not inhibited, indicating that Nodal is exposed to extracellular convertases before entering the TGN/endosomal system. Density fractionation and antibody uptake experiments showed that Cripto guides the Nodal precursor in detergent-resistant membranes to endocytic microdomains marked by GFP-Flotillin. We conclude that Nodal processing and endocytosis are coupled in signal-receiving cells.

  16. Pre-Steady-State Decoding of the Bicoid Morphogen Gradient

    PubMed Central

    Bergmann, Sven; Sandler, Oded; Sberro, Hila; Shnider, Sara; Schejter, Eyal; Shilo, Ben-Zion; Barkai, Naama

    2007-01-01

    Morphogen gradients are established by the localized production and subsequent diffusion of signaling molecules. It is generally assumed that cell fates are induced only after morphogen profiles have reached their steady state. Yet, patterning processes during early development occur rapidly, and tissue patterning may precede the convergence of the gradient to its steady state. Here we consider the implications of pre-steady-state decoding of the Bicoid morphogen gradient for patterning of the anterior–posterior axis of the Drosophila embryo. Quantitative analysis of the shift in the expression domains of several Bicoid targets (gap genes) upon alteration of bcd dosage, as well as a temporal analysis of a reporter for Bicoid activity, suggest that a transient decoding mechanism is employed in this setting. We show that decoding the pre-steady-state morphogen profile can reduce patterning errors caused by fluctuations in the rate of morphogen production. This can explain the surprisingly small shifts in gap and pair-rule gene expression domains observed in response to alterations in bcd dosage. PMID:17298180

  17. Morphogen rules: design principles of gradient-mediated embryo patterning.

    PubMed

    Briscoe, James; Small, Stephen

    2015-12-01

    The Drosophila blastoderm and the vertebrate neural tube are archetypal examples of morphogen-patterned tissues that create precise spatial patterns of different cell types. In both tissues, pattern formation is dependent on molecular gradients that emanate from opposite poles. Despite distinct evolutionary origins and differences in time scales, cell biology and molecular players, both tissues exhibit striking similarities in the regulatory systems that establish gene expression patterns that foreshadow the arrangement of cell types. First, signaling gradients establish initial conditions that polarize the tissue, but there is no strict correspondence between specific morphogen thresholds and boundary positions. Second, gradients initiate transcriptional networks that integrate broadly distributed activators and localized repressors to generate patterns of gene expression. Third, the correct positioning of boundaries depends on the temporal and spatial dynamics of the transcriptional networks. These similarities reveal design principles that are likely to be broadly applicable to morphogen-patterned tissues.

  18. Morphogen rules: design principles of gradient-mediated embryo patterning

    PubMed Central

    Briscoe, James; Small, Stephen

    2015-01-01

    The Drosophila blastoderm and the vertebrate neural tube are archetypal examples of morphogen-patterned tissues that create precise spatial patterns of different cell types. In both tissues, pattern formation is dependent on molecular gradients that emanate from opposite poles. Despite distinct evolutionary origins and differences in time scales, cell biology and molecular players, both tissues exhibit striking similarities in the regulatory systems that establish gene expression patterns that foreshadow the arrangement of cell types. First, signaling gradients establish initial conditions that polarize the tissue, but there is no strict correspondence between specific morphogen thresholds and boundary positions. Second, gradients initiate transcriptional networks that integrate broadly distributed activators and localized repressors to generate patterns of gene expression. Third, the correct positioning of boundaries depends on the temporal and spatial dynamics of the transcriptional networks. These similarities reveal design principles that are likely to be broadly applicable to morphogen-patterned tissues. PMID:26628090

  19. Quantifying the Gurken Morphogen Gradient in Drosophila Oogenesis

    PubMed Central

    Goentoro, Lea A.; Reeves, Gregory T.; Kowal, Craig P.; Martinelli, Luigi; Schüpbach, Trudi; Shvartsman, Stanislav Y.

    2014-01-01

    Summary Quantitative information about the distribution of morphogens is crucial for understanding their effects on cell-fate determination, yet it is difficult to obtain through direct measurements. We have developed a parameter estimation approach for quantifying the spatial distribution of Gurken, a TGFα-like EGFR ligand that acts as a morphogen in Drosophila oogenesis. Modeling of Gurken/EGFR system shows that the shape of the Gurken gradient is controlled by a single dimensionless parameter, the Thiele modulus, which reflects the relative importance of ligand diffusion and degradation. By combining the model with genetic alterations of EGFR levels, we have estimated the value of the Thiele modulus in the wild-type egg chamber. This provides a direct characterization of the shape of the Gurken gradient and demonstrates how parameter estimation techniques can be used to quantify morphogen gradients in development. PMID:16890165

  20. ProNodal acts via FGFR3 to govern duration of Shh expression in the prechordal mesoderm

    PubMed Central

    Ellis, Pamela S.; Burbridge, Sarah; Soubes, Sandrine; Ohyama, Kyoji; Ben-Haim, Nadav; Chen, Canhe; Dale, Kim; Shen, Michael M.; Constam, Daniel; Placzek, Marysia

    2015-01-01

    The secreted glycoprotein sonic hedgehog (Shh) is expressed in the prechordal mesoderm, where it plays a crucial role in induction and patterning of the ventral forebrain. Currently little is known about how Shh is regulated in prechordal tissue. Here we show that in the embryonic chick, Shh is expressed transiently in prechordal mesoderm, and is governed by unprocessed Nodal. Exposure of prechordal mesoderm microcultures to Nodal-conditioned medium, the Nodal inhibitor CerS, or to an ALK4/5/7 inhibitor reveals that Nodal is required to maintain both Shh and Gsc expression, but whereas Gsc is largely maintained through canonical signalling, Nodal signals through a non-canonical route to maintain Shh. Further, Shh expression can be maintained by a recombinant Nodal cleavage mutant, proNodal, but not by purified mature Nodal. A number of lines of evidence suggest that proNodal acts via FGFR3. ProNodal and FGFR3 co-immunoprecipitate and proNodal increases FGFR3 tyrosine phosphorylation. In microcultures, soluble FGFR3 abolishes Shh without affecting Gsc expression. Further, prechordal mesoderm cells in which Fgfr3 expression is reduced by Fgfr3 siRNA fail to bind to proNodal. Finally, targeted electroporation of Fgfr3 siRNA to prechordal mesoderm in vivo results in premature Shh downregulation without affecting Gsc. We report an inverse correlation between proNodal-FGFR3 signalling and pSmad1/5/8, and show that proNodal-FGFR3 signalling antagonises BMP-mediated pSmad1/5/8 signalling, which is poised to downregulate Shh. Our studies suggest that proNodal/FGFR3 signalling governs Shh duration by repressing canonical BMP signalling, and that local BMPs rapidly silence Shh once endogenous Nodal-FGFR3 signalling is downregulated. PMID:26417042

  1. ROBUSTNESS OF MORPHOGEN GRADIENTS WITH "BUCKET BRIGADE" TRANSPORT THROUGH MEMBRANE-ASSOCIATED NON-RECEPTORS.

    PubMed

    Lei, Jinzhi; Wang, Dongyong; Song, You; Nie, Qing; Wan, Frederic Y M

    2013-05-01

    Robust multiple-fate morphogen gradients are essential for embryo development. Here, we analyze mathematically a model of morphogen gradient (such as Dpp in Drosophila wing imaginal disc) formation in the presence of non-receptors with both diffusion of free morphogens and the movement of morphogens bound to non-receptors. Under the assumption of rapid degradation of unbound morphogen, we introduce a method of functional boundary value problem and prove the existence, uniqueness and linear stability of a biologically acceptable steady-state solution. Next, we investigate the robustness of this steady-state solution with respect to significant changes in the morphogen synthesis rate. We prove that the model is able to produce robust biological morphogen gradients when production and degradation rates of morphogens are large enough and non-receptors are abundant. Our results provide mathematical and biological insight to a mechanism of achieving stable robust long distance morphogen gradients. Key elements of this mechanism are rapid turnover of morphogen to non-receptors of neighoring cells resulting in significant degradation and transport of non-receptor-morphogen complexes, the latter moving downstream through a "bucket brigade" process.

  2. Morphogenic role for acetylcholinesterase in axonal outgrowth during neural development.

    PubMed Central

    Bigbee, J W; Sharma, K V; Gupta, J J; Dupree, J L

    1999-01-01

    Acetylcholinesterase (AChE) is the enzyme that hydrolyzes the neurotransmitter acetylcholine at cholinergic synapses and neuromuscular junctions. However, results from our laboratory and others indicate that AChE has an extrasynaptic, noncholinergic role during neural development. This article is a review of our findings demonstrating the morphogenic role of AChE, using a neuronal cell culture model. We also discuss how these data suggest that AChE has a cell adhesive function during neural development. These results could have additional significance as AChE is the target enzyme of agricultural organophosphate and carbamate pesticides as well as the commonly used household organophosphate chlorpyrifos (Dursban). Prenatal exposure to these agents could have adverse effects on neural development by interfering with the morphogenic function of AChE. Images Figure 1 Figure 2 Figure 4 Figure 5 Figure 6 Figure 7 PMID:10229710

  3. Hepatocyte growth factor/scatter factor induces a variety of tissue- specific morphogenic programs in epithelial cells

    PubMed Central

    1995-01-01

    Hepatocyte growth factor/scatter factor (HGF/SF) is the mesenchymal ligand of the epithelial tyrosine kinase receptor c-Met. In vitro, HGF/SF has morphogenic properties, e.g., induces kidney epithelial cells to form branching ducts in collagen gels. Mutation of the HGF/SF gene in mice results in embryonic lethality due to severe liver and placenta defects. Here, we have evaluated the morphogenic activity of HGF/SF with a large variety of epithelial cells grown in three- dimensional collagen matrices. We found that HGF/SF induces SW 1222 colon carcinoma cells to form crypt-like structures. In these organoids, cells exhibit apical/basolateral polarity and build a well- developed brush border towards the lumen. Capan 2 pancreas carcinoma cells, upon addition of HGF/SF, develop large hollow spheroids lined with a tight layer of polarized cells. Collagen inside the cysts is digested and the cells show features of pancreatic ducts. HGF/SF induces EpH4 mammary epithelial cells to form long branches with end- buds that resemble developing mammary ducts. pRNS-1-1 prostate epithelial cells in the presence of HGF/SF develop long ducts with distal branching as found in the prostate. Finally, HGF/SF simulates alveolar differentiation in LX-1 lung carcinoma cells. Expression of transfected HGF/SF cDNA in LX-1 lung carcinoma and EpH4 mammary epithelial cells induce morphogenesis in an autocrine manner. In the cell lines tested, HGF/SF activated the Met receptor by phosphorylation of tyrosine residues. These data show that HGF/SF induces intrinsic, tissue-specific morphogenic activities in a wide variety of epithelial cells. Apparently, HGF/SF triggers respective endogenous programs and is thus an inductive, not an instructive, mesenchymal effector for epithelial morphogenesis. PMID:8522613

  4. Nicalin and its binding partner Nomo are novel Nodal signaling antagonists.

    PubMed

    Haffner, Christof; Frauli, Mélanie; Topp, Stephanie; Irmler, Martin; Hofmann, Kay; Regula, Jörg T; Bally-Cuif, Laure; Haass, Christian

    2004-08-04

    Nodals are signaling factors of the transforming growth factor-beta (TGFbeta) superfamily with a key role in vertebrate development. They control a variety of cell fate decisions required for the establishment of the embryonic body plan. We have identified two highly conserved transmembrane proteins, Nicalin and Nomo (Nodal modulator, previously known as pM5), as novel antagonists of Nodal signaling. Nicalin is distantly related to Nicastrin, a component of the Alzheimer's disease-associated gamma-secretase, and forms a complex with Nomo. Ectopic expression of both proteins in zebrafish embryos causes cyclopia, a phenotype that can arise from a defect in mesendoderm patterning mediated by the Nodal signaling pathway. Accordingly, downregulation of Nomo resulted in an increase in anterior axial mesendoderm and the development of an enlarged hatching gland. Inhibition of Nodal signaling by ectopic expression of Lefty was rescued by reducing Nomo levels. Furthermore, Nodal- as well as Activin-induced signaling was inhibited by Nicalin and Nomo in a cell-based reporter assay. Our data demonstrate that the Nicalin/Nomo complex antagonizes Nodal signaling during mesendodermal patterning in zebrafish.

  5. Nicalin and its binding partner Nomo are novel Nodal signaling antagonists

    PubMed Central

    Haffner, Christof; Frauli, Mélanie; Topp, Stephanie; Irmler, Martin; Hofmann, Kay; Regula, Jörg T; Bally-Cuif, Laure; Haass, Christian

    2004-01-01

    Nodals are signaling factors of the transforming growth factor-β (TGFβ) superfamily with a key role in vertebrate development. They control a variety of cell fate decisions required for the establishment of the embryonic body plan. We have identified two highly conserved transmembrane proteins, Nicalin and Nomo (Nodal modulator, previously known as pM5), as novel antagonists of Nodal signaling. Nicalin is distantly related to Nicastrin, a component of the Alzheimer's disease-associated γ-secretase, and forms a complex with Nomo. Ectopic expression of both proteins in zebrafish embryos causes cyclopia, a phenotype that can arise from a defect in mesendoderm patterning mediated by the Nodal signaling pathway. Accordingly, downregulation of Nomo resulted in an increase in anterior axial mesendoderm and the development of an enlarged hatching gland. Inhibition of Nodal signaling by ectopic expression of Lefty was rescued by reducing Nomo levels. Furthermore, Nodal- as well as Activin-induced signaling was inhibited by Nicalin and Nomo in a cell-based reporter assay. Our data demonstrate that the Nicalin/Nomo complex antagonizes Nodal signaling during mesendodermal patterning in zebrafish. PMID:15257293

  6. Recombinant bone morphogenic protein-2 in orthopaedic surgery: a review.

    PubMed

    Valdes, Mauricio A; Thakur, Nikhil A; Namdari, Surena; Ciombor, Deborah M; Palumbo, Mark

    2009-12-01

    Bone morphogenic proteins (BMPs) are pleiotropic regulators of bone volume, skeletal organogenesis and bone regeneration after a fracture. They function as signaling agents to affect cellular events like proliferation, differentiation and extracellular matrix synthesis. Clinically utilized rhBMP-2 combines rhBMP-2 with an osteoconductive carrier to induce bone growth and acts as a bone graft substitute. rhBMP-2, initially released in 2002, has been used primarily in spinal fusions in the lumbar and cervical regions. Recently, the application of rhBMP-2 has extended into the orthopedic trauma setting with increased application in open tibia fractures. This review outlines the history of development, molecular characteristics, toxicity and clinical applications.

  7. Assembly of embryonic and extra-embryonic stem cells to mimic embryogenesis in vitro.

    PubMed

    Harrison, Sarah Ellys; Sozen, Berna; Christodoulou, Neophytos; Kyprianou, Christos; Zernicka-Goetz, Magdalena

    2017-03-02

    Mammalian embryogenesis requires intricate interactions between embryonic and extra-embryonic tissues to orchestrate and coordinate morphogenesis with changes in developmental potential. Here, we combine mouse embryonic stem cells (ESCs) and extra-embryonic trophoblast stem cells (TSCs) in a 3D-scaffold to generate structures whose morphogenesis is remarkably similar to natural embryos. By using genetically-modified stem cells and specific inhibitors, we show embryogenesis of ESC- and TSC-derived embryos, ETS-embryos, depends on crosstalk involving Nodal signaling. When ETS-embryos develop, they spontaneously initiate expression of mesoderm and primordial germ cell markers asymmetrically on the embryonic and extra-embryonic border, in response to Wnt and BMP signaling. Our study demonstrates the ability of distinct stem cell types to self-assemble in vitro to generate embryos whose morphogenesis, architecture, and constituent cell-types resemble natural embryos.

  8. Heterogeneous treatment in the variational nodal method

    SciTech Connect

    Fanning, T.H.; Palmiotti, G.

    1995-06-01

    The variational nodal transport method is reduced to its diffusion form and generalized for the treatment of heterogeneous nodes while maintaining nodal balances. Adapting variational methods to heterogeneous nodes requires the ability to integrate over a node with discontinuous cross sections. In this work, integrals are evaluated using composite gaussian quadrature rules, which permit accurate integration while minimizing computing time. Allowing structure within a nodal solution scheme avoids some of the necessity of cross section homogenization, and more accurately defines the intra-nodal flux shape. Ideally, any desired heterogeneity can be constructed within the node; but in reality, the finite set of basis functions limits the practical resolution to which fine detail can be defined within the node. Preliminary comparison tests show that the heterogeneous variational nodal method provides satisfactory results even if some improvements are needed for very difficult, configurations.

  9. Effects of Bone Morphogenic Proteins on Engineered Cartilage

    NASA Technical Reports Server (NTRS)

    Gooch, Keith, J.; Blunk, Torsten; Courter, Donald L.; Sieminski, Alisha; Vunjak-Novakovic, Gordana; Freed, Lisa E.

    2007-01-01

    A report describes experiments on the effects of bone morphogenic proteins (BMPs) on engineered cartilage grown in vitro. In the experiments, bovine calf articular chondrocytes were seeded onto biodegradable polyglycolic acid scaffolds and cultured in, variously, a control medium or a medium supplemented with BMP-2, BMP-12, or BMP-13 in various concentrations. Under all conditions investigated, cell-polymer constructs cultivated for 4 weeks macroscopically and histologically resembled native cartilage. At a concentration of 100 ng/mL, BMP-2, BMP-12, or BMP-13 caused (1) total masses of the constructs to exceed those of the controls by 121, 80, or 62 percent, respectively; (2) weight percentages of glycosaminoglycans in the constructs to increase by 27, 18, or 15, respectively; and (3) total collagen contents of the constructs to decrease to 63, 89, or 83 percent of the control values, respectively. BMP-2, but not BMP-12 or BMP-13, promoted chondrocyte hypertrophy. These observations were interpreted as suggesting that the three BMPs increase the growth rates and modulate the compositions of engineered cartilage. It was also concluded that in vitro engineered cartilage is a suitable system for studying effects of BMPs on chondrogenesis in a well-defined environment.

  10. Symmetry Breaking in a Model for Nodal Cilia

    NASA Astrophysics Data System (ADS)

    Brokaw, Charles J.

    2005-03-01

    Nodal cilia are very short cilia found in the embryonic node on the ventral surface of early mammalian embryos. They create a right to left fluid flow that is responsible for determining the normal asymmetry of the internal organs of the mammalian body. To do this, the distal end of the cilium must circle in a counterclockwise sense. Computer simulations with 3-dimensional models of flagella allow examination of 3-dimensional movements such as those of nodal cilia. 3-dimensional circling motions of short cilia can be achieved with velocity controlled models, in which dynein activity is regulated by sliding velocity. If dyneins on one outer doublet are controlled by the sliding velocity experienced by that doublet, the system is symmetric, and the 3-dimensional models can show either clockwise or counterclockwise circling. My computer simulations have examined two possible symmetry breaking mechanisms: 1) dyneins on doublet N are regulated by a mixture of the sliding velocities experienced by doublets N and N+1 (numbered in a clockwise direction, looking from the base). or 2) symmetry is broken by an off-axis force that produces a right-handed twist of the axoneme, consistent with observations that some dyneins can rotate their substrate microtubules in a clockwise direction.

  11. Optical conductivity of nodal metals

    PubMed Central

    Homes, C. C.; Tu, J. J.; Li, J.; Gu, G. D.; Akrap, A.

    2013-01-01

    Fermi liquid theory is remarkably successful in describing the transport and optical properties of metals; at frequencies higher than the scattering rate, the optical conductivity adopts the well-known power law behavior σ1(ω) ∝ ω−2. We have observed an unusual non-Fermi liquid response σ1(ω) ∝ ω−1±0.2 in the ground states of several cuprate and iron-based materials which undergo electronic or magnetic phase transitions resulting in dramatically reduced or nodal Fermi surfaces. The identification of an inverse (or fractional) power-law behavior in the residual optical conductivity now permits the removal of this contribution, revealing the direct transitions across the gap and allowing the nature of the electron-boson coupling to be probed. The non-Fermi liquid behavior in these systems may be the result of a common Fermi surface topology of Dirac cone-like features in the electronic dispersion. PMID:24336241

  12. Distributions of Nodal Prices in PJM Market

    NASA Astrophysics Data System (ADS)

    Kunio, Matsumoto; Yoshio, Ichida; Michiko, Makino; Hiroaki, Tanaka

    As the deregulation of electric business proceeds, it is important to analyze the distributions of prices in the power market. In this paper, we analyze the nodal prices of the PJM market, which is representative of power markets in the US. First, we verify Weibull’s property of the distribution of nodal prices. Then we verify Poisson’s property of the interval of loss process.

  13. Nodal network generator for CAVE3

    NASA Technical Reports Server (NTRS)

    Palmieri, J. V.; Rathjen, K. A.

    1982-01-01

    A new extension of CAVE3 code was developed that automates the creation of a finite difference math model in digital form ready for input to the CAVE3 code. The new software, Nodal Network Generator, is broken into two segments. One segment generates the model geometry using a Tektronix Tablet Digitizer and the other generates the actual finite difference model and allows for graphic verification using Tektronix 4014 Graphic Scope. Use of the Nodal Network Generator is described.

  14. Data supporting regulating temporospatial dynamics of morphogen for structure formation of the lacrimal gland by chitosan biomaterials.

    PubMed

    Hsiao, Ya-Chuan; Yang, Tsung-Lin

    2017-02-01

    The lacrimal gland is responsible for tear synthesis and secretion, and is derived from the epithelia of ocular surface and generated by branching morphogenesis. The dataset presented in this article is to support the research results of the effect of chitosan biomaterials on facilitating the structure formation of the lacrimal gland by regulating temporospatial dynamics of morphogen. The embryonic lacrimal gland explants were used as the standard experimental model for investigating lacrimal gland branching morphogenesis. Chitosan biomaterials promoted lacrimal gland branching with a dose-dependent effect. It helped in vivo binding of hepatocyte growth factor (HGF) related molecules in the epithelial-mesenchymal boundary of emerging epithelial branches. When mitogen-activated protein kinase (MAPK) or protein kinase B (Akt/PKB) inhibitors applied, the chitosan effects reduced. Nonetheless, the ratios of MAPK and Akt/PKB phosphorylation were still greater in the chitosan group than the control. The data demonstrated here confirm the essential role of HGF-signaling in chitosan-promoted structure formation of the lacrimal gland.

  15. Temporal control of self-organized pattern formation without morphogen gradients in bacteria

    PubMed Central

    Payne, Stephen; Li, Bochong; Cao, Yangxiaolu; Schaeffer, David; Ryser, Marc D; You, Lingchong

    2013-01-01

    Diverse mechanisms have been proposed to explain biological pattern formation. Regardless of their specific molecular interactions, the majority of these mechanisms require morphogen gradients as the spatial cue, which are either predefined or generated as a part of the patterning process. However, using Escherichia coli programmed by a synthetic gene circuit, we demonstrate here the generation of robust, self-organized ring patterns of gene expression in the absence of an apparent morphogen gradient. Instead of being a spatial cue, the morphogen serves as a timing cue to trigger the formation and maintenance of the ring patterns. The timing mechanism enables the system to sense the domain size of the environment and generate patterns that scale accordingly. Our work defines a novel mechanism of pattern formation that has implications for understanding natural developmental processes. PMID:24104480

  16. Nodal Quasiparticle in Pseudogapped Colossal Magnetoresistive Manganites

    SciTech Connect

    Mannella, N.

    2010-06-02

    A characteristic feature of the copper oxide high-temperature superconductors is the dichotomy between the electronic excitations along the nodal (diagonal) and antinodal (parallel to the Cu-O bonds) directions in momentum space, generally assumed to be linked to the d-wave symmetry of the superconducting state. Angle-resolved photoemission measurements in the superconducting state have revealed a quasiparticle spectrum with a d-wave gap structure that exhibits a maximum along the antinodal direction and vanishes along the nodal direction. Subsequent measurements have shown that, at low doping levels, this gap structure persists even in the high-temperature metallic state, although the nodal points of the superconducting state spread out in finite Fermi arcs. This is the so-called pseudogap phase, and it has been assumed that it is closely linked to the superconducting state, either by assigning it to fluctuating superconductivity or by invoking orders which are natural competitors of d-wave superconductors. Here we report experimental evidence that a very similar pseudogap state with a nodal-antinodal dichotomous character exists in a system that is markedly different from a superconductor: the ferromagnetic metallic groundstate of the colossal magnetoresistive bilayer manganite La{sub 1.2}Sr{sub 1.8}Mn{sub 2}O{sub 7}. Our findings therefore cast doubt on the assumption that the pseudogap state in the copper oxides and the nodal-antinodal dichotomy are hallmarks of the superconductivity state.

  17. MURR nodal analysis with simple interactive simulation

    NASA Astrophysics Data System (ADS)

    Enani, Mohammad Abdulsamad

    The main goal of this research is to design and produce computer codes that should do a NODAL analysis of the core of Missouri University Research Reactor 'MURR' with a simple neutron transient simulation. These codes should be executed on any of the family of the widely used modern IBM/PC (or IBM/PS) microcomputers (or compatibles). The nodal analysis code should find the power (or flux) distribution inside the reactor core and calculate fuel burnup for each of the fuel elements by using the nodal analysis technique described in chapter 3. The simulator code is a relatively simple, educational aid of MURR reactor kinetics simulation that uses one group point reactor model.

  18. An ultrastructural study of sinuatrial node cells in the embryonic rat heart.

    PubMed Central

    Domenech-Mateu, J M; Boya-Vegué, J

    1975-01-01

    Sinuatrial nodal tissue, obtained from rat embryos of 15, 16 and 17 days, was examined with the electron microscope. Embryonic nodal cells were generally similar to adult cells except that (1) they showed thick prolongations of the cytoplasm which insinuated themselves between neighbouring cells; (2) they possessed osmiophilic granules with a predeliction for the region of the Golgi complex; (3) they exhibited a lesser and variable degree of pinocytosis. Images Fig. 1 Fig. 2 Fig. 3 PMID:1133091

  19. Visualization of an endogenous retinoic acid gradient across embryonic development.

    PubMed

    Shimozono, Satoshi; Iimura, Tadahiro; Kitaguchi, Tetsuya; Higashijima, Shin-Ichi; Miyawaki, Atsushi

    2013-04-18

    In vertebrate development, the body plan is determined by primordial morphogen gradients that suffuse the embryo. Retinoic acid (RA) is an important morphogen involved in patterning the anterior-posterior axis of structures, including the hindbrain and paraxial mesoderm. RA diffuses over long distances, and its activity is spatially restricted by synthesizing and degrading enzymes. However, gradients of endogenous morphogens in live embryos have not been directly observed; indeed, their existence, distribution and requirement for correct patterning remain controversial. Here we report a family of genetically encoded indicators for RA that we have termed GEPRAs (genetically encoded probes for RA). Using the principle of fluorescence resonance energy transfer we engineered the ligand-binding domains of RA receptors to incorporate cyan-emitting and yellow-emitting fluorescent proteins as fluorescence resonance energy transfer donor and acceptor, respectively, for the reliable detection of ambient free RA. We created three GEPRAs with different affinities for RA, enabling the quantitative measurement of physiological RA concentrations. Live imaging of zebrafish embryos at the gastrula and somitogenesis stages revealed a linear concentration gradient of endogenous RA in a two-tailed source-sink arrangement across the embryo. Modelling of the observed linear RA gradient suggests that the rate of RA diffusion exceeds the spatiotemporal dynamics of embryogenesis, resulting in stability to perturbation. Furthermore, we used GEPRAs in combination with genetic and pharmacological perturbations to resolve competing hypotheses on the structure of the RA gradient during hindbrain formation and somitogenesis. Live imaging of endogenous concentration gradients across embryonic development will allow the precise assignment of molecular mechanisms to developmental dynamics and will accelerate the application of approaches based on morphogen gradients to tissue engineering and

  20. Nodal·Gdf1 Heterodimers with Bound Prodomains Enable Serum-independent Nodal Signaling and Endoderm Differentiation

    PubMed Central

    Fuerer, Christophe; Nostro, M. Cristina; Constam, Daniel B.

    2014-01-01

    The TGFβ family member Nodal is central to control pluripotent stem cell fate, but its use as a stem cell differentiation factor is limited by low specific activity. During development, Nodal depends on growth and differentiation factor (Gdf)-1 and on the shared co-receptor Cryptic to specify visceral left-right axis asymmetry. We therefore asked whether the functionality of Nodal can be augmented by Gdf1. Because Nodal and Gdf1 coimmunoprecipitate each other, they were predicted to form heterodimers, possibly to facilitate diffusion or to increase the affinity for signaling receptors. Here, we report that Gdf1 suppresses an unexpected dependence of Nodal on serum proteins and that it is critically required for non-autonomous signaling in cells expressing Cryptic. Nodal, Gdf1, and their cleaved propeptides copurified as a heterodimeric low molecular weight complex that stimulated Activin receptor (Acvr) signaling far more potently than Nodal alone. Although heterodimerization with Gdf1 did not increase binding of Nodal to Fc fusions of co-receptors or Acvr extracellular domains, it was essential for soluble Acvr2 to inhibit Nodal signaling. This implies that Gdf1 potentiates Nodal activity by stabilizing a low molecular weight fraction that is susceptible to neutralization by soluble Acvr2. Finally, in differentiating human ES cells, endodermal markers were more efficiently induced by Nodal·Gdf1 than by Nodal, suggesting that Nodal·Gdf1 is an attractive new reagent to direct stem cell differentiation. PMID:24798330

  1. Stepwise renal lineage differentiation of mouse embryonic stem cells tracing in vivo development

    SciTech Connect

    Nishikawa, Masaki; Yanagawa, Naomi; Kojima, Nobuhiko; Yuri, Shunsuke; Hauser, Peter V.; Jo, Oak D.; Yanagawa, Norimoto

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer We induced renal lineages from mESCs by following the in vivo developmental cues. Black-Right-Pointing-Pointer We induced nephrogenic intermediate mesoderm by stepwise addition of factors. Black-Right-Pointing-Pointer We induced two types of renal progenitor cells by reciprocal conditioned media. Black-Right-Pointing-Pointer We propose the potential role of CD24 for the enrichment of renal lineage cells. -- Abstract: The in vitro derivation of renal lineage progenitor cells is essential for renal cell therapy and regeneration. Despite extensive studies in the past, a protocol for renal lineage induction from embryonic stem cells remains unestablished. In this study, we aimed to induce renal lineages from mouse embryonic stem cells (mESC) by following in vivo developmental stages, i.e., the induction of mesoderm (Stage I), intermediate mesoderm (Stage II) and renal lineages (Stage III). For stage I induction, in accordance with known signaling pathways involved in mesoderm development in vivo, i.e., Nodal, bone morphogenic proteins (BMPs) and Wnt, we found that the sequential addition of three factors, i.e., Activin-A (A), a surrogate for Nodal signaling, during days 0-2, A plus BMP-4 (4) during days 2-4, and A4 plus lithium (L), a surrogate for Wnt signaling, during days 4-6, was most effective to induce the mesodermal marker, Brachyury. For stage II induction, the addition of retinoic acid (R) in the continuous presence of A4L during days 6-8 was most effective to induce nephrogenic intermediate mesodermal markers, such as Pax2 and Lim1. Under this condition, more than 30% of cells were stained positive for Pax2, and there was a concomitant decrease in the expression of non-mesodermal markers. For stage III induction, in resemblance to the reciprocal induction between ureteric bud (UB) and metanephric mesenchyme (MM) during kidney development, we found that the exposure to conditioned media derived from UB and MM cells was

  2. Pathology of extra-nodal non Hodgkin lymphomas.

    PubMed

    Wright, D H

    2012-06-01

    In the management of extra-nodal lymphomas it is important to determine whether the tumour has disseminated and whether lymph nodes are involved. Some extra-nodal lymphomas may be the result of random spread of nodal lymphoma. Specific homing, however, determines the site of many extra-nodal lymphomas, as exemplified by cutaneous T-cell lymphomas, which seem to be derived from skin-homing T-cells and mucosa-associated lymphoid tissue lymphomas that show features of the mucosal immune system. Enteropathy-associated T-cell lymphoma is derived from mucosal T-cells in patients with coeliac disease. Immunological sanctuary accounts for the localisation of primary brain, eye and testicular lymphoma. Mantle cell lymphoma frequently causes tumours in the gastrointestinal tract. Random biopsies have shown that a high proportion of patients with this lymphoma have extensive occult involvement of the gastrointestinal tract at the time of first diagnosis. Follicular lymphoma occurs at both nodal and extra-nodal sites, but uncommonly at both sites at the same time. Extra-nodal follicular lymphomas frequently lack t(14;18)(q32;q21) and do not express bcl-2, which are characteristics of the nodal disease. At extra-nodal sites, follicular lymphoma is more likely to be curable than nodal follicular lymphoma. The behaviour of extra-nodal lymphomas cannot be assumed to follow that of their nodal counterparts.

  3. Microfluidic-based patterning of embryonic stem cells for in vitro development studies.

    PubMed

    Suri, Shalu; Singh, Ankur; Nguyen, Anh H; Bratt-Leal, Andres M; McDevitt, Todd C; Lu, Hang

    2013-12-07

    In vitro recapitulation of mammalian embryogenesis and examination of the emerging behaviours of embryonic structures require both the means to engineer complexity and accurately assess phenotypes of multicellular aggregates. Current approaches to study multicellular populations in 3D configurations are limited by the inability to create complex (i.e. spatially heterogeneous) environments in a reproducible manner with high fidelity thus impeding the ability to engineer microenvironments and combinations of cells with similar complexity to that found during morphogenic processes such as development, remodelling and wound healing. Here, we develop a multicellular embryoid body (EB) fusion technique as a higher-throughput in vitro tool, compared to a manual assembly, to generate developmentally relevant embryonic patterns. We describe the physical principles of the EB fusion microfluidic device design; we demonstrate that >60 conjoined EBs can be generated overnight and emulate a development process analogous to mouse gastrulation during early embryogenesis. Using temporal delivery of bone morphogenic protein 4 (BMP4) to embryoid bodies, we recapitulate embryonic day 6.5 (E6.5) during mouse embryo development with induced mesoderm differentiation in murine embryonic stem cells leading to expression of Brachyury-T-green fluorescent protein (T-GFP), an indicator of primitive streak development and mesoderm differentiation during gastrulation. The proposed microfluidic approach could be used to manipulate hundreds or more of individual embryonic cell aggregates in a rapid fashion, thereby allowing controlled differentiation patterns in fused multicellular assemblies to generate complex yet spatially controlled microenvironments.

  4. Nodal resonance in a strong standing wave

    NASA Astrophysics Data System (ADS)

    Fernández C., David J.; Mielnik, Bogdan

    1990-06-01

    The motion of charged particles in a standing electromagnetic wave is considered. For amplitudes that are not too high, the wave causes an effect of attraction of particles to the nodal points, resembling the channeling effect reported by Salomon, Dalibard, Aspect, Metcalf, and Cohen-Tannoudji [Phys. Rev. Lett. 59, 1659 (1987)] consistent with the ``high-frequency potential'' of Kapitza [Zh. Eksp. Teor. Fiz. 21, 588 (1951)]. For high-field intensities, however, the nodal points undergo a qualitative metamorphosis, converting themselves from particle attractors into resonant centers. Some chaotic phenomena arise and the description of the oscillating field in terms of an ``effective potential'' becomes inappropriate. The question of a correct Floquet Hamiltonian that could describe the standing wave within this amplitude and frequency regime is open.

  5. Intrinsic Noise Profoundly Alters the Dynamics and Steady State of Morphogen-Controlled Bistable Genetic Switches

    PubMed Central

    Page, Karen M.

    2016-01-01

    During tissue development, patterns of gene expression determine the spatial arrangement of cell types. In many cases, gradients of secreted signalling molecules—morphogens—guide this process by controlling downstream transcriptional networks. A mechanism commonly used in these networks to convert the continuous information provided by the gradient into discrete transitions between adjacent cell types is the genetic toggle switch, composed of cross-repressing transcriptional determinants. Previous analyses have emphasised the steady state output of these mechanisms. Here, we explore the dynamics of the toggle switch and use exact numerical simulations of the kinetic reactions, the corresponding Chemical Langevin Equation, and Minimum Action Path theory to establish a framework for studying the effect of gene expression noise on patterning time and boundary position. This provides insight into the time scale, gene expression trajectories and directionality of stochastic switching events between cell states. Taking gene expression noise into account predicts that the final boundary position of a morphogen-induced toggle switch, although robust to changes in the details of the noise, is distinct from that of the deterministic system. Moreover, the dramatic increase in patterning time close to the boundary predicted from the deterministic case is substantially reduced. The resulting stochastic switching introduces differences in patterning time along the morphogen gradient that result in a patterning wave propagating away from the morphogen source with a velocity determined by the intrinsic noise. The wave sharpens and slows as it advances and may never reach steady state in a biologically relevant time. This could explain experimentally observed dynamics of pattern formation. Together the analysis reveals the importance of dynamical transients for understanding morphogen-driven transcriptional networks and indicates that gene expression noise can qualitatively

  6. Arbitrarily high order nodal and characteristic methods

    SciTech Connect

    Azmy, Y.Y.

    1994-09-01

    The quest for higher computational efficiency initially led researchers in the neutron transport area to develop and implement high-order approximations for solving the linear Boltzmann equational. This drive aimed at achieving higher accuracy on coarse meshes, thereby resulting in a net savings of computational resources represented by execution time and memory. Many endeavors succeeded in reaching this goal, producing a variety of elegent, albeit complicated, formalisms, that proved extremely accurate and efficient in solving test, as well as practical applications, problems. The two main classes of high order transport methods that recieved the most attention are the Nodal and Characteristic methods. A de facto linear order standard for the spatial approximation (even though Quadratic Nodal Methods were also considered) was dictated by the algebraic complexity of the derivation of the discrete variable equations, the programming complexity of implementing and verifying them in codes, and limitations on computational resources available to run such codes. The significant advances in computational resources in terms of hardware capacity and speed, as well as architectural innovations such as vector and parallel processing, all but eliminated the third (above) obstacle towards the development and implementation of even higher order methods. The algebraic and programming complexities, on the other hand, were alleviated to some extent by the development of Arbitrarily High Order Transport methods of the Nodal and the Characteristic types, which are discussed in this report.

  7. Multiple nodal locoregional recurrence of pheochromocytoma

    PubMed Central

    Ramírez-Plaza, César Pablo; Cárdenas, Elena Margarita Sanchiz; Humanes, Rocío Soler

    2015-01-01

    Introduction Malignancy is present in 10% of pheochromocytomas (PCC) and is defined as local/vascular infiltration of surrounding tissues or the presence of chromaffin cells deposits in distant organs. The presence of isolated nodal recurrence is very rare and only 7 cases have been reported in the medical literature. Presentation of the case The case of a 32-y male with a symptomatic recurrence of a previously operated (2-years ago) PCC is presented. Radiological and functional imaging studies confirmed the presence of multiple nodules in the surgical site. A radical left nephrectomy with extensive lymphatic clearance in order to get an R0 resection was performed. The pathologist confirmed the diagnosis of massive locoregional nodal invasion. Discussion A detailed histological report and a thorough genetic study must be considered in every operated PCC in order to identify mutations and profiles of risk for malignancy. When recurrence or metastastic disease is suspected, imaging and functional exams are done in order to obtain a proper staging. Radical surgery for the metastatic disease is the only treatment that may provide prolonged survival. If an R0 resection is not possible, then a debulking surgery is a good option when the benefit/risk ratio is acceptable. Conclusion Isolated lymph nodal recurrence is very rare in malignant PCC, with only 7 cases previously published. The role of surgery is essential to get long-term survival because provides clinical and functional control of the disease. PMID:26117450

  8. A microparticle approach to morphogen delivery within pluripotent stem cell aggregates

    PubMed Central

    Bratt-Leal, Andrés M.; Nguyen, Anh H.; Hammersmith, Katy A.; Singh, Ankur; McDevitt, Todd C.

    2013-01-01

    Stem cell fate and specification is largely controlled by extrinsic cues that comprise the 3D microenvironment. Biomaterials can serve to control the spatial and temporal presentation of morphogenic molecules in order to direct stem cell fate decisions. Here we describe a microparticle (MP)-based approach to deliver growth factors within multicellular aggregates to direct pluripotent stem cell differentiation. Compared to conventional soluble delivery methods, gelatin MPs laden with BMP4 or noggin induced efficient gene expression of mesoderm and ectoderm lineages, respectively, despite using nearly 12-fold less total growth factor. BMP4-laden MPs increased the percentage of cells expressing GFP under the control of the Brachyury-T promoter as visualized by whole-mount confocal imaging and quantified by flow cytometry. Furthermore, the ability to localize MPs laden with different morphogens within a particular hemisphere of stem cell aggregates allowed for spatial control of differentiation within 3D cultures. Overall, localized delivery of growth factors within multicellular aggregates from microparticle delivery vehicles is an important step towards scalable differentiation technologies and the study of morphogen gradients in pluripotent stem cell differentiation. PMID:23827184

  9. JAK/STAT controls organ size and fate specification by regulating morphogen production and signalling

    PubMed Central

    Recasens-Alvarez, Carles; Ferreira, Ana; Milán, Marco

    2017-01-01

    A stable pool of morphogen-producing cells is critical for the development of any organ or tissue. Here we present evidence that JAK/STAT signalling in the Drosophila wing promotes the cycling and survival of Hedgehog-producing cells, thereby allowing the stable localization of the nearby BMP/Dpp-organizing centre in the developing wing appendage. We identify the inhibitor of apoptosis dIAP1 and Cyclin A as two critical genes regulated by JAK/STAT and contributing to the growth of the Hedgehog-expressing cell population. We also unravel an early role of JAK/STAT in guaranteeing Wingless-mediated appendage specification, and a later one in restricting the Dpp-organizing activity to the appendage itself. These results unveil a fundamental role of the conserved JAK/STAT pathway in limb specification and growth by regulating morphogen production and signalling, and a function of pro-survival cues and mitogenic signals in the regulation of the pool of morphogen-producing cells in a developing organ. PMID:28045022

  10. SoxB1-driven transcriptional network underlies neural-specific interpretation of morphogen signals.

    PubMed

    Oosterveen, Tony; Kurdija, Sanja; Ensterö, Mats; Uhde, Christopher W; Bergsland, Maria; Sandberg, Magnus; Sandberg, Rickard; Muhr, Jonas; Ericson, Johan

    2013-04-30

    The reiterative deployment of a small cadre of morphogen signals underlies patterning and growth of most tissues during embyogenesis, but how such inductive events result in tissue-specific responses remains poorly understood. By characterizing cis-regulatory modules (CRMs) associated with genes regulated by Sonic hedgehog (Shh), retinoids, or bone morphogenetic proteins in the CNS, we provide evidence that the neural-specific interpretation of morphogen signaling reflects a direct integration of these pathways with SoxB1 proteins at the CRM level. Moreover, expression of SoxB1 proteins in the limb bud confers on mesodermal cells the potential to activate neural-specific target genes upon Shh, retinoid, or bone morphogenetic protein signaling, and the collocation of binding sites for SoxB1 and morphogen-mediatory transcription factors in CRMs faithfully predicts neural-specific gene activity. Thus, an unexpectedly simple transcriptional paradigm appears to conceptually explain the neural-specific interpretation of pleiotropic signaling during vertebrate development. Importantly, genes induced in a SoxB1-dependent manner appear to constitute repressive gene regulatory networks that are directly interlinked at the CRM level to constrain the regional expression of patterning genes. Accordingly, not only does the topology of SoxB1-driven gene regulatory networks provide a tissue-specific mode of gene activation, but it also determines the spatial expression pattern of target genes within the developing neural tube.

  11. Embryonic chirality and the evolution of spiralian left–right asymmetries

    PubMed Central

    2016-01-01

    The group Spiralia includes species with one of the most significant cases of left–right asymmetries in animals: the coiling of the shell of gastropod molluscs (snails). In this animal group, an early event of embryonic chirality controlled by cytoskeleton dynamics and the subsequent differential activation of the genes nodal and Pitx determine the left–right axis of snails, and thus the direction of coiling of the shell. Despite progressive advances in our understanding of left–right axis specification in molluscs, little is known about left–right development in other spiralian taxa. Here, we identify and characterize the expression of nodal and Pitx orthologues in three different spiralian animals—the brachiopod Novocrania anomala, the annelid Owenia fusiformis and the nemertean Lineus ruber—and demonstrate embryonic chirality in the biradial-cleaving spiralian embryo of the bryozoan Membranipora membranacea. We show asymmetric expression of nodal and Pitx in the brachiopod and annelid, respectively, and symmetric expression of Pitx in the nemertean. Our findings indicate that early embryonic chirality is widespread and independent of the cleavage programme in the Spiralia. Additionally, our study illuminates the evolution of nodal and Pitx signalling by demonstrating embryonic asymmetric expression in lineages without obvious adult left–right asymmetries. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’. PMID:27821523

  12. Small renal tumor with lymph nodal enlargement: A histopathological surprise

    PubMed Central

    Thottathil, Mujeeburahiman; Verma, Ashish; D’souza, Nischith; Khan, Altaf

    2016-01-01

    Renal cancer with lymph nodal mass on the investigation is clinically suggestive of an advanced tumor. Small renal cancers are not commonly associated with lymph nodal metastasis. Association of renal cell carcinoma with renal tuberculosis (TB) in the same kidney is also rare. We report here a case of small renal cancer with multiple hilar and paraaortic lymph nodes who underwent radical nephrectomy, and histopathology report showed renal and lymph nodal TB too. PMID:27453671

  13. Topological surface states in nodal superconductors.

    PubMed

    Schnyder, Andreas P; Brydon, Philip M R

    2015-06-24

    Topological superconductors have become a subject of intense research due to their potential use for technical applications in device fabrication and quantum information. Besides fully gapped superconductors, unconventional superconductors with point or line nodes in their order parameter can also exhibit nontrivial topological characteristics. This article reviews recent progress in the theoretical understanding of nodal topological superconductors, with a focus on Weyl and noncentrosymmetric superconductors and their protected surface states. Using selected examples, we review the bulk topological properties of these systems, study different types of topological surface states, and examine their unusual properties. Furthermore, we survey some candidate materials for topological superconductivity and discuss different experimental signatures of topological surface states.

  14. Nodal lines and nodal loops in nonsymmorphic odd-parity superconductors

    NASA Astrophysics Data System (ADS)

    Micklitz, T.; Norman, M. R.

    2017-01-01

    We discuss the nodal structure of odd-parity superconductors in the presence of nonsymmorphic crystal symmetries, both with and without spin-orbit coupling, and with and without time-reversal symmetry. We comment on the relation of our work to previous work in the literature, and also the implications for unconventional superconductors such as UPt3.

  15. A composite nodal finite element for hexagons

    SciTech Connect

    Hennart, J.P.; Mund, E.H. |; Valle, E. Del

    1997-10-01

    A nodal algorithm for the solution of the multigroup diffusion equations in hexagonal arrays is analyzed. Basically, the method consists of dividing each hexagon into four quarters and mapping the hexagon quarters onto squares. The resulting boundary value problem on a quadrangular domain is solved in primal weak formulation. Nodal finite element methods like the Raviart-Thomas RTk schemes provide accurate analytical expansions of the solution in the hexagons. Transverse integration cannot be performed on the equations in the quadrangular domain as simply as it is usually done on squares because these equations have essentially variable coefficients. However, by considering an auxiliary problem with constant coefficients (on the same quadrangular domain) and by using a preconditioning approach, transverse integration can be performed as for rectangular geometry. A description of the algorithm is given for a one-group diffusion equation. Numerical results are presented for a simple model problem with a known analytical solution and for k{sub eff} evaluations of some benchmark problems proposed in the literature. For the analytical problem, the results indicate that the theoretical convergence orders of RTk schemes (k = 0,1) are obtained, yielding accurate solutions at the expense of a few preconditioning iterations.

  16. Physical interpretation of mean local accumulation time of morphogen gradient formation

    PubMed Central

    Berezhkovskii, Alexander M.; Shvartsman, Stanislav Y.

    2011-01-01

    The paper deals with a reaction-diffusion problem that arises in developmental biology when describing the formation of the concentration profiles of signaling molecules, called morphogens, which control gene expression and, hence, cell differentiation. The mean local accumulation time, which is the mean time required to reach the steady state at a fixed point of a patterned tissue, is an important characteristic of the formation process. We show that this time is a sum of two times, the conditional mean first-passage time from the source to the observation point and the mean local accumulation time in the situation when the source is localized at the observation point. PMID:22029305

  17. Epithelial to mesenchymal transition in human skin wound healing is induced by tumor necrosis factor-alpha through bone morphogenic protein-2.

    PubMed

    Yan, Chunli; Grimm, Wesley A; Garner, Warren L; Qin, Lan; Travis, Taryn; Tan, Neiman; Han, Yuan-Ping

    2010-05-01

    Epithelial-mesenchymal transition (EMT), characterized by loss of epithelial adhesion and gain of mesenchymal features, is an important mechanism to empower epithelial cells into the motility that occurs during embryonic development and recurs in cancer and fibrosis. Whether and how EMT occurs in wound healing and fibrosis in human skin remains unknown. In this study we found that migrating epithelial cells in wound margins and deep epithelial ridges had gained mesenchymal features such as vimentin and FSP1 expression. In hypertrophic scars, EMT-related genes were elevated along with inflammatory cytokines, indicating a causal relationship. To reconstitute EMT in vitro, normal human skin and primary keratinocytes were exposed to cytokines such as tumor necrosis factor-alpha (TNF-alpha), resulting in expression of vimentin, FSP1, and matrix metalloproteinases. Moreover, TNF-alpha-induced EMT was impaired by antagonists against bone morphogen proteins (BMP) 2/4, suggesting that BMP mediates the TNF-alpha-induced EMT in human skin. Indeed, TNF-alpha could induce BMP-2 and its receptor (BMPR1A) in human skin and primary keratinocytes, and BMP2 could induce EMT features in skin explants and primary keratinocytes. In summary, we uncovered EMT features in both acute and fibrotic cutaneous wound healing of human skin. Moreover, we propose that the mesenchymal induction in wound healing is motivated by TNF-alpha, in part, through induction of BMP.

  18. Combination of Controllably Released Platelet Rich Plasma Alginate Beads and Bone Morphogenic Protein-2 Gene-Modified Mesenchymal Stem Cells for Bone Regeneration

    PubMed Central

    Fernandes, Gabriela; Wang, Changdong; Yuan, Xue; Liu, Zunpeng; Dziak, Rosemary; Yang, Shuying

    2016-01-01

    Background Platelet rich plasma (PRP) consists of platelet derived growth factor (PDGF) and Transforming growth factor-beta (TGF-β) that increase cell proliferation of mesenchymal stem cells (MSCs), whereas, bone morphogenic Protein-2 (BMP2) promotes osteogenic differentiation of MSCs. However, the high degradation rate of fibrin leads to the dissociation of cytokines even before the process of bone regeneration has begun. Hence, for the first time, we studied the combined effect of sustained released PRP from alginate beads on BMP2 modified MSCs osteogenic differentiation in vitro and of sustained PRP alone on a fracture defect model ex vivo as well as its effect on the calvarial suture closure. Methods After optimizing the concentration of alginate for the microspheres, the osteogenic and mineralization effect of PRP and BMP2 in combinations on MSCs was studied. A self-setting alginate hydrogel carrying PRP was tested on a femur defect model ex-vivo. The effect of PRP was studied on the closure of the embryonic (E15) mouse calvaria sutures ex vivo. Results Increase of PRP concentration promoted cellular proliferation of MSCs. 2.5%–10% of PRP displayed gradually increased ALP activity on the cells in a dose dependent manner. Sustained release PRP and BMP2 demonstrated a significantly higher ALP and mineralization activity (p<0.05). The radiographs of alginate hydrogel with PRP treated bone demonstrated a nearly complete healing of the fracture and the histological sections of the embryonic calvaria revealed that PRP leads to suture fusion. Conclusions Sustained release of PRP along with BMP2 gene modified MSCs can significantly promote bone regeneration. PMID:26745613

  19. Market redesign and technology upgrade: a nodal implementation

    SciTech Connect

    Isemonger, Alan G.

    2009-10-15

    The California ISO and its market participants collectively cut over to a new nodal-based market on April 1, largely without incident and 11 years to the day from the initial startup in 1998. Thus far, the new nodal framework has proven robust, and the inevitable design and implementation issues that have emerged since cutover have been manageable. (author)

  20. Takotsubo Cardiomyopathy following a L2–L5 Laminectomy and Fusion In Situ with Bone Morphogenic Protein

    PubMed Central

    Eubanks, Jason

    2013-01-01

    Takotsubo cardiomyopathy (TC) is a rare, transient cardiomyopathy, with symptoms mimicking myocardial infarction. It has been reported to typically occur in postmenopausal women and is often triggered by an intense physical or emotional event with stimulation of the sympathetic response; the exact etiology, however, is uncertain. Bone morphogenic protein (BMP) is widely used in spinal fusions and has been associated with numerous perioperative complications. BMP is known to stimulate sympathetic pathways. In this paper, we present the case of a patient with a 7-hour episode of TC after a spinal fusion with bone morphogenic protein. The patient's symptoms resolved and long-term followup has been uneventful. This is the first paper to describe TC in the setting of spine or other major orthopaedic surgery and it suggests another possible area for further investigation in peri-operative events potentially associated with the use of bone morphogenic protein. PMID:23585979

  1. Stem cell-derived nodal-like cardiomyocytes as a novel pharmacologic tool: insights from sinoatrial node development and function.

    PubMed

    Barbuti, Andrea; Robinson, Richard B

    2015-01-01

    Since the first reports on the isolation and differentiation of stem cells, and in particular since the early success in driving these cells down a cardiac lineage, there has been interest in the potential of such preparations in cardiac regenerative therapy. Much of the focus of such research has been on improving mechanical function after myocardial infarction; however, electrophysiologic studies of these preparations have revealed a heterogeneous mix of action potential characteristics, including some described as "pacemaker" or "nodal-like," which in turn led to interest in the therapeutic potential of these preparations in the treatment of rhythm disorders; several proof-of-concept studies have used these cells to create a biologic alternative to electronic pacemakers. Further, there are additional potential applications of a preparation of pacemaker cells derived from stem cells, for example, in high-throughput screens of new chronotropic agents. All such applications require reasonably efficient methods for selecting or enriching the "nodal-like" cells, however, which in turn depends on first defining what constitutes a nodal-like cell since not all pacemaking cells are necessarily of nodal lineage. This review discusses the current state of the field in terms of characterizing sinoatrial-like cardiomyocytes derived from embryonic and induced pluripotent stem cells, markers that might be appropriate based on the current knowledge of the gene program leading to sinoatrial node development, what functional characteristics might be expected and desired based on studies of the sinoatrial node, and recent efforts at enrichment and selection of nodal-like cells.

  2. Left-right symmetry breaking in mice by left-right dynein may occur via a biased chromatid segregation mechanism, without directly involving the Nodal gene

    PubMed Central

    Sauer, Stephan; Klar, Amar J. S.

    2012-01-01

    Ever since cloning the classic iv (inversed viscerum) mutation identified the “left-right dynein” (lrd) gene in mice, most research on body laterality determination has focused on its function in motile cilia at the node embryonic organizer. This model is attractive, as it links chirality of cilia architecture to asymmetry development. However, lrd is also expressed in blastocysts and embryonic stem cells, where it was shown to bias the segregation of recombined sister chromatids away from each other in mitosis. These data suggested that lrd is part of a cellular mechanism that recognizes and selectively segregates sister chromatids based on their replication history: old “Watson” versus old “Crick” strands. We previously proposed that the mouse left-right axis is established via an asymmetric cell division prior to/or during gastrulation. In this model, left-right dynein selectively segregates epigenetically differentiated sister chromatids harboring a hypothetical “left-right axis development 1” (“lra1”) gene during the left-right axis establishing cell division. Here, asymmetry development would be ultimately governed by the chirality of the cytoskeleton and the DNA molecule. Our model predicts that randomization of chromatid segregation in lrd mutants should produce embryos with 25% situs solitus, 25% situs inversus, and 50% embryonic death due to heterotaxia and isomerism. Here we confirmed this prediction by using two distinct lrd mutant alleles. Other than lrd, thus far Nodal gene is the most upstream function implicated in visceral organs laterality determination. We next tested whether the Nodal gene constitutes the lra1 gene hypothesized in the model by testing mutant’s effect on 50% embryonic lethality observed in lrd mutants. Since Nodal mutation did not suppress lethality, we conclude that Nodal is not equivalent to the lra1 gene. In summary, we describe the origin of 50% lethality in lrd mutant mice not yet explained by any other

  3. Left-right symmetry breaking in mice by left-right dynein may occur via a biased chromatid segregation mechanism, without directly involving the Nodal gene.

    PubMed

    Sauer, Stephan; Klar, Amar J S

    2012-01-01

    Ever since cloning the classic iv (inversedviscerum) mutation identified the "left-right dynein" (lrd) gene in mice, most research on body laterality determination has focused on its function in motile cilia at the node embryonic organizer. This model is attractive, as it links chirality of cilia architecture to asymmetry development. However, lrd is also expressed in blastocysts and embryonic stem cells, where it was shown to bias the segregation of recombined sister chromatids away from each other in mitosis. These data suggested that lrd is part of a cellular mechanism that recognizes and selectively segregates sister chromatids based on their replication history: old "Watson" versus old "Crick" strands. We previously proposed that the mouse left-right axis is established via an asymmetric cell division prior to/or during gastrulation. In this model, left-right dynein selectively segregates epigenetically differentiated sister chromatids harboring a hypothetical "left-right axis development 1" ("lra1") gene during the left-right axis establishing cell division. Here, asymmetry development would be ultimately governed by the chirality of the cytoskeleton and the DNA molecule. Our model predicts that randomization of chromatid segregation in lrd mutants should produce embryos with 25% situs solitus, 25% situs inversus, and 50% embryonic death due to heterotaxia and isomerism. Here we confirmed this prediction by using two distinct lrd mutant alleles. Other than lrd, thus far Nodal gene is the most upstream function implicated in visceral organs laterality determination. We next tested whether the Nodal gene constitutes the lra1 gene hypothesized in the model by testing mutant's effect on 50% embryonic lethality observed in lrd mutants. Since Nodal mutation did not suppress lethality, we conclude that Nodal is not equivalent to the lra1 gene. In summary, we describe the origin of 50% lethality in lrd mutant mice not yet explained by any other laterality

  4. The structure and morphogenic changes of antennae of Matsucoccus matsumurae (Hemiptera: Coccoidea: Matsucoccidae) in different instars.

    PubMed

    Wang, Xu; Xie, Yingping; Zhang, Yanfeng; Liu, Weimin; Wu, Jun

    2016-05-01

    To better understand the functioning and morphogenic changes of the antennae of Matsucoccus matsumurae (Kuwana) in different instars, the antennae are examined using light microscopy, scanning and transmission electron microscopy. The results show that the antennae of M. matsumurae display three different styles in morphology and sensillar distribution in different instars. The antennae of first instar nymphs are relatively simple, including one campaniform sensillum (Ca), four smooth aporous trichoid sensilla (SAt), two intersegmental sensilla (Ins), two coeloconic sensilla (Co), three multiporous pegs (Mp) and four uniporous pegs (Up). The antennae of adult females and third instar male nymphs both possess similar antennae, and exhibit seven types of sensilla. Adult female antennae have in total 82-108 sensilla, including 9-16 Böhm's bristle (Bb), 3-7 Ca, 50-75 SAt, 0-3 Ins, 3-10 Co, 8 Mp and 5 Up, whereas third instar male nymph antennae possess approximately 62-79 sensilla. Adult male antennae are the most developed, possessing 259-312 sensilla, including 7-15 Bb, 2-5 Ca, 7-11 grooved aporous trichoid sensilla, 4-9 SAt, 0-3 Ins, 2-7 Co, 23-29 knobbed seta sensilla, 179-230 multiporous trichoid sensilla and 8 Mp. Based on these results, the main functions and morphogenic changes of antennae M. matsumurae in different instars are discussed.

  5. Vertebrate limb development: moving from classical morphogen gradients to an integrated 4-dimensional patterning system.

    PubMed

    Bénazet, Jean-Denis; Zeller, Rolf

    2009-10-01

    A wealth of classical embryological manipulation experiments taking mainly advantage of the chicken limb buds identified the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) as the respective ectodermal and mesenchymal key signaling centers coordinating proximodistal (PD) and anteroposterior (AP) limb axis development. These experiments inspired Wolpert's French flag model, which is a classic among morphogen gradient models. Subsequent molecular and genetic analysis in the mouse identified retinoic acid as proximal signal, and fibroblast growth factors (FGFs) and sonic hedgehog (SHH) as the essential instructive signals produced by AER and ZPA, respectively. Recent studies provide good evidence that progenitors are specified early with respect to their PD and AP fates and that morpho-regulatory signaling is also required for subsequent proliferative expansion of the specified progenitor pools. The determination of particular fates seems to occur rather late and depends on additional signals such as bone morphogenetic proteins (BMPs), which indicates that cells integrate signaling inputs over time and space. The coordinate regulation of PD and AP axis patterning is controlled by an epithelial-mesenchymal feedback signaling system, in which transcriptional regulation of the BMP antagonist Gremlin1 integrates inputs from the BMP, SHH, and FGF pathways. Vertebrate limb-bud development is controlled by a 4-dimensional (4D) patterning system integrating positive and negative regulatory feedback loops, rather than thresholds set by morphogen gradients.

  6. Intrinsic facilitation of adult peripheral nerve regeneration by the Sonic hedgehog morphogen.

    PubMed

    Martinez, Jose A; Kobayashi, Masaki; Krishnan, Anand; Webber, Christine; Christie, Kimberly; Guo, GuiFang; Singh, Vandana; Zochodne, Douglas W

    2015-09-01

    Intrinsic molecular determinants of neurodevelopmental outcomes assume new, albeit related roles during adult neural regeneration. Here we studied and identified a facilitatory role for Sonic hedgehog protein (Shh), a morphogen that influences motor neuron floor plate architecture, during adult peripheral neuron regeneration. Shh and its receptors were expressed in adult dorsal root ganglia (DRG) neurons, axons and glia and trended toward higher levels following axotomy injury. Knockdown of Shh in adult sensory neurons resulted in decreased outgrowth and branching in vitro, identifying a role for Shh in facilitating outgrowth. The findings argued for an intrinsic action to support neuron regeneration. Support of advancement and turning however, were not identified in adult sensory neuron growth cones in response to local extrinsic gradients of Shh. That intrinsic Shh supported the regrowth of peripheral nerves after injury was confirmed by the analysis of axon regrowth from the proximal stumps of transected sciatic nerves. By exposing regenerating axons to local infusions of Shh siRNA in vivo within a conduit bridging the transected proximal and distal stumps, we achieved local knockdown of Shh. In response, there was attenuated axonal and Schwann cell outgrowth beyond the transection zone. Unlike its role during neurodevelopment, Shh facilitates but does not confer regenerative outgrowth properties to adult neurons alone. Exploring the differing properties of morphogens and related proteins in the adult nervous system identifies new and important roles for them.

  7. Radar response from vegetation with nodal structure

    NASA Technical Reports Server (NTRS)

    Blanchard, B. J.; Oneill, P. E.

    1984-01-01

    Radar images from the SEASAT synthetic aperture radar (SAR) produced unusually high returns from corn and sorghum fields, which seem to indicate a correlation between nodal separation in the stalk and the wavelength of the radar. These images also show no difference in return from standing or harvested corn. Further investigation using images from the Shuttle Imaging Radar (SIR-A) substantiated these observations and showed a degradation of the high return with time after harvest. From portions of corn and sweet sorghum stalks that were sampled to measure stalk water content, it was determined that near and after maturity the water becomes more concentrated in the stalk nodes. The stalk then becomes a linear sequence of alternating dielectrics as opposed to a long slender cylinder with uniform dielectric properties.

  8. Experience with advanced nodal codes at YAEC

    SciTech Connect

    Cacciapouti, R.J.

    1990-01-01

    Yankee Atomic Electric Company (YAEC) has been performing reload licensing analysis since 1969. The basic pressurized water reactor (PWR) methodology involves the use of LEOPARD for cross-section generation, PDQ for radial power distributions and integral control rod worth, and SIMULATE for axial power distributions and differential control rod worth. In 1980, YAEC began performing reload licensing analysis for the Vermont Yankee boiling water reactor (BWR). The basic BWR methodology involves the use of CASMO for cross-section generation and SIMULATE for three-dimensional power distributions. In 1986, YAEC began investigating the use of CASMO-3 for cross-section generation and the advanced nodal code SIMULATE-3 for power distribution analysis. Based on the evaluation, the CASMO-3/SIMULATE-3 methodology satisfied all requirements. After careful consideration, the cost of implementing the new methodology is expected to be offset by reduced computing costs, improved engineering productivity, and fuel-cycle performance gains.

  9. Incessant junctional reciprocating tachycardia caused by dual atrioventricular nodal pathways and atrio-nodal bypass tract.

    PubMed Central

    Santarelli, P; Sosa, E; Denes, P

    1982-01-01

    A case is described with clinical and electrocardiographic findings of incessant junctional reciprocating tachycardia. Electrophysiological study showed that longitudinal dissociation of the atrioventricular node into two pathways was responsible for the maintenance of the arrhythmia. The two intranodal pathways had different refractory periods but reciprocally related and overlapping conduction times (anterograde fast, retrograde slow, and vice versa). Induction and termination of the arrhythmia was related to the presence of a partial atrio-nodal bypass tract. Images PMID:7082510

  10. [A Complex Morpho-Histological Approach to the In Vitro Study of Morphogenic Structures in a Wheat Anther Culture].

    PubMed

    Seldimirova, O A; Titova, G E; Kruglova, N N

    2016-01-01

    The external morphological and internal histological features of morphogenic structures (embryoids, calli with embryoids, and calli with buds and roots) have been studied in vitro in a wheat anther culture by light microscopy. The results of this study have been compared with data obtained earlier by scanning electron microscopy.

  11. The Wnt and BMP Families of Signaling Morphogens at the Vertebrate Neuromuscular Junction

    PubMed Central

    Henríquez, Juan P.; Krull, Catherine E.; Osses, Nelson

    2011-01-01

    The neuromuscular junction has been extensively employed in order to identify crucial determinants of synaptogenesis. At the vertebrate neuromuscular synapse, extracellular matrix and signaling proteins play stimulatory and inhibitory roles on the assembly of functional synapses. Studies in invertebrate species have revealed crucial functions of early morphogens during the assembly and maturation of the neuromuscular junction. Here, we discuss growing evidence addressing the function of Wnt and Bone morphogenetic protein (BMP) signaling pathways at the vertebrate neuromuscular synapse. We focus on the emerging role of Wnt proteins as positive and negative regulators of postsynaptic differentiation. We also address the possible involvement of BMP pathways on motor neuron behavior for the assembly and/or regeneration of the neuromuscular junction. PMID:22272112

  12. Biomaterial delivery of morphogens to mimic the natural healing cascade in bone

    PubMed Central

    Mehta, Manav; Schmidt-Bleek, Katharina; Duda, Georg N; Mooney, David J

    2012-01-01

    Complications in treatment of large bone defects using bone grafting still remain. Our understanding of the endogenous bone regeneration cascade has inspired the exploration of a wide variety of growth factors (GFs) in an effort to mimic the natural signaling that controls bone healing. Biomaterial-based delivery of single exogenous GFs has shown therapeutic efficacy, and this likely relates to its ability to recruit and promote replication of cells involved in tissue development and the healing process. However, as the natural bone healing cascade involves the action of multiple factors, each acting in a specific spatiotemporal pattern, strategies aiming to mimic the critical aspects of this process will likely benefit from the usage of multiple therapeutic agents. This article reviews the current status of approaches to deliver single GFs, as well as ongoing efforts to develop sophisticated delivery platforms to deliver multiple lineage-directing morphogens (multiple GFs) during bone healing. PMID:22626978

  13. Local apoptosis modulates early mammalian brain development through the elimination of morphogen-producing cells.

    PubMed

    Nonomura, Keiko; Yamaguchi, Yoshifumi; Hamachi, Misato; Koike, Masato; Uchiyama, Yasuo; Nakazato, Kenichi; Mochizuki, Atsushi; Sakaue-Sawano, Asako; Miyawaki, Atsushi; Yoshida, Hiroki; Kuida, Keisuke; Miura, Masayuki

    2013-12-23

    Apoptotic cells are observed in the early developing brain. Apoptosis deficiency is proposed to cause brain overgrowth, but here we show that brain malformations in apoptosis-deficient mutants are due to insufficient brain ventricle expansion as a result of uncompleted cranial neural tube closure. Apoptosis eliminates Fgf8-expressing cells in the anterior neural ridge (ANR), which acts as an organizing center of the forebrain by producing FGF8 morphogen. Deficiency of apoptosis leads to the accumulation of undead and nonproliferative cells in the ventral part of the ANR. The undead cells in apoptosis-deficient mutants express Fgf8 continuously, which perturbs gene expression in the ventral forebrain. Thus, apoptosis within a specific subdomain of the ANR is required for correct temporal elimination of an FGF8-producing region within a limited developmental time window, thereby ensuring proper forebrain development.

  14. Self-construction of supramolecular polyrotaxane films by an electrotriggered morphogen-driven process.

    PubMed

    Rydzek, Gaulthier; Garnier, Tony; Schaaf, Pierre; Voegel, Jean-Claude; Senger, Bernard; Frisch, Benoît; Haikel, Youssef; Petit, Corinne; Schlatter, Guy; Jierry, Loïc; Boulmedais, Fouzia

    2013-08-27

    The design of films using a one-pot process has recently attracted increasing interest in the field of polymer thin film formation. Herein we describe the preparation of one-pot supramolecular polyrotaxane (PRX) films using the morphogen-driven self-construction process. This one-pot buildup strategy where the film growth is triggered by the electrochemical formation and diffusion of a catalyst in close vicinity of the substrate has recently been introduced by our group. A one-pot mixture was used that contained (i) poly(acrylic acid) (PAA) functionalized by azide groups grafted on the polymer chain through oligo(ethylene glycol) (EG) arms, leading to PAA-EG13-N3, (ii) cyclodextrins (α and β CD), as macrocycles that can be threaded along EG arms, (iii) alkyne-functionalized stoppers (ferrocene or adamantane), to cap the PRX assembly by click chemistry, and (iv) copper sulfate. The one-pot mixture solution was brought into contact with a gold electrode. Cu(I), the morphogen, was generated electrochemically from Cu(II) at the electrode/one-pot solution interface. This electrotriggered click reaction leads to the capping of polypseudorotaxane yielding to PRXs. The PRXs can self-assemble through lateral supramolecular interactions to form aggregates and ensure the cohesion of the film. The film buildup was investigated using different types of CD and alkyne functionalized stoppers. Supramolecular PRX aggregates were characterized by X-ray diffraction measurements. The film topographies were imaged by atomic force microscopy. The influence of the concentration in CD and the presence of a competitor were studied as well. The stability of the resulting film was tested in contact with 8 M urea and during the electrochemical oxidation of ferrocene.

  15. Distinct modes of SMAD2 chromatin binding and remodeling shape the transcriptional response to NODAL/Activin signaling

    PubMed Central

    Coda, Davide M; Gaarenstroom, Tessa; East, Philip; Patel, Harshil; Miller, Daniel S J; Lobley, Anna; Matthews, Nik; Stewart, Aengus; Hill, Caroline S

    2017-01-01

    NODAL/Activin signaling orchestrates key processes during embryonic development via SMAD2. How SMAD2 activates programs of gene expression that are modulated over time however, is not known. Here we delineate the sequence of events that occur from SMAD2 binding to transcriptional activation, and the mechanisms underlying them. NODAL/Activin signaling induces dramatic chromatin landscape changes, and a dynamic transcriptional network regulated by SMAD2, acting via multiple mechanisms. Crucially we have discovered two modes of SMAD2 binding. SMAD2 can bind pre-acetylated nucleosome-depleted sites. However, it also binds to unacetylated, closed chromatin, independently of pioneer factors, where it induces nucleosome displacement and histone acetylation. For a subset of genes, this requires SMARCA4. We find that long term modulation of the transcriptional responses requires continued NODAL/Activin signaling. Thus SMAD2 binding does not linearly equate with transcriptional kinetics, and our data suggest that SMAD2 recruits multiple co-factors during sustained signaling to shape the downstream transcriptional program. DOI: http://dx.doi.org/10.7554/eLife.22474.001 PMID:28191871

  16. Nodal Solutions for Supercritical Laplace Equations

    NASA Astrophysics Data System (ADS)

    Dalbono, Francesca; Franca, Matteo

    2016-11-01

    In this paper we study radial solutions for the following equation Δ u(x)+f (u(x), |x|) = 0, where {x in {Rn}}, n > 2, f is subcritical for r small and u large and supercritical for r large and u small, with respect to the Sobolev critical exponent {2^{*} = 2n/n-2}. The solutions are classified and characterized by their asymptotic behaviour and nodal properties. In an appropriate super-linear setting, we give an asymptotic condition sufficient to guarantee the existence of at least one ground state with fast decay with exactly j zeroes for any j ≥ 0. Under the same assumptions, we also find uncountably many ground states with slow decay, singular ground states with fast decay and singular ground states with slow decay, all of them with exactly j zeroes. Our approach, based on Fowler transformation and invariant manifold theory, enables us to deal with a wide family of potentials allowing spatial inhomogeneity and a quite general dependence on u. In particular, for the Matukuma-type potential, we show a kind of structural stability.

  17. The genetics of nodal marginal zone lymphoma

    PubMed Central

    Spina, Valeria; Khiabanian, Hossein; Messina, Monica; Monti, Sara; Cascione, Luciano; Bruscaggin, Alessio; Spaccarotella, Elisa; Holmes, Antony B.; Arcaini, Luca; Lucioni, Marco; Tabbò, Fabrizio; Zairis, Sakellarios; Diop, Fary; Cerri, Michaela; Chiaretti, Sabina; Marasca, Roberto; Ponzoni, Maurilio; Deaglio, Silvia; Ramponi, Antonio; Tiacci, Enrico; Pasqualucci, Laura; Paulli, Marco; Falini, Brunangelo; Inghirami, Giorgio; Bertoni, Francesco; Foà, Robin; Rabadan, Raul; Gaidano, Gianluca

    2016-01-01

    Nodal marginal zone lymphoma (NMZL) is a rare, indolent B-cell tumor that is distinguished from splenic marginal zone lymphoma (SMZL) by the different pattern of dissemination. NMZL still lacks distinct markers and remains orphan of specific cancer gene lesions. By combining whole-exome sequencing, targeted sequencing of tumor-related genes, whole-transcriptome sequencing, and high-resolution single nucleotide polymorphism array analysis, we aimed at disclosing the pathways that are molecularly deregulated in NMZL and we compare the molecular profile of NMZL with that of SMZL. These analyses identified a distinctive pattern of nonsilent somatic lesions in NMZL. In 35 NMZL patients, 41 genes were found recurrently affected in ≥3 (9%) cases, including highly prevalent molecular lesions of MLL2 (also known as KMT2D; 34%), PTPRD (20%), NOTCH2 (20%), and KLF2 (17%). Mutations of PTPRD, a receptor-type protein tyrosine phosphatase regulating cell growth, were enriched in NMZL across mature B-cell tumors, functionally caused the loss of the phosphatase activity of PTPRD, and were associated with cell-cycle transcriptional program deregulation and increased proliferation index in NMZL. Although NMZL shared with SMZL a common mutation profile, NMZL harbored PTPRD lesions that were otherwise absent in SMZL. Collectively, these findings provide new insights into the genetics of NMZL, identify PTPRD lesions as a novel marker for this lymphoma across mature B-cell tumors, and support the distinction of NMZL as an independent clinicopathologic entity within the current lymphoma classification. PMID:27335277

  18. Nodal aberration theory for wild-filed asymmetric optical systems

    NASA Astrophysics Data System (ADS)

    Chen, Yang; Cheng, Xuemin; Hao, Qun

    2016-10-01

    Nodal Aberration Theory (NAT) was used to calculate the zero field position in Full Field Display (FFD) for the given aberration term. Aiming at wide-filed non-rotational symmetric decentered optical systems, we have presented the nodal geography behavior of the family of third-order and fifth-order aberrations. Meanwhile, we have calculated the wavefront aberration expressions when one optical element in the system is tilted, which was not at the entrance pupil. By using a three-piece-cellphone lens example in optical design software CodeV, the nodal geography is testified under several situations; and the wavefront aberrations are calculated when the optical element is tilted. The properties of the nodal aberrations are analyzed by using Fringe Zernike coefficients, which are directly related with the wavefront aberration terms and usually obtained by real ray trace and wavefront surface fitting.

  19. Nodal signalling and asymmetry of the nervous system.

    PubMed

    Signore, Iskra A; Palma, Karina; Concha, Miguel L

    2016-12-19

    The role of Nodal signalling in nervous system asymmetry is still poorly understood. Here, we review and discuss how asymmetric Nodal signalling controls the ontogeny of nervous system asymmetry using a comparative developmental perspective. A detailed analysis of asymmetry in ascidians and fishes reveals a critical context-dependency of Nodal function and emphasizes that bilaterally paired and midline-unpaired structures/organs behave as different entities. We propose a conceptual framework to dissect the developmental function of Nodal as asymmetry inducer and laterality modulator in the nervous system, which can be used to study other types of body and visceral organ asymmetries. Using insights from developmental biology, we also present novel evolutionary hypotheses on how Nodal led the evolution of directional asymmetry in the brain, with a particular focus on the epithalamus. We intend this paper to provide a synthesis on how Nodal signalling controls left-right asymmetry of the nervous system.This article is part of the themed issue 'Provocative questions in left-right asymmetry'.

  20. The influence of exercise on bone morphogenic enzyme activity of immature equine subchondral bone.

    PubMed

    van de Lest, Chris H A; Brama, Pieter A J; van Weeren, P R

    2003-01-01

    This study aimed at the determination of the influence of exercise on the levels of a number of bone morphogenic enzymes in subchondral bone and at the comparison of these data with other (subchondral) bone-related parameters that have been investigated in the same experimental population.Forty-three foals were reared until weaning at 5 months of age under similar conditions, except for the type and amount of exercise. Fifteen foals remained at pasture (Pasture group and also control group), 14 foals were kept in box stalls (Box group) and 14 foals were kept in the same box stalls but were subjected daily to an increasing number of gallop sprints (Training group). After weaning 8 foals from each group were euthanised. All remaining 19 animals were housed together in a loose box with access to a small paddock to study a possible reversibility of exercise-induced effects. Post mortem subchondral bone samples were collected from the femoropatellar joint and analysed for the bone morphogenic enzymes alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP) and lysyl oxidase (LO). Data were compared to calcium content, numbers of collagen cross-links, bone mineral density (BMD) and cross-sectional area (CSA) collected in other bone-related studies in the same group of experimental animals. At 5 months of age, ALP levels were significantly lower and TRAP levels higher in both the Box and the Training group, making the ALP : TRAP ratio reversed in relation to the Pasture group. LO levels were lower in the Box group only. The ALP and TRAP data corresponded with changes in CSA, but not with calcium and BMD, the levels of which were the same in the Training and Pasture groups. The LO levels corresponded nicely with hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) cross-links. At 11 months of age ALP and TRAP levels had reached similar levels in most groups, normalising the ALP : TRAP ratio. TRAP levels in the former Training group lagged somewhat behind

  1. [Role of G-protein alpha sub-units in the morphogenic processes of filamentous Ascomycota fungi].

    PubMed

    García-Rico, Ramón O; Fierro, Francisco

    The phylum Ascomycota comprises about 75% of all the fungal species described, and includes species of medical, phytosanitary, agricultural, and biotechnological importance. The ability to spread, explore, and colonise new substrates is a feature of critical importance for this group of organisms. In this regard, basic processes such as conidial germination, the extension of hyphae and sporulation, make up the backbone of development in most filamentous fungi. These processes require specialised morphogenic machinery, coordinated and regulated by mechanisms that are still being elucidated. In recent years, substantial progress has been made in understanding the role of the signalling pathway mediated by heterotrimericG proteins in basic biological processes of many filamentous fungi. This review focuses on the role of the alpha subunits of heterotrimericG proteins in the morphogenic processes of filamentous Ascomycota.

  2. Special Morphological Features at the Interface of the Renal Stem/Progenitor Cell Niche Force to Reinvestigate Transport of Morphogens During Nephron Induction

    PubMed Central

    Minuth, Will W.; Denk, Lucia

    2016-01-01

    Abstract Formation of a nephron depends on reciprocal signaling of different morphogens between epithelial and mesenchymal cells within the renal stem/progenitor cell niche. Previously, it has been surmised that a close proximity exists between both involved cell types and that morphogens are transported between them by diffusion. However, actual morphological data illustrate that mesenchymal and epithelial stem/progenitor cell bodies are separated by a striking interface. Special fixation of specimens by glutaraldehyde (GA) solution including cupromeronic blue, ruthenium red, or tannic acid for electron microscopy depicts that the interface is not void but filled in extended areas by textured extracellular matrix. Surprisingly, projections of mesenchymal cells cross the interface to contact epithelial cells. At those sites the plasma membranes of a mesenchymal and an epithelial cell are connected via tunneling nanotubes. Regarding detected morphological features in combination with involved morphogens, their transport cannot longer be explained solely by diffusion. Instead, it has to be sorted according to biophysical properties of morphogens and to detected environment. Thus, the new working hypothesis is that morphogens with good solubility such as glial cell line-derived neurotrophic factor (GDNF) or fibroblast growth factors (FGFs) are transported by diffusion. Morphogens with minor solubility such as bone morphogenetic proteins (BMPs) are secreted and stored for delivery on demand in illustrated extracellular matrix. In contrast, morphogens with poor solubility such as Wnts are transported in mesenchymal cell projections along the plasma membrane or via illustrated tunneling nanotubes. However, the presence of an intercellular route between mesenchymal and epithelial stem/progenitor cells by tunneling nanotubes also makes it possible that all morphogens are transported this way. PMID:26862472

  3. Millennium recurrence interval of morphogenic earthquakes on the Qingchuan fault, northeastern segment of the Longmen Shan Thrust Belt, China

    NASA Astrophysics Data System (ADS)

    Lin, Aiming; Yan, Bing; Rao, Gang

    2016-04-01

    The 2008 M w 7.9 Wenchuan produced a ˜285-300-km-long coseismic surface rupture zone, including a 60-km-long segment along the Qingchuan fault, the northeastern segment of the Longmen Shan Thrust Belt (LSTB), Sichuan Basin, central China. Field investigations, trench excavations, and radiocarbon dating results reveal that (i) the Qingchuan fault is currently active as a seismogenic fault, along which four morphogenic earthquakes including the 2008 Wenchuan earthquake occurred in the past ca. 3500 years, suggesting an average millennium recurrence interval of morphogenic earthquakes in the late Holocene; (ii) the most recent event prior to the 2008 Wenchuan earthquake took place in the period between AD 1400 and AD 1100; (iii) the penultimate paleoseismic event occurred in the period around 2000 years BP in the Han Dynasty (206 BC-AD 220); (iv) the third paleoseismic event occurred in the period between 900 and 1800 BC; and (v) at least three seismic faulting events occurred in the early Holocene. The present results are comparable with those inferred in the central and southwestern segments of the LSTB within which the Wenchuan magnitude earthquakes occurred in a millennium recurrence interval, that are in contrast with previous estimates of 2000-10,000 years for the recurrence interval of morphogenic earthquakes within the LSTB and thereby necessitating substantial modifications to existing seismic hazard models for the densely populated region at the Sichuan region.

  4. Cadmium uptake, localization and stress-induced morphogenic response in the fern Pteris vittata.

    PubMed

    Balestri, Mirko; Ceccarini, Alessio; Forino, Laura Maria Costantina; Zelko, Ivan; Martinka, Michal; Lux, Alexander; Ruffini Castiglione, Monica

    2014-05-01

    Cadmium uptake, tissue localization and structural changes induced at cellular level are essential to understand Cd tolerance in plants. In this study we have exposed plants of Pteris vittata to different concentrations of CdCl2 (0, 30, 60, 100 μM) to evaluate the tolerance of the fern to cadmium. Cadmium content determination and its histochemical localization showed that P. vittata not only takes up, but also transports and accumulates cadmium in the aboveground tissues, delocalizing it mainly in the less bioactive tissues of the frond, the trichomes and the scales. Cadmium tolerance in P. vittata was strictly related to morphogenic response induced by the metal itself in the root system. Adaptive response regarded changes of the root apex size, the developmental pattern of root hairs, the differentiation of xylem elements and endodermal suberin lamellae. All the considered parameters suggest that, in our experimental conditions, 60 μM of Cd may represent the highest concentration that P. vittata can tolerate; indeed this Cd level even improves the absorbance features of the root and allows good transport and accumulation of the metal in the fronds. The results of this study can provide useful information for phytoremediation strategies of soils contaminated by Cd, exploiting the established ability of P. vittata to transport, delocalize in the aboveground biomass and accumulate polluting metals.

  5. Morphogen-based simulation model of ray growth and joint patterning during fin development and regeneration.

    PubMed

    Rolland-Lagan, Anne-Gaëlle; Paquette, Mathieu; Tweedle, Valerie; Akimenko, Marie-Andrée

    2012-03-01

    The fact that some organisms are able to regenerate organs of the correct shape and size following amputation is particularly fascinating, but the mechanism by which this occurs remains poorly understood. The zebrafish (Danio rerio) caudal fin has emerged as a model system for the study of bone development and regeneration. The fin comprises 16 to 18 bony rays, each containing multiple joints along its proximodistal axis that give rise to segments. Experimental observations on fin ray growth, regeneration and joint formation have been described, but no unified theory has yet been put forward to explain how growth and joint patterns are controlled. We present a model for the control of fin ray growth during development and regeneration, integrated with a model for joint pattern formation, which is in agreement with published, as well as new, experimental data. We propose that fin ray growth and joint patterning are coordinated through the interaction of three morphogens. When the model is extended to incorporate multiple rays across the fin, it also accounts for how the caudal fin acquires its shape during development, and regains its correct size and shape following amputation.

  6. [Morpho-functional characteristics of the lingual epithelium after administration of hydra peptide morphogen].

    PubMed

    Kulaeva, V V; Bykov, V L

    2007-01-01

    Using histological, morphometric and quantitative histoenzymological methods, the changes of lingual epithelium were studied in 40 outbred albino mice after 5 intraperitoneal injections of 100 micrograms of hydra peptide morphogen (HPM) per 1 kg of body weight. Administration of HPM was found to increase the total thickness of epithelial layer on the dorsal tongue surface in the interpapillary regions, while in the area of filiform papillae these changes were not significant. On the ventral tongue surface HPM induced a marked increase of total thickness of the epithelial layer as compared to that in control animals. Mitotic activity was increased in the epithelium covering the ventral surface and in the interpapillary regions on the dorsal tongue surface. Histoenzymologic study which involved the demonstration of NADH-diaphorase, succinate- and lactate-dehydrogenase (LDH) activities, followed by a cytophotometric evaluation of enzyme activity, has shown a stimulatory effect of HPM on the activity of all the enzymes studied, which was most pronounced in respect to LDH and was maximally expressed on the dorsal tongue surface. These findings collectively suggest that HPM exerts a stimulatory effect on proliferation activity and metabolism of lingual epithelium, which is differentially expressed in its variuoe topographical zones.

  7. A novel cranioplasty technique incorporating cancellous femoral bone and recombinant bone morphogenic protein 2.

    PubMed

    Wang, Frederick; Hoang, Don; Medvecky, Michael; Amankulor, Nduka; Teng, Edward; Narayan, Deepak

    2012-07-01

    Large calvarial defects in the setting of chronic infection and limited autologous donor sites present challenging problems for the reconstructive surgeon. We report on a novel osteogenic implant as a potential calvarial reconstruction solution. Two patients with an extensive history of severe traumatic brain injury and multiple cranial operations desired delayed calvarial reconstruction subsequent to removal of infected acrylic and titanium implants. These patients underwent harvesting of cancellous femoral bone and bone marrow, which was placed between 2 layers of recombinant bone morphogenic protein 2 impregnated in acellular collagen sponges and an outer layer of sturdily pliable Vicryl mesh to create a moldable osteogenic implant construct. The construct was molded into the shape of the defect and secured with sutures to the skull surrounding the defect. The osteogenic implant showed evidence of bone formation and maintained coverage over the original calvarial defect at 26 months postoperatively as well as subjective satisfaction by both patients and the senior surgeon. This technically straightforward technique with acceptable functional and aesthetic outcomes may be useful to reconstructing selected calvarial defects.

  8. Bone morphogenic protein signalling suppresses differentiation of pluripotent cells by maintaining expression of E-Cadherin.

    PubMed

    Malaguti, Mattias; Nistor, Paul A; Blin, Guillaume; Pegg, Amy; Zhou, Xinzhi; Lowell, Sally

    2013-12-17

    Bone morphogenic protein (BMP) signalling contributes towards maintenance of pluripotency and favours mesodermal over neural fates upon differentiation, but the mechanisms by which BMP controls differentiation are not well understood. We report that BMP regulates differentiation by blocking downregulation of Cdh1, an event that accompanies the earliest stages of neural and mesodermal differentiation. We find that loss of Cdh1 is a limiting requirement for differentiation of pluripotent cells, and that experimental suppression of Cdh1 activity rescues the BMP-imposed block to differentiation. We further show that BMP acts prior to and independently of Cdh1 to prime pluripotent cells for mesoderm differentiation, thus helping to reinforce the block to neural differentiation. We conclude that differentiation depends not only on exposure to appropriate extrinsic cues but also on morphogenetic events that control receptivity to those differentiation cues, and we explain how a key pluripotency signal, BMP, feeds into this control mechanism. DOI: http://dx.doi.org/10.7554/eLife.01197.001.

  9. Bone morphogenic protein signalling suppresses differentiation of pluripotent cells by maintaining expression of E-Cadherin

    PubMed Central

    Malaguti, Mattias; Nistor, Paul A; Blin, Guillaume; Pegg, Amy; Zhou, Xinzhi; Lowell, Sally

    2013-01-01

    Bone morphogenic protein (BMP) signalling contributes towards maintenance of pluripotency and favours mesodermal over neural fates upon differentiation, but the mechanisms by which BMP controls differentiation are not well understood. We report that BMP regulates differentiation by blocking downregulation of Cdh1, an event that accompanies the earliest stages of neural and mesodermal differentiation. We find that loss of Cdh1 is a limiting requirement for differentiation of pluripotent cells, and that experimental suppression of Cdh1 activity rescues the BMP-imposed block to differentiation. We further show that BMP acts prior to and independently of Cdh1 to prime pluripotent cells for mesoderm differentiation, thus helping to reinforce the block to neural differentiation. We conclude that differentiation depends not only on exposure to appropriate extrinsic cues but also on morphogenetic events that control receptivity to those differentiation cues, and we explain how a key pluripotency signal, BMP, feeds into this control mechanism. DOI: http://dx.doi.org/10.7554/eLife.01197.001 PMID:24347544

  10. Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress stimulates an inflammatory response

    NASA Technical Reports Server (NTRS)

    Sorescu, George P.; Sykes, Michelle; Weiss, Daiana; Platt, Manu O.; Saha, Aniket; Hwang, Jinah; Boyd, Nolan; Boo, Yong C.; Vega, J. David; Taylor, W. Robert; Jo, Hanjoong

    2003-01-01

    Atherosclerosis is now viewed as an inflammatory disease occurring preferentially in arterial regions exposed to disturbed flow conditions, including oscillatory shear stress (OS), in branched arteries. In contrast, the arterial regions exposed to laminar shear (LS) are relatively lesion-free. The mechanisms underlying the opposite effects of OS and LS on the inflammatory and atherogenic processes are not clearly understood. Here, through DNA microarrays, protein expression, and functional studies, we identify bone morphogenic protein 4 (BMP4) as a mechanosensitive and pro-inflammatory gene product. Exposing endothelial cells to OS increased BMP4 protein expression, whereas LS decreased it. In addition, we found BMP4 expression only in the selective patches of endothelial cells overlying foam cell lesions in human coronary arteries. The same endothelial patches also expressed higher levels of intercellular cell adhesion molecule-1 (ICAM-1) protein compared with those of non-diseased areas. Functionally, we show that OS and BMP4 induced ICAM-1 expression and monocyte adhesion by a NFkappaB-dependent mechanism. We suggest that BMP4 is a mechanosensitive, inflammatory factor playing a critical role in early steps of atherogenesis in the lesion-prone areas.

  11. On the Nodal Lines of Eisenstein Series on Schottky Surfaces

    NASA Astrophysics Data System (ADS)

    Jakobson, Dmitry; Naud, Frédéric

    2017-04-01

    On convex co-compact hyperbolic surfaces {X=Γ backslash H2}, we investigate the behavior of nodal curves of real valued Eisenstein series {F_λ(z,ξ)}, where {λ} is the spectral parameter, {ξ} the direction at infinity. Eisenstein series are (non-{L^2}) eigenfunctions of the Laplacian {Δ_X} satisfying {Δ_X F_λ=(1/4+λ^2)F_λ}. As {λ} goes to infinity (the high energy limit), we show that, for generic {ξ}, the number of intersections of nodal lines with any compact segment of geodesic grows like {λ}, up to multiplicative constants. Applications to the number of nodal domains inside the convex core of the surface are then derived.

  12. Spin-Orbit Nodal Semimetals in the Layer Groups

    NASA Astrophysics Data System (ADS)

    Wieder, Benjamin; Kim, Youngkuk; Kane, Charles

    Recent interest in point and line node semimetals has lead to the proposal and discovery of these phenomena in numerous systems. Frequently, though, these nodal systems are described in terms of individual properties reliant on specific space group intricacies or band-tuning conditions. Restricting ourselves to cases with strong spin-orbit interaction, we develop a more general framework which captures existing systems and predicts new examples of nodal materials. In many previously proposed systems, the three-dimensional nature of the space group has obscured key generalities. Therefore, we show how within our framework one can predict and characterize a diverse set of nodal phenomena even in two-dimensional systems constructed of three-dimensional sites, known as the ``Layer Groups''. Introducing a set of simple models, we characterize the allowed semimetallic structures in the layer groups and draw connections to analogous three-dimensional systems.

  13. A computational study of nodal-based tetrahedral element behavior.

    SciTech Connect

    Gullerud, Arne S.

    2010-09-01

    This report explores the behavior of nodal-based tetrahedral elements on six sample problems, and compares their solution to that of a corresponding hexahedral mesh. The problems demonstrate that while certain aspects of the solution field for the nodal-based tetrahedrons provide good quality results, the pressure field tends to be of poor quality. Results appear to be strongly affected by the connectivity of the tetrahedral elements. Simulations that rely on the pressure field, such as those which use material models that are dependent on the pressure (e.g. equation-of-state models), can generate erroneous results. Remeshing can also be strongly affected by these issues. The nodal-based test elements as they currently stand need to be used with caution to ensure that their numerical deficiencies do not adversely affect critical values of interest.

  14. Distant nodal metastasis: is it always an unresectable disease?

    PubMed Central

    Celotti, Andrea; Molfino, Sarah; Baggi, Paolo; Tarasconi, Antonio; Baronio, Gianluca; Arru, Luca; Gheza, Federico; Tiberio, Guido; Portolani, Nazario

    2017-01-01

    This article aims at analyzing the published literature concerning the treatment of patients with gastric cancer and distant nodal metastases, actually considered metastatic disease. A systematic search was undertaken using Medline, Embase, Cochrane and Web-of-Science libraries. No specific restriction on year of publication was used; preference was given to English papers. Both clinical series and literature reviews were selected. Only 11 papers address the issue of surgery for nodal basins outside the D2 dissection area. From these papers, in selected cases extended surgery may prove useful in prolonging survival, when a comprehensive therapeutic pathway including chemotherapy is scheduled. In conclusion, in presence of nodal metastases outside the loco-regional nodes, surgery may be considered for metastatic nodes in stations 13 and 16, in selected cases. PMID:28217751

  15. A transient, quadratic nodal method for triangular-Z geometry

    SciTech Connect

    DeLorey, T.F.

    1993-06-01

    Many systematically-derived nodal methods have been developed for Cartesian geometry due to the extensive interest in Light Water Reactors. These methods typically model the transverse-integrated flux as either an analytic or low order polynomial function of position within the node. Recently, quadratic nodal methods have been developed for R-Z and hexagonal geometry. A static and transient quadratic nodal method is developed for triangular-Z geometry. This development is particularly challenging because the quadratic expansion in each node must be performed between the node faces and the triangular points. As a consequence, in the 2-D plane, the flux and current at the points of the triangles must be treated. Quadratic nodal equations are solved using a non-linear iteration scheme, which utilizes the corrected, mesh-centered finite difference equations, and forces these equations to match the quadratic equations by computing discontinuity factors during the solution. Transient nodal equations are solved using the improved quasi-static method, which has been shown to be a very efficient solution method for transient problems. Several static problems are used to compare the quadratic nodal method to the Coarse Mesh Finite Difference (CMFD) method. The quadratic method is shown to give more accurate node-averaged fluxes. However, it appears that the method has difficulty predicting node leakages near reactor boundaries and severe material interfaces. The consequence is that the eigenvalue may be poorly predicted for certain reactor configurations. The transient methods are tested using a simple analytic test problem, a heterogeneous heavy water reactor benchmark problem, and three thermal hydraulic test problems. Results indicate that the transient methods have been implemented correctly.

  16. Chiral Spin-Orbital Liquids with Nodal Lines

    NASA Astrophysics Data System (ADS)

    Natori, W. M. H.; Andrade, E. C.; Miranda, E.; Pereira, R. G.

    2016-07-01

    Strongly correlated materials with strong spin-orbit coupling hold promise for realizing topological phases with fractionalized excitations. Here, we propose a chiral spin-orbital liquid as a stable phase of a realistic model for heavy-element double perovskites. This spin liquid state has Majorana fermion excitations with a gapless spectrum characterized by nodal lines along the edges of the Brillouin zone. We show that the nodal lines are topological defects of a non-Abelian Berry connection and that the system exhibits dispersing surface states. We discuss some experimental signatures of this state and compare them with properties of the spin liquid candidate Ba2YMoO6.

  17. Nodal metastases in thyroid cancer: prognostic implications and management.

    PubMed

    Wang, Laura Y; Ganly, Ian

    2016-04-01

    The significance of cervical lymph node metastases in differentiated thyroid cancer has been controversial and continues to evolve. Current staging systems consider nodal metastases to confer a poorer prognosis, particularly in older patients. Increasingly, the literature suggests that characteristics of the metastatic lymph nodes such as size and number are also prognostic. There is a growing trend toward less aggressive treatment of low-volume nodal disease. The aim of this review is to summarize the current literature and discuss prognostic and management implications of lymph node metastases in differentiated thyroid cancer.

  18. Preoperative staging of nodal status in gastric cancer

    PubMed Central

    Berlth, Felix; Chon, Seung-Hun; Chevallay, Mickael; Jung, Minoa Karin

    2017-01-01

    An accurate preoperative staging of nodal status is crucial in gastric cancer, because it has a great impact on prognosis and therapeutic decision-making. Different staging methods have been evaluated for gastric cancer in order to predict nodal involvement. So far, no technique could meet the necessary requirements, which include a high detection rate of infiltrated lymph nodes and a low frequency of false-positive results. This article summarizes different staging methods used to assess lymph node status in patients with gastric cancer, evaluates the evidence, and proposes to establish new methods. PMID:28217758

  19. Long period nodal motion of sun synchronous orbits

    NASA Technical Reports Server (NTRS)

    Duck, K. I.

    1975-01-01

    An approximative model is formulated for assessing these perturbations that significantly affect long term modal motion of sun synchronous orbits. Computer simulations with several independent computer programs consider zonal and tesseral gravitational harmonics, third body gravitational disturbances induced by the sun and the moon, and atmospheric drag. A pendulum model consisting of evenzonal harmonics through order 4 and solar gravity dominated nodal motion approximation. This pendulum motion results from solar gravity inducing an inclination oscillation which couples into the nodal precession induced by the earth's oblateness. The pendulum model correlated well with simulations observed flight data.

  20. Isolation and Culture of Avian Embryonic Valvular Progenitor Cells

    PubMed Central

    Mahler, Gretchen; Gould, Russell; Butcher, Johnathan

    2010-01-01

    Proper formation and function of embryonic heart valves is critical for developmental progression. The early embryonic heart is a U-shaped tube of endocardium surrounded by myocardium. The myocardium secretes cardiac jelly, a hyaluronan-rich gelatinous matrix, into the atrioventricular (AV) junction and outflow tract (OFT) lumen. At stage HH14 valvulogenesis begins when a subset of endocardial cells receive signals from the myocardium, undergo endocardial to mesenchymal transformation (EMT), and invade the cardiac jelly. At stage HH25 the valvular cushions are fully mesenchymalized, and it is this mesenchyme that eventually forms the valvular and septal apparatus of the heart. Understanding the mechanisms that initiate and modulate the process of EMT and cell differentiation are important because of their connection to serious congenital heart defects. In this study we present methods to isolate pre-EMT endocardial and post-EMT mesenchymal cells, which are the two different cell phenotypes of the prevalvular cushion. Pre-EMT endocardial cells can be cultured with or without the myocardium. Post-EMT AV cushion mesenchymal cells can be cultured inside mechanically constrained or stress-free collagen gels. These 3D in vitro models mimic key valvular morphogenic events and are useful for deconstructing the mechanisms of early and late stage valvulogenesis. PMID:21085095

  1. A neurodegenerative disease affecting synaptic connections in Drosophila mutant for the tumor suppressor morphogen Patched

    PubMed Central

    Gazi, Michal; Shyamala, Baragur V.; Bhat, Krishna Moorthi

    2009-01-01

    The tumor-suppressor morphogen, Patched (Ptc), has extensive homology to the Niemann-Pick-C 1 (NPC1) protein. The NPC disease is a paediatric, progressive and fatal neurodegenerative disorder thought to be due to an abnormal accumulation of cholesterol in neurons. Here, we report that patched mutant adults develop a progressive neurodegenerative disease and their brain contains membranous and lamellar inclusions. There is also a significant reduction in the number of synaptic terminals in the brain of the mutant adults. Interestingly, feeding cholesterol to wild type flies generates inclusions in the brain, but does not cause the disease. However, feeding cholesterol to mutant flies increases synaptic connections and suppresses the disease. Our results suggest that sequestration of cholesterol in the mutant brain in the form of membranous material and inclusions affects available pool of cholesterol for cellular functions. This, in turn, negatively affects the synaptic number and contributes to the disease-state. Consistent with this, in ptc mutants there is a reduction in the pool of cholesterol esters, and cholesterol-mediated suppression of the disease accompanies an increase in cholesterol esters. We further show that Ptc does not function directly in this process since gain-of-function for Hedgehog also induces the same disease with a reduction in the level of cholesterol esters. We believe that loss of function for ptc causes neurodegeneration via two distinct ways: de-repression of genes that interfere with lipid trafficking, and de-repression of genes outside of the lipid trafficking; the functions of both classes of genes ultimately converge on synaptic connections. PMID:19635474

  2. Public awareness of the bone morphogenic protein controversy: Evidence from news publications

    PubMed Central

    Drazin, Doniel; Shweikeh, Faris; Wieshofer, Erich; Kim, Terrence T.; Johnson, J. Patrick

    2014-01-01

    Background: Use of recombinant human bone morphogenic protein-2 (rhBMP-2) in spinal fusion has seen a tremendous increase. Public awareness of rhBMP-2 and its complications has not been assessed. The authors studied published news media articles to analyze information provided to the public on this bone graft substitute. Methods: We utilized the academic database, LexisNexis, to locate newspaper articles published between January 2001 and July 2013. All articles were coded by a coder and reviewed by the principal investigator. Results: The search identified 87 national and 99 local newspaper articles. Complications mentioned in national newspapers included cancer (24%), retrograde ejaculation (24%), and abnormal bone growth (14%). Local newspapers cited cancer (14%), inflammation (14%), and retrograde ejaculation (9.2%) most frequently. Fifty national (59%) and 35 local (54%) articles had no mention of complications. Sources of evidence cited by articles were (in order of frequency): Governmental agencies, medical research or published studies, healthcare personnel or patients, and companies or corporations. Conclusions: Only a small percentage of newspaper articles presented potential complications. Despite lack of clear scientific causal relationship between rhBMP-2 and cancer, this risk was disproportionately reported. Additionally, many did not cite scientific sources. Lack of reliable information available to the public reiterates the role of physicians in discussing risks and benefits BMP use in spinal surgery, assuring that patients are making informed decisions. Future news media articles should present risks in an impartial and evidence-based manner. Collaboration between advocacy groups, medical institutions, and media outlets would be beneficial in achieving this goal. PMID:25593772

  3. Rapid Activation of Bone Morphogenic Protein 9 by Receptor-mediated Displacement of Pro-domains*

    PubMed Central

    Kienast, Yvonne; Jucknischke, Ute; Scheiblich, Stefan; Thier, Martina; de Wouters, Mariana; Haas, Alexander; Lehmann, Christian; Brand, Verena; Bernicke, Dirk; Honold, Konrad; Lorenz, Stefan

    2016-01-01

    By non-covalent association after proteolytic cleavage, the pro-domains modulate the activities of the mature growth factor domains across the transforming growth factor-β family. In the case of bone morphogenic protein 9 (BMP9), however, the pro-domains do not inhibit the bioactivity of the growth factor, and the BMP9·pro-domain complexes have equivalent biological activities as the BMP9 mature ligand dimers. By using real-time surface plasmon resonance, we could demonstrate that either binding of pro-domain-complexed BMP9 to type I receptor activin receptor-like kinase 1 (ALK1), type II receptors, co-receptor endoglin, or to mature BMP9 domain targeting antibodies leads to immediate and complete displacement of the pro-domains from the complex. Vice versa, pro-domain binding by an anti-pro-domain antibody results in release of the mature BMP9 growth factor. Based on these findings, we adjusted ELISA assays to measure the protein levels of different BMP9 variants. Although mature BMP9 and inactive precursor BMP9 protein were directly detectable by ELISA, BMP9·pro-domain complex could only be measured indirectly as dissociated fragments due to displacement of mature growth factor and pro-domains after antibody binding. Our studies provide a model in which BMP9 can be readily activated upon getting into contact with its receptors. This increases the understanding of the underlying biology of BMP9 activation and also provides guidance for ELISA development for the detection of circulating BMP9 variants. PMID:26677222

  4. Morphogen Electrochemically Triggered Self-Construction of Polymeric Films Based on Mussel-Inspired Chemistry.

    PubMed

    Maerten, Clément; Garnier, Tony; Lupattelli, Paolo; Chau, Nguyet Trang Thanh; Schaaf, Pierre; Jierry, Loïc; Boulmedais, Fouzia

    2015-12-15

    Inspired by the strong chemical adhesion mechanism of mussels, we designed a catechol-based electrochemically triggered self-assembly of films based on ethylene glycol molecules bearing catechol groups on both sides and denoted as bis-catechol molecules. These molecules play the role of morphogens and, in contrast to previously investigated systems, they are also one of the constituents, after reaction, of the film. Unable to interact together, commercially available poly(allylamine hydrochloride) (PAH) chains and bis-catechol molecules are mixed in an aqueous solution and brought in contact with an electrode. By application of defined potential cycles, bis-catechol molecules undergo oxidation leading to molecules bearing "reactive" quinone groups which diffuse toward the solution. In this active state, the quinones react with amino groups of PAH through Michael addition and Schiff's base condensation reaction. The application of cyclic voltammetry (CV) between 0 and 500 mV (vs Ag/AgCl, scan rate of 50 mV/s) of a PAH/bis-catechol solution results in a fast self-construction of a film that reaches a thickness of 40 nm after 60 min. The films present a spiky structure which is attributed to the use of bis-functionalized molecules as one component of the films. XPS measurements show the presence of both PAH and bis-catechol cross-linked together in a covalent way. We show that the amine/catechol ratio is an important parameter which governs the film buildup. For a given amine/catechol ratio, it does exist an optimum CV scan rate leading to a maximum of the film thickness as a function of the scan rate.

  5. Polymorphic nodal elements and their application in discontinuous Galerkin methods

    NASA Astrophysics Data System (ADS)

    Gassner, Gregor J.; Lörcher, Frieder; Munz, Claus-Dieter; Hesthaven, Jan S.

    2009-03-01

    In this work, we discuss two different but related aspects of the development of efficient discontinuous Galerkin methods on hybrid element grids for the computational modeling of gas dynamics in complex geometries or with adapted grids. In the first part, a recursive construction of different nodal sets for hp finite elements is presented. They share the property that the nodes along the sides of the two-dimensional elements and along the edges of the three-dimensional elements are the Legendre-Gauss-Lobatto points. The different nodal elements are evaluated by computing the Lebesgue constants of the corresponding Vandermonde matrix. In the second part, these nodal elements are applied within the modal discontinuous Galerkin framework. We still use a modal based formulation, but introduce a nodal based integration technique to reduce computational cost in the spirit of pseudospectral methods. We illustrate the performance of the scheme on several large scale applications and discuss its use in a recently developed space-time expansion discontinuous Galerkin scheme.

  6. PoroTomo Subtask 6.3 Nodal Seismometers Metadata

    SciTech Connect

    Lesley Parker

    2016-03-28

    Metadata for the nodal seismometer array deployed at the POROTOMO's Natural Laboratory in Brady Hot Spring, Nevada during the March 2016 testing. Metadata includes location and timing for each instrument as well as file lists of data to be uploaded in a separate submission.

  7. Nodal Structure and the Partitioning of Equivalence Classes

    ERIC Educational Resources Information Center

    Fields, Lanny; Watanabe-Rose, Mari

    2008-01-01

    By definition, all of the stimuli in an equivalence class have to be functionally interchangeable with each other. The present experiment, however, demonstrated that this was not the case when using post-class-formation dual-option response transfer tests. With college students, two 4-node 6-member equivalence classes with nodal structures of…

  8. The Penn State Nodal Expansion Transient Analysis Technique with thermal-hydraulic feedback

    SciTech Connect

    Borkowski, J.; Bandini, B.; Baratta, A. )

    1989-11-01

    The nuclear engineering department of the Pennsylvania State University has under development a nodal neutron kinetics code. The PEnn State Nodal Expansion TRansient Analysis TEchnique (PENETRATE) performs two-group, three-dimensional nodal kinetics calculations using the nodal expansion method (NEM). The focus of this discussion is its performance in the solution of the Langenbuch-Maurer-Werner light water rector (LMW LWR) problem. This transient requires an accurate model of both control rod motion and coupled thermal-hydraulic feedback.

  9. Functional mathematical model of dual pathway AV nodal conduction.

    PubMed

    Climent, A M; Guillem, M S; Zhang, Y; Millet, J; Mazgalev, T N

    2011-04-01

    Dual atrioventricular (AV) nodal pathway physiology is described as two different wave fronts that propagate from the atria to the His bundle: one with a longer effective refractory period [fast pathway (FP)] and a second with a shorter effective refractory period [slow pathway (SP)]. By using His electrogram alternance, we have developed a mathematical model of AV conduction that incorporates dual AV nodal pathway physiology. Experiments were performed on five rabbit atrial-AV nodal preparations to develop and test the presented model. His electrogram alternances from the inferior margin of the His bundle were used to identify fast and slow wave front propagations. The ability to predict AV conduction time and the interaction between FP and SP wave fronts have been analyzed during regular and irregular atrial rhythms (e.g., atrial fibrillation). In addition, the role of dual AV nodal pathway wave fronts in the generation of Wenckebach periodicities has been illustrated. Finally, AV node ablative modifications have been evaluated. The model accurately reproduced interactions between FP and SP during regular and irregular atrial pacing protocols. In all experiments, specificity and sensitivity higher than 85% were obtained in the prediction of the pathway responsible for conduction. It has been shown that, during atrial fibrillation, the SP ablation significantly increased the mean HH interval (204 ± 39 vs. 274 ± 50 ms, P < 0.05), whereas FP ablation did not produce significant slowing of ventricular rate. The presented mathematical model can help in understanding some of the intriguing AV node mechanisms and should be considered as a step forward in the studies of AV nodal conduction.

  10. Dynamics of Drosophila embryonic patterning network perturbed in space and time using microfluidics.

    PubMed

    Lucchetta, Elena M; Lee, Ji Hwan; Fu, Lydia A; Patel, Nipam H; Ismagilov, Rustem F

    2005-04-28

    Biochemical networks are perturbed both by fluctuations in environmental conditions and genetic variation. These perturbations must be compensated for, especially when they occur during embryonic pattern formation. Complex chemical reaction networks displaying spatiotemporal dynamics have been controlled and understood by perturbing their environment in space and time. Here, we apply this approach using microfluidics to investigate the robust network in Drosophila melanogaster that compensates for variation in the Bicoid morphogen gradient. We show that the compensation system can counteract the effects of extremely unnatural environmental conditions--a temperature step--in which the anterior and posterior halves of the embryo are developing at different temperatures and thus at different rates. Embryonic patterning was normal under this condition, suggesting that a simple reciprocal gradient system is not the mechanism of compensation. Time-specific reversals of the temperature step narrowed down the critical period for compensation to between 65 and 100 min after onset of embryonic development. The microfluidic technology used here may prove useful to future studies, as it allows spatial and temporal regulation of embryonic development.

  11. Dynamics of Drosophila embryonic patterning network perturbed in space and time using microfluidics

    NASA Astrophysics Data System (ADS)

    Lucchetta, Elena M.; Lee, Ji Hwan; Fu, Lydia A.; Patel, Nipam H.; Ismagilov, Rustem F.

    2005-04-01

    Biochemical networks are perturbed both by fluctuations in environmental conditions and genetic variation. These perturbations must be compensated for, especially when they occur during embryonic pattern formation. Complex chemical reaction networks displaying spatiotemporal dynamics have been controlled and understood by perturbing their environment in space and time. Here, we apply this approach using microfluidics to investigate the robust network in Drosophila melanogaster that compensates for variation in the Bicoid morphogen gradient. We show that the compensation system can counteract the effects of extremely unnatural environmental conditions-a temperature step-in which the anterior and posterior halves of the embryo are developing at different temperatures and thus at different rates. Embryonic patterning was normal under this condition, suggesting that a simple reciprocal gradient system is not the mechanism of compensation. Time-specific reversals of the temperature step narrowed down the critical period for compensation to between 65 and 100min after onset of embryonic development. The microfluidic technology used here may prove useful to future studies, as it allows spatial and temporal regulation of embryonic development.

  12. Chordin forms a self-organizing morphogen gradient in the extracellular space between ectoderm and mesoderm in the Xenopus embryo

    PubMed Central

    Plouhinec, Jean-Louis; Zakin, Lise; Moriyama, Yuki; De Robertis, Edward M.

    2013-01-01

    The vertebrate body plan follows stereotypical dorsal–ventral (D-V) tissue differentiation controlled by bone morphogenetic proteins (BMPs) and secreted BMP antagonists, such as Chordin. The three germ layers—ectoderm, mesoderm, and endoderm—are affected coordinately by the Chordin–BMP morphogen system. However, extracellular morphogen gradients of endogenous proteins have not been directly visualized in vertebrate embryos to date. In this study, we improved immunolocalization methods in Xenopus embryos and analyzed the distribution of endogenous Chordin using a specific antibody. Chordin protein secreted by the dorsal Spemann organizer was found to diffuse along a narrow region that separates the ectoderm from the anterior endoderm and mesoderm. This Fibronectin-rich extracellular matrix is called “Brachet’s cleft” in the Xenopus gastrula and is present in all vertebrate embryos. Chordin protein formed a smooth gradient that encircled the embryo, reaching the ventral-most Brachet cleft. Depletion with morpholino oligos showed that this extracellular gradient was regulated by the Chordin protease Tolloid and its inhibitor Sizzled. The Chordin gradient, as well as the BMP signaling gradient, was self-regulating and, importantly, was able to rescale in dorsal half-embryos. Transplantation of Spemann organizer tissue showed that Chordin diffused over long distances along this signaling highway between the ectoderm and mesoderm. Chordin protein must reach very high concentrations in this narrow region. We suggest that as ectoderm and mesoderm undergo morphogenetic movements during gastrulation, cells in both germ layers read their positional information coordinately from a single morphogen gradient located in Brachet’s cleft. PMID:24284174

  13. Activin/Nodal Signaling Supports Retinal Progenitor Specification in a Narrow Time Window during Pluripotent Stem Cell Neuralization

    PubMed Central

    Bertacchi, Michele; Lupo, Giuseppe; Pandolfini, Luca; Casarosa, Simona; D’Onofrio, Mara; Pedersen, Roger A.; Harris, William A.; Cremisi, Federico

    2015-01-01

    Summary Retinal progenitors are initially found in the anterior neural plate region known as the eye field, whereas neighboring areas undertake telencephalic or hypothalamic development. Eye field cells become specified by switching on a network of eye field transcription factors, but the extracellular cues activating this network remain unclear. In this study, we used chemically defined media to induce in vitro differentiation of mouse embryonic stem cells (ESCs) toward eye field fates. Inhibition of Wnt/β-catenin signaling was sufficient to drive ESCs to telencephalic, but not retinal, fates. Instead, retinal progenitors could be generated from competent differentiating mouse ESCs by activation of Activin/Nodal signaling within a narrow temporal window corresponding to the emergence of primitive anterior neural progenitors. Activin also promoted eye field gene expression in differentiating human ESCs. Our results reveal insights into the mechanisms of eye field specification and open new avenues toward the generation of retinal progenitors for translational medicine. PMID:26388287

  14. Nodal metastasis and elective nodal level treatment in sinonasal small-cell and sinonasal undifferentiated carcinoma: a surveillance, epidemiology and end results analysis

    PubMed Central

    Mitra, Nandita; Alonso-Basanta, Michelle; Adappa, Nithin D; Palmer, James N; O'Malley, Bert W; Rassekh, Christopher H; Chalian, Ara; Cohen, Roger B; Lin, Alexander

    2016-01-01

    Objective: Risk of nodal involvement in patients with sinonasal small-cell carcinoma and sinonasal undifferentiated carcinoma (SNUC) has not been well defined because of their rarity. We describe a population-based assessment of specific nodal level involvement in this group of rare neuroectodermal tumours. Methods: The Surveillance, Epidemiology and End Results (SEER) database from 2004 to 2011 identified patients with SNUC and sinonasal small-cell carcinoma. Overall neck involvement and individual nodal level involvement at presentation were assessed, and comparison was made with a contemporaneous cohort of patients with a borderline clinically significant risk of nodal involvement and recurrence. Results: Of 141 patients, 31 (22%) had gross nodal involvement at presentation (range 14–33% by site and histology). Non-nasal, non-ethmoid site with SNUC histology has the highest rates of initial nodal involvement, whereas higher stage and size do not predict for higher nodal involvement rates. Bilateral Levels 2–3 for all sinonasal small cell; Levels 2–3 for nasal or ethmoid SNUC; and bilateral Levels 1–3 in non-nasal/non-ethmoid SNUC have the highest rates of involvement compared with a clinical reference standard. Conclusion: We found high rates of initial nodal involvement in all SNUC and sinonasal small-cell carcinoma. We found higher initial involvement of Levels 2 and 3 and in certain cases to the Level 1 nodal levels, hypothesizing benefit for elective treatment to those levels. Advances in knowledge: With small single-institution series reporting conflicting nodal involvement rates, our data support high rates of nodal presentation at diagnosis, hypothesizing benefit for elective nodal treatment in this cohort. PMID:26559439

  15. Bone Morphogenic Protein Is a Viable Adjunct for Fusion in Minimally Invasive Transforaminal Lumbar Interbody Fusion

    PubMed Central

    Siddiqui, M Mashfiqul Arafin; Sta.Ana, Ana Rosario P.; Yeo, William

    2016-01-01

    Study Design Comparison of prospectively collected data of patients undergoing minimally invasive surgery transforaminal lumbar interbody fusion (MIS-TLIF) with and without recombinant human bone morphogenic protein 2 (BMP). Purpose To compare the clinical, radiological outcome and complications of patients undergoing MIS-TLIF with and without BMP. Overview of Literature BMP is an effective fusion enhancer with potential complications. Direct comparison of MIS-TLIF with and without BMP is limited to retrospective studies with short follow-up. Methods From June 2005 to February 2011, consecutive cases of MIS-TLIF performed by a single surgeon were included. North American Spine Society (NASS) score, Oswestry disability index (ODI), Short Form-36 (SF-36), and visual analogue score (VAS) were assessed preoperatively and at 6 and 24 months postoperatively. Fusion rates and complications were noted. Results The 252 cases comprised 104 non-BMP and 148 BMP cases. The BMP group was significantly older (mean age, 60.2 vs. 53.9; p<0.01). Preoperative scores were similar. Immediate postoperative morphine usage was significantly lower in the BMP group (12.4 mg vs. 20.1 mg, p<0.01). At 6 months, the BMP group had lower VAS back and leg pain scores (p<0.01). At 2 years, the BMP group had better leg pain scores (p<0.01), ODI (15.4 vs. 20.3, p=0.04) and NASS scores (8.8 vs. 15.8, p<0.01). Both groups showed significant clinical improvement compared to their preoperative levels. The BMP group attained a significantly higher rate of fusion at 6 months follow-up (88.4% vs. 76.8%, p=0.016) with no difference at 2 years. The non-BMP and BMP group had 12 (11.5%) and 9 (6.1%) complications and 5 (4.8%) and 2 (1.4%) reoperations, respectively. Conclusions The use of BMP to augment fusion in MIS-TLIF is an acceptable alternative that has potential benefits of less pain in early and intermediate postoperative follow-up. PMID:27994786

  16. Nodal failure index approach to groundwater remediation design

    USGS Publications Warehouse

    Lee, J.; Reeves, H.W.; Dowding, C.H.

    2008-01-01

    Computer simulations often are used to design and to optimize groundwater remediation systems. We present a new computationally efficient approach that calculates the reliability of remedial design at every location in a model domain with a single simulation. The estimated reliability and other model information are used to select a best remedial option for given site conditions, conceptual model, and available data. To evaluate design performance, we introduce the nodal failure index (NFI) to determine the number of nodal locations at which the probability of success is below the design requirement. The strength of the NFI approach is that selected areas of interest can be specified for analysis and the best remedial design determined for this target region. An example application of the NFI approach using a hypothetical model shows how the spatial distribution of reliability can be used for a decision support system in groundwater remediation design. ?? 2008 ASCE.

  17. Anomalous contagion and renormalization in networks with nodal mobility

    NASA Astrophysics Data System (ADS)

    Manrique, Pedro D.; Qi, Hong; Zheng, Minzhang; Xu, Chen; Hui, Pak Ming; Johnson, Neil F.

    2016-07-01

    A common occurrence in everyday human activity is where people join, leave and possibly rejoin clusters of other individuals —whether this be online (e.g. social media communities) or in real space (e.g. popular meeting places such as cafes). In the steady state, the resulting interaction network would appear static over time if the identities of the nodes are ignored. Here we show that even in this static steady-state limit, a non-zero nodal mobility leads to a diverse set of outbreak profiles that is dramatically different from known forms, and yet matches well with recent real-world social outbreaks. We show how this complication of nodal mobility can be renormalized away for a particular class of networks.

  18. Off-diagonal Jacobian support for Nodal BCs

    SciTech Connect

    Peterson, John W.; Andrs, David; Gaston, Derek R.; Permann, Cody J.; Slaughter, Andrew E.

    2015-01-01

    In this brief note, we describe the implementation of o-diagonal Jacobian computations for nodal boundary conditions in the Multiphysics Object Oriented Simulation Environment (MOOSE) [1] framework. There are presently a number of applications [2{5] based on the MOOSE framework that solve complicated physical systems of partial dierential equations whose boundary conditions are often highly nonlinear. Accurately computing the on- and o-diagonal Jacobian and preconditioner entries associated to these constraints is crucial for enabling ecient numerical solvers in these applications. Two key ingredients are required for properly specifying the Jacobian contributions of nonlinear nodal boundary conditions in MOOSE and nite element codes in general: 1. The ability to zero out entire Jacobian matrix rows after \

  19. Radial nodalization effects on BWR (boiling water reactor) stability calculations

    SciTech Connect

    March-Leuba, J.

    1990-01-01

    Computer simulations have shown that stability calculations in boiling water reactors (BWRs) are very sensitive to a number of input parameters and modeling assumptions. In particular, the number of thermohydraulic regions (i.e., channels) used in the calculation can affect the results of decay ratio calculations by as much as 30%. This paper presents the background theory behind the observed effects of radial nodalization in BWR stability calculations. The theory of how a radial power distribution can be simulated in time or frequency domain codes by using representative'' regions is developed. The approximations involved in this method of solution are reviewed, and some examples of the effect of radial nodalization are presented based on LAPUR code solutions. 2 refs., 4 figs., 2 tabs.

  20. Predicting embryonic patterning using mutual entropy fitness and in silico evolution.

    PubMed

    François, Paul; Siggia, Eric D

    2010-07-01

    During vertebrate embryogenesis, the expression of Hox genes that define anterior-posterior identity follows general rules: temporal colinearity and posterior prevalence. A mathematical measure for the quality or fitness of the embryonic pattern produced by a gene regulatory network is derived. Using this measure and in silico evolution we derive gene interaction networks for anterior-posterior (AP) patterning under two developmental paradigms. For patterning during growth (paradigm I), which is appropriate for vertebrates and short germ-band insects, the algorithm creates gene expression patterns reminiscent of Hox gene expression. The networks operate through a timer gene, the level of which measures developmental progression (a candidate is the widely conserved posterior morphogen Caudal). The timer gene provides a simple mechanism to coordinate patterning with growth rate. The timer, when expressed as a static spatial gradient, functions as a classical morphogen (paradigm II), providing a natural way to derive the AP patterning, as seen in long germ-band insects that express their Hox genes simultaneously, from the ancestral short germ-band system. Although the biochemistry of Hox regulation in higher vertebrates is complex, the actual spatiotemporal expression phenotype is not, and simple activation and repression by Hill functions suffices in our model. In silico evolution provides a quantitative demonstration that continuous positive selection can generate complex phenotypes from simple components by incremental evolution, as Darwin proposed.

  1. Nodal equivalence theory for hexagonal geometry, thermal reactor analysis

    SciTech Connect

    Zika, M.; Downar, T. )

    1992-01-01

    An important aspect of advanced nodal methods is the determination of equivalent few-group parameters for the relatively large homogenized regions used in the nodal flux solution. The theoretical foundation for light water reactor (LWR) assembly homogenization methods has been clearly established, and during the last several years, its successes have secured its position in the stable of dependable LWR analysis methods. Groupwise discontinuity factors that correct for assembly homogenization errors are routinely generated along with the group constants during lattice physics analysis. During the last several years, there has been interest in applying equivalence theory to other reactor types and other geometries. A notable effort has been the work at Argonne National Laboratory to incorporate nodal equivalence theory (NET) for hexagonal lattices into the nodal diffusion option of the DIF3D code. This work was originally intended to improve the neutronics methods used for the analysis of the Experimental Breeder Reactor II (EBR-II), and Ref. 4 discusses the success of that application. More recently, however, attempts were made to apply NET to advanced, thermal reactor designs such as the modular high-temperature gas reactor (MHTGR) and the new production heavy water reactor (NPR/HWR). The same methods that were successful for EBR-II have encountered problems for these reactors. Our preliminary analysis indicates that the sharp global flux gradients in these cores requires large discontinuity factors (greater than 4 or 5) to reproduce the reference solution. This disrupts the convergence of the iterative methods used to solve for the node-wise flux moments and partial currents. Several attempts to remedy the problem have been made over the last few years, including bounding the discontinuity factors and providing improved initial guesses for the flux solution, but nothing has been satisfactory.

  2. NODAL PATHWAY GENES ARE DOWNREGULATED IN FACIAL ASYMMETRY

    PubMed Central

    Nicot, Romain; Hottenstein, Molly; Raoul, Gwenael; Ferri, Joel; Horton, Michael; Tobias, John W.; Barton, Elisabeth; Gelé, Patrick; Sciote, James J.

    2014-01-01

    Purpose Facial asymmetry is a common comorbid condition in patients with jaw deformation malocclusion. Heritability of malocclusion is advancing rapidly, but very little is known regarding genetic contributions to asymmetry. This study identifies differences in expression of key asymmetry-producing genes which are down regulated in facial asymmetry patients. Material and Methods Masseter muscle samples were collected during BSSO orthognathic surgery to correct skeletal-based malocclusion. Patients were classified as Class II or III and open or deep bite malocclusion with or without facial asymmetry. Muscle samples were analyzed for gene expression differences on Affymetrix HT2.0 microarray global expression chips. Results Overall gene expression was different for asymmetric patients compared to other malocclusion classifications by principal component analysis (P<0.05). We identified differences in the nodal signaling pathway (NSP) which promotes development of mesoderm and endoderm and left-right patterning during embryogenesis. Nodal and Lefty expression was 1.39–1.84 fold greater (P<3.41×10−5) whereas integral membrane Nodal-modulators Nomo1,2,3 were −5.63 to −5.81 (P<3.05×10−4) less in asymmetry subjects. Fold differences among intracellular pathway members were negative in the range of −7.02 to −2.47 (P<0.003). Finally Pitx2, a upstream effector of Nodal known to influence the size of type II skeletal muscle fibers was also significantly decreased in facial asymmetry (P<0.05). Conclusions When facial asymmetry is part of skeletal malocclusion there are decreases of NSP genes in masseter muscle. This data suggests that the NSP is down regulated to help promote development of asymmetry. Pitx2 expression differences also contributed to both skeletal and muscle development in this condition. PMID:25364968

  3. The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells

    SciTech Connect

    Simian, Marina; Hirai, Yohei; Navre, Marc; Werb, Zena; Lochter, Andre; Bissell, Mina J.

    2002-03-06

    The mammary gland develops its adult form by a process referred to as branching morphogenesis. Many factors have been reported to affect this process. We have used cultured primary mammary epithelial organoids and mammary epithelial cell lines in three-dimensional collagen gels to elucidate which growth factors, matrix metalloproteinases (MMPs) and mammary morphogens interact in branching morphogenesis. Branching stimulated by stromal fibroblasts, epidermal growth factor, fibroblast growth factor 7, fibroblast growth factor 2 and hepatocyte growth factor was strongly reduced by inhibitors of MMPs, indicating the requirement of MMPs for three-dimensional growth involved in morphogenesis. Recombinant stromelysin 1/MMP-3 alone was sufficient to drive branching in the absence of growth factors in the organoids. Plasmin also stimulated branching; however, plasmin-dependent branching was abolished by both inhibitors of plasmin and MMPs, suggesting that plasmin activates MMPs. To differentiate between signals for proliferation and morphogenesis, we used a cloned mammary epithelial cell line that lacks epimorphin, an essential mammary morphogen. Both epimorphin and MMPs were required for morphogenesis, but neither was required for epithelial cell proliferation. These results provide direct evidence for a critical role of MMPs in branching in mammary epithelium and suggest that, in addition to epimorphin, MMP activity is a minimum requirement for branching morphogenesis in the mammary gland.

  4. Embryonal cancers in Europe.

    PubMed

    Gatta, Gemma; Ferrari, Andrea; Stiller, Charles A; Pastore, Guido; Bisogno, Gianni; Trama, Annalisa; Capocaccia, Riccardo

    2012-07-01

    Embryonal cancers are a heterogeneous group of rare cancers which mainly occur in children and adolescents. The aim of the present study was to estimate the burden (incidence, prevalence, survival and proportion of cured) for the principal embryonal cancers in Europe (EU27), using population-based data from cancer registries (CRs) participating in RARECARE. We identified 3322 cases diagnosed from 1995 to 2002 (latest period for which data are available): 44% neuroblastoma, 35% nephroblastoma, 13% retinoblastoma and 6% hepatoblastoma. Very few cases of pulmonary blastoma (43 cases) and pancreatoblastoma (seven cases) were diagnosed. About 2000 new embryonal cancers were estimated every year in EU27, for an annual incidence rate of 4 per million (1.8 neuroblastoma, 1.4 nephroblastoma, and 0.5 retinoblastoma); 91% of cases occurred in patients under 15 years. Five-year relative survival for all embryonal cancers was 80% (99% retinoblastoma, 90% nephroblastoma, 71% hepatoblastoma and 68% neuroblastoma). Overall survival was lower in adolescents and adults than in those under 15 years. The cure rate was estimated at 80%. Slightly less than 40,000 persons were estimated alive in EU27 with a diagnosis of embryonal cancer in 2008. Nephroblastoma was the most prevalent (18,150 cases in EU27), followed by neuroblastoma (12,100), retinoblastoma (5200), hepatoblastoma (2700) and pulmonary blastoma (614). This is the first study to delineate the embryonal cancer burden in Europe by age, sex and European region. Survival/cure rate is generally high, but there are considerable gaps in our understanding of the natural histories of these rare diseases particularly in adults.

  5. Nodal Dependent Differential Localisation of Dishevelled-2 Demarcates Regions of Differing Cell Behaviour in the Visceral Endoderm

    PubMed Central

    Trichas, Georgios; Wilkins, Vivienne; Clements, Melanie; Tada, Masazumi; Rodriguez, Tristan A.; Srinivas, Shankar

    2011-01-01

    The anterior visceral endoderm (AVE), a signalling centre within the simple epithelium of the visceral endoderm (VE), is required for anterior-posterior axis specification in the mouse embryo. AVE cells migrate directionally within the VE, thereby properly positioning the future anterior of the embryo and orientating the primary body axis. AVE cells consistently come to an abrupt stop at the border between the anterior epiblast and extra-embryonic ectoderm, which represents an end-point to their proximal migration. Little is known about the underlying basis for this barrier and how surrounding cells in the VE respond to or influence AVE migration. We use high-resolution 3D reconstructions of protein localisation patterns and time-lapse microscopy to show that AVE cells move by exchanging neighbours within an intact epithelium. Cell movement and mixing is restricted to the VE overlying the epiblast, characterised by the enrichment of Dishevelled-2 (Dvl2) to the lateral plasma membrane, a hallmark of Planar Cell Polarity (PCP) signalling. AVE cells halt upon reaching the adjoining region of VE overlying the extra-embryonic ectoderm, which displays reduced neighbour exchange and in which Dvl2 is excluded specifically from the plasma membrane. Though a single continuous sheet, these two regions of VE show distinct patterns of F-actin localisation, in cortical rings and an apical shroud, respectively. We genetically perturb PCP signalling and show that this disrupts the localisation pattern of Dvl2 and F-actin and the normal migration of AVE cells. In Nodal null embryos, membrane localisation of Dvl2 is reduced, while in mutants for the Nodal inhibitor Lefty1, Dvl2 is ectopically membrane localised, establishing a role for Nodal in modulating PCP signalling. These results show that the limits of AVE migration are determined by regional differences in cell behaviour and protein localisation within an otherwise apparently uniform VE. In addition to coordinating global

  6. Topological phase transitions in line-nodal superconductors

    NASA Astrophysics Data System (ADS)

    Han, SangEun; Cho, Gil Young; Moon, Eun-Gook

    2017-03-01

    Fathoming interplay between symmetry and topology of many-electron wave functions has deepened our understanding of quantum many-body systems, particularly after the discovery of topological insulators. Topology of electron wave functions often enforces and protects emergent gapless excitation, and symmetry is intrinsically tied to the topological protection of the excitations. Namely, unless the symmetry is broken, the topological nature of the excitations is intact. We show intriguing phenomena of interplay between symmetry and topology in three-dimensional topological phase transitions associated with line-nodal superconductors. More specifically, we discover an exotic universality class out of topological line-nodal superconductors. The order parameter of broken symmetries is strongly correlated with underlying line-nodal fermions, and this gives rise to a large anomalous dimension in sharp contrast to that of the Landau-Ginzburg theory. Remarkably, hyperscaling violation and emergent relativistic scaling appear in spite of the presence of nonrelativistic fermionic excitation. We also propose characteristic experimental signatures around the phase transitions, for example, a linear phase boundary in a temperature-tuning parameter phase diagram, and discuss the implication of recent experiments in pnictides and heavy-fermion systems.

  7. Anomalous scaling of the penetration depth in nodal superconductors

    NASA Astrophysics Data System (ADS)

    She, Jian-Huang; Lawler, Michael J.; Kim, Eun-Ah

    2015-07-01

    Recent findings of anomalous superlinear scaling of low-temperature (T ) penetration depth (PD) in several nodal superconductors near putative quantum critical points suggest that the low-temperature PD can be a useful probe of quantum critical fluctuations in a superconductor. On the other hand, cuprates, which are poster child nodal superconductors, have not shown any such anomalous scaling of PD, despite growing evidence of quantum critical points (QCP). Then it is natural to ask when and how can quantum critical fluctuations cause anomalous scaling of PD? Carrying out the renormalization group calculation for the problem of two-dimensional superconductors with point nodes, we show that quantum critical fluctuations associated with a point group symmetry reduction result in nonuniversal logarithmic corrections to the T dependence of the PD. The resulting apparent power law depends on the bare velocity anisotropy ratio. We then compare our results to data sets from two distinct nodal superconductors: YBa2Cu3O6.95 and CeCoIn5. Considering all symmetry-lowering possibilities of the point group of interest, C4 v, we find our results to be remarkably consistent with YBa2Cu3O6.95 being near a vertical nematic QCP and CeCoIn5 being near a diagonal nematic QCP. Our results motivate a search for diagonal nematic fluctuations in CeCoIn5.

  8. A nodal domain theorem for integrable billiards in two dimensions

    SciTech Connect

    Samajdar, Rhine; Jain, Sudhir R.

    2014-12-15

    Eigenfunctions of integrable planar billiards are studied — in particular, the number of nodal domains, ν of the eigenfunctions with Dirichlet boundary conditions are considered. The billiards for which the time-independent Schrödinger equation (Helmholtz equation) is separable admit trivial expressions for the number of domains. Here, we discover that for all separable and non-separable integrable billiards, ν satisfies certain difference equations. This has been possible because the eigenfunctions can be classified in families labelled by the same value of mmodkn, given a particular k, for a set of quantum numbers, m,n. Further, we observe that the patterns in a family are similar and the algebraic representation of the geometrical nodal patterns is found. Instances of this representation are explained in detail to understand the beauty of the patterns. This paper therefore presents a mathematical connection between integrable systems and difference equations. - Highlights: • We find that the number of nodal domains of eigenfunctions of integrable, planar billiards satisfy a class of difference equations. • The eigenfunctions labelled by quantum numbers (m,n) can be classified in terms of mmodkn. • A theorem is presented, realising algebraic representations of geometrical patterns exhibited by the domains. • This work presents a connection between integrable systems and difference equations.

  9. Histogenesis of metaplastic breast carcinoma and axillary nodal metastases.

    PubMed

    Osako, Tomo; Horii, Rie; Ogiya, Akiko; Iijima, Kotaro; Iwase, Takuji; Akiyama, Futoshi

    2009-02-01

    A 40-year-old breast-feeding woman presented with left breast swelling. On physical examination a 7 cm mass was found in the breast. Because biopsy demonstrated malignant tissue, mastectomy with axillary nodal dissection was performed. Pathological findings were consistent with metaplastic breast carcinoma with nodal metastases. The primary tumor consisted of three types of invasion: ductal, squamous, and sarcomatous. Furthermore, three morphological transitions were observed: ductal-squamous, ductal-sarcomatous, and squamous-sarcomatous. Ductal-squamous (12/18 microscopy slides) and squamous-sarcomatous transitions (10/18) were more commonly observed than ductal-sarcomatous transition (3/18). Furthermore, immunohistochemistry showed loss of epithelial marker (cytokeratin) and acquisition of mesenchymal markers (vimentin and alpha-smooth muscle actin) in the sarcomatous component. These findings suggested that epithelial-mesenchymal transition had occurred in the tumor and that two pathways, ductal-squamous-sarcomatous and ductal-sarcomatous transition, were involved in progression of metaplastic breast carcinoma. The main pathway appeared to be ductal-squamous-sarcomatous transition. Regarding the nodal metastases, of 13 positive nodes, ductal, squamous, and sarcomatous components were observed in 13, seven, and two nodes, respectively. Moreover, as in the primary tumor, ductal-squamous and squamous-sarcomatous transitions were observed. This suggested that the ductal component metastasized to the nodes and that epithelial-mesenchymal transition subsequently occurred within the nodes.

  10. Topological Phase Transitions in Line-nodal Superconductors

    NASA Astrophysics Data System (ADS)

    Cho, Gil Young; Han, Sangeun; Moon, Eun-Gook

    Fathoming interplay between symmetry and topology of many-electron wave-functions deepens our understanding in quantum nature of many particle systems. Topology often protects zero-energy excitation, and in a certain class, symmetry is intrinsically tied to the topological protection. Namely, unless symmetry is broken, topological nature is intact. We study one specific case of such class, symmetry-protected line-nodal superconductors in three spatial dimensions (3d). Mismatch between phase spaces of order parameter fluctuation and line-nodal fermion excitation induces an exotic universality class in a drastic contrast to one of the conventional ϕ4 theory in 3d. Hyper-scaling violation and relativistic dynamic scaling with unusually large quantum critical region are main characteristics, and their implication in experiments is discussed. For example, continuous phase transition out of line-nodal superconductors has a linear phase boundary in a temperature-tuning parameter phase-diagram. This work was supported by the Brain Korea 21 PLUS Project of Korea Government and KAIST start-up funding.

  11. Complete Meiosis from Embryonic Stem Cell-Derived Germ Cells In Vitro.

    PubMed

    Zhou, Quan; Wang, Mei; Yuan, Yan; Wang, Xuepeng; Fu, Rui; Wan, Haifeng; Xie, Mingming; Liu, Mingxi; Guo, Xuejiang; Zheng, Ying; Feng, Guihai; Shi, Qinghua; Zhao, Xiao-Yang; Sha, Jiahao; Zhou, Qi

    2016-03-03

    In vitro generation of functional gametes is a promising approach for treating infertility, although faithful replication of meiosis has proven to be a substantial obstacle to deriving haploid gamete cells in culture. Here we report complete in vitro meiosis from embryonic stem cell (ESC)-derived primordial germ cells (PGCLCs). Co-culture of PGCLCs with neonatal testicular somatic cells and sequential exposure to morphogens and sex hormones reproduced key hallmarks of meiosis, including erasure of genetic imprinting, chromosomal synapsis and recombination, and correct nuclear DNA and chromosomal content in the resulting haploid cells. Intracytoplasmic injection of the resulting spermatid-like cells into oocytes produced viable and fertile offspring, showing that this robust stepwise approach can functionally recapitulate male gametogenesis in vitro. These findings provide a platform for investigating meiotic mechanisms and the potential generation of human haploid spermatids in vitro.

  12. Critical Timing without a Timer for Embryonic Development

    PubMed Central

    Tufcea, Daniel E.; François, Paul

    2015-01-01

    Timing of embryonic development is precisely controlled, but the mechanisms underlying biological timers are still unclear. Here, a validated model for timing under control of Sonic Hedgehog is revisited and generalized to an arbitrary number of genes. The developmental dynamics where a temporal sequence of gene expression recapitulates a steady-state spatial pattern can be realized through a simple network close to criticality, controlled by the duration of exposure to a morphogen. Criticality simultaneously accounts for many observed biological properties, such as timing, multistability, and canalization of genetic expression. This process can be parsimoniously generalized in many dimensions with a minimum number of genes, all repressing each other with asymmetrical strengths, which also explains sequential activation of different fates. Separation of timescales allows for a simple analytical interpretation. Finally, it is shown that even in the presence of noise, coupling between cells preserves criticality and robust patterning. The model offers a simple theoretical framework for the study of emergent developmental timers. PMID:26488664

  13. Cadherins in cerebellar development: translation of embryonic patterning into mature functional compartmentalization.

    PubMed

    Redies, Christoph; Neudert, Franziska; Lin, Juntang

    2011-09-01

    Cadherins are cell adhesion molecules with multiple morphogenic functions in brain development, for example, in neuroblast migration and aggregation, axon navigation, neural circuit formation, and synaptogenesis. More than 100 members of the cadherin superfamily are expressed in the developing and mature brain. Most of the cadherins investigated, in particular classic cadherins and δ-protocadherins, are expressed in the cerebellum. For several cadherin subtypes, expression begins at early embryonic stages and persists until mature stages of cerebellar development. At intermediate stages, distinct Purkinje cell clusters exhibit unique rostrocaudal and mediolateral expression profiles for each cadherin. In the chicken, mouse, and other species, the Purkinje cell clusters are separated by intervening raphes of migrating granule cells. This pattern of Purkinje cell clusters/raphes is, at least in part, continuous with the parasagittal striping pattern that is apparent in the mature cerebellar cortex, for example, for zebrin II/aldolase C. Moreover, subregions of the deep cerebellar nuclei, vestibular nuclei and the olivary complex also express cadherins differentially. Neuroanatomical evidence suggests that the nuclear subregions and cortical domains that express the same cadherin subtype are connected to each other, to form neural subcircuits of the cerebellar system. Cadherins thus provide a molecular code that specifies not only embryonic structures but also functional cerebellar compartmentalization. By following the implementation of this code, it can be revealed how mature functional architecture emerges from embryonic patterning during cerebellar development. Dysfunction of some cadherins is associated with psychiatric diseases and developmental impairments and may also affect cerebellar function.

  14. Organoids and the genetically encoded self‐assembly of embryonic stem cells

    PubMed Central

    Baillie‐Johnson, Peter

    2015-01-01

    Understanding the mechanisms of early embryonic patterning and the timely allocation of specific cells to embryonic regions and fates as well as their development into tissues and organs, is a fundamental problem in Developmental Biology. The classical explanation for this process had been built around the notion of positional information. Accordingly the programmed appearance of sources of Morphogens at localized positions within a field of cells directs their differentiation. Recently, the development of organs and tissues from unpatterned and initially identical stem cells (adult and embryonic) has challenged the need for positional information and even the integrity of the embryo, for pattern formation. Here we review the emerging area of organoid biology from the perspective of Developmental Biology. We argue that the events underlying the development of these systems are not purely linked to “self‐organization,” as often suggested, but rather to a process of genetically encoded self‐assembly where genetic programs encode and control the emergence of biological structures. PMID:26666846

  15. Topological Dirac nodal lines and surface charges in fcc alkaline earth metals.

    PubMed

    Hirayama, Motoaki; Okugawa, Ryo; Miyake, Takashi; Murakami, Shuichi

    2017-01-11

    In nodal-line semimetals, the gaps close along loops in k space, which are not at high-symmetry points. Typical mechanisms for the emergence of nodal lines involve mirror symmetry and the π Berry phase. Here we show via ab initio calculations that fcc calcium (Ca), strontium (Sr) and ytterbium (Yb) have topological nodal lines with the π Berry phase near the Fermi level, when spin-orbit interaction is neglected. In particular, Ca becomes a nodal-line semimetal at high pressure. Owing to nodal lines, the Zak phase becomes either π or 0, depending on the wavevector k, and the π Zak phase leads to surface polarization charge. Carriers eventually screen it, leaving behind large surface dipoles. In materials with nodal lines, both the large surface polarization charge and the emergent drumhead surface states enhance Rashba splitting when heavy adatoms are present, as we have shown to occur in Bi/Sr(111) and in Bi/Ag(111).

  16. Topological Dirac nodal lines and surface charges in fcc alkaline earth metals

    NASA Astrophysics Data System (ADS)

    Hirayama, Motoaki; Okugawa, Ryo; Miyake, Takashi; Murakami, Shuichi

    2017-01-01

    In nodal-line semimetals, the gaps close along loops in k space, which are not at high-symmetry points. Typical mechanisms for the emergence of nodal lines involve mirror symmetry and the π Berry phase. Here we show via ab initio calculations that fcc calcium (Ca), strontium (Sr) and ytterbium (Yb) have topological nodal lines with the π Berry phase near the Fermi level, when spin-orbit interaction is neglected. In particular, Ca becomes a nodal-line semimetal at high pressure. Owing to nodal lines, the Zak phase becomes either π or 0, depending on the wavevector k, and the π Zak phase leads to surface polarization charge. Carriers eventually screen it, leaving behind large surface dipoles. In materials with nodal lines, both the large surface polarization charge and the emergent drumhead surface states enhance Rashba splitting when heavy adatoms are present, as we have shown to occur in Bi/Sr(111) and in Bi/Ag(111).

  17. Topological nodal line semimetals with and without spin-orbital coupling

    NASA Astrophysics Data System (ADS)

    Fang, Chen; Chen, Yige; Kee, Hae-Young; Fu, Liang

    2015-08-01

    We theoretically study three-dimensional topological semimetals (TSMs) with nodal lines protected by crystalline symmetries. Compared to TSMs with point nodes, e.g., Weyl semimetals and Dirac semimetals, where the conduction and the valence bands touch at discrete points, in these TSMs the two bands cross at closed lines in the Brillouin zone. We propose two different classes of symmetry protected nodal lines in the absence and in the presence of spin-orbital coupling (SOC), respectively. In the former, we discuss nodal lines that are protected by a combination of inversion symmetry and time-reversal symmetry, yet, unlike previously studied nodal lines in the same symmetry class, each nodal line has a Z2 monopole charge and can only be created (annihilated) in pairs. In the second class, with SOC, we show that a nonsymmorphic symmetry (screw axis) protects a four-band crossing nodal line in systems having both inversion and time-reversal symmetries.

  18. A Nodal-independent and tissue-intrinsic mechanism controls heart-looping chirality

    NASA Astrophysics Data System (ADS)

    Noël, Emily S.; Verhoeven, Manon; Lagendijk, Anne Karine; Tessadori, Federico; Smith, Kelly; Choorapoikayil, Suma; den Hertog, Jeroen; Bakkers, Jeroen

    2013-11-01

    Breaking left-right symmetry in bilateria is a major event during embryo development that is required for asymmetric organ position, directional organ looping and lateralized organ function in the adult. Asymmetric expression of Nodal-related genes is hypothesized to be the driving force behind regulation of organ laterality. Here we identify a Nodal-independent mechanism that drives asymmetric heart looping in zebrafish embryos. In a unique mutant defective for the Nodal-related southpaw gene, preferential dextral looping in the heart is maintained, whereas gut and brain asymmetries are randomized. As genetic and pharmacological inhibition of Nodal signalling does not abolish heart asymmetry, a yet undiscovered mechanism controls heart chirality. This mechanism is tissue intrinsic, as explanted hearts maintain ex vivo retain chiral looping behaviour and require actin polymerization and myosin II activity. We find that Nodal signalling regulates actin gene expression, supporting a model in which Nodal signalling amplifies this tissue-intrinsic mechanism of heart looping.

  19. The "bone morphogenic proteins" pathways in bone and joint diseases: translational perspectives from physiopathology to therapeutic targets.

    PubMed

    Biver, Emmanuel; Hardouin, Pierre; Caverzasio, Joseph

    2013-02-01

    A large body of evidence supports an important role of bone morphogenic proteins (BMPs) pathways in skeletal development in the embryo. BMPs are also involved in skeletal homeostasis and diseases in the adult. They were first identified as major bone anabolic agents and recent advances indicate that they also regulate osteoclastogenesis and joint components via multiple cross-talks with other signaling pathways. This review attempts to integrate these data in the pathogenesis of bone and joints diseases, such as osteoporosis, fracture healing, osteoarthritis, inflammatory arthritis, or bone metastasis. The use of recombinant BMPs in bone tissue engineering and in the treatment of skeletal diseases, or future therapeutic strategies targeting BMPs signal and its regulators, will be discussed based on these considerations.

  20. Approximate Schur complement preconditioning of the lowest order nodal discretizations

    SciTech Connect

    Moulton, J.D.; Ascher, U.M.; Morel, J.E.

    1996-12-31

    Particular classes of nodal methods and mixed hybrid finite element methods lead to equivalent, robust and accurate discretizations of 2nd order elliptic PDEs. However, widespread popularity of these discretizations has been hindered by the awkward linear systems which result. The present work exploits this awkwardness, which provides a natural partitioning of the linear system, by defining two optimal preconditioners based on approximate Schur complements. Central to the optimal performance of these preconditioners is their sparsity structure which is compatible with Dendy`s black box multigrid code.

  1. Topological insulating phases from two-dimensional nodal loop semimetals

    NASA Astrophysics Data System (ADS)

    Li, Linhu; Araújo, Miguel A. N.

    2016-10-01

    Starting from a minimal model for a two-dimensional nodal loop semimetal, we study the effect of chiral mass gap terms. The resulting Dirac loop anomalous Hall insulator's Chern number is the phase-winding number of the mass gap terms on the loop. We provide simple lattice models, analyze the topological phases, and generalize a previous index characterizing topological transitions. The responses of the Dirac loop anomalous Hall and quantum spin Hall insulators to a magnetic field's vector potential are also studied both in weak- and strong-field regimes, as well as the edge states in a ribbon geometry.

  2. Gravity and embryonic development

    NASA Technical Reports Server (NTRS)

    Young, R. S.

    1976-01-01

    The relationship between the developing embryo (both plant and animal) and a gravitational field has long been contemplated. The difficulty in designing critical experiments on the surface of the earth because of its background of 1 g, has been an obstacle to a resolution of the problem. Biological responses to gravity (particularly in plants) are obvious in many cases; however, the influence of gravity as an environmental input to the developing embryo is not as obvious and has proven to be extremely difficult to define. In spite of this, over the years numerous attempts have been made using a variety of embryonic materials to come to grips with the role of gravity in development. Three research tools are available: the centrifuge, the clinostat, and the orbiting spacecraft. Experimental results are now available from all three sources. Some tenuous conclusions are drawn, and an attempt at a unifying theory of gravitational influence on embryonic development is made.

  3. Radiotherapy studies and extra-nodal non-Hodgkin lymphomas, progress and challenges.

    PubMed

    Specht, L

    2012-06-01

    Extra-nodal lymphomas may arise in any organ, and different histological subtypes occur in distinct patterns. Prognosis and treatment depend not only on the histological subtype and disease extent, but also on the particular involved extra-nodal organ. The clinical course and response to treatment for the more common extra-nodal organs, e.g. stomach, Waldeyer's ring, skin and brain, are fairly well known and show significant variation. A few randomised trials have been carried out testing the role of radiotherapy in these lymphomas. However, for most extra-nodal lymphomas, randomised trials have not been carried out, and treatment decisions are made on small patient series and extrapolations from nodal lymphomas. Hopefully, wide international collaboration will make controlled clinical trials possible in the less common extra-nodal lymphomas. Modern highly conformal radiotherapy allows better coverage of extra-nodal lymphomatous involvement with better sparing of normal tissues. The necessary radiation doses and volumes need to be defined for the different extra-nodal lymphoma entities. The challenge is to optimise the use of radiotherapy in the modern multimodality treatment of extra-nodal lymphomas.

  4. Magnon nodal-line semimetals and drumhead surface states in anisotropic pyrochlore ferromagnets

    NASA Astrophysics Data System (ADS)

    Mook, Alexander; Henk, Jürgen; Mertig, Ingrid

    2017-01-01

    We introduce a type of topological magnon matter: the magnonic pendant to electronic nodal-line semimetals. Magnon spectra of anisotropic pyrochlore ferromagnets feature twofold degeneracies of magnon bands along a closed loop in reciprocal space. These magnon nodal lines are topologically protected by the coexistence of inversion and time-reversal symmetry; they require the absence of spin-orbit interaction (no Dzyaloshinskii-Moriya interaction). We calculate the topological invariants of the nodal lines and show that details of the associated magnon drumhead surface states depend strongly on the termination of the surface. Magnon nodal-line semimetals complete the family of topological magnons in three-dimensional ferromagnetic materials.

  5. Nodal line optimization and its application to violin top plate design

    NASA Astrophysics Data System (ADS)

    Yu, Yonggyun; Jang, In Gwun; Kim, In Kyum; Kwak, Byung Man

    2010-10-01

    In the literature, most problems of structural vibration have been formulated to adjust a specific natural frequency: for example, to maximize the first natural frequency. In musical instruments like a violin; however, mode shapes are equally important because they are related to sound quality in the way that natural frequencies are related to the octave. The shapes of nodal lines, which represent the natural mode shapes, are generally known to have a unique feature for good violins. Among the few studies on mode shape optimization, one typical study addresses the optimization of nodal point location for reducing vibration in a one-dimensional beam structure. However, nodal line optimization, which is required in violin plate design, has not yet been considered. In this paper, the central idea of controlling the shape of the nodal lines is proposed and then applied to violin top plate design. Finite element model for a violin top plate was constructed using shell elements. Then, optimization was performed to minimize the square sum of the displacement of selected nodes located along the target nodal lines by varying the thicknesses of the top plate. We conducted nodal line optimization for the second and the fifth modes together at the same time, and the results showed that the nodal lines obtained match well with the target nodal lines. The information on plate thickness distribution from nodal line optimization would be valuable for tailored trimming of a violin top plate for the given performances.

  6. Evaluation of the use of nodal methods for MTR neutronic analysis

    SciTech Connect

    Reitsma, F.; Mueller, E.Z.

    1997-08-01

    Although modern nodal methods are used extensively in the nuclear power industry, their use for research reactor analysis has been very limited. The suitability of nodal methods for material testing reactor analysis is investigated with the emphasis on the modelling of the core region (fuel assemblies). The nodal approach`s performance is compared with that of the traditional finite-difference fine mesh approach. The advantages of using nodal methods coupled with integrated cross section generation systems are highlighted, especially with respect to data preparation, simplicity of use and the possibility of performing a great variety of reactor calculations subject to strict time limitations such as are required for the RERTR program.

  7. Pseudospin Vortex Ring with a Nodal Line in Three Dimensions

    NASA Astrophysics Data System (ADS)

    Lim, Lih-King; Moessner, Roderich

    2017-01-01

    We present a model of a topological semimetal in three dimensions whose energy spectrum exhibits a nodal line acting as a vortex ring; this in turn is linked by a pseudospin structure akin to that of a smoke ring. Contrary to a Weyl point node spectrum, the vortex ring gives rise to Skyrmionic pseudospin patterns in cuts on both sides of the nodal ring plane; this pattern covers the full Brillouin zone, thus leading to a fully extended chiral Fermi arc and a new, "maximal," anomalous Hall effect in a 3D semimetal. Tuning a model parameter shrinks the vortex ring until it vanishes, giving way to a pair of Weyl nodes of opposite chirality. This establishes a connection between two distinct momentum-space topologies—that of a vortex ring (a circle of singularity) and a monopole-antimonopole pair (two point singularities). We present the model both as a low-energy continuum and a two-band tight-binding lattice model. Its simplicity permits an analytical computation of its Landau level spectrum.

  8. Amyloid precursor protein at node of Ranvier modulates nodal formation

    PubMed Central

    Xu, De-En; Zhang, Wen-Min; Yang, Zara Zhuyun; Zhu, Hong-Mei; Yan, Ke; Li, Shao; Bagnard, Dominique; Dawe, Gavin S; Ma, Quan-Hong; Xiao, Zhi-Cheng

    2014-01-01

    Amyloid precursor protein (APP), commonly associated with Alzheimer disease, is upregulated and distributes evenly along the injured axons, and therefore, also known as a marker of demyelinating axonal injury and axonal degeneration. However, the physiological distribution and function of APP along myelinated axons was unknown. We report that APP aggregates at nodes of Ranvier (NOR) in the myelinated central nervous system (CNS) axons but not in the peripheral nervous system (PNS). At CNS NORs, APP expression co-localizes with tenascin-R and is flanked by juxtaparanodal potassium channel expression demonstrating that APP localized to NOR. In APP-knockout (KO) mice, nodal length is significantly increased, while sodium channels are still clustered at NORs. Moreover, APP KO and APP-overexpressing transgenic (APP TG) mice exhibited a decreased and an increased thickness of myelin in spinal cords, respectively, although the changes are limited in comparison to their littermate WT mice. The thickness of myelin in APP KO sciatic nerve also increased in comparison to that in WT mice. Our observations indicate that APP acts as a novel component at CNS NORs, modulating nodal formation and has minor effects in promoting myelination. PMID:25482638

  9. Nodal Diffusion Burnable Poison Treatment for Prismatic Reactor Cores

    SciTech Connect

    A. M. Ougouag; R. M. Ferrer

    2010-10-01

    The prismatic block version of the High Temperature Reactor (HTR) considered as a candidate Very High Temperature Reactor (VHTR)design may use burnable poison pins in locations at some corners of the fuel blocks (i.e., assembly equivalent structures). The presence of any highly absorbing materials, such as these burnable poisons, within fuel blocks for hexagonal geometry, graphite-moderated High Temperature Reactors (HTRs) causes a local inter-block flux depression that most nodal diffusion-based method have failed to properly model or otherwise represent. The location of these burnable poisons near vertices results in an asymmetry in the morphology of the assemblies (or blocks). Hence the resulting inadequacy of traditional homogenization methods, as these “spread” the actually local effect of the burnable poisons throughout the assembly. Furthermore, the actual effect of the burnable poison is primarily local with influence in its immediate vicinity, which happens to include a small region within the same assembly as well as similar regions in the adjacent assemblies. Traditional homogenization methods miss this artifact entirely. This paper presents a novel method for treating the local effect of the burnable poison explicitly in the context of a modern nodal method.

  10. [Teratogenesis and gene targets of 17alpha-ethynylestradiol on embryonic development in zebrafish].

    PubMed

    Tong, Jun-Wei; Zhang, Jing-Pu; Meng, Jie

    2011-01-01

    The pharmaceutical ethynylestradiol (EE) is a potent endocrine modulator. Application enlargement of ethynylestradiol in clinics and abuse in livestock farming and fishing make it important to explore ethynylestradiol toxicological action on vertebrate embryonic development and to establish an in vivo method for EE toxicity detection efficiently and conveniently. In the present study, using a model animal zebrafish and 17alpha-ethynylestradiol as a representative compound, we have investigated EE2 teratogenicity, target tissues and target genes on zebrafish embryo. The results show that median teratogenesis concentration (TC50) of EE2 is 0.8 microg x mL(-1), and median lethal dose (LD50) is 3.3 microg x mL(-1). Targets of EE2 action were implicated in brain, eyes, heart, muscle, skeleton, pigment and viscera. Embryonic cardiac arrhythmia caused by EE2 is probably resulted from heart abnormal structure. The embryonic stage sensitive to EE2 mainly started at cleavage and last up to the organogenesis with time-accumulating effect. RT-PCR results indicate that EE2 treatment disturbed gene expression pattern at the early period of zebrafish embryonic development by suppressing transcription of gene boz that promotes brain development, upregulating genes for trunk and tail, such as ntl, spt, shh, and perturbing Nodal signal expression of TGFbeta superfamily, for example, cyc, sqt and oep. Using zebrafish, an efficient in vivo method for quick evaluation of EE toxicity on embryonic development has been developed.

  11. Prevention of AV Nodal Reentry Tachycardia by Oral Amiodarone: An Alternative Mechanism of Action

    PubMed Central

    Gold, Robert L.; Haffajee, Charles I.; Entes, Kenneth L.

    1987-01-01

    A 73-year-old man was noted to have atrioventricular (AV) nodal reentry tachycardia, which was induced during programmed electrical stimulation. After 1 month of oral amiodarone therapy, AV nodal reentry tachycardia was prevented by the prolongation of atrial refractoriness and not by direct action on the AV node itself. (Texas Heart Institute Journal 1987; 14:99-101) PMID:15227337

  12. 47 CFR 101.503 - Digital Electronic Message Service Nodal Stations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES 24 GHz Service and Digital Electronic Message Service § 101.503 Digital Electronic Message Service Nodal Stations. 10.6 GHz DEMS Nodal Stations may be... 47 Telecommunication 5 2014-10-01 2014-10-01 false Digital Electronic Message Service...

  13. 47 CFR 101.503 - Digital Electronic Message Service Nodal Stations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES 24 GHz Service and Digital Electronic Message Service § 101.503 Digital Electronic Message Service Nodal Stations. 10.6 GHz DEMS Nodal Stations may be... 47 Telecommunication 5 2012-10-01 2012-10-01 false Digital Electronic Message Service...

  14. 47 CFR 101.503 - Digital Electronic Message Service Nodal Stations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES 24 GHz Service and Digital Electronic Message Service § 101.503 Digital Electronic Message Service Nodal Stations. 10.6 GHz DEMS Nodal Stations may be... 47 Telecommunication 5 2013-10-01 2013-10-01 false Digital Electronic Message Service...

  15. 47 CFR 101.503 - Digital Electronic Message Service Nodal Stations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES 24 GHz Service and Digital Electronic Message Service § 101.503 Digital Electronic Message Service Nodal Stations. 10.6 GHz DEMS Nodal Stations may be... 47 Telecommunication 5 2011-10-01 2011-10-01 false Digital Electronic Message Service...

  16. Prognostic value of whole-body SUVmax of nodal and extra-nodal lesions detected by 18F-FDG PET/CT in extra-nodal NK/T-cell lymphoma

    PubMed Central

    Gale, Robert Peter; Wang, Li; Xu, Ji; Qu, Xiao-Yan; Fan, Lei; Li, Tian-Lv; Li, Jian-Yong; Xu, Wei

    2017-01-01

    We analyzed data from 54 newly-diagnosed persons with extra-nodal natural killer/T-cell (NK/T) lymphoma, who had a pretreatment 18F-FDG PET/CT study, to determine whether the sum of SUVmax of all the nodal and extra-nodal lesions predicted progression-free survival (PFS) and/or overall survival (OS). Three models (WB1SUVmax, WB2SUVmax, WB3SUVmax) based on the basis of the sum of SUVmax of the whole-body SUVmax of 11 nodal and 10 extra-nodal lesions were tested. The discrimination value of these models was evaluated using time-dependent receiver-operator characteristic (ROC) curves and corresponding areas under the curve (AUC) in training and validation cohorts. Findings were validated in an independent cohort of 15 subjects. ROC curve analysis showed the optimal cut-off values for WB1SUVmax, WB2SUVmax and WB3SUVmax were 15.8 (sensitivity 92%, specificity 67%, AUC 0.811; P<0.001), 12.7 (sensitivity 96%; specificity 57%; AUC 0.785; P<0.001) and 15.8 (sensitivity 88%; specificity 70%; AUC 0.793; P<0.001). Multivariate analyses indicated WB3SUVmax was independently associated with PFS (hazard ratio [HR]=3.67, 95% confidence interval [95% CI]=1.19, 11.29; P=0.023) and OS (HR= 4.51 [1.02, 19.91]; P=0.047). WB3SUVmax calculated based of the sum of the SUVmax of 3 nodal and 10 extra-nodal lesions was significantly associated with PFS and OS. PMID:27974685

  17. Augmented weighted diamond form of the linear nodal scheme for Cartesian coordinate systems

    SciTech Connect

    Walters, W.F.

    1985-01-01

    The equations of the high order linear nodal numerical scheme are cast in an augmented weighted difference form for three-dimensional Cartesian nodes. The coupling exhibited by these equations indicate that this new algorithm is simpler and hence faster than previous nodal schemes of this degree of accuracy. A well-logging problem and a fast reactor problem are examined. The new scheme developed here is compared with the classical linear-linear nodal scheme and the diamond difference scheme. For the well-logging problem, it is found that the new scheme is both faster and simpler than the classical linear-linear nodal scheme while sacrificing little in accuracy. Even though the new scheme is more accurate than the diamond difference scheme for the reactor problem, the results indicate that state of the art acceleration methods are needed for nodal schemes.

  18. Magnetic susceptibility in three-dimensional nodal semimetals

    NASA Astrophysics Data System (ADS)

    Koshino, Mikito; Hizbullah, Intan Fatimah

    2016-01-01

    We study the magnetic susceptibility in various three-dimensional gapless systems, including Dirac and Weyl semimetals, and a line-node semimetal. The susceptibility is decomposed into the orbital term, the spin term and also the spin-orbit cross term, which is caused by the spin-orbit interaction. We show that the orbital susceptibility logarithmically diverges at the band touching energy in the point-node case, while it exhibits a stronger δ -function singularity in the line node case. The spin-orbit cross term is shown to be paramagnetic in the electron side while diamagnetic in the hole side, in contrast with other two terms which are both even functions in Fermi energy. The spin-orbit cross term in the nodal semimetal is found to be directly related to the chiral surface current induced by the topological surface modes.

  19. Magnetic response in three-dimensional nodal semimetals

    NASA Astrophysics Data System (ADS)

    Koshino, Mikito; Hizbullah, Intan Fatimah

    We study the magnetic response in various three-dimensional gapless systems, including Dirac and Weyl semimetals and a line-node semimetal. We show that the susceptibility is decomposed into the orbital term, the spin term and also the spin-orbit cross term which is caused by the spin-orbit interaction. We show that the orbital susceptibility logarithmically diverges at the band touching energy in the point-node case, while it exhibits a stronger delta-function singularity in the line node case. The spin-orbit cross term is shown to be paramagnetic in the electron side while diamagnetic in the hole side, in contrast with other two terms which are both even functions in Fermi energy. The spin-orbit cross term in the nodal semimetal is found to be directly related to the chiral surface current induced by the topological surface modes.

  20. CAISO flicks switch on nodal scheme and lights stay on

    SciTech Connect

    2009-06-15

    In 2000-01, two years after introducing a competitive wholesale power auction in California - with a separate day-ahead zonal market operated by the California Power Exchange and a zonal market for ancillary services and balancing energy operated by the California Independent System Operator (CAISO) - the California market collapsed from exorbitant prices, flagrant gaming, and abuse of market power. Nine years later, CAISO introduced a nodal pricing auction for the wholesale market in April, replacing the zonal scheme, which was among many causes of the original market's demise. With nearly 3,000 nodes on the network, high prices in one region do not affect prices everywhere on the system. After investing some $200 million to upgrade the software, countless delays, and 18 months of market simulation and testing, the new auction was introduced and nothing unusual happened.

  1. Improving the Accuracy of High-Order Nodal Transport Methods

    SciTech Connect

    Azmy, Y.Y.; Buscaglia, G.C.; Zamonsky, O.M.

    1999-09-27

    This paper outlines some recent advances towards improving the accuracy of neutron transport calculations using the Arbitrarily High Order Transport-Nodal (AHOT-N) Method. These advances consist of several contributions: (a) A formula for the spatial weights that allows for the polynomial order to be raised arbitrarily high without suffering adverse effects from round-off error; (b) A reconstruction technique for the angular flux, based upon a recursive formula, that reduces the pointwise error by one ordeq (c) An a posterior error indicator that estimates the true error and its distribution throughout the domain, so that it can be used for adaptively refining the approximation. Present results are mainly for ID, extension to 2D-3D is in progress.

  2. Improving the Accuracy of High-Order Nodal Transport Methods

    SciTech Connect

    Azmy, Y.Y.; Buscaglia, G.C.; Zamonsky, O.M.

    1999-09-27

    This paper outlines some recent advances towards improving the accuracy of neutron calculations using the Arbitrarily High Order Transport-Nodal (AHOT-N) Method. These transport advances consist of several contributions: (a) A formula for the spatial weights that allows for the polynomial order to be raised arbitrarily high without suffering from pollution from round-off, error; (b) A reconstruction technique for the angular flux, based upon a recursive formula, that reduces the pointwise error by one order; (c) An a posterior error indicator that estimates the true error and its distribution throughout the domain, so that it can be used for adaptively reftig the approximation. Present results are mainly for ID, extension to 2D-3D is in progress.

  3. Nodal staging of colorectal carcinomas and sentinel nodes

    PubMed Central

    Cserni, G

    2003-01-01

    This review surveys the staging systems used for the classification of colorectal carcinomas, including the TNM system, and focuses on the assessment of the nodal stage of the disease. It reviews the quantitative requirements for a regional metastatic work up, and some qualitative features of lymph nodes that may help in the selection of positive and negative lymph nodes. Identification of the sentinel lymph nodes (those lymph nodes that have direct drainage from the primary tumour site) is one such qualitative feature that is claimed to allow the upstaging of colorectal carcinomas via an oriented, enhanced pathological work up. Current evidence in favour of a change in the requisite of assessing as may lymph nodes as is possible, and concentrating the efforts on only a selected number of lymph nodes, is weak. PMID:12719450

  4. Contemporary Management of Recurrent Nodal Disease in Differentiated Thyroid Carcinoma

    PubMed Central

    Na’ara, Shorook; Amit, Moran; Fridman, Eran; Gil, Ziv

    2016-01-01

    Differentiated thyroid carcinoma (DTC) comprises over 90% of thyroid tumors and includes papillary and follicular carcinomas. Patients with DTC have an excellent prognosis, with a 10-year survival rate of over 90%. However, the risk of recurrent tumor ranges between 5% and 30% within 10 years of the initial diagnosis. Cervical lymph node disease accounts for the majority of recurrences and in most cases is detected during follow-up by ultrasound or elevated levels of serum thyroglobulin. Recurrent disease is accompanied by increased morbidity. The mainstay of treatment of nodal recurrence is surgical management. We provide an overview of the literature addressing surgical management of recurrent or persistent lymph node disease in patients with DTC. PMID:26886954

  5. Static benchmarking of the NESTLE advanced nodal code

    SciTech Connect

    Mosteller, R.D.

    1997-05-01

    Results from the NESTLE advanced nodal code are presented for multidimensional numerical benchmarks representing four different types of reactors, and predictions from NESTLE are compared with measured data from pressurized water reactors (PWRs). The numerical benchmarks include cases representative of PWRs, boiling water reactors (BWRs), CANDU heavy water reactors (HWRs), and high-temperature gas-cooled reactors (HTGRs). The measured PWR data include critical soluble boron concentrations and isothermal temperature coefficients of reactivity. The results demonstrate that NESTLE correctly solves the multigroup diffusion equations for both Cartesian and hexagonal geometries, that it reliably calculates k{sub eff} and reactivity coefficients for PWRs, and that--subsequent to the incorporation of additional thermal-hydraulic models--it will be able to perform accurate calculations for the corresponding parameters in BWRs, HWRs, and HTGRs as well.

  6. On-line application of the PANTHER advanced nodal code

    SciTech Connect

    Hutt, P.K.; Knight, M.P. )

    1992-01-01

    Over the last few years, Nuclear Electric has developed an integrated core performance code package for both light water reactors (LWRs) and advanced gas-cooled reactors (AGRs) that can perform a comprehensive range of calculations for fuel cycle design, safety analysis, and on-line operational support for such plants. The package consists of the following codes: WIMS for lattice physics, PANTHER whole reactor nodal flux and AGR thermal hydraulics, VIPRE for LWR thermal hydraulics, and ENIGMA for fuel performance. These codes are integrated within a UNIX-based interactive system called the Reactor Physics Workbench (RPW), which provides an interactive graphic user interface and quality assurance records/data management. The RPW can also control calculational sequences and data flows. The package has been designed to run both off-line and on-line accessing plant data through the RPW.

  7. [Crucial stages of embryogenesis of R. arvalis: Part 1. Linear measurements of embryonic structures].

    PubMed

    Severtsova, E A; Severtsov, A S

    2011-01-01

    Investigations of individual variability have allowed us to reveal the crucial (= nodal) stages in embryogenesis of the moor frog (Rana arvalis Nills.). These crucial stages are: the late gastrula stage (stages 18-20), the hatching stages (stages 32-33) and, apparently, early metamorphosis (stage 39). Moreover, we have found that each embryonic structure passes through its specific crucial stages. For example, stage 34 is crucial for the trait "tail width" but is internodal for all other embryonic traits. At this stage, larva passes from an attached to a free-swimming life style. We also found considerable differences between the different frog populations in the the level of developmental variability. These differences were associated with internodal developmental stages.

  8. Modulation of ornithine decarboxylase activity in the normal and regenerating rat liver by various doses of the peptide morphogen of Hydra

    SciTech Connect

    Yarygin, K.N.; Kazimirskii, A.N.; Kositskii, G.I.; Rubina, A.Yu.; Vinogradov, V.A.; Pylaev, A.S.

    1986-11-01

    In this investigation, changes in ornithine decarboxylase (ODC) activity were studied in the normal and regenerating liver of rats receiving injections of various doses of Hydra peptide morphogen (HPM). Activity of ODC was determined by a radioisotope method based on liberation of /sup 14/CO/sub 2/ from L-(1-/sup 14/C)-ornithine. The results indicate in the author's opinion that HPM may have a role in the regulation of anabolic processes and, in particular, of regenerative processes in mammals.

  9. The morphogenic/cytotoxic and prostaglandin-stimulating activities of interleukin-1 beta in the rat ovary are nitric oxide independent.

    PubMed Central

    Ben-Shlomo, I; Adashi, E Y; Payne, D W

    1994-01-01

    Nitric oxide (NO) has been implicated as a mediator of physiologic and pathologic cellular injury. Since the cytokine interleukin-1 beta (IL-1 beta) induces nitric oxide synthase (NOS) activity as well as effects morphogenic/cytotoxic changes and increased prostaglandin (PGE2) levels in cultured whole ovarian dispersates, we set out to determine whether these actions are interrelated. Treatment with IL-1 beta resulted in a marked increase in media nitrite and nitrate accumulation, morphological alterations, and increased release of lactate dehydrogenase (LDH) into media. Addition of IL-1 receptor antagonist (RA) eliminated these IL-1 beta effects. In contrast, specific inhibitors of NOS failed to reverse IL-1 beta-induced morphogenic changes or LDH release in spite of complete reduction of media nitrite to control levels. Similarly, treatment with transforming growth factor beta 1, inhibited IL-1 beta-induced nitrite accumulation, but had no effect on the morphologic or cytotoxic endpoints. Moreover, the addition of sodium nitroprusside, an NO generator, resulted in progressive increments in media nitrite content without a corresponding increase in the IL-1 beta-associated morphogenic changes or media LDH content. Furthermore, IL-1-induced PGE2 accumulation remained unaffected by specific NOS inhibition. These observations support the view that NO does not mediate the morphogenic/cytotoxic or inflammatory-like (e.g., PGE2 inducing) properties of IL-1 beta in cultured whole ovarian dispersates. Although the precise role of NO in ovarian physiology remains unknown, it is possible that NO participates in the periovulatory modulation of ovarian blood flow by virtue of its potent vasodilatory activity. Images PMID:7523451

  10. The morphogen Decapentaplegic employs a two-tier mechanism to activate target retinal determining genes during ectopic eye formation in Drosophila

    PubMed Central

    Aggarwal, Poonam; Gera, Jayati; Mandal, Lolitika; Mandal, Sudip

    2016-01-01

    Understanding the role of morphogen in activating its target genes, otherwise epigenetically repressed, during change in cell fate specification is a very fascinating yet relatively unexplored domain. Our in vivo loss-of-function genetic analyses reveal that specifically during ectopic eye formation, the morphogen Decapentaplegic (Dpp), in conjunction with the canonical signaling responsible for transcriptional activation of retinal determining (RD) genes, triggers another signaling cascade. Involving dTak1 and JNK, this pathway down-regulates the expression of polycomb group of genes to do away with their repressive role on RD genes. Upon genetic inactivation of members of this newly identified pathway, the canonical Dpp signaling fails to trigger RD gene expression beyond a threshold, critical for ectopic photoreceptor differentiation. Moreover, the drop in ectopic RD gene expression and subsequent reduction in ectopic photoreceptor differentiation resulting from inactivation of dTak1 can be rescued by down-regulating the expression of polycomb group of genes. Our results unravel an otherwise unknown role of morphogen in coordinating simultaneous transcriptional activation and de-repression of target genes implicating its importance in cellular plasticity. PMID:27270790

  11. The role of hepatocyte hemojuvelin in the regulation of bone morphogenic protein-6 and hepcidin expression in vivo.

    PubMed

    Zhang, An-Sheng; Gao, Junwei; Koeberl, Dwight D; Enns, Caroline A

    2010-05-28

    Both hemojuvelin (HJV) and bone morphogenic protein-6 (BMP6) are essential for hepcidin expression. Hepcidin is the key peptide hormone in iron homeostasis, and is secreted predominantly by hepatocytes. HJV expression is detected in hepatocytes, as well as in skeletal and heart muscle. HJV binds BMP6 and increases hepcidin expression presumably by acting as a BMP co-receptor. We characterized the role of hepatocyte HJV in the regulation of BMP6 and hepcidin expression. In HJV-null (Hjv(-/-)) mice that have severe iron overload and marked suppression of hepcidin expression, we detected 4-fold higher hepatic BMP6 mRNA than in wild-type counterparts. These results indicate that Hjv(-/-) mice do not lack BMP6. Furthermore, iron depletion in Hjv(-/-) mice decreased hepatic BMP6 mRNA. Expression of HJV in hepatocytes of Hjv(-/-) mice using an AAV2/8 vector, increased hepatic hepcidin mRNA by 65-fold and phosphorylated Smad1/5/8 in the liver by about 2.5-fold. However, no significant change in BMP6 mRNA was detected in either the liver or the small intestine of these animals. Our results revealed a close correlation of hepatic BMP6 mRNA expression with hepatic iron-loading. Together, our data indicate that the regulation of hepatic BMP6 expression by iron is independent of HJV, and that expression of HJV in hepatocytes plays an essential role in hepcidin expression by potentiating the BMP6-mediated signaling.

  12. A Biphasic Calcium Sulphate/Hydroxyapatite Carrier Containing Bone Morphogenic Protein-2 and Zoledronic Acid Generates Bone.

    PubMed

    Raina, Deepak Bushan; Isaksson, Hanna; Hettwer, Werner; Kumar, Ashok; Lidgren, Lars; Tägil, Magnus

    2016-05-18

    In orthopedic surgery, large amount of diseased or injured bone routinely needs to be replaced. Autografts are mainly used but their availability is limited. Commercially available bone substitutes allow bone ingrowth but lack the capacity to induce bone formation. Thus, off-the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone, and zoledronic acid (ZA) to delay early resorption. In-vitro, the biphasic material released 90% of rhBMP-2 and 10% of ZA in the first week. No major changes were found in the surface structure using scanning electron microscopy (SEM) or in the mechanical properties after adding rhBMP-2 or ZA. In-vivo bone formation was studied in an abdominal muscle pouch model in rats (n = 6/group). The mineralized volume was significantly higher when the biphasic material was combined with both rhBMP-2 and ZA (21.4 ± 5.5 mm(3)) as compared to rhBMP-2 alone (10.9 ± 2.1 mm(3)) when analyzed using micro computed tomography (μ-CT) (p < 0.01). In the clinical setting, the biphasic material combined with both rhBMP-2 and ZA can potentially regenerate large volumes of bone.

  13. Vaccinia virus A12L protein and its AG/A proteolysis play an important role in viral morphogenic transition

    PubMed Central

    Yang, Su Jung; Hruby, Dennis E

    2007-01-01

    Like the major vaccinia virus (VV) core protein precursors, p4b and p25K, the 25 kDa VV A12L late gene product (p17K) is proteolytically maturated at the conserved Ala-Gly-Ala motif. However, the association of the precursor and its cleavage product with the core of mature virion suggests that both of the A12L proteins may be required for virus assembly. Here, in order to test the requirement of the A12L protein and its proteolysis in viral replication, a conditional lethal mutant virus (vvtetOA12L) was constructed to regulate A12L expression by the presence or absence of an inducer, tetracycline. In the absence of tetracycline, replication of vvtetOA12L was inhibited by 80% and this inhibition could be overcome by transient expression of the wild-type copy of the A12L gene. In contrast, mutation of the AG/A site abrogated the ability of the transfected A12L gene to rescue, indicating that A12L proteolysis plays an important role in viral replication. Electron microscopy analysis of the A12L deficient virus demonstrated the aberrant virus particles, which were displayed by the AG/A site mutation. Thus, we concluded that the not only A12L protein but also its cleavage processing plays an essential role in virus morphogenic transition. PMID:17625005

  14. Nodal promotes mir206 expression to control convergence and extension movements during zebrafish gastrulation.

    PubMed

    Liu, Xiuli; Ma, Yuanqing; Zhang, Congwei; Wei, Shi; Cao, Yu; Wang, Qiang

    2013-10-20

    Nodal, a member of the transforming growth factor β (TGF-β) superfamily, has been shown to play a role in mesendoderm induction and gastrulation movements. The activity of Nodal signaling can be modulated by microRNAs (miRNAs) as previously reported, but little is known about which miRNAs are regulated by Nodal during gastrulation. In the present study, we found that the expression of mir206, one of the most abundant miRNAs during zebrafish early embryo development, is regulated by Nodal signaling. Abrogation of Nodal signal activity results in defective convergence and extension (CE) movements, and these cell migration defects can be rescued by supplying an excess of mir206, suggesting that mir206 acts downstream of Nodal signaling to regulate CE movements. Furthermore, in mir206 morphants, the expression of cell adhesion molecule E-cadherin is significantly increased, while the key transcriptional repressor of E-cadherin, snail1a, is depressed. Our study uncovers a novel mechanism by which Nodal-regulated mir206 modulates gastrulation movements in connection with the Snail/E-cadherin pathway.

  15. Differential gene expression patterns during embryonic development of sea urchin exposed to triclosan.

    PubMed

    Hwang, Jinik; Suh, Sung-Suk; Park, Mirye; Park, So Yun; Lee, Sukchan; Lee, Taek-Kyun

    2017-02-01

    Triclosan (TCS; 2,4,4'-trichloro-2'-hydroxydiphenyl ether) is a broad-spectrum antibacterial agent used in common industrial, personal care and household products which are eventually rinsed down the drain and discharged with wastewater effluent. It is therefore commonly found in the aquatic environment, leading to the continual exposure of aquatic organisms to TCS and the accumulation of the antimicrobial and its harmful degradation products in their bodies. Toxic effects of TCS on reproductive and developmental progression of some aquatic organisms have been suggested but the underlying molecular mechanisms have not been defined. We investigated the expression patterns of genes involved in the early development of TCS-treated sea urchin Strongylocentrotus nudus using cDNA microarrays. We observed that the predominant consequence of TCS treatment in this model system was the widespread repression of TCS-modulated genes. In particular, empty spiracles homeobox 1 (EMX-1), bone morphogenic protein, and chromosomal binding protein genes showed a significant decrease in expression in response to TCS. These results suggest that TCS can induce abnormal development of sea urchin embryos through the concomitant suppression of a number of genes that are necessary for embryonic differentiation in the blastula stage. Our data provide new insight into the crucial role of genes associated with embryonic development in response to TCS. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 426-433, 2017.

  16. Identification and functional characterization of NODAL rare variants in heterotaxy and isolated cardiovascular malformations

    PubMed Central

    Mohapatra, Bhagyalaxmi; Casey, Brett; Li, Hua; Ho-Dawson, Trang; Smith, Liana; Fernbach, Susan D.; Molinari, Laura; Niesh, Stephen R.; Jefferies, John Lynn; Craigen, William J.; Towbin, Jeffrey A.; Belmont, John W.; Ware, Stephanie M.

    2009-01-01

    NODAL and its signaling pathway are known to play a key role in specification and patterning of vertebrate embryos. Mutations in several genes encoding components of the NODAL signaling pathway have previously been implicated in the pathogenesis of human left–right (LR) patterning defects. Therefore, NODAL, a member of TGF-β superfamily of developmental regulators, is a strong candidate to be functionally involved in congenital LR axis patterning defects or heterotaxy. Here we have investigated whether variants in NODAL are present in patients with heterotaxy and/or isolated cardiovascular malformations (CVM) thought to be caused by abnormal heart tube looping. Analysis of a large cohort of cases (n = 269) affected with either classic heterotaxy or looping CVM revealed four different missense variants, one in-frame insertion/deletion and two conserved splice site variants in 14 unrelated subjects (14/269, 5.2%). Although similar with regard to other associated defects, individuals with the NODAL mutations had a significantly higher occurrence of pulmonary valve atresia (P = 0.001) compared with cases without a detectable NODAL mutation. Functional analyses demonstrate that the missense variant forms of NODAL exhibit significant impairment of signaling as measured by decreased Cripto (TDGF-1) co-receptor-mediated activation of artificial reporters. Expression of these NODAL proteins also led to reduced induction of Smad2 phosphorylation and impaired Smad2 nuclear import. Taken together, these results support a role for mutations and rare deleterious variants in NODAL as a cause for sporadic human LR patterning defects. PMID:19064609

  17. Cerberus-Nodal-Lefty-Pitx signaling cascade controls left-right asymmetry in amphioxus.

    PubMed

    Li, Guang; Liu, Xian; Xing, Chaofan; Zhang, Huayang; Shimeld, Sebastian M; Wang, Yiquan

    2017-04-04

    Many bilaterally symmetrical animals develop genetically programmed left-right asymmetries. In vertebrates, this process is under the control of Nodal signaling, which is restricted to the left side by Nodal antagonists Cerberus and Lefty. Amphioxus, the earliest diverging chordate lineage, has profound left-right asymmetry as a larva. We show that Cerberus, Nodal, Lefty, and their target transcription factor Pitx are sequentially activated in amphioxus embryos. We then address their function by transcription activator-like effector nucleases (TALEN)-based knockout and heat-shock promoter (HSP)-driven overexpression. Knockout of Cerberus leads to ectopic right-sided expression of Nodal, Lefty, and Pitx, whereas overexpression of Cerberus represses their left-sided expression. Overexpression of Nodal in turn represses Cerberus and activates Lefty and Pitx ectopically on the right side. We also show Lefty represses Nodal, whereas Pitx activates Nodal These data combine in a model in which Cerberus determines whether the left-sided gene expression cassette is activated or repressed. These regulatory steps are essential for normal left-right asymmetry to develop, as when they are disrupted embryos may instead form two phenotypic left sides or two phenotypic right sides. Our study shows the regulatory cassette controlling left-right asymmetry was in place in the ancestor of amphioxus and vertebrates. This includes the Nodal inhibitors Cerberus and Lefty, both of which operate in feedback loops with Nodal and combine to establish asymmetric Pitx expression. Cerberus and Lefty are missing from most invertebrate lineages, marking this mechanism as an innovation in the lineage leading to modern chordates.

  18. Influencing hematopoietic differentiation of mouse embryonic stem cells using soluble heparin and heparan sulfate saccharides.

    PubMed

    Holley, Rebecca J; Pickford, Claire E; Rushton, Graham; Lacaud, Georges; Gallagher, John T; Kouskoff, Valerie; Merry, Catherine L R

    2011-02-25

    Heparan sulfate proteoglycans (HSPG) encompass some of the most abundant macromolecules on the surface of almost every cell type. Heparan sulfate (HS) chains provide a key interaction surface for the binding of numerous proteins such as growth factors and morphogens, helping to define the ability of a cell to respond selectively to environmental cues. The specificity of HS-protein interactions are governed predominantly by the order and positioning of sulfate groups, with distinct cell types expressing unique sets of HS epitopes. Embryos deficient in HS-synthesis (Ext1(-/-)) exhibit pre-gastrulation lethality and lack recognizable organized mesoderm and extraembryonic tissues. Here we demonstrate that embryonic stem cells (ESCs) derived from Ext1(-/-) embryos are unable to differentiate into hematopoietic lineages, instead retaining ESC marker expression throughout embryoid body (EB) culture. However hematopoietic differentiation can be restored by the addition of soluble heparin. Consistent with specific size and composition requirements for HS:growth factor signaling, chains measuring at least 12 saccharides were required for partial rescue of hematopoiesis with longer chains (18 saccharides or more) required for complete rescue. Critically N- and 6-O-sulfate groups were essential for rescue. Heparin addition restored the activity of multiple signaling pathways including bone morphogenic protein (BMP) with activation of phospho-SMADs re-established by the addition of heparin. Heparin addition to wild-type cultures also altered the outcome of differentiation, promoting hematopoiesis at low concentrations, yet inhibiting blood formation at high concentrations. Thus altering the levels of HS and HS sulfation within differentiating ESC cultures provides an attractive and accessible mechanism for influencing cell fate.

  19. Detection of 18.6 year nodal induced drought in the Patagonian Andes

    NASA Astrophysics Data System (ADS)

    Currie, Robert G.

    1983-11-01

    Analysis of tree-ring chronologies from the Patagonian Andes yields evidence for the 18.6 yr lunar nodal term in drought/flood. The mean discrepancy between epochs of drought/flood and the nodal tide since AD 1600 is 0.7 ± 2.2 yr, but the polarity of the signal is apparently bimodal. From nodal epoch 1750.0 through 1898.9 drought and tide were in phase, whereas prior to 1750.0 and subsequent to 1898.9 drought and tide were out of phase. There is evidence also for the solar cycle drought signal in the data.

  20. Relation between finite element methods and nodal methods in transport theory

    SciTech Connect

    Walters, W.F.

    1985-01-01

    This paper examines the relationship between nodal methods and finite-element methods for solving the discrete-ordinates form of the transport equation in x-y geometry. Specifically, we will examine the relation of three finite-element schemes to the linear-linear (LL) and linear-nodal (LN) nodal schemes. The three finite-element schemes are the linear-continuous-diamond-difference (DD) scheme, the linear-discontinuous (LD) scheme, and the quadratic-discontinuous (QD) scheme. A brief derivation of the (LL) and (LN) nodal schemes is given in the third section of this paper. The approximations that cause the LL scheme to reduce to the DD, LD, and QD schemes are then indicated. An extremely simple method of deriving the finite-element schemes is then introduced.

  1. Nodal Domain Statistics for Quantum Maps, Percolation, and Stochastic Loewner Evolution

    SciTech Connect

    Keating, J. P.; Marklof, J.; Williams, I. G.

    2006-07-21

    We develop a percolation model for nodal domains in the eigenvectors of quantum chaotic torus maps. Our model follows directly from the assumption that the quantum maps are described by random matrix theory. Its accuracy in predicting statistical properties of the nodal domains is demonstrated for perturbed cat maps and supports the use of percolation theory to describe the wave functions of general Hamiltonian systems. We also demonstrate that the nodal domains of the perturbed cat maps obey the Cardy crossing formula and find evidence that the boundaries of the nodal domains are described by stochastic Loewner evolution with diffusion constant {kappa} close to the expected value of 6, suggesting that quantum chaotic wave functions may exhibit conformal invariance in the semiclassical limit.

  2. ANOVA-HDMR structure of the higher order nodal diffusion solution

    SciTech Connect

    Bokov, P. M.; Prinsloo, R. H.; Tomasevic, D. I.

    2013-07-01

    Nodal diffusion methods still represent a standard in global reactor calculations, but employ some ad-hoc approximations (such as the quadratic leakage approximation) which limit their accuracy in cases where reference quality solutions are sought. In this work we solve the nodal diffusion equations utilizing the so-called higher-order nodal methods to generate reference quality solutions and to decompose the obtained solutions via a technique known as High Dimensional Model Representation (HDMR). This representation and associated decomposition of the solution provides a new formulation of the transverse leakage term. The HDMR structure is investigated via the technique of Analysis of Variance (ANOVA), which indicates why the existing class of transversely-integrated nodal methods prove to be so successful. Furthermore, the analysis leads to a potential solution method for generating reference quality solutions at a much reduced calculational cost, by applying the ANOVA technique to the full higher order solution. (authors)

  3. Dose-dependent Nodal/Smad signals pattern the early mouse embryo.

    PubMed

    Robertson, Elizabeth J

    2014-08-01

    Nodal signals in the early post-implantation stage embryo are essential to establish initial proximal-distal (P-D) polarity and generate the final anterior-posterior (A-P) body axis. Nodal signaling in the epiblast results in the phosphorylation of Smad2 in the overlying visceral endoderm necessary to induce the AVE, in part via Smad2-dependent activation of the T-box gene Eomesodermin. Slightly later following mesoderm induction a continuum of dose-dependent Nodal signaling during the process of gastrulation underlies specification of mesodermal and definitive endoderm progenitors. Dynamic Nodal expression during the critical 72 h time window immediately following implantation, accomplished by a series of feed-back and feed-forward mechanisms serves to provide key positional cues required for establishment of the body plan and controls cell fate decisions in the early mammalian embryo.

  4. The Role of Hepatocyte Hemojuvelin in the Regulation of Bone Morphogenic Protein-6 and Hepcidin Expression in Vivo*

    PubMed Central

    Zhang, An-Sheng; Gao, Junwei; Koeberl, Dwight D.; Enns, Caroline A.

    2010-01-01

    Both hemojuvelin (HJV) and bone morphogenic protein-6 (BMP6) are essential for hepcidin expression. Hepcidin is the key peptide hormone in iron homeostasis, and is secreted predominantly by hepatocytes. HJV expression is detected in hepatocytes, as well as in skeletal and heart muscle. HJV binds BMP6 and increases hepcidin expression presumably by acting as a BMP co-receptor. We characterized the role of hepatocyte HJV in the regulation of BMP6 and hepcidin expression. In HJV-null (Hjv−/−) mice that have severe iron overload and marked suppression of hepcidin expression, we detected 4-fold higher hepatic BMP6 mRNA than in wild-type counterparts. These results indicate that Hjv−/− mice do not lack BMP6. Furthermore, iron depletion in Hjv−/− mice decreased hepatic BMP6 mRNA. Expression of HJV in hepatocytes of Hjv−/− mice using an AAV2/8 vector, increased hepatic hepcidin mRNA by 65-fold and phosphorylated Smad1/5/8 in the liver by about 2.5-fold. However, no significant change in BMP6 mRNA was detected in either the liver or the small intestine of these animals. Our results revealed a close correlation of hepatic BMP6 mRNA expression with hepatic iron-loading. Together, our data indicate that the regulation of hepatic BMP6 expression by iron is independent of HJV, and that expression of HJV in hepatocytes plays an essential role in hepcidin expression by potentiating the BMP6-mediated signaling. PMID:20363739

  5. A Biphasic Calcium Sulphate/Hydroxyapatite Carrier Containing Bone Morphogenic Protein-2 and Zoledronic Acid Generates Bone

    PubMed Central

    Raina, Deepak Bushan; Isaksson, Hanna; Hettwer, Werner; Kumar, Ashok; Lidgren, Lars; Tägil, Magnus

    2016-01-01

    In orthopedic surgery, large amount of diseased or injured bone routinely needs to be replaced. Autografts are mainly used but their availability is limited. Commercially available bone substitutes allow bone ingrowth but lack the capacity to induce bone formation. Thus, off-the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone, and zoledronic acid (ZA) to delay early resorption. In-vitro, the biphasic material released 90% of rhBMP-2 and 10% of ZA in the first week. No major changes were found in the surface structure using scanning electron microscopy (SEM) or in the mechanical properties after adding rhBMP-2 or ZA. In-vivo bone formation was studied in an abdominal muscle pouch model in rats (n = 6/group). The mineralized volume was significantly higher when the biphasic material was combined with both rhBMP-2 and ZA (21.4 ± 5.5 mm3) as compared to rhBMP-2 alone (10.9 ± 2.1 mm3) when analyzed using micro computed tomography (μ-CT) (p < 0.01). In the clinical setting, the biphasic material combined with both rhBMP-2 and ZA can potentially regenerate large volumes of bone. PMID:27189411

  6. Bone morphogenic protein-2 regulates the myogenic differentiation of PMVECs in CBDL rat serum-induced pulmonary microvascular remodeling.

    PubMed

    Liu, Chang; Chen, Lin; Zeng, Jing; Cui, Jian; Ning, Jiao-Nin; Wang, Guan-Song; Belguise, Karine; Wang, Xiaobo; Qian, Gui-Sheng; Lu, Kai-Zhi; Yi, Bin

    2015-08-01

    Hepatopulmonary syndrome (HPS) is characterized by an arterial oxygenation defect induced by intrapulmonary vasodilation (IPVD) that increases morbidity and mortality. In our previous study, it was determined that both the proliferation and the myogenic differentiation of pulmonary microvascular endothelial cells (PMVECs) play a key role in the development of IPVD. However, the molecular mechanism underlying the relationship between IPVD and the myogenic differentiation of PMVECs remains unknown. Additionally, it has been shown that bone morphogenic protein-2 (BMP2), via the control of protein expression, may regulate cell differentiation including cardiomyocyte differentiation, neuronal differentiation and odontoblastic differentiation. In this study, we observed that common bile duct ligation (CBDL)-rat serum induced the upregulation of the expression of several myogenic proteins (SM-α-actin, calponin, SM-MHC) and enhanced the expression levels of BMP2 mRNA and protein in PMVECs. We also observed that both the expression levels of Smad1/5 and the activation of phosphorylated Smad1/5 were significantly elevated in PMVECs following exposure to CBDL-rat serum, which was accompanied by the down-regulation of Smurf1. The blockage of the BMP2/Smad signaling pathway with Noggin inhibited the myogenic differentiation of PMVECs, a process that was associated with relatively low expression levels of both SM-α-actin and calponin in the setting of CBDL-rat serum exposure, although SM-MHC expression was not affected. These findings suggested that the BMP2/Smad signaling pathway is involved in the myogenic differentiation of the PMVECs. In conclusion, our data highlight the pivotal role of BMP2 in the CBDL-rat serum-induced myogenic differentiation of PMVECs via the activation of both Smad1 and Smad5 and the down-regulation of Smurf1, which may represent a potential therapy for HPS-induced pulmonary vascular remodeling.

  7. Final Report, NERI Project: ''An Innovative Reactor Analysis Methodology Based on a Quasidiffusion Nodal Core Model''

    SciTech Connect

    Dmitriy Y. Anistratov; Marvin L. Adams; Todd S. Palmer; Kord S. Smith; Kevin Clarno; Hikaru Hiruta; Razvan Nes

    2003-08-04

    OAK (B204) Final Report, NERI Project: ''An Innovative Reactor Analysis Methodology Based on a Quasidiffusion Nodal Core Model'' The present generation of reactor analysis methods uses few-group nodal diffusion approximations to calculate full-core eigenvalues and power distributions. The cross sections, diffusion coefficients, and discontinuity factors (collectively called ''group constants'') in the nodal diffusion equations are parameterized as functions of many variables, ranging from the obvious (temperature, boron concentration, etc.) to the more obscure (spectral index, moderator temperature history, etc.). These group constants, and their variations as functions of the many variables, are calculated by assembly-level transport codes. The current methodology has two main weaknesses that this project addressed. The first weakness is the diffusion approximation in the full-core calculation; this can be significantly inaccurate at interfaces between different assemblies. This project used the nodal diffusion framework to implement nodal quasidiffusion equations, which can capture transport effects to an arbitrary degree of accuracy. The second weakness is in the parameterization of the group constants; current models do not always perform well, especially at interfaces between unlike assemblies. The project developed a theoretical foundation for parameterization and homogenization models and used that theory to devise improved models. The new models were extended to tabulate information that the nodal quasidiffusion equations can use to capture transport effects in full-core calculations.

  8. Topological Dirac nodal lines and surface charges in fcc alkaline earth metals

    PubMed Central

    Hirayama, Motoaki; Okugawa, Ryo; Miyake, Takashi; Murakami, Shuichi

    2017-01-01

    In nodal-line semimetals, the gaps close along loops in k space, which are not at high-symmetry points. Typical mechanisms for the emergence of nodal lines involve mirror symmetry and the π Berry phase. Here we show via ab initio calculations that fcc calcium (Ca), strontium (Sr) and ytterbium (Yb) have topological nodal lines with the π Berry phase near the Fermi level, when spin–orbit interaction is neglected. In particular, Ca becomes a nodal-line semimetal at high pressure. Owing to nodal lines, the Zak phase becomes either π or 0, depending on the wavevector k, and the π Zak phase leads to surface polarization charge. Carriers eventually screen it, leaving behind large surface dipoles. In materials with nodal lines, both the large surface polarization charge and the emergent drumhead surface states enhance Rashba splitting when heavy adatoms are present, as we have shown to occur in Bi/Sr(111) and in Bi/Ag(111). PMID:28074835

  9. The nodal inhibitor Coco is a critical target of leftward flow in Xenopus.

    PubMed

    Schweickert, Axel; Vick, Philipp; Getwan, Maike; Weber, Thomas; Schneider, Isabelle; Eberhardt, Melanie; Beyer, Tina; Pachur, Anke; Blum, Martin

    2010-04-27

    Vertebrate laterality, which is manifested by asymmetrically placed organs [1], depends on asymmetric activation of the Nodal signaling cascade in the left lateral plate mesoderm [2]. In fish, amphibians, and mammals, a cilia-driven leftward flow of extracellular fluid acts upstream of the Nodal cascade [3-6]. The direct target of flow has remained elusive. In Xenopus, flow occurs at the gastrocoel roof plate (GRP) in the dorsal midline of the embryo [4, 7]. The GRP is bordered by a second, bilaterally symmetrical Nodal expression domain [8]. Here we identify the Nodal inhibitor Coco as a critical target of flow. Coco and Xenopus Nodal-related 1 (Xnr1) are coexpressed in the lateralmost ciliated GRP cells. Coco becomes downregulated on the left side of the GRP as a direct readout of flow. Ablation of flow prevented Coco repression, whereas Xnr1 expression was independent of flow. Loss of flow-induced laterality defects were rescued by knockdown of Coco on the left side. Parallel knockdown of Coco and Xnr1 in GRP cells restored laterality defects in flow-impaired embryos, demonstrating that Coco acted through GRP-expressed Xnr1. Coco thus acts as a critical target of flow, suggesting that symmetry is broken by flow-mediated left-asymmetric release of Nodal repression at the midline.

  10. A quasi-static polynomial nodal method for nuclear reactor analysis

    SciTech Connect

    Gehin, J.C.

    1992-09-01

    Modern nodal methods are currently available which can accurately and efficiently solve the static and transient neutron diffusion equations. Most of the methods, however, are limited to two energy groups for practical application. The objective of this research is the development of a static and transient, multidimensional nodal method which allows more than two energy groups and uses a non-linear iterative method for efficient solution of the nodal equations. For both the static and transient methods, finite-difference equations which are corrected by the use of discontinuity factors are derived. The discontinuity factors are computed from a polynomial nodal method using a non-linear iteration technique. The polynomial nodal method is based upon a quartic approximation and utilizes a quadratic transverse-leakage approximation. The solution of the time-dependent equations is performed by the use of a quasi-static method in which the node-averaged fluxes are factored into shape and amplitude functions. The application of the quasi-static polynomial method to several benchmark problems demonstrates that the accuracy is consistent with that of other nodal methods. The use of the quasi-static method is shown to substantially reduce the computation time over the traditional fully-implicit time-integration method. Problems involving thermal-hydraulic feedback are accurately, and efficiently, solved by performing several reactivity/thermal-hydraulic updates per shape calculation.

  11. TGF-β promotes glioma cell growth via activating Nodal expression through Smad and ERK1/2 pathways

    SciTech Connect

    Sun, Jing; Liu, Su-zhi; Lin, Yan; Cao, Xiao-pan; Liu, Jia-ming

    2014-01-17

    Highlights: •TGF-β promoted Nodal expression in glioma cells. •TGF-β promoted Nodal expression via activating Smad and ERK1/2 pathways. •TGF-β promotes glioma cell growth via activating Nodal expression. -- Abstract: While there were certain studies focusing on the mechanism of TGF-β promoting the growth of glioma cells, the present work revealed another novel mechanism that TGF-β may promote glioma cell growth via enhancing Nodal expression. Our results showed that Nodal expression was significantly upregulated in glioma cells when TGF-β was added, whereas the TGF-β-induced Nodal expression was evidently inhibited by transfection Smad2 or Smad3 siRNAs, and the suppression was especially significant when the Smad3 was downregulated. Another, the attenuation of TGF-β-induced Nodal expression was observed with blockade of the ERK1/2 pathway also. Further detection of the proliferation, apoptosis, and invasion of glioma cells indicated that Nodal overexpression promoted the proliferation and invasion of tumor cells and inhibited their apoptosis, resembling the effect of TGF-β addition. Downregulation of Nodal expression via transfection Nodal-specific siRNA in the presence of TGF-β weakened the promoting effect of the latter on glioma cells growth, and transfecting Nodal siRNA alone in the absence of exogenous TGF-β more profoundly inhibited the growth of glioma cells. These results demonstrated that while both TGF-β and Nodal promoted glioma cells growth, the former might exert such effect by enhancing Nodal expression, which may form a new target for glioma therapy.

  12. A Monte Carlo based nodal diffusion model for criticality analysis, and, Application of high-order cross section homogenization method to two-group nodal diffusion

    NASA Astrophysics Data System (ADS)

    Ilas, Germina

    In the first part, an accurate and fast computational method is presented as an alternative to the Monte Carlo or deterministic transport theory codes currently used to determine the subcriticality of spent fuel storage lattices. The method is capable of analyzing storage configurations with simple or complex lattice cell geometry. It is developed based on two-group nodal diffusion theory, with the nodal cross sections and discontinuity factors determined from continuous-energy Monte Carlo simulations of each unique node (spent fuel assembly type). Three different approaches are developed to estimate the node-averaged diffusion coefficient. The applicability and the accuracy of the nodal method are assessed in two-dimensional geometry through several benchmark configurations typical at Savannah River Site. It is shown that the multiplication constant of the analyzed configurations is within 1% of the MCNP results. In the second part, the high-order cross section homogenization method, recently developed by McKinley and Rahnema, is implemented in the context of two-group nodal diffusion theory. The method corrects the generalized equivalence theory homogenization parameters for the effect of the core environment. The reconstructed fine-mesh (fuel pin) flux and power distributions are a natural byproduct of this method. The method was not tested for multigroup problems, where it was assumed that the multigroup flux expansion in terms of the perturbation parameter is a convergent series. Here the applicability of the method to two-group problems is studied, and it is shown that the perturbation expansion series converges for the multigroup case. A two-group nodal diffusion code with a bilinear intra-nodal flux shape is developed for the implementation of the high-order homogenization method in the context of the generalized equivalence theory. The method is tested by using as a benchmark a core configuration typical of a BWR in slab geometry, which has large

  13. Mechanotransduction in Embryonic Vascular Development

    PubMed Central

    Roman, Beth L.; Pekkan, Kerem

    2015-01-01

    A plethora of biochemical signals provides spatial and temporal cues that carefully orchestrate the complex process of vertebrate embryonic development. The embryonic vasculature develops not only in the context of these biochemical cues, but also in the context of the biomechanical forces imparted by blood flow. In the mature vasculature, different blood flow regimes induce distinct genetic programs, and significant progress has been made toward understanding how these forces are perceived by endothelial cells and transduced into biochemical signals. However, it cannot be assumed that paradigms that govern the mature vasculature are pertinent to the developing embryonic vasculature. The embryonic vasculature can respond to the mechanical forces of blood flow, and these responses are critical in vascular remodeling, certain aspects of sprouting angiogenesis, and maintenance of arterial-venous identity. Here, we review data regarding mechanistic aspects of endothelial cell mechanotransduction, with a focus on the response to shear stress, and elaborate upon the multifarious effects of shear stress on the embryonic vasculature. In addition, we discuss emerging predictive vascular growth models and highlight the prospect of combining signaling pathway information with computational modeling. We assert that correlation of precise measurements of hemodynamic parameters with effects on endothelial cell gene expression and cell behavior is required for fully understanding how blood flow-induced loading governs normal vascular development and shapes congenital cardiovascular abnormalities. PMID:22744845

  14. Embryonic death and the creation of human embryonic stem cells.

    PubMed

    Landry, Donald W; Zucker, Howard A

    2004-11-01

    The creation of human embryonic stem cells through the destruction of a human embryo pits the value of a potential therapeutic tool against that of an early human life. This contest of values has resulted in a polarized debate that neglects areas of common interest and perspective. We suggest that a common ground for pursuing research on human embryonic stem cells can be found by reconsidering the death of the human embryo and by applying to this research the ethical norms of essential organ donation.

  15. Extra-nodal extension is a significant prognostic factor in lymph node positive breast cancer

    PubMed Central

    Aziz, Sura; Wik, Elisabeth; Davidsen, Benedicte; Aas, Hans; Aas, Turid; Akslen, Lars A.

    2017-01-01

    Presence of lymph node (LN) metastasis is a strong prognostic factor in breast cancer, whereas the importance of extra-nodal extension and other nodal tumor features have not yet been fully recognized. Here, we examined microscopic features of lymph node metastases and their prognostic value in a population-based cohort of node positive breast cancer (n = 218), as part of the prospective Norwegian Breast Cancer Screening Program NBCSP (1996–2009). Sections were reviewed for the largest metastatic tumor diameter (TD-MET), nodal afferent and efferent vascular invasion (AVI and EVI), extra-nodal extension (ENE), number of ENE foci, as well as circumferential (CD-ENE) and perpendicular (PD-ENE) diameter of extra-nodal growth. Number of positive lymph nodes, EVI, and PD-ENE were significantly increased with larger primary tumor (PT) diameter. Univariate survival analysis showed that several features of nodal metastases were associated with disease-free (DFS) or breast cancer specific survival (BCSS). Multivariate analysis demonstrated an independent prognostic value of PD-ENE (with 3 mm as cut-off value) in predicting DFS and BCSS, along with number of positive nodes and histologic grade of the primary tumor (for DFS: P = 0.01, P = 0.02, P = 0.01, respectively; for BCSS: P = 0.02, P = 0.008, P = 0.02, respectively). To conclude, the extent of ENE by its perpendicular diameter was independently prognostic and should be considered in line with nodal tumor burden in treatment decisions of node positive breast cancer. PMID:28199370

  16. Effects of exogenous recombinant human bone morphogenic protein-7 on the corneal epithelial mesenchymal transition and fibrosis

    PubMed Central

    Chung, Jin Kwon; Park, Shin Ae; Hwang, Hee Sun; Kim, Kwang Sung; Cho, Yang Je; You, Yong Sung; Kim, Young Sik; Jang, Ju Woong; Lee, Sung Jin

    2017-01-01

    AIM To evaluate the effect of exogenous recombinant human bone morphogenic protein-7 (rhBMP-7) on transforming growth factor-β (TGF-β)-induced epithelial mesenchymal cell transition (EMT) and assessed its antifibrotic effect via topical application. METHODS The cytotoxic effect of rhBMP-7 was evaluated and the EMT of human corneal epithelial cells (HECEs) was induced by TGF-β. HECEs were then cultured in the presence of rhBMP-7 and/or hyaluronic acid (HA). EMT markers, fibronectin, E-cadherin, α-smooth muscle actin (α-SMA), and matrix metaloproteinase-9 (MMP-9), were evaluated. The level of corneal fibrosis and the reepithelization rate were evaluated using a rabbit keratectomy model. Expression of α-SMA in keratocytes were quantified following treatment with different concentrations of rhBMP-7. RESULTS Treatment with rhBMP-7 attenuated TGF-β-induced EMT in HECEs. It significantly attenuated fibronectin secretion (31.6%; P<0.05), the α-SMA protein level (72.2%; P<0.01), and MMP-9 expression (23.6%, P<0.05) in HECEs compared with cells grown in the presence of TGF-β alone. E-cadherin expression was significantly enhanced (289.7%; P<0.01) in the presence of rhBMP-7. Topical application of rhBMP-7 combined with 0.1% HA significantly reduced the amount of α-SMA+ cells by 43.18% (P<0.05) at a concentration of 2.5 µg/mL and by 47.73% (P<0.05) at 25 µg/mL, compared with the control group, without disturbing corneal reepithelization. CONCLUSION rhBMP-7 attenuates TGF-β-induced EMT in vitro, and topical application of rhBMP-7 reduces keratocyte myodifferentiation during the early wound healing stages in vivo without hindering reepithelization. Topical rhBMP-7 application as biological eye drops seems to be feasible in diseases involving TGF-β-related corneal fibrosis with corneal reepithelization disorders.

  17. Bone morphogenic protein-2 regulates the myogenic differentiation of PMVECs in CBDL rat serum-induced pulmonary microvascular remodeling

    SciTech Connect

    Liu, Chang; Chen, Lin; Zeng, Jing; Cui, Jian; Ning, Jiao-nin; Wang, Guan-song; Belguise, Karine; Wang, Xiaobo; Qian, Gui-sheng; Lu, Kai-zhi; Yi, Bin

    2015-08-01

    Hepatopulmonary syndrome (HPS) is characterized by an arterial oxygenation defect induced by intrapulmonary vasodilation (IPVD) that increases morbidity and mortality. In our previous study, it was determined that both the proliferation and the myogenic differentiation of pulmonary microvascular endothelial cells (PMVECs) play a key role in the development of IPVD. However, the molecular mechanism underlying the relationship between IPVD and the myogenic differentiation of PMVECs remains unknown. Additionally, it has been shown that bone morphogenic protein-2 (BMP2), via the control of protein expression, may regulate cell differentiation including cardiomyocyte differentiation, neuronal differentiation and odontoblastic differentiation. In this study, we observed that common bile duct ligation (CBDL)-rat serum induced the upregulation of the expression of several myogenic proteins (SM-α-actin, calponin, SM-MHC) and enhanced the expression levels of BMP2 mRNA and protein in PMVECs. We also observed that both the expression levels of Smad1/5 and the activation of phosphorylated Smad1/5 were significantly elevated in PMVECs following exposure to CBDL-rat serum, which was accompanied by the down-regulation of Smurf1. The blockage of the BMP2/Smad signaling pathway with Noggin inhibited the myogenic differentiation of PMVECs, a process that was associated with relatively low expression levels of both SM-α-actin and calponin in the setting of CBDL-rat serum exposure, although SM-MHC expression was not affected. These findings suggested that the BMP2/Smad signaling pathway is involved in the myogenic differentiation of the PMVECs. In conclusion, our data highlight the pivotal role of BMP2 in the CBDL-rat serum-induced myogenic differentiation of PMVECs via the activation of both Smad1 and Smad5 and the down-regulation of Smurf1, which may represent a potential therapy for HPS-induced pulmonary vascular remodeling. - Highlights: • CBDL-rat serum promotes the myogenic

  18. The bicoid morphogen system.

    PubMed

    Porcher, Aude; Dostatni, Nathalie

    2010-03-09

    Several fundamental concepts of developmental biology have emerged from studies on the early development of the Drosophila melanogaster embryo. In the late 1980s, studies on Bicoid provided the first solid experimental evidence for the existence of morphogenetic gradients and their implication in axial patterning. Bicoid has since stimulated further research, bringing together developmental and cell biologists, physicists and theoreticians to address fundamental biological questions. These include mechanistic aspects of transcriptional and translational control, molecular and functional aspects of evolution and, more recently with the development of quantitative approaches, the robustness of axial patterning in a systems biology view. However, recent studies provide data which lead to contradictory interpretations. Here, we discuss these recent observations, highlighting the data helping to understand how anterior patterning is achieved under the control of Bicoid and point to novel challenges for future studies.

  19. Nodal signaling activates the Smad2/3 pathway to regulate stem cell-like properties in breast cancer cells

    PubMed Central

    Gong, Wenchen; Sun, Baocun; Sun, Huizhi; Zhao, Xiulan; Zhang, Danfang; Liu, Tieju; Zhao, Nan; Gu, Qiang; Dong, Xueyi; Liu, Fang

    2017-01-01

    Nodal signaling plays several vital roles in the embryogenesis process. However, its reexpression in breast cancer is correlated with cancer progression, metastasis and poor prognosis. Recently, Nodal has also been reported to regulate self-renewal capacity in pancreatic cancer. This study aimed to explore the role of Nodal in breast cancer stem cells (BCSCs) and the underlying mechanisms. Therefore, the immunohistochemistry staining of Nodal in 135 human breast cancer cases was performed to analyzed the relationship of Nodal signaling, clinical outcomes and BCSC marker. And the results showed that high Nodal expression was positively correlated with poor prognosis and BCSC marker expression in breast cancer samples. We further assessed the effects of Nodal in regulating the BCSC properties in breast cancer cell lines and xenografts. Then, SB431542 was administered in vitro and in vivo to explore the function of the Smad2/3 pathway. And we demonstrated that Nodal signaling up-regulated the expression of ALDH1, CD44, CD133, Sox2, Oct4 and Nanog by activating the Smad2/3 pathway, thereby enhancing the tumorigenicity and sphere-forming ability of breast cancer cells. Furthermore, treatment with SB431542 could inhibit the properties of BCSCs in vitro and in vivo. In conclusion, these findings indicate that Nodal signaling may play a vital role in maintaining the BCSC phenotype in breast cancer and serve as a potential target to explore BCSC-specific therapies.

  20. The retinaldehyde reductase DHRS3 is essential for preventing the formation of excess retinoic acid during embryonic development

    PubMed Central

    Billings, Sara E.; Pierzchalski, Keely; Butler Tjaden, Naomi E.; Pang, Xiao-Yan; Trainor, Paul A.; Kane, Maureen A.; Moise, Alexander R.

    2013-01-01

    Oxidation of retinol via retinaldehyde results in the formation of the essential morphogen all-trans-retinoic acid (ATRA). Previous studies have identified critical roles in the regulation of embryonic ATRA levels for retinol, retinaldehyde, and ATRA-oxidizing enzymes; however, the contribution of retinaldehyde reductases to ATRA metabolism is not completely understood. Herein, we investigate the role of the retinaldehyde reductase Dhrs3 in embryonic retinoid metabolism using a Dhrs3-deficient mouse. Lack of DHRS3 leads to a 40% increase in the levels of ATRA and a 60% and 55% decrease in the levels of retinol and retinyl esters, respectively, in Dhrs3−/− embryos compared to wild-type littermates. Furthermore, accumulation of excess ATRA is accompanied by a compensatory 30–50% reduction in the expression of ATRA synthetic genes and a 120% increase in the expression of the ATRA catabolic enzyme Cyp26a1 in Dhrs3−/− embryos vs. controls. Excess ATRA also leads to alterations (40–80%) in the expression of several developmentally important ATRA target genes. Consequently, Dhrs3−/− embryos die late in gestation and display defects in cardiac outflow tract formation, atrial and ventricular septation, skeletal development, and palatogenesis. These data demonstrate that the reduction of retinaldehyde by DHRS3 is critical for preventing formation of excess ATRA during embryonic development.—Billings, S. E., Pierzchalski, K., Butler Tjaden, N. E., Pang, X.-Y., Trainor, P. A., Kane, M. A., Moise, A. R. The retinaldehyde reductase DHRS3 is essential for preventing the formation of excess retinoic acid during embryonic development. PMID:24005908

  1. Topological nodal-line fermions in spin-orbit metal PbTaSe2

    PubMed Central

    Bian, Guang; Chang, Tay-Rong; Sankar, Raman; Xu, Su-Yang; Zheng, Hao; Neupert, Titus; Chiu, Ching-Kai; Huang, Shin-Ming; Chang, Guoqing; Belopolski, Ilya; Sanchez, Daniel S.; Neupane, Madhab; Alidoust, Nasser; Liu, Chang; Wang, BaoKai; Lee, Chi-Cheng; Jeng, Horng-Tay; Zhang, Chenglong; Yuan, Zhujun; Jia, Shuang; Bansil, Arun; Chou, Fangcheng; Lin, Hsin; Hasan, M. Zahid

    2016-01-01

    Topological semimetals can support one-dimensional Fermi lines or zero-dimensional Weyl points in momentum space, where the valence and conduction bands touch. While the degeneracy points in Weyl semimetals are robust against any perturbation that preserves translational symmetry, nodal lines require protection by additional crystalline symmetries such as mirror reflection. Here we report, based on a systematic theoretical study and a detailed experimental characterization, the existence of topological nodal-line states in the non-centrosymmetric compound PbTaSe2 with strong spin-orbit coupling. Remarkably, the spin-orbit nodal lines in PbTaSe2 are not only protected by the reflection symmetry but also characterized by an integer topological invariant. Our detailed angle-resolved photoemission measurements, first-principles simulations and theoretical topological analysis illustrate the physical mechanism underlying the formation of the topological nodal-line states and associated surface states for the first time, thus paving the way towards exploring the exotic properties of the topological nodal-line fermions in condensed matter systems. PMID:26829889

  2. Role of Nodal-PITX2C signaling pathway in glucose-induced cardiomyocyte hypertrophy.

    PubMed

    Su, Dongmei; Jing, Sun; Guan, Lina; Li, Qian; Zhang, Huiling; Gao, Xiaobo; Ma, Xu

    2014-06-01

    Pathological cardiac hypertrophy is a major cause of morbidity and mortality in cardiovascular disease. Recent studies have shown that cardiomyocytes, in response to high glucose (HG) stimuli, undergo hypertrophic growth. While much work still needs to be done to elucidate this important mechanism of hypertrophy, previous works have showed that some pathways or genes play important roles in hypertrophy. In this study, we showed that sublethal concentrations of glucose (25 mmol/L) could induce cardiomyocyte hypertrophy with an increase in the cellular surface area and the upregulation of the atrial natriuretic peptide (ANP) gene, a hypertrophic marker. High glucose (HG) treatments resulted in the upregulation of the Nodal gene, which is under-expressed in cardiomyocytes. We also determined that the knockdown of the Nodal gene resisted HG-induced cardiomyocyte hypertrophy. The overexpression of Nodal was able to induce hypertrophy in cardiomyocytes, which was associated with the upregulation of the PITX2C gene. We also showed that increases in the PITX2C expression, in response to Nodal, were mediated by the Smad4 signaling pathway. This study is highly relevant to the understanding of the effects of the Nodal-PITX2C pathway on HG-induced cardiomyocyte hypertrophy, as well as the related molecular mechanisms.

  3. Topological nodal-line fermions in spin-orbit metal PbTaSe2

    SciTech Connect

    Bian, Guang; Chang, Tay-Rong; Sankar, Raman; Xu, Su-Yang; Zheng, Hao; Neupert, Titus; Chiu, Ching-Kai; Huang, Shin-Ming; Chang, Guoqing; Belopolski, Ilya; Sanchez, Daniel S.; Neupane, Madhab; Alidoust, Nasser; Liu, Chang; Wang, BaoKai; Lee, Chi-Cheng; Jeng, Horng-Tay; Zhang, Chenglong; Yuan, Zhujun; Jia, Shuang; Bansil, Arun; Chou, Fangcheng; Lin, Hsin; Hasan, M. Zahid

    2016-02-02

    Here we discuss how topological semimetals can support one-dimensional Fermi lines or zero-dimensional Weyl points in momentum space, where the valence and conduction bands touch. While the degeneracy points in Weyl semimetals are robust against any perturbation that preserves translational symmetry, nodal lines require protection by additional crystalline symmetries such as mirror reflection. Here we report, based on a systematic theoretical study and a detailed experimental characterization, the existence of topological nodal-line states in the non-centrosymmetric compound PbTaSe2 with strong spin-orbit coupling. Remarkably, the spin-orbit nodal lines in PbTaSe2 are not only protected by the reflection symmetry but also characterized by an integer topological invariant. Our detailed angle-resolved photoemission measurements, first-principles simulations and theoretical topological analysis illustrate the physical mechanism underlying the formation of the topological nodal-line states and associated surface states for the first time, thus paving the way towards exploring the exotic properties of the topological nodal-line fermions in condensed matter systems.

  4. Topological nodal-line fermions in spin-orbit metal PbTaSe2

    DOE PAGES

    Bian, Guang; Chang, Tay-Rong; Sankar, Raman; ...

    2016-02-02

    Here we discuss how topological semimetals can support one-dimensional Fermi lines or zero-dimensional Weyl points in momentum space, where the valence and conduction bands touch. While the degeneracy points in Weyl semimetals are robust against any perturbation that preserves translational symmetry, nodal lines require protection by additional crystalline symmetries such as mirror reflection. Here we report, based on a systematic theoretical study and a detailed experimental characterization, the existence of topological nodal-line states in the non-centrosymmetric compound PbTaSe2 with strong spin-orbit coupling. Remarkably, the spin-orbit nodal lines in PbTaSe2 are not only protected by the reflection symmetry but also characterizedmore » by an integer topological invariant. Our detailed angle-resolved photoemission measurements, first-principles simulations and theoretical topological analysis illustrate the physical mechanism underlying the formation of the topological nodal-line states and associated surface states for the first time, thus paving the way towards exploring the exotic properties of the topological nodal-line fermions in condensed matter systems.« less

  5. The impact of surgical technique on neck dissection nodal yield: making a difference.

    PubMed

    Lörincz, Balazs B; Langwieder, Felix; Möckelmann, Nikolaus; Sehner, Susanne; Knecht, Rainald

    2016-05-01

    The nodal yield of neck dissections is an independent prognostic factor in several types of head and neck cancer. The authors aimed to determine whether the applied dissection technique has a significant impact on nodal yield. This is a single-institution, prospective study with internal control group (level of evidence: 2A). Data of 150 patients undergoing 223 neck dissections between February 2011 and March 2013 have been collected in a comprehensive cancer centre. Eighty-two patients underwent neck dissection with unwrapping the cervical fascia from lateral to medial, while 68 patients were operated without specifically unwrapping the fascia, in a caudal to cranial fashion. The standardised, horizontal neck dissection technique along the fascial planes resulted in a significantly higher nodal count in Levels I, II, III and IV, as well as in terms of overall nodal yield (mean: n = 22.53) than that of the vertical dissection applied in the control group (mean: n = 15.00). This is the first publication showing a direct correlation between neck dissection nodal yield and surgical technique. Therefore, it is paramount to optimise the applied surgical concept to maximise the oncological benefit.

  6. Interaction of pupil offset and fifth-order nodal aberration field properties in rotationally symmetric telescopes.

    PubMed

    Hu, Haili; Liu, Jianjun; Fan, Zhigang

    2013-07-29

    In this paper we succeeded in deriving changes in the nodal positions of aberrations that belong to the fifth-order class in pupil dependence by applying a system level pupil decentration vector. Our treatment is specifically for rotationally symmetric multi-mirror optical designs that simply use an offset pupil as a means of creating an unobscured optical design. When the pupil is offset, only the vectors to determine the node locations are modified by the pupil decentration vector, while the nodal properties originally developed for titled/decentered optical systems are retained. In general, the modifications to the nodal vectors for any particular aberration type are contributed only by terms of higher order pupil dependence.

  7. Topological nodal line semimetals in the CaP3 family of materials

    NASA Astrophysics Data System (ADS)

    Xu, Qiunan; Yu, Rui; Fang, Zhong; Dai, Xi; Weng, Hongming

    2017-01-01

    By using first-principles calculations and a k .p model analysis, we propose that the three-dimensional topological nodal line semimetal state can be realized in the CaP3 family of materials, which includes CaP3,CaAs3,SrP3,SrAs3, and BaAs3, when spin-orbit coupling (SOC) is ignored. The closed topological nodal line near the Fermi energy is protected by time reversal symmetry and spatial inversion symmetry. Moreover, drumheadlike two-dimensional surface states are also obtained on the c -direction surface of these materials. When SOC is included, the gaps open along the nodal line and these materials become strong topological insulators with Z2 indices as (1 ;010 ) .

  8. Potential for Infra-Nodal Heart Block and Cardiogenic Shock With Propofol Administration

    PubMed Central

    Olson, Nicholas; Lim, Michael J.; Ferreira, Scott W.; Mehdirad, Ali A.

    2013-01-01

    We report a case of infra-nodal complete heart block and cardiogenic shock in a previously healthy 64-year-old man after administration of 180 mg of intravenous Propofol. Although bradycardia, hypotension, and heart block are commonly seen with propofol administration, such findings are transient and respond quickly to administration of vagolytic or sympathomimetic agents suggesting an AV nodal mechanism of heart block. Sustained left ventricular systolic dysfunction and cardiogenic shock by an alternative, non-autonomic mechanism has also been described in the setting of Propofol administration. Our case is the first to note sustained complete infra-nodal heart block in this setting. Early recognition of such a complication, restoration of atrio-ventricular (A-V) synchrony with dual chamber pacing, and aggressive circulatory support is essential in bridging such patients to recovery.

  9. Doping-Dependent Nodal Fermi Velocity in Bi-2212 Revealed by High-Resolution ARPES

    SciTech Connect

    Vishik, I. M.

    2011-08-19

    The improved resolution of laser-based angle-resolved photoemission spectroscopy (ARPES) allows reliable access to fine structures in the spectrum. We present a systematic, doping-dependent study of a recently discovered low-energy kink in the nodal dispersion of Bi{sub 2}Sr{sub 2}CaCu{sub 2}O{sub 8+{delta}} (Bi-2212), which demonstrates the ubiquity and robustness of this kink in underdoped Bi-2212. The renormalization of the nodal velocity due to this kink becomes stronger with underdoping, revealing that the nodal Fermi velocity is non-universal, in contrast to assumed phenomenology. This is used together with laser-ARPES measurements of the gap velocity, v{sub 2}, to resolve discrepancies with thermal conductivity measurements.

  10. All-trans retinol and retinol-binding protein from embryonic cerebrospinal fluid exhibit dynamic behaviour during early central nervous system development.

    PubMed

    Parada, Carolina; Gato, Angel; Bueno, David

    2008-06-11

    Embryonic cerebrospinal fluid (E-CSF) is involved in the regulation of survival, proliferation and neurogenesis of neuroectodermal progenitor cells, as well as in the control of mesencephalic gene expression in collaboration with the isthmic organizer. Recently, we showed the presence of retinol-binding protein (RBP) within the E-CSF proteome. RBP is an all-trans retinol carrier, a molecule that can be metabolized into retinoic acid, a morphogen involved in central nervous system (CNS) morphogenesis and patterning. Here we demonstrate the presence of all-trans retinol within the E-CSF and analyse the dynamics of RBP and all-trans retinol within this fluid, as well as the expression of retinoic acid-synthesizing enzymes during early CNS development. Our results suggest a relationship between the dynamics of these molecules and the early events of CNS patterning.

  11. Why the embryo still matters: CSF and the neuroepithelium as interdependent regulators of embryonic brain growth, morphogenesis and histiogenesis.

    PubMed

    Gato, Angel; Desmond, Mary E

    2009-03-15

    The key focus of this review is that both the neuroepithelium and embryonic cerebrospinal fluid (CSF) work in an integrated way to promote embryonic brain growth, morphogenesis and histiogenesis. The CSF generates pressure and also contains many biologically powerful trophic factors; both play key roles in early brain development. Accumulation of fluid via an osmotic gradient creates pressure that promotes rapid expansion of the early brain in a developmental regulated way, since the rates of growth differ between the vesicles and for different species. The neuroepithelium and ventricles both contribute to this growth but by different and coordinated mechanisms. The neuroepithelium grows primarily by cell proliferation and at the same time the ventricle expands via hydrostatic pressure generated by active transport of Na(+) and transport or secretion of proteins and proteoglycans that create an osmotic gradient which contribute to the accumulation of fluid inside the sealed brain cavity. Recent evidence shows that the CSF regulates relevant aspects of neuroepithelial behavior such as cell survival, replication and neurogenesis by means of growth factors and morphogens. Here we try to highlight that early brain development requires the coordinated interplay of the CSF contained in the brain cavity with the surrounding neuroepithelium. The information presented is essential in order to understand the earliest phases of brain development and also how neuronal precursor behavior is regulated.

  12. The 18.6 yr nodal modulation in the tides of Southern European coasts

    NASA Astrophysics Data System (ADS)

    Shaw, A. G. P.; Tsimplis, M. N.

    2010-02-01

    The nodal modulation of the diurnal ( K1 and O1) and semi-diurnal ( M2 and K2) tidal constituents at the coasts of the Mediterranean Sea and the eastern Atlantic is estimated and its spatial variability mapped. Fourteen hourly tide gauge records each spanning more than 18 years are considered in this analysis. Ten tide gauges are located in the Mediterranean Sea and four in the Bay of Biscay. The nodal modulation of the most energetic tidal constituent ( M2) reaches up to 5 cm at the eastern Atlantic coasts, while within the Mediterranean Sea its modulation is in general less than 1.1 cm. The largest K2 nodal modulation found is 3.7 cm in the eastern Atlantic coasts. In the Mediterranean Sea, smaller modulation amplitudes, ranging between 0.4 and 1.4 cm are found. The K1 tide constituent has the largest amplitude nodal modulation within the Mediterranean Sea of 1.9 cm in the north Adriatic Sea, which is also larger than the modulation of this constituent at the eastern Atlantic coasts. The O1 tide constituent has the highest amplitude nodal modulation (1.4 cm) at the eastern Atlantic coasts. In the Mediterranean Sea the maximum value is 1 cm in the north Adriatic Sea. The derived nodal modulations of the diurnal and semi-diurnal constituents follow, in general, the equilibrium tidal theory. The tidal amplitudes for all four components do not indicate significant secular trends for most tide gauges. The tidal phases indicate significant negative trends for all four tidal constituents within the central and eastern Mediterranean Sea.

  13. A predictive index of axillary nodal involvement in operable breast cancer.

    PubMed Central

    De Laurentiis, M.; Gallo, C.; De Placido, S.; Perrone, F.; Pettinato, G.; Petrella, G.; Carlomagno, C.; Panico, L.; Delrio, P.; Bianco, A. R.

    1996-01-01

    We investigated the association between pathological characteristics of primary breast cancer and degree of axillary nodal involvement and obtained a predictive index of the latter from the former. In 2076 cases, 17 histological features, including primary tumour and local invasion variables, were recorded. The whole sample was randomly split in a training (75% of cases) and a test sample. Simple and multiple correspondence analysis were used to select the variables to enter in a multinomial logit model to build an index predictive of the degree of nodal involvement. The response variable was axillary nodal status coded in four classes (N0, N1-3, N4-9, N > or = 10). The predictive index was then evaluated by testing goodness-of-fit and classification accuracy. Covariates significantly associated with nodal status were tumour size (P < 0.0001), tumour type (P < 0.0001), type of border (P = 0.048), multicentricity (P = 0.003), invasion of lymphatic and blood vessels (P < 0.0001) and nipple invasion (P = 0.006). Goodness-of-fit was validated by high concordance between observed and expected number of cases in each decile of predicted probability in both training and test samples. Classification accuracy analysis showed that true node-positive cases were well recognised (84.5%), but there was no clear distinction among the classes of node-positive cases. However, 10 year survival analysis showed a superimposible prognostic behaviour between predicted and observed nodal classes. Moreover, misclassified node-negative patients (i.e. those who are predicted positive) showed an outcome closer to patients with 1-3 metastatic nodes than to node-negative ones. In conclusion, the index cannot completely substitute for axillary node information, but it is a predictor of prognosis as accurate as nodal involvement and identifies a subgroup of node-negative patients with unfavourable prognosis. PMID:8630286

  14. Melanocytes Affect Nodal Expression and Signaling in Melanoma Cells: A Lesson from Pediatric Large Congenital Melanocytic Nevi.

    PubMed

    Margaryan, Naira V; Gilgur, Alina; Seftor, Elisabeth A; Purnell, Chad; Arva, Nicoleta C; Gosain, Arun K; Hendrix, Mary J C; Strizzi, Luigi

    2016-03-22

    Expression of Nodal, a Transforming Growth Factor-beta (TGF-β) related growth factor, is associated with aggressive melanoma. Nodal expression in adult dysplastic nevi may predict the development of aggressive melanoma in some patients. A subset of pediatric patients diagnosed with giant or large congenital melanocytic nevi (LCMN) has shown increased risk for development of melanoma. Here, we investigate whether Nodal expression can help identify the rare cases of LCMN that develop melanoma and shed light on why the majority of these patients do not. Immunohistochemistry (IHC) staining results show varying degree of Nodal expression in pediatric dysplastic nevi and LCMN. Moreover, median scores from Nodal IHC expression analysis were not significantly different between these two groups. Additionally, none of the LCMN patients in this study developed melanoma, regardless of Nodal IHC levels. Co-culture experiments revealed reduced tumor growth and lower levels of Nodal and its signaling molecules P-SMAD2 and P-ERK1/2 when melanoma cells were grown in vivo or in vitro with normal melanocytes. The same was observed in melanoma cells cultured with melanocyte conditioned media containing pigmented melanocyte derived melanosomes (MDM). Since MDM contain molecules capable of inactivating radical oxygen species, to investigate potential anti-oxidant effect of MDM on Nodal expression and signaling in melanoma, melanoma cells were treated with either N-acetyl-l-cysteine (NAC), a component of the anti-oxidant glutathione or synthetic melanin, which in addition to providing pigmentation can also exert free radical scavenging activity. Melanoma cells treated with NAC or synthetic melanin showed reduced levels of Nodal, P-SMAD2 and P-ERK1/2 compared to untreated melanoma cells. Thus, the potential role for Nodal in melanoma development in LCMN is less evident than in adult dysplastic nevi possibly due to melanocyte cross-talk in LCMN capable of offsetting or delaying the pro

  15. On bistable phasing of 18.6 year nodal induced flood in India

    NASA Astrophysics Data System (ADS)

    Currie, Robert G.

    1984-01-01

    In agreement with Campbell (1983), Flood Area Indices (FAI) for India are interpreted as being modulated by tidal forcing at the 18.6 yr lunar nodal period. There is evidence maximum flood was approximately out of phase with nodal epoch 1898.9 whereas at epochs 1917.5, 1936,1, 1954.7, and 1973.3 maximum flood was approximately in phase. This interpretation implies that India should be experiencing widespread dryness in an interval ±2 to 3 years centered at mid-epoch 1982.6.

  16. Nodal superconductivity in FeS: Evidence from quasiparticle heat transport

    NASA Astrophysics Data System (ADS)

    Ying, T. P.; Lai, X. F.; Hong, X. C.; Xu, Y.; He, L. P.; Zhang, J.; Wang, M. X.; Yu, Y. J.; Huang, F. Q.; Li, S. Y.

    2016-09-01

    We report low-temperature heat transport measurements on superconducting iron sulfide FeS with Tc≈5 K, which has the same crystal structure and similar electronic band structure to the superconducting iron selenide FeSe. In zero magnetic field, a significant residual linear term κ0/T is observed. At low field, κ0/T increases rapidly with increasing field. These results suggest a nodal superconducting gap in FeS. We compare it with the sister compound FeSe and other iron-based superconductors with nodal gaps.

  17. Embryonic Stem Cell Growth Factors Regulate eIF2α Phosphorylation

    PubMed Central

    Friend, Kyle; Brooks, Hunter A.; Propson, Nicholas E.; Thomson, James A.; Kimble, Judith

    2015-01-01

    Growth factors and transcription factors are well known to regulate pluripotent stem cells, but less is known about translational control in stem cells. Here, we use embryonic stem cells (ESCs) to investigate a connection between ESC growth factors and eIF2α-mediated translational control (eIF2α phosphorylation promotes protein expression from mRNAs with upstream open-reading frames, or uORFs). We find abundant phosphorylated P-eIF2α (P-eIF2α) in both pluripotent mouse and human ESCs, but little P-eIF2α in ESCs triggered to differentiate. We show that the growth factors LIF (leukemia inhibitory factor) and BMP4 (bone morphogenic protein 4) both maintain P-eIF2α in mESCs, but use distinct mechanisms: LIF inhibits an eIF2α phosphatase whereas BMP4 activates an eIF2α kinase. The mRNAs encoding the pluripotency factors Nanog and c-Myc possess uORFs while Oct4 mRNA does not. We find that salubrinal, a chemical that increases eIF2α phosphorylation, promotes Nanog and c-Myc expression, but not Oct4 expression. These experiments connect ESC growth factors to eIF2α phosphorylation and suggest a chemical substitute for LIF to enhance Nanog and c-Myc expression. PMID:26406898

  18. Embryonic markers of cone differentiation

    PubMed Central

    Rodgers, Helen M.; Belcastro, Marycharmain; Sokolov, Maxim

    2016-01-01

    Purpose Photoreceptor cells are born in two distinct phases of vertebrate retinogenesis. In the mouse retina, cones are born primarily during embryogenesis, while rod formation occurs later in embryogenesis and early postnatal ages. Despite this dichotomy in photoreceptor birthdates, the visual pigments and phototransduction machinery are not reactive to visual stimulus in either type of photoreceptor cell until the second postnatal week. Several markers of early cone formation have been identified, including Otx2, Crx, Blimp1, NeuroD, Trβ2, Rorβ, and Rxrγ, and all are thought to be involved in cellular determination. However, little is known about the expression of proteins involved in cone visual transduction during early retinogenesis. Therefore, we sought to characterize visual transduction proteins that are expressed specifically in photoreceptors during mouse embryogenesis. Methods Eye tissue was collected from control and phosducin-null mice at embryonic and early postnatal ages. Immunohistochemistry and quantitative reverse transcriptase-PCR (qPCR) were used to measure the spatial and temporal expression patterns of phosducin (Pdc) and cone transducin γ (Gngt2) proteins and transcripts in the embryonic and early postnatal mouse retina. Results We identified the embryonic expression of phosducin (Pdc) and cone transducin γ (Gngt2) that coincides temporally and spatially with the earliest stages of cone histogenesis. Using immunohistochemistry, the phosducin protein was first detected in the retina at embryonic day (E)12.5, and cone transducin γ was observed at E13.5. The phosducin and cone transducin γ proteins were seen only in the outer neuroblastic layer, consistent with their expression in photoreceptors. At the embryonic ages, phosducin was coexpressed with Rxrγ, a known cone marker, and with Otx2, a marker of photoreceptors. Pdc and Gngt2 mRNAs were detected as early as E10.5 with qPCR, although at low levels. Conclusions Visual transduction

  19. Nodal Quasiparticle Meltdown in Ultra-High Resolution Pump-Probe Angle-Resolved Photoemission

    SciTech Connect

    Graf, Jeff; Jozwiak, Chris; Smallwood, Chris L.; Eisaki, H.; Kaindl, Robert A.; Lee, Dung-Hai; Lanzara, Alessandra

    2011-06-03

    High-T{sub c} cuprate superconductors are characterized by a strong momentum-dependent anisotropy between the low energy excitations along the Brillouin zone diagonal (nodal direction) and those along the Brillouin zone face (antinodal direction). Most obvious is the d-wave superconducting gap, with the largest magnitude found in the antinodal direction and no gap in the nodal direction. Additionally, while antin- odal quasiparticle excitations appear only below T{sub c}, superconductivity is thought to be indifferent to nodal excitations as they are regarded robust and insensitive to T{sub c}. Here we reveal an unexpected tie between nodal quasiparticles and superconductivity using high resolution time- and angle-resolved photoemission on optimally doped Bi{sub 2}Sr{sub 2}CaCu{sub 2}O{sub 8+{delta}} . We observe a suppression of the nodal quasiparticle spectral weight following pump laser excitation and measure its recovery dynamics. This suppression is dramatically enhanced in the superconducting state. These results reduce the nodal-antinodal dichotomy and challenge the conventional view of nodal excitation neutrality in superconductivity. The electronic structures of high-Tc cuprates are strongly momentum-dependent. This is one reason why the momentum-resolved technique of angle-resolved photoemission spectroscopy (ARPES) has been a central tool in the field of high-temperature superconductivity. For example, coherent low energy excitations with momenta near the Brillouin zone face, or antinodal quasiparticles (QPs), are only observed below T{sub c} and have been linked to superfluid density. They have therefore been the primary focus of ARPES studies. In contrast, nodal QPs, with momenta along the Brillouin zone diagonal, have received less attention and are usually regarded as largely immune to the superconducting transition because they seem insensitive to perturbations such as disorder, doping, isotope exchange, charge ordering, and temperature. Clearly

  20. Impact of Incidental Irradiation on Clinically Uninvolved Nodal Regions in Patients With Advanced Non-Small-Cell Lung Cancer Treated With Involved-Field Radiation Therapy: Does Incidental Irradiation Contribute to the Low Incidence of Elective Nodal Failure?

    SciTech Connect

    Kimura, Tomoki; Togami, Taro; Nishiyama, Yoshihiro; Ohkawa, Motoomi; Takashima, Hitoshi

    2010-06-01

    Purpose: To evaluate the incidental irradiation dose to elective nodal regions in the treatment of advanced non-small-cell lung cancer with involved-field radiation therapy (IF-RT) and the pattern of elective nodal failure (ENF). Methods and Materials: Fifty patients with advanced non-small-cell lung cancer, who received IF-RT at Kagawa University were enrolled. To evaluate the dose of incidental irradiation, we delineated nodal regions with a Japanese map and the American Thoracic Society map (levels 1-11) in each patient retrospectively and calculated the dose parameters such as mean dose, D95, and V95 (40 Gy as the prescribed dose of elective nodal irradiation). Results: Using the Japanese map, the median mean dose was more than 40 Gy in most of the nodal regions, except at levels 1, 3, and 7. In particular, each dosimetric parameter of level 1 was significantly lower than those at other levels, and each dosimetric parameter of levels 10 to 11 ipsilateral (11I) was significantly higher than those in other nodal regions. Using the American Thoracic Society map, basically, the results were similar to those of the Japanese map. ENF was observed in 4 patients (8%), five nodal regions, and no mean dose to the nodal region exceeded 40 Gy. On the Japanese map, each parameter of these five nodal region was significantly lower than those of the other nodal regions. Conclusions: These results show that a high dose of incidental irradiation may contribute to the low incidence of ENF in patients who have received IF-RT.

  1. Retinoid-independent motor neurogenesis from human embryonic stem cells reveals a medial columnar ground state

    PubMed Central

    Patani, R.; Hollins, A. J.; Wishart, T. M.; Puddifoot, C. A.; Álvarez, S.; de Lera, A. R.; Wyllie, D. J. A.; Compston, D. A. S.; Pedersen, R. A.; Gillingwater, T. H.; Hardingham, G. E.; Allen, N. D.; Chandran, S.

    2011-01-01

    A major challenge in neurobiology is to understand mechanisms underlying human neuronal diversification. Motor neurons (MNs) represent a diverse collection of neuronal subtypes, displaying differential vulnerability in different human neurodegenerative diseases. The ability to manipulate cell subtype diversification is critical to establish accurate, clinically relevant in vitro disease models. Retinoid signalling contributes to caudal precursor specification and subsequent MN subtype diversification. Here we investigate the necessity for retinoic acid in motor neurogenesis from human embryonic stem cells. We show that activin/nodal signalling inhibition, followed by sonic hedgehog agonist treatment, is sufficient for MN precursor specification, which occurs even in the presence of retinoid pathway antagonists. Importantly, precursors mature into HB9/ChAT-expressing functional MNs. Furthermore, retinoid-independent motor neurogenesis results in a ground state biased to caudal, medial motor columnar identities from which a greater retinoid-dependent diversity of MNs, including those of lateral motor columns, can be selectively derived in vitro. PMID:21364553

  2. Cripto is essential to capture mouse epiblast stem cell and human embryonic stem cell pluripotency.

    PubMed

    Fiorenzano, Alessandro; Pascale, Emilia; D'Aniello, Cristina; Acampora, Dario; Bassalert, Cecilia; Russo, Francesco; Andolfi, Gennaro; Biffoni, Mauro; Francescangeli, Federica; Zeuner, Ann; Angelini, Claudia; Chazaud, Claire; Patriarca, Eduardo J; Fico, Annalisa; Minchiotti, Gabriella

    2016-09-02

    Known molecular determinants of developmental plasticity are mainly transcription factors, while the extrinsic regulation of this process has been largely unexplored. Here we identify Cripto as one of the earliest epiblast markers and a key extracellular determinant of the naive and primed pluripotent states. We demonstrate that Cripto sustains mouse embryonic stem cell (ESC) self-renewal by modulating Wnt/β-catenin, whereas it maintains mouse epiblast stem cell (EpiSC) and human ESC pluripotency through Nodal/Smad2. Moreover, we provide unprecedented evidence that Cripto controls the metabolic reprogramming in ESCs to EpiSC transition. Remarkably, Cripto deficiency attenuates ESC lineage restriction in vitro and in vivo, and permits ESC transdifferentiation into trophectoderm lineage, suggesting that Cripto has earlier functions than previously recognized. All together, our studies provide novel insights into the current model of mammalian pluripotency and contribute to the understanding of the extrinsic regulation of the first cell lineage decision in the embryo.

  3. Cripto is essential to capture mouse epiblast stem cell and human embryonic stem cell pluripotency

    PubMed Central

    Fiorenzano, Alessandro; Pascale, Emilia; D'Aniello, Cristina; Acampora, Dario; Bassalert, Cecilia; Russo, Francesco; Andolfi, Gennaro; Biffoni, Mauro; Francescangeli, Federica; Zeuner, Ann; Angelini, Claudia; Chazaud, Claire; Patriarca, Eduardo J.; Fico, Annalisa; Minchiotti, Gabriella

    2016-01-01

    Known molecular determinants of developmental plasticity are mainly transcription factors, while the extrinsic regulation of this process has been largely unexplored. Here we identify Cripto as one of the earliest epiblast markers and a key extracellular determinant of the naive and primed pluripotent states. We demonstrate that Cripto sustains mouse embryonic stem cell (ESC) self-renewal by modulating Wnt/β-catenin, whereas it maintains mouse epiblast stem cell (EpiSC) and human ESC pluripotency through Nodal/Smad2. Moreover, we provide unprecedented evidence that Cripto controls the metabolic reprogramming in ESCs to EpiSC transition. Remarkably, Cripto deficiency attenuates ESC lineage restriction in vitro and in vivo, and permits ESC transdifferentiation into trophectoderm lineage, suggesting that Cripto has earlier functions than previously recognized. All together, our studies provide novel insights into the current model of mammalian pluripotency and contribute to the understanding of the extrinsic regulation of the first cell lineage decision in the embryo. PMID:27586544

  4. Embryonic development during chronic acceleration

    NASA Technical Reports Server (NTRS)

    Smith, A. H.; Abbott, U. K.

    1982-01-01

    Experiments carried out on chicken eggs indicate that the embryo is affected during very early development, especially over the first four days, and during hatching. In the first four days, the brain develops as well as the anlage for all other organs. In addition, the heart commences to function and the extraembryonic membranes that compartmentalize the egg contents form. The latter require an appreciable extension and folding of tissue which may be disrupted by the mechanical load. Observations of embryonic abnormalities that occur during chronic acceleration suggest an inhibition of development of the axial skeleton, which is rarely seen otherwise, a general retardation of embryonic growth, and circulatory problems. The final stages of development (after 18 days) involve the uptake of fluids, the transition to aerial respiration, and the reorientation of the embryo into a normal hatching position. At 4 G mortality is very high during this period, with a majority of embryos failing to reorient into the normal hatching position.

  5. Electroporation of Embryonic Kidney Explants

    NASA Astrophysics Data System (ADS)

    Haddad, Nicholas; Houle, Daniel; Gupta, Indra R.

    Metanephric kidney development in the mouse begins at embryonic day (E) 10.5, when the ureteric bud (UB), an outgrowth of the epithelial nephric duct, invades the neighboring metanephric mesenchyme (MM). The ureteric bud then undergoes a series of branching events to form the collecting duct network of the adult kidney (Fig. 19.1). As each ureteric bud tip forms, the adjacent undifferentiated mesenchyme is induced to epithelialize and form a nephron, the functional unit of the adult kidney that filters waste. Rodent embryonic kidneys can be dissected and cultured as explants such that branching morphogenesis and nephrogenesis can be observed ex vivo (Rothenpieler and Dressler, 1993; Vega et al., 1996; Piscione et al., 1997; Gupta et al., 2003).

  6. Lefty Glycoproteins in Human Embryonic Stem Cells: Extracellular Delivery Route and Posttranslational Modification in Differentiation.

    PubMed

    Khalkhali-Ellis, Zhila; Galat, Vasiliy; Galat, Yekaterina; Gilgur, Alina; Seftor, Elisabeth A; Hendrix, Mary J C

    2016-09-19

    Lefty is a member of transforming growth factor-beta (TGF-β) superfamily and a potent antagonist of the TGF-β/Nodal/Activin signaling pathway. Lefty is critical in sustaining self-renewal/pluripotency status, and implicated in the differentiation of embryonic stem cells (ESCs). However, emerging studies depict Lefty as a multifaceted protein involved in myriad cellular events. Lefty proteins (human Lefty A and B) are secreted glycoproteins, but their mode of secretion and the significance of their "glycan" moiety remain mostly unexplored. By employing an in vitro system of human ESCs (hESCs), we observed that Lefty protein(s) are encased in exosomes for extracellular release. The exosomal- and cell-associated Lefty diverge in their proteolytic processing, and possess N-glycan structures of high mannose and complex nature. Differentiation of hESCs to mesenchymal cells (MSCs) or neuronal progenitor cells (NPCs) entails distinct changes in the Lefty A/Lefty B gene(s), and protein expression. Specifically, the proteolytic cleavage and N-glycan composition of the cell-associated and exosomal Lefty differ in the differentiated progenies. These modifications affected Lefty's inhibitory effect on Nodal signaling in aggressive melanoma cells. The microheterogeneity in the processing and glycosylation of Lefty protein(s) between hESCs, MSCs, and NPCs could present efficient means of diversifying the endogenous functions of Lefty. Whether Lefty's diverse functions in embryonic patterning, as well as its diffusion range in the extracellular environment, are similarly affected remains to be determined. Our studies underscore the potential relevance of Lefty-packaged exosomes for combating debilitating diseases such as cancer.

  7. Embryonic Development of the Central Nervous System.

    PubMed

    de Lahunta, Alexander; Glass, Eric N; Kent, Marc

    2016-03-01

    Ultimately, it is only with an understanding of normal embryologic development that there can be an understanding of why and how a specific malformation develops. Knowing from where and when a specific part of the nervous system develops and what morphogens are at play will enable us to identify undescribed malformation as well as better define causality. The following article reviews the normal embryologic development of the mammalian nervous system and is intended to serve as a foundation for the understanding of the various malformations presented in this issue.

  8. The 18.6 yr nodal cycle and its impact on tidal sedimentation

    NASA Astrophysics Data System (ADS)

    Oost, A. P.; de Haas, H.; Ijnsen, F.; van den Boogert, J. M.; de Boer, P. L.

    1993-09-01

    The 18.6 yr nodal cycle modulates tidal amplitudes and currents, and consequently sedimentation in tide-influenced sedimentary environments. Data are presented which show that such effects are obvious along the coast of the Dutch barrier islands and in the sedimentary fill of abandoned channels.

  9. Nodal Analysis Optimization Based on the Use of Virtual Current Sources: A Powerful New Pedagogical Method

    ERIC Educational Resources Information Center

    Chatzarakis, G. E.

    2009-01-01

    This paper presents a new pedagogical method for nodal analysis optimization based on the use of virtual current sources, applicable to any linear electric circuit (LEC), regardless of its complexity. The proposed method leads to straightforward solutions, mostly arrived at by inspection. Furthermore, the method is easily adapted to computer…

  10. Precision evaluation of lens systems using a nodal slide/MTF optical bench

    NASA Astrophysics Data System (ADS)

    Doherty, Victor J.; Chapnik, Philip D.

    1992-01-01

    A compact, self-contained production instrument designed to permit the rapid and precise performance characterization of a wide variety of lenses and optical systems has been developed by Eidolon Corporation. The Eidolon Production Nodal Slide/MTF Measurement System can be used to measure effective focal length (EFL), distortion, field curvature, chromatic aberration, spot size, and modulation transfer function (MTF).

  11. Nodal surface approximations to the P, G, D and I-WP triply periodic minimal surfaces

    NASA Astrophysics Data System (ADS)

    Gandy, Paul J. F.; Bardhan, Sonny; Mackay, Alan L.; Klinowski, Jacek

    2001-03-01

    The cubic P, G, D and I-WP triply periodic minimal surfaces (TPMS) may be closely approximated using periodic nodal surfaces (PNS) with few Fourier terms, thus enabling easy generation of TPMS for use in various chemical and physical applications. The accuracy of such approximations is quantitatively discussed and represented visually using a colour coding.

  12. 5-Hydroxymethylcytosine expression in metastatic melanoma versus nodal nevus in sentinel lymph node biopsies.

    PubMed

    Lee, Jonathan J; Granter, Scott R; Laga, Alvaro C; Saavedra, Arturo P; Zhan, Qian; Guo, Weimin; Xu, Shuyun; Murphy, George F; Lian, Christine G

    2015-02-01

    Sentinel lymph node biopsies are conducted to stage patients with newly diagnosed melanomas that have histopathological attributes conferring defined levels of metastatic potential. Because benign nevic cells may also form 'deposits' in lymph nodes (nodal nevus), the pathological evaluation for metastatic melanoma within sentinel lymph nodes can be challenging. Twenty-eight sentinel lymph node biopsy cases containing either metastatic melanoma (N=18) or nodal nevi (N=10) were retrieved from the archives of the Brigham and Women's Hospital, Department of Pathology (2011-2014). In addition, two sentinel lymph node cases that were favored to represent metastatic disease but whose histopathological features were viewed as equivocal, with melanoma favored, were also included. Dual labeling for the melanocyte lineage marker, MART-1, and the epigenetic marker, 5-hydroxymethylcytosine, a functionally significant indicator that has been shown to distinguish benign nevi from melanoma, was performed on all cases using immunohistochemistry and/or direct immunofluorescence. All (18 of 18) metastatic melanoma cases showed complete loss of 5-hydroxymethylcytosine nuclear staining in MART-1-positive cells, and all (10 of 10) nodal nevus cases demonstrated 5-hydroxymethylcytosine nuclear staining in MART-1-positive cells. In addition, 5-hydroxymethylcytosine staining confirmed the favored diagnoses of metastatic melanoma in the two 'equivocal' cases. Thus, 5-hydroxymethylcytosine may be a useful adjunctive marker to distinguish between benign nodal nevi and metastatic melanoma during the evaluation of sentinel lymph node biopsies for metastatic melanoma.

  13. Nodal Green’s Function Method Singular Source Term and Burnable Poison Treatment in Hexagonal Geometry

    SciTech Connect

    A.A. Bingham; R.M. Ferrer; A.M. ougouag

    2009-09-01

    An accurate and computationally efficient two or three-dimensional neutron diffusion model will be necessary for the development, safety parameters computation, and fuel cycle analysis of a prismatic Very High Temperature Reactor (VHTR) design under Next Generation Nuclear Plant Project (NGNP). For this purpose, an analytical nodal Green’s function solution for the transverse integrated neutron diffusion equation is developed in two and three-dimensional hexagonal geometry. This scheme is incorporated into HEXPEDITE, a code first developed by Fitzpatrick and Ougouag. HEXPEDITE neglects non-physical discontinuity terms that arise in the transverse leakage due to the transverse integration procedure application to hexagonal geometry and cannot account for the effects of burnable poisons across nodal boundaries. The test code being developed for this document accounts for these terms by maintaining an inventory of neutrons by using the nodal balance equation as a constraint of the neutron flux equation. The method developed in this report is intended to restore neutron conservation and increase the accuracy of the code by adding these terms to the transverse integrated flux solution and applying the nodal Green’s function solution to the resulting equation to derive a semi-analytical solution.

  14. NOKIN1D: one-dimensional neutron kinetics based on a nodal collocation method

    NASA Astrophysics Data System (ADS)

    Verdú, G.; Ginestar, D.; Miró, R.; Jambrina, A.; Barrachina, T.; Soler, Amparo; Concejal, Alberto

    2014-06-01

    The TRAC-BF1 one-dimensional kinetic model is a formulation of the neutron diffusion equation in the two energy groups' approximation, based on the analytical nodal method (ANM). The advantage compared with a zero-dimensional kinetic model is that the axial power profile may vary with time due to thermal-hydraulic parameter changes and/or actions of the control systems but at has the disadvantages that in unusual situations it fails to converge. The nodal collocation method developed for the neutron diffusion equation and applied to the kinetics resolution of TRAC-BF1 thermal-hydraulics, is an adaptation of the traditional collocation methods for the discretization of partial differential equations, based on the development of the solution as a linear combination of analytical functions. It has chosen to use a nodal collocation method based on a development of Legendre polynomials of neutron fluxes in each cell. The qualification is carried out by the analysis of the turbine trip transient from the NEA benchmark in Peach Bottom NPP using both the original 1D kinetics implemented in TRAC-BF1 and the 1D nodal collocation method.

  15. 47 CFR 101.503 - Digital Electronic Message Service Nodal Stations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Digital Electronic Message Service Nodal Stations. 101.503 Section 101.503 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES 24 GHz Service and Digital Electronic...

  16. A Developmentally Based Categorization of Branching in Trifolium repens L.: Influence of Nodal Roots

    PubMed Central

    THOMAS, R. G.; HAY, M. J. M.; NEWTON, P. C. D.

    2002-01-01

    This study describes the successive stages of development of branches from axillary buds in fully rooted plants of Trifolium repens grown in near optimal conditions, and the way in which this developmental pathway differs when nodal root formation is prevented as plants grow out from a rooted base. Cuttings of a single genotype were established in a glasshouse with nodal root systems on the two basal phytomers and grown on so that nodal rooting was either permitted (+R) or prevented (–R). In +R plants, axillary tissues could be assigned to one of four developmental categories: unemerged buds, emerged buds, unbranched lateral branches or secondarily branched lateral branches. In –R plants, branch development was retarded, with the retardation becoming increasingly pronounced as the number of –R phytomers on the primary stolon increased. Retarded elongation of the internodes of lateral shoots on –R plants resulted in the formation of a distinct fifth developmental category: short shoots (defined as branches with two or more leaves but with mean internode length equal to, or less than, 10 % of that of the immediately proximal internode on the parent stolon) which had reduced phytomer appearance rates but retained the potential to develop into lateral branches. Transfer of +R plants to –R conditions, and vice versa, after 66 d demonstrated that subsequent branch development was wholly under the control of the youngest nodal root present, regardless of the age and number of root systems proximal to it. PMID:12234150

  17. Nodal Structure and Stimulus Relatedness in Equivalence Classes: Post-Class Formation Preference Tests

    ERIC Educational Resources Information Center

    Moss-Lourenco, Patricia; Fields, Lanny

    2011-01-01

    Three experiments used postclass formation within-class preference test performances to evaluate the effects of nodal distance on the relatedness of stimuli in equivalence classes. In Experiment 1, two 2-node four-member equivalence classes were established using the simultaneous protocol in which all of the baseline relations were trained…

  18. Photoacoustic intra-operative nodal staging using clinically approved superparamagnetic iron oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Grootendorst, Diederik J.; Fratila, Raluca M.; Visscher, Martijn; Ten Haken, Bennie; van Wezel, Richard; Steenbergen, Wiendelt; Manohar, Srirang; Ruers, Theo J. M.

    2013-02-01

    Detection of tumor metastases in the lymphatic system is essential for accurate staging of various malignancies, however fast, accurate and cost-effective intra-operative evaluation of the nodal status remains difficult to perform with common available medical imaging techniques. In recent years, numerous studies have confirmed the additional value of superparamagnetic iron oxide dispersions (SPIOs) for nodal staging purposes, prompting the clearance of different SPIO dispersions for clinical practice. We evaluate whether a combination of photoacoustic (PA) imaging and a clinically approved SPIO dispersion, could be applied for intra-operative nodal staging. Metastatic adenocarcinoma was inoculated in Copenhagen rats for 5 or 8 days. After SPIO injection, the lymph nodes were photoacoustically imaged both in vivo and ex vivo whereafter imaging results were correlated with MR and histology. Results were compared to a control group without tumor inoculation. In the tumor groups clear irregularities, as small as 1 mm, were observed in the PA contrast pattern of the nodes together with an decrease of PA response. These irregularities could be correlated to the absence of contrast in the MR images and could be linked to metastatic deposits seen in the histological slides. The PA and MR images of the control animals did not show these features. We conclude that the combination of photoacoustic imaging with a clinically approved iron oxide nanoparticle dispersion is able to detect lymph node metastases in an animal model. This approach opens up new possibilities for fast intra-operative nodal staging in a clinical setting.

  19. Anomalous nodal count and singularities in the dispersion relation of honeycomb graphs

    NASA Astrophysics Data System (ADS)

    Band, Ram; Berkolaiko, Gregory; Weyand, Tracy

    2015-12-01

    We study the nodal count of the so-called bi-dendral graphs and show that it exhibits an anomaly: the nodal surplus is never equal to 0 or β, the first Betti number of the graph. According to the nodal-magnetic theorem, this means that bands of the magnetic spectrum (dispersion relation) of such graphs do not have maxima or minima at the "usual" symmetry points of the fundamental domain of the reciprocal space of magnetic parameters. In search of the missing extrema, we prove a necessary condition for a smooth critical point to happen inside the reciprocal fundamental domain. Using this condition, we identify the extrema as the singularities in the dispersion relation of the maximal Abelian cover of the graph (the honeycomb graph being an important example). In particular, our results show that the anomalous nodal count is an indication of the presence of conical points in the dispersion relation of the maximal universal cover. We also discover that the conical points are present in the dispersion relation of graphs with much less symmetry than was required in previous investigations.

  20. Static and dynamic posterior cingulate cortex nodal topology of default mode network predicts attention task performance.

    PubMed

    Lin, Pan; Yang, Yong; Jovicich, Jorge; De Pisapia, Nicola; Wang, Xiang; Zuo, Chun S; Levitt, James Jonathan

    2016-03-01

    Characterization of the default mode network (DMN) as a complex network of functionally interacting dynamic systems has received great interest for the study of DMN neural mechanisms. In particular, understanding the relationship of intrinsic resting-state DMN brain network with cognitive behaviors is an important issue in healthy cognition and mental disorders. However, it is still unclear how DMN functional connectivity links to cognitive behaviors during resting-state. In this study, we hypothesize that static and dynamic DMN nodal topology is associated with upcoming cognitive task performance. We used graph theory analysis in order to understand better the relationship between the DMN functional connectivity and cognitive behavior during resting-state and task performance. Nodal degree of the DMN was calculated as a metric of network topology. We found that the static and dynamic posterior cingulate cortex (PCC) nodal degree within the DMN was associated with task performance (Reaction Time). Our results show that the core node PCC nodal degree within the DMN was significantly correlated with reaction time, which suggests that the PCC plays a key role in supporting cognitive function.

  1. Partial Unroofed Coronary Sinus Associated With Upper Septal Ventricular Tachycardia and Atrioventricular Nodal Reentrant Tachycardia

    PubMed Central

    Bohora, Shomu; Singh, Parvindar; Shah, Kaushal

    2016-01-01

    A 58 year old gentleman with complaints of palpitations and documented tachycardia was found to have a dilated right atrium, right ventricle and coronary sinus, which were due to partial unroofed coronary sinus without a left superior vena cava. He had upper septal ventricular tachycardia and atrio-ventricular nodal reentrant tachycardia, which was successfully treated by radiofrequency ablation. PMID:25852246

  2. Analysis of nodal aberration properties in off-axis freeform system design.

    PubMed

    Shi, Haodong; Jiang, Huilin; Zhang, Xin; Wang, Chao; Liu, Tao

    2016-08-20

    Freeform surfaces have the advantage of balancing off-axis aberration. In this paper, based on the framework of nodal aberration theory (NAT) applied to the coaxial system, the third-order astigmatism and coma wave aberration expressions of an off-axis system with Zernike polynomial surfaces are derived. The relationship between the off-axis and surface shape acting on the nodal distributions is revealed. The nodal aberration properties of the off-axis freeform system are analyzed and validated by using full-field displays (FFDs). It has been demonstrated that adding Zernike terms, up to nine, to the off-axis system modifies the nodal locations, but the field dependence of the third-order aberration does not change. On this basis, an off-axis two-mirror freeform system with 500 mm effective focal length (EFL) and 300 mm entrance pupil diameter (EPD) working in long-wave infrared is designed. The field constant aberrations induced by surface tilting are corrected by selecting specific Zernike terms. The design results show that the nodes of third-order astigmatism and coma move back into the field of view (FOV). The modulation transfer function (MTF) curves are above 0.4 at 20 line pairs per millimeter (lp/mm) which meets the infrared reconnaissance requirement. This work provides essential insight and guidance for aberration correction in off-axis freeform system design.

  3. An approach to model reactor core nodalization for deterministic safety analysis

    SciTech Connect

    Salim, Mohd Faiz Samsudin, Mohd Rafie; Mamat Ibrahim, Mohd Rizal; Roslan, Ridha Sadri, Abd Aziz; Farid, Mohd Fairus Abd

    2016-01-22

    Adopting good nodalization strategy is essential to produce an accurate and high quality input model for Deterministic Safety Analysis (DSA) using System Thermal-Hydraulic (SYS-TH) computer code. The purpose of such analysis is to demonstrate the compliance against regulatory requirements and to verify the behavior of the reactor during normal and accident conditions as it was originally designed. Numerous studies in the past have been devoted to the development of the nodalization strategy for small research reactor (e.g. 250kW) up to the bigger research reactor (e.g. 30MW). As such, this paper aims to discuss the state-of-arts thermal hydraulics channel to be employed in the nodalization for RTP-TRIGA Research Reactor specifically for the reactor core. At present, the required thermal-hydraulic parameters for reactor core, such as core geometrical data (length, coolant flow area, hydraulic diameters, and axial power profile) and material properties (including the UZrH{sub 1.6}, stainless steel clad, graphite reflector) have been collected, analyzed and consolidated in the Reference Database of RTP using standardized methodology, mainly derived from the available technical documentations. Based on the available information in the database, assumptions made on the nodalization approach and calculations performed will be discussed and presented. The development and identification of the thermal hydraulics channel for the reactor core will be implemented during the SYS-TH calculation using RELAP5-3D{sup ®} computer code. This activity presented in this paper is part of the development of overall nodalization description for RTP-TRIGA Research Reactor under the IAEA Norwegian Extra-Budgetary Programme (NOKEBP) mentoring project on Expertise Development through the Analysis of Reactor Thermal-Hydraulics for Malaysia, denoted as EARTH-M.

  4. ARPES Study of Nodal Quasiparticles Using Low-Energy Tunable Photons

    NASA Astrophysics Data System (ADS)

    Ino, Akihiro

    2006-03-01

    Low-energy quasiparticle excitations govern the thermodynamic properties of a superconductor both in the zero-field and vortex-mixed states. For a d-wave superconductor, nodal quasiparticles are crucial excitations starting from zero energy. So far, however, the nodal quasiparticle dynamics of high-Tc cuprates has been controversial. For example, it has been reported by an angle-resolved-photoemission (ARPES) experiment that the marginal-Fermi-liquid behavior persists into the superconducting state without appreciable change in the scattering rate, while microwave conductivity increases upon the superconducting transition. Here, we show a new ARPES result that solves the controversies with unprecedented momentum-resolution. Low-energy tunable photons have enabled us to resolve a small nodal bilayer splitting clearly, and to reveal the detailed temperature- and energy-dependence of the scattering rate, indicating the behaviors unique to the nodal quasiparticles. Due to the opening of the d-wave gap, the nodal scattering rate is remarkably suppressed, and shows a linear energy dependence. The difference in the energy-linear term between the bilayer-resolved scattering rates hints the nature of impurities involved. This work was done in collaboration with T. Yamasaki, T. Kamo, K. Yamazaki, H. Anzai, M. Arita, H. Namatame, M. Taniguchi, Grad. Sch. of Science and Hiroshima Synchrotron Radiation Center, Hiroshima Univ., A. Fujimori, Dept. of Complexity Science and Engineering, Univ. of Tokyo, Z.-X. Shen, Dept. of Physics, Applied Physics and SSRL, Stanford Univ., M. Ishikado, K. Fujita, and S. Uchida, Dept. of Physics, Univ. of Tokyo.

  5. A nodal triangle-based spectral element method for the shallow water equations on the sphere

    NASA Astrophysics Data System (ADS)

    Giraldo, F. X.; Warburton, T.

    2005-07-01

    A nodal triangle-based spectral element (SE) method for the shallow water equations on the sphere is presented. The original SE method uses quadrilateral elements and high-order nodal Lagrange polynomials, constructed from a tensor-product of the Legendre-Gauss-Lobatto points. In this work, we construct the high-order Lagrange polynomials directly on the triangle using nodal sets obtained from the electrostatics principle [J.S. Hesthaven, From electrostatics to almost optimal nodal sets for polynomial interpolation in a simplex, SIAM Journal on Numerical Analysis 35 (1998) 655-676] and Fekete points [M.A. Taylor, B.A. Wingate, R.E. Vincent, An algorithm for computing Fekete points in the triangle, SIAM Journal on Numerical Analysis 38 (2000) 1707-1720]. These points have good approximation properties and far better Lebesgue constants than any other nodal set derived for the triangle. By employing triangular elements as the basic building-blocks of the SE method and the Cartesian coordinate form of the equations, we can use any grid imaginable including adaptive unstructured grids. Results for six test cases are presented to confirm the accuracy and stability of the method. The results show that the triangle-based SE method yields the expected exponential convergence and that it can be more accurate than the quadrilateral-based SE method even while using 30-60% fewer grid points especially when adaptive grids are used to align the grid with the flow direction. However, at the moment, the quadrilateral-based SE method is twice as fast as the triangle-based SE method because the latter does not yield a diagonal mass matrix.

  6. Combined-modality therapy for patients with regional nodal metastases from melanoma

    SciTech Connect

    Ballo, Matthew T. . E-mail: mballo@mdanderson.org; Ross, Merrick I.; Cormier, Janice N.; Myers, Jeffrey N.; Lee, Jeffrey E.; Gershenwald, Jeffrey E.; Hwu, Patrick; Zagars, Gunar K.

    2006-01-01

    Purpose: To evaluate the outcome and patterns of failure for patients with nodal metastases from melanoma treated with combined-modality therapy. Methods and Materials: Between 1983 and 2003, 466 patients with nodal metastases from melanoma were managed with lymphadenectomy and radiation, with or without systemic therapy. Surgery was a therapeutic procedure for clinically apparent nodal disease in 434 patients (regionally advanced nodal disease). Adjuvant radiation was generally delivered with a hypofractionated regimen. Adjuvant systemic therapy was delivered to 154 patients. Results: With a median follow-up of 4.2 years, 252 patients relapsed and 203 patients died of progressive disease. The actuarial 5-year disease-specific, disease-free, and distant metastasis-free survival rates were 49%, 42%, and 44%, respectively. By multivariate analysis, increasing number of involved lymph nodes and primary ulceration were associated with an inferior 5-year actuarial disease-specific and distant metastasis-free survival. Also, the number of involved lymph nodes was associated with the development of brain metastases, whereas thickness was associated with lung metastases, and primary ulceration was associated with liver metastases. The actuarial 5-year regional (in-basin) control rate for all patients was 89%, and on multivariate analysis there were no patient or disease characteristics associated with inferior regional control. The risk of lymphedema was highest for those patients with groin lymph node metastases. Conclusions: Although regional nodal disease can be satisfactorily controlled with lymphadenectomy and radiation, the risk of distant metastases and melanoma death remains high. A management approach to these patients that accounts for the competing risks of distant metastases, regional failure, and long-term toxicity is needed.

  7. An approach to model reactor core nodalization for deterministic safety analysis

    NASA Astrophysics Data System (ADS)

    Salim, Mohd Faiz; Samsudin, Mohd Rafie; Mamat @ Ibrahim, Mohd Rizal; Roslan, Ridha; Sadri, Abd Aziz; Farid, Mohd Fairus Abd

    2016-01-01

    Adopting good nodalization strategy is essential to produce an accurate and high quality input model for Deterministic Safety Analysis (DSA) using System Thermal-Hydraulic (SYS-TH) computer code. The purpose of such analysis is to demonstrate the compliance against regulatory requirements and to verify the behavior of the reactor during normal and accident conditions as it was originally designed. Numerous studies in the past have been devoted to the development of the nodalization strategy for small research reactor (e.g. 250kW) up to the bigger research reactor (e.g. 30MW). As such, this paper aims to discuss the state-of-arts thermal hydraulics channel to be employed in the nodalization for RTP-TRIGA Research Reactor specifically for the reactor core. At present, the required thermal-hydraulic parameters for reactor core, such as core geometrical data (length, coolant flow area, hydraulic diameters, and axial power profile) and material properties (including the UZrH1.6, stainless steel clad, graphite reflector) have been collected, analyzed and consolidated in the Reference Database of RTP using standardized methodology, mainly derived from the available technical documentations. Based on the available information in the database, assumptions made on the nodalization approach and calculations performed will be discussed and presented. The development and identification of the thermal hydraulics channel for the reactor core will be implemented during the SYS-TH calculation using RELAP5-3D® computer code. This activity presented in this paper is part of the development of overall nodalization description for RTP-TRIGA Research Reactor under the IAEA Norwegian Extra-Budgetary Programme (NOKEBP) mentoring project on Expertise Development through the Analysis of Reactor Thermal-Hydraulics for Malaysia, denoted as EARTH-M.

  8. Radiotherapy for Esthesioneuroblastoma: Is Elective Nodal Irradiation Warranted in the Multimodality Treatment Approach?

    SciTech Connect

    Noh, O Kyu; Lee, Sang-wook; Yoon, Sang Min; Kim, Sung Bae; Kim, Sang Yoon; Kim, Chang Jin; Jo, Kyung Ja; Choi, Eun Kyung; Song, Si Yeol; Kim, Jong Hoon; Ahn, Seung Do

    2011-02-01

    Purpose: The role of elective nodal irradiation (ENI) in radiotherapy for esthesioneuroblastoma (ENB) has not been clearly defined. We analyzed treatment outcomes of patients with ENB and the frequency of cervical nodal failure in the absence of ENI. Methods and Materials: Between August 1996 and December 2007, we consulted with 19 patients with ENB regarding radiotherapy. Initial treatment consisted of surgery alone in 2 patients; surgery and postoperative radiotherapy in 4; surgery and adjuvant chemotherapy in 1; surgery, postoperative radiotherapy, and chemotherapy in 3; and chemotherapy followed by radiotherapy or concurrent chemoradiotherapy in 5. Five patients did not receive planned radiotherapy because of disease progression. Including 2 patients who received salvage radiotherapy, 14 patients were treated with radiotherapy. Elective nodal irradiation was performed in 4 patients with high-risk factors, including 3 with cervical lymph node metastasis at presentation. Results: Fourteen patients were analyzable, with a median follow-up of 27 months (range, 7-64 months). The overall 3-year survival rate was 73.4%. Local failure occurred in 3 patients (21.4%), regional cervical failure in 3 (21.4%), and distant failure in 2 (14.3%). No cervical nodal failure occurred in patients treated with combined systemic chemotherapy regardless of ENI. Three cervical failures occurred in the 4 patients treated with ENI or neck dissection (75%), none of whom received systemic chemotherapy. Conclusions: ENI during radiotherapy for ENB seems to play a limited role in preventing cervical nodal failure. Omitting ENI may be an option if patients are treated with a combination of radiotherapy and chemotherapy.

  9. Correlation effects and quantum oscillations in topological nodal-loop semimetals

    NASA Astrophysics Data System (ADS)

    Liu, Jianpeng; Balents, Leon

    2017-02-01

    We study the unique physical properties of topological nodal-loop semimetals protected by the coexistence of time-reversal and inversion symmetries with negligible spin-orbit coupling. We argue that strong correlation effects occur at the surface of such systems for relatively small Hubbard interaction U , due to the narrow bandwidth of the "drumhead" surface states. In the Hartree-Fock approximation, at small U we obtain a surface ferromagnetic phase through a continuous quantum phase transition characterized by the surface-mode divergence of the spin susceptibility, while the bulk states remain very robust against local interactions and remain nonordered. At slightly increased interaction strength, the system quickly changes from a surface ferromagnetic phase to a surface charge-ordered phase through a first-order transition. When Rashba-type spin-orbit coupling is applied to the surface states, a canted ferromagnetic phase occurs at the surface for intermediate values of U . The quantum critical behavior of the surface ferromagnetic transition is nontrivial in the sense that the surface spin order parameter couples to Fermi-surface excitations from both surface and bulk states. This leads to unconventional Landau damping and consequently a naïve dynamical critical exponent z ≈1 when the Fermi level is close to the bulk nodal energy. We also show that, already without interactions, quantum oscillations arise due to bulk states, despite the absence of a Fermi surface when the chemical potential is tuned to the energy of the nodal loop. The bulk magnetic susceptibility diverges logarithmically whenever the nodal loop exactly overlaps with a quantized magnetic orbit in the bulk Brillouin zone. These correlation and transport phenomena are unique signatures of nodal-loop states.

  10. Mammographic Density and Prediction of Nodal Status in Breast Cancer Patients

    PubMed Central

    Hack, C. C.; Häberle, L.; Geisler, K.; Schulz-Wendtland, R.; Hartmann, A.; Fasching, P. A.; Uder, M.; Wachter, D. L.; Jud, S. M.; Loehberg, C. R.; Lux, M. P.; Rauh, C.; Beckmann, M. W.; Heusinger, K.

    2013-01-01

    Aim: Nodal status remains one of the most important prognostic factors in breast cancer. The cellular and molecular reasons for the spread of tumor cells to the lymph nodes are not well understood and there are only few predictors in addition to tumor size and multifocality that give an insight into additional mechanisms of lymphatic spread. Aim of our study was therefore to investigate whether breast characteristics such as mammographic density (MD) add to the predictive value of the presence of lymph node metastases in patients with primary breast cancer. Methods: In this retrospective study we analyzed primary, metastasis-free breast cancer patients from one breast center for whom data on MD and staging information were available. A total of 1831 patients were included into this study. MD was assessed as percentage MD (PMD) using a semiautomated method and two readers for every patient. Multiple logistic regression analyses with nodal status as outcome were used to investigate the predictive value of PMD in addition to age, tumor size, Ki-67, estrogen receptor (ER), progesterone receptor (PR), grading, histology, and multi-focality. Results: Multifocality, tumor size, Ki-67 and grading were relevant predictors for nodal status. Adding PMD to a prediction model which included these factors did not significantly improve the prediction of nodal status (p = 0.24, likelihood ratio test). Conclusion: Nodal status could be predicted quite well with the factors multifocality, tumor size, Ki-67 and grading. PMD does not seem to play a role in the lymphatic spread of tumor cells. It could be concluded that the amount of extracellular matrix and stromal cell content of the breast which is reflected by MD does not influence the probability of malignant breast cells spreading from the primary tumor to the lymph nodes. PMID:24771910

  11. Nodal signaling is required for mesodermal and ventral but not for dorsal fates in the indirect developing hemichordate, Ptychodera flava

    PubMed Central

    Röttinger, Eric; DuBuc, Timothy Q.; Amiel, Aldine R.; Martindale, Mark Q.

    2015-01-01

    ABSTRACT Nodal signaling plays crucial roles in vertebrate developmental processes such as endoderm and mesoderm formation, and axial patterning events along the anteroposterior, dorsoventral and left-right axes. In echinoderms, Nodal plays an essential role in the establishment of the dorsoventral axis and left-right asymmetry, but not in endoderm or mesoderm induction. In protostomes, Nodal signaling appears to be involved only in establishing left-right asymmetry. Hence, it is hypothesized that Nodal signaling has been co-opted to pattern the dorsoventral axis of deuterostomes and for endoderm, mesoderm formation as well as anteroposterior patterning in chordates. Hemichordata, together with echinoderms, represent the sister taxon to chordates. In this study, we analyze the role of Nodal signaling in the indirect developing hemichordate Ptychodera flava. In particular, we show that during gastrulation nodal transcripts are detected in a ring of cells at the vegetal pole that gives rise to endomesoderm and in the ventral ectoderm at later stages of development. Inhibition of Nodal function disrupts dorsoventral fates and also blocks formation of the larval mesoderm. Interestingly, molecular analysis reveals that only mesodermal, apical and ventral gene expression is affected while the dorsal side appears to be patterned correctly. Taken together, this study suggests that the co-option of Nodal signaling in mesoderm formation and potentially in anteroposterior patterning has occurred prior to the emergence of chordates and that Nodal signaling on the ventral side is uncoupled from BMP signaling on the dorsal side, representing a major difference from the molecular mechanisms of dorsoventral patterning events in echinoderms. PMID:25979707

  12. Nodal signaling is required for mesodermal and ventral but not for dorsal fates in the indirect developing hemichordate, Ptychodera flava.

    PubMed

    Röttinger, Eric; DuBuc, Timothy Q; Amiel, Aldine R; Martindale, Mark Q

    2015-05-15

    Nodal signaling plays crucial roles in vertebrate developmental processes such as endoderm and mesoderm formation, and axial patterning events along the anteroposterior, dorsoventral and left-right axes. In echinoderms, Nodal plays an essential role in the establishment of the dorsoventral axis and left-right asymmetry, but not in endoderm or mesoderm induction. In protostomes, Nodal signaling appears to be involved only in establishing left-right asymmetry. Hence, it is hypothesized that Nodal signaling has been co-opted to pattern the dorsoventral axis of deuterostomes and for endoderm, mesoderm formation as well as anteroposterior patterning in chordates. Hemichordata, together with echinoderms, represent the sister taxon to chordates. In this study, we analyze the role of Nodal signaling in the indirect developing hemichordate Ptychodera flava. In particular, we show that during gastrulation nodal transcripts are detected in a ring of cells at the vegetal pole that gives rise to endomesoderm and in the ventral ectoderm at later stages of development. Inhibition of Nodal function disrupts dorsoventral fates and also blocks formation of the larval mesoderm. Interestingly, molecular analysis reveals that only mesodermal, apical and ventral gene expression is affected while the dorsal side appears to be patterned correctly. Taken together, this study suggests that the co-option of Nodal signaling in mesoderm formation and potentially in anteroposterior patterning has occurred prior to the emergence of chordates and that Nodal signaling on the ventral side is uncoupled from BMP signaling on the dorsal side, representing a major difference from the molecular mechanisms of dorsoventral patterning events in echinoderms.

  13. Culture and Manipulation of Embryonic Cells

    PubMed Central

    Edgar, Lois G.; Goldstein, Bob

    2012-01-01

    The direct manipulation of embryonic cells is an important tool for addressing key questions in cell and developmental biology. C. elegans is relatively unique among genetic model systems in being amenable to manipulation of embryonic cells. Embryonic cell manipulation has allowed the identification of cell interactions by direct means, and it has been an important technique for dissecting mechanisms by which cell fates are specified, cell divisions are oriented, and morphogenesis is accomplished. Here, we present detailed methods for isolating, manipulating and culturing embryonic cells of C. elegans. PMID:22226523

  14. [Obvious or inapparent Wolff-Parkinson-White syndrome associated with duality of nodal conduction. Apropos of 4 cases].

    PubMed

    Motté, G; Belhassen, B; Bodereau, P

    1979-03-01

    In a series of 48 patients undergoing electrophysiological investigation for attacks of reciprocating tachycardia related to concealed or overt Wolff-Parkinson-White syndrome in sinus rhythm, 4 patients were found to have duality of nodal conduction. This association was responsible for several tachycardia circuits: in 2 patients the activation passed constantly retrogradely through the accessory pathway and then either through the slow nodal pathway or the rapid nodal pathway in the anterograde direction. In the other two patients, in addition to classical orthodromic tachycardia, purely intranodal reciprocating rhythms giving rise to sustained tachycardia in one case and to simple echos in the other, were observed.

  15. An amphioxus nodal gene (AmphiNodal) with early symmetrical expression in the organizer and mesoderm and later asymmetrical expression associated with left-right axis formation

    NASA Technical Reports Server (NTRS)

    Yu, Jr-Kai; Holland, Linda Z.; Holland, Nicholas D.

    2002-01-01

    The full-length sequence and zygotic expression of an amphioxus nodal gene are described. Expression is first detected in the early gastrula just within the dorsal lip of the blastopore in a region of hypoblast that is probably comparable with the vertebrate Spemann's organizer. In the late gastrula and early neurula, expression remains bilaterally symmetrical, limited to paraxial mesoderm and immediately overlying regions of the neural plate. Later in the neurula stage, all neural expression disappears, and mesodermal expression disappears from the right side. All along the left side of the neurula, mesodermal expression spreads into the left side of the gut endoderm. Soon thereafter, all expression is down-regulated except near the anterior and posterior ends of the animal, where transcripts are still found in the mesoderm and endoderm on the left side. At this time, expression also begins in the ectoderm on the left side of the head, in the region where the mouth later forms. These results suggest that amphioxus and vertebrate nodal genes play evolutionarily conserved roles in establishing Spemann's organizer, patterning the mesoderm rostrocaudally and setting up the asymmetrical left-right axis of the body.

  16. Cholesterol-derived glucocorticoids control early fate specification in embryonic stem cells

    PubMed Central

    Cabral-Teixeira, Joaquim; Martinez-Fernandez, Almudena; Cai, Wenqing; Terzic, Andre; Mercola, Mark; Willems, Erik

    2015-01-01

    Summary Aside from its role in cell membrane integrity, cholesterol is a key component in steroid hormone production. The vital functions of steroid hormones such as estrogen, testosterone, glucocorticoids (Gcrts) and mineralocorticoids (Mnrts) in perinatal and adult life are well understood; however, their role during early embryonic development remains largely unexplored. Here we show that siRNA-mediated perturbation of steroid hormone production during mesoderm formation has important consequences on cardiac differentiation in mouse embryonic stem cells (mESC). Both Gcrts and Mnrts are capable of driving cardiac differentiation in mESC. Interestingly, the Gcrt receptor is widely expressed during gastrulation in the mouse, and is exclusively localized in the nuclei - and thus active - in visceral endoderm cells, suggesting that it functions much earlier than previously anticipated. We therefore studied Gcrt signaling in mESC as a model of the gastrulating embryo, and found that Gcrt signaling regulates expression of the transcription factor Hnf4a and the secreted Nodal and BMP inhibitor Cer1 in the early visceral endoderm. RNAi-mediated knockdown of Gcrt function blocked cardiomyocyte differentiation, with limited effects on other cardiovascular cell types including vascular endothelial cells and smooth muscle. Furthermore, the cardiogenic effect of Gcrts required Hnf4a and paracrine Cer1. These results establish a novel function for cholesterol-derived steroid hormones and identify Gcrt signaling in visceral endoderm cells as a regulator of Cer1 and cardiac fate. PMID:26024790

  17. Self-energy of a nodal fermion in a d -wave superconductor

    NASA Astrophysics Data System (ADS)

    Chubukov, A. V.; Tsvelik, A. M.

    2006-06-01

    We reconsider the self-energy of a nodal (Dirac) fermion in a two-dimensional d -wave superconductor. A conventional belief is that ImΣ(ω,T)˜max(ω3,T3) . We show that Σ(ω,k,T) for k along the nodal direction is actually a complex function of ω,T , and the deviation from the mass shell. In particular, the second-order self-energy diverges at a finite T when either ω or k-kF vanish. We show that the full summation of infinite diagrammatic series recovers a finite result for Σ , but the full angle-resolved photoemission spectroscopy spectral function is nonmonotonic and has a kink whose location compared to the mass shell differs qualitatively for spin-and charge-mediated interactions.

  18. The ancestral role of nodal signalling in breaking L/R symmetry in the vertebrate forebrain.

    PubMed

    Lagadec, Ronan; Laguerre, Laurent; Menuet, Arnaud; Amara, Anis; Rocancourt, Claire; Péricard, Pierre; Godard, Benoît G; Rodicio, Maria Celina; Rodriguez-Moldes, Isabel; Mayeur, Hélène; Rougemont, Quentin; Mazan, Sylvie; Boutet, Agnès

    2015-03-30

    Left-right asymmetries in the epithalamic region of the brain are widespread across vertebrates, but their magnitude and laterality varies among species. Whether these differences reflect independent origins of forebrain asymmetries or taxa-specific diversifications of an ancient vertebrate feature remains unknown. Here we show that the catshark Scyliorhinus canicula and the lampreys Petromyzon marinus and Lampetra planeri exhibit conserved molecular asymmetries between the left and right developing habenulae. Long-term pharmacological treatments in these species show that nodal signalling is essential to their generation, rather than their directionality as in teleosts. Moreover, in contrast to zebrafish, habenular left-right differences are observed in the absence of overt asymmetry of the adjacent pineal field. These data support an ancient origin of epithalamic asymmetry, and suggest that a nodal-dependent asymmetry programme operated in the forebrain of ancestral vertebrates before evolving into a variable trait in bony fish.

  19. The effect of viscosity on steady transonic flow with a nodal solution topology

    NASA Technical Reports Server (NTRS)

    Owocki, Stanley P.; Zank, Gary P.

    1991-01-01

    The effect of viscosity on a steady, transonic flow for which the inviscid limit has a nodal solution topology near the critical point is investigated. For the accelerating case, viscous solutions tend to repel each other, so that a very delicate choice of initial conditions is required to prevent them from diverging. Only the two critical solutions extend to arbitrarily large distances into both the subsonic and supersonic flows. For the decelerating case, the solutions tend to attract, and so an entire two-parameter family of solutions now extends over large distances. The general effect of viscosity on the solution degeneracy of a nodal topology is thus to reduce or limit it for the accelerating case and to enhance it for the decelerating case. The astrophysical implications of these findings are addressed.

  20. The General-Use Nodal Network Solver (GUNNS) Modeling Package for Space Vehicle Flow System Simulation

    NASA Technical Reports Server (NTRS)

    Harvey, Jason; Moore, Michael

    2013-01-01

    The General-Use Nodal Network Solver (GUNNS) is a modeling software package that combines nodal analysis and the hydraulic-electric analogy to simulate fluid, electrical, and thermal flow systems. GUNNS is developed by L-3 Communications under the TS21 (Training Systems for the 21st Century) project for NASA Johnson Space Center (JSC), primarily for use in space vehicle training simulators at JSC. It has sufficient compactness and fidelity to model the fluid, electrical, and thermal aspects of space vehicles in real-time simulations running on commodity workstations, for vehicle crew and flight controller training. It has a reusable and flexible component and system design, and a Graphical User Interface (GUI), providing capability for rapid GUI-based simulator development, ease of maintenance, and associated cost savings. GUNNS is optimized for NASA's Trick simulation environment, but can be run independently of Trick.

  1. Anisotropic properties of unconventional superconductors in a magnetic field: testing the nodal stucture

    NASA Astrophysics Data System (ADS)

    Vorontsov, Anton; Vekhter, Ilya

    2006-03-01

    We present a calculation of electronic specific heat and heat conductivity in a vortex state of quasi-two dimensional d-wave superconductors. We employ quasiclassical theory and use the Brand-Pesch-Tewordt approximation to model the superconducting state at moderate to high magnetic fields. Within this framework we investigate the dependence of heat capacity and heat conductivity on the angle of rotation of magnetic field with respect to the nodal directions. We find that the fourfold anisotropy due to nodal structure in both quantities changes sign in the temperature-field plane. This result helps resolve the apparent disagreement about the gap symmetry reached from the specific heat and the thermal conductivity measurements in CeCoIn5. We comment on the physics behind the difference between our results and those obtained in the Doppler shift approximation.

  2. Unidimensional Measurement May Evaluate Target Lymph Nodal Response After Induction Chemotherapy for Nasopharyngeal Carcinoma

    PubMed Central

    Chen, Chuanben; Zhang, Mingwei; Xu, Yuanji; Yue, Qiuyuan; Bai, Penggang; Zhou, Lin; Xiao, Youping; Zheng, Dechun; Lin, Kongqi; Qiu, Sufang; Chen, Yunbin; Pan, Jianji

    2016-01-01

    Abstract The aim of the study was to evaluate whether short axis and long axis on axial and coronal magnetic resonance imaging planes would reflect the tumor burden or alteration in size after induction chemotherapy in nasopharyngeal carcinoma. Patients with pathologically confirmed nasopharyngeal carcinoma (n = 37) with at least 1 positive cervical lymph node (axial short axis ≥15 mm) were consecutively enrolled in this prospective study. Lymph nodal measurements were performed along its short axis and long axis in both axial and coronal magnetic resonance imaging planes at diagnosis and after 2 cycles of induction chemotherapy. In addition, lymph nodal volumes were automatically calculated in 3D treatment-planning system, which were used as reference standard. Student's t test or nonparametric Mann–Whitney U test was used to compare the continuous quantitative variables. Meanwhile, the κ statistic and McNemar's test were used to evaluate the degree of agreement and discordance in response categorization among different measurements. Axial short axis was significantly associated with volumes at diagnosis (P < 0.001). A good agreement (κ=0.583) was found between axial short axis and volumetric criteria. However, the inconsistent lymph nodal shrinkage in 4 directions was observed. Axial short-axis shrinking was more rapid than the other 3 parameters. Interestingly, when utilizing the alternative planes for unidimensional measurements to assess tumor response, coronal short-axis showed the best concordance (κ=0.792) to the volumes. Axial short axis may effectively reflect tumor burden or change in tumor size in the assessment of target lymph nodal response after induction chemotherapy for nasopharyngeal carcinoma. However, it should be noted that axial short axis may amplify the therapeutic response. In addition, the role of coronal short axis in the assessment of tumor response needs further evaluation. PMID:26945354

  3. Nodal recovery, dual pathway physiology, and concealed conduction determine complex AV dynamics in human atrial tachyarrhythmias.

    PubMed

    Masè, Michela; Glass, Leon; Disertori, Marcello; Ravelli, Flavia

    2012-11-15

    The genesis of complex ventricular rhythms during atrial tachyarrhythmias in humans is not fully understood. To clarify the dynamics of atrioventricular (AV) conduction in response to a regular high-rate atrial activation, 29 episodes of spontaneous or pacing-induced atrial flutter (AFL), covering a wide range of atrial rates (cycle lengths from 145 to 270 ms), were analyzed in 10 patients. AV patterns were identified by applying firing sequence and surrogate data analysis to atrial and ventricular activation series, whereas modular simulation with a difference-equation AV node model was used to correlate the patterns with specific nodal properties. AV node response at high atrial rate was characterized by 1) AV patterns of decreasing conduction ratios at the shortening of atrial cycle length (from 236.3 ± 32.4 to 172.6 ± 17.8 ms) according to a Farey sequence ordering (conduction ratio from 0.34 ± 0.12 to 0.23 ± 0.06; P < 0.01); 2) the appearance of high-order alternating Wenckebach rhythms, such as 6:2, 10:2, and 12:2, associated with ventricular interval oscillations of large amplitude (407.7 ± 150.4 ms); and 3) the deterioration of pattern stability at advanced levels of block, with the percentage of stable patterns decreasing from 64.3 ± 35.2% to 28.3 ± 34.5% (P < 0.01). Simulations suggested these patterns to originate from the combined effect of nodal recovery, dual pathway physiology, and concealed conduction. These results indicate that intrinsic nodal properties may account for the wide spectrum of AV block patterns occurring during regular atrial tachyarrhythmias. The characterization of AV nodal function during different AFL forms constitutes an intermediate step toward the understanding of complex ventricular rhythms during atrial fibrillation.

  4. Numerical divergence effects of equivalence theory in the nodal expansion method

    SciTech Connect

    Zika, M.R.; Downar, T.J. )

    1993-11-01

    Accurate solutions of the advanced nodal equations require the use of discontinuity factors (DFs) to account for the homogenization errors that are inherent in all coarse-mesh nodal methods. During the last several years, nodal equivalence theory (NET) has successfully been implemented for the Cartesian geometry and has received widespread acceptance in the light water reactor industry. The extension of NET to other reactor types has had limited success. Recent efforts to implement NET within the framework of the nodal expansion method have successfully been applied to the fast breeder reactor. However, attempts to apply the same methods to thermal reactors such as the Modular High-Temperature Gas Reactor (MHTGR) have led to numerical divergence problems that can be attributed directly to the magnitude of the DFs. In the work performed here, it was found that the numerical problems occur in the inner and upscatter iterations of the solution algorithm. These iterations use a Gauss-Seidel iterative technique that is always convergent for problems with unity DFs. However, for an MHTGR model that requires large DFs, both the inner and upscatter iterations were divergent. Initial investigations into methods for bounding the DFs have proven unsatisfactory as a means of remedying the convergence problems. Although the DFs could be bounded to yield a convergent solution, several cases were encountered where the resulting flux solution was less accurate than the solution without DFs. For the specific case of problems without upscattering, an alternate numerical method for the inner iteration, an LU decomposition, was identified and shown to be feasible.

  5. Gastroblastoma in a 28-year-old man with nodal metastasis: proof of the malignant potential.

    PubMed

    Wey, Elizabeth A; Britton, Andrew J; Sferra, Joseph J; Kasunic, Tim; Pepe, Linda R; Appelman, Henry D

    2012-08-01

    Gastroblastoma is a newly defined neoplasm of children and young adults with only 4 reported cases to date. Morphologically, the tumor is a mixture of epithelial structures and stromal elements with minimal cytologic atypia. In these 4 reported cases, there were no metastases or postresection recurrences. We report a case of gastroblastoma in a 28-year-old man with a histologic nodal metastasis and clinical distant metastases.

  6. Nodal collocation approximation for the multidimensional PL equations applied to transport source problems

    SciTech Connect

    Verdu, G.; Capilla, M.; Talavera, C. F.; Ginestar, D.

    2012-07-01

    PL equations are classical high order approximations to the transport equations which are based on the expansion of the angular dependence of the angular neutron flux and the nuclear cross sections in terms of spherical harmonics. A nodal collocation method is used to discretize the PL equations associated with a neutron source transport problem. The performance of the method is tested solving two 1D problems with analytical solution for the transport equation and a classical 2D problem. (authors)

  7. NODAL in the uterus is necessary for proper placental development and maintenance of pregnancy.

    PubMed

    Park, Craig B; DeMayo, Francesco J; Lydon, John P; Dufort, Daniel

    2012-06-01

    Preterm birth is the single leading cause of perinatal mortality in developed countries, affecting approximately 12% of pregnancies and accounting for 75% of neonatal loss in the United States. Despite the prevalence and severity of premature delivery, the causes and mechanisms that underlie spontaneous and idiopathic preterm birth remain unknown. Our inability to elucidate these fundamental causes has been attributed to a poor understanding of the signaling pathways associated with the premature induction of parturition and a lack of suitable animal models available for preterm birth research. In this study, we describe the generation and analysis of a novel conditional knockout of the transforming growth factor beta (TGFB) superfamily member, Nodal, from the maternal reproductive tract of mice. Strikingly, uterine Nodal knockout females exhibited a severe malformation of the maternal decidua basalis during placentation, leading to significant intrauterine growth restriction, and ultimately preterm birth and fetal loss on Day 17.5 of gestation. Using several approaches, we characterized aberrant placental development and demonstrated that reduced proliferation combined with increased apoptosis resulted in a diminished decidua basalis and compromised maternal-fetal interface. Last, we evaluated various components of the established parturition cascade and determined that preterm birth derived from the maternal Nodal knockout occurs prior to PTGS2 (COX-2) upregulation at the placental interface. Taken together, the results presented in this study highlight an in vivo role for maternal NODAL during placentation, present an interesting link between disrupted decidua basalis formation and premature parturition, and describe a potentially valuable model toward elucidating the complex processes that underlie preterm birth.

  8. Nodal soliton solutions for generalized quasilinear Schrödinger equations

    SciTech Connect

    Deng, Yinbin Peng, Shuangjie; Wang, Jixiu

    2014-05-15

    This paper is concerned with constructing nodal radial solutions for generalized quasilinear Schrödinger equations in R{sup N} which arise from plasma physics, fluid mechanics, as well as high-power ultashort laser in matter. For any given integer k ⩾ 0, by using a change of variables and minimization argument, we obtain a sign-changing minimizer with k nodes of a minimization problem.

  9. Three-Dimensional Conformal Radiation Therapy for Esophageal Squamous Cell Carcinoma: Is Elective Nodal Irradiation Necessary?

    SciTech Connect

    Zhao Kuaile; Ma Jinbo; Liu Guang; Wu Kailiang; Shi Xuehui; Jiang Guoliang

    2010-02-01

    Purpose: To evaluate the local control, survival, and toxicity associated with three-dimensional conformal radiotherapy (3D-CRT) for squamous cell carcinoma (SCC) of the esophagus, to determine the appropriate target volumes, and to determine whether elective nodal irradiation is necessary in these patients. Methods and Materials: A prospective study of 3D-CRT was undertaken in patients with esophageal SCC without distant metastases. Patients received 68.4 Gy in 41 fractions over 44 days using late-course accelerated hyperfractionated 3D-CRT. Only the primary tumor and positive lymph nodes were irradiated. Isolated out-of-field regional nodal recurrence was defined as a recurrence in an initially uninvolved regional lymph node. Results: All 53 patients who made up the study population tolerated the irradiation well. No acute or late Grade 4 or 5 toxicity was observed. The median survival time was 30 months (95% confidence interval, 17.7-41.8). The overall survival rate at 1, 2, and 3 years was 77%, 56%, and 41%, respectively. The local control rate at 1, 2, and 3 years was 83%, 74%, and 62%, respectively. Thirty-nine of the 53 patients (74%) showed treatment failure. Seventeen of the 39 (44%) developed an in-field recurrence, 18 (46%) distant metastasis with or without regional failure, and 3 (8%) an isolated out-of-field nodal recurrence only. One patient died of disease in an unknown location. Conclusions: In patients treated with 3D-CRT for esophageal SCC, the omission of elective nodal irradiation was not associated with a significant amount of failure in lymph node regions not included in the planning target volume. Local failure and distant metastases remained the predominant problems.

  10. Disrupted Nodal and Hub Organization Account for Brain Network Abnormalities in Parkinson’s Disease

    PubMed Central

    Koshimori, Yuko; Cho, Sang-Soo; Criaud, Marion; Christopher, Leigh; Jacobs, Mark; Ghadery, Christine; Coakeley, Sarah; Harris, Madeleine; Mizrahi, Romina; Hamani, Clement; Lang, Anthony E.; Houle, Sylvain; Strafella, Antonio P.

    2016-01-01

    The recent application of graph theory to brain networks promises to shed light on complex diseases such as Parkinson’s disease (PD). This study aimed to investigate functional changes in sensorimotor and cognitive networks in Parkinsonian patients, with a focus on inter- and intra-connectivity organization in the disease-associated nodal and hub regions using the graph theoretical analyses. Resting-state functional MRI data of a total of 65 participants, including 23 healthy controls (HCs) and 42 patients, were investigated in 120 nodes for local efficiency, betweenness centrality, and degree. Hub regions were identified in the HC and patient groups. We found nodal and hub changes in patients compared with HCs, including the right pre-supplementary motor area (SMA), left anterior insula, bilateral mid-insula, bilateral dorsolateral prefrontal cortex (DLPFC), and right caudate nucleus. In general, nodal regions within the sensorimotor network (i.e., right pre-SMA and right mid-insula) displayed weakened connectivity, with the former node associated with more severe bradykinesia, and impaired integration with default mode network regions. The left mid-insula also lost its hub properties in patients. Within the executive networks, the left anterior insular cortex lost its hub properties in patients, while a new hub region was identified in the right caudate nucleus, paralleled by an increased level of inter- and intra-connectivity in the bilateral DLPFC possibly representing compensatory mechanisms. These findings highlight the diffuse changes in nodal organization and regional hub disruption accounting for the distributed abnormalities across brain networks and the clinical manifestations of PD. PMID:27891090

  11. EXTENSION OF THE 1D FOUR-GROUP ANALYTIC NODAL METHOD TO FULL MULTIGROUP

    SciTech Connect

    B. D. Ganapol; D. W. Nigg

    2008-09-01

    In the mid 80’s, a four-group/two-region, entirely analytical 1D nodal benchmark appeared. It was readily acknowledged that this special case was as far as one could go in terms of group number and still achieve an analytical solution. In this work, we show that by decomposing the solution to the multigroup diffusion equation into homogeneous and particular solutions, extension to any number of groups is a relatively straightforward exercise using the mathematics of linear algebra.

  12. Atrioventricular Nodal Re-entry Tachycardia in Identical Twins: A Case Report and Literature Review

    PubMed Central

    Barake, Walid; Caldwell, Jane; Baranchuk, Adrian

    2013-01-01

    This report details the case of 17 year old identical twins who both presented with paroxysmal supraventricular tachycardia (PSVT). Electrophysiological studies revealed atrioventricular nodal reentry tachycardia (AVNRT) in both twins. Successful but technically challenging slow pathway ablation was performed in both twins. This is the first reported case of confirmed AVNRT in identical twins which adds strong evidence to heritability of the dual AV node physiology and AVNRT. A review of the current literature regarding PSVT in monozygotic twins is provided. PMID:23329875

  13. Ionic mechanisms involved in the nodal swelling of myelinated axons caused by marine toxins.

    PubMed

    Benoit, Evelyne; Mattei, Cesar; Ouanounou, Gilles; Meunier, Frederic A; Suput, Dusan; Le Gall, Frederic; Marquais, Michel; Dechraoui, Marie Y; Molgo, Jordi

    2002-01-01

    This review describes the ionic mechanisms involved in the nodal swelling of frog myelinated axons caused by specific marine neurotoxins (ciguatoxins, brevetoxins, Conus consors toxin and equinatoxin-II), analysed using confocal laser scanning microscopy. We have focussed on toxins that either target neuronal voltage-dependent Na+ channels, or that form cation-selective pores and indirectly affect the functioning of the Na(+)-Ca(++)exchanger.

  14. Notch activity induces Nodal expression and mediates the establishment of left–right asymmetry in vertebrate embryos

    PubMed Central

    Raya, Ángel; Kawakami, Yasuhiko; Rodríguez-Esteban, Concepción; Büscher, Dirk; Koth, Christopher M.; Itoh, Tohru; Morita, Masanobu; Raya, R. Marina; Dubova, Ilir; Bessa, Joaquín Grego; de la Pompa, José Luis; Belmonte, Juan Carlos Izpisúa

    2003-01-01

    Left-sided expression of Nodal in the lateral plate mesoderm is a conserved feature necessary for the establishment of normal left–right asymmetry during vertebrate embryogenesis. By using gain- and loss-of-function experiments in zebrafish and mouse, we show that the activity of the Notch pathway is necessary and sufficient for Nodal expression around the node, and for proper left–right determination. We identify Notch-responsive elements in the Nodal promoter, and unveil a direct relationship between Notch activity and Nodal expression around the node. Our findings provide evidence for a mechanism involving Notch activity that translates an initial symmetry-breaking event into asymmetric gene expression. PMID:12730123

  15. A coarse-mesh nodal method-diffusive-mesh finite difference method

    SciTech Connect

    Joo, H.; Nichols, W.R.

    1994-05-01

    Modern nodal methods have been successfully used for conventional light water reactor core analyses where the homogenized, node average cross sections (XSs) and the flux discontinuity factors (DFs) based on equivalence theory can reliably predict core behavior. For other types of cores and other geometries characterized by tightly-coupled, heterogeneous core configurations, the intranodal flux shapes obtained from a homogenized nodal problem may not accurately portray steep flux gradients near fuel assembly interfaces or various reactivity control elements. This may require extreme values of DFs (either very large, very small, or even negative) to achieve a desired solution accuracy. Extreme values of DFs, however, can disrupt the convergence of the iterative methods used to solve for the node average fluxes, and can lead to a difficulty in interpolating adjacent DF values. Several attempts to remedy the problem have been made, but nothing has been satisfactory. A new coarse-mesh nodal scheme called the Diffusive-Mesh Finite Difference (DMFD) technique, as contrasted with the coarse-mesh finite difference (CMFD) technique, has been developed to resolve this problem. This new technique and the development of a few-group, multidimensional kinetics computer program are described in this paper.

  16. Nodal gap detection through polar angle-resolved density of states measurements in uniaxial superconductors

    NASA Astrophysics Data System (ADS)

    Tsutsumi, Yasumasa; Nomoto, Takuya; Ikeda, Hiroaki; Machida, Kazushige

    2016-12-01

    We propose a spectroscopic method to identify the nodal gap structure in unconventional superconductors. This method is best suited for locating the horizontal line node and for pinpointing the isolated point nodes by measuring polar angle (θ ) resolved zero-energy density of states N (θ ) . This is measured by specific heat or thermal conductivity at low temperatures under a magnetic field. We examine a variety of uniaxially symmetric nodal structures, including point and/or line nodes with linear and quadratic dispersions, by solving the Eilenberger equation in vortex states. It is found that (a) the maxima of N (θ ) continuously shift from the antinodal to the nodal direction (θn) as a field increases accompanying the oscillation pattern reversal at low and high fields. Furthermore, (b) local minima emerge next to θn on both sides, except for the case of the linear point node. These features are robust and detectable experimentally. Experimental results of N (θ ) performed on several superconductors, UPd2Al3,URu2Si2,CuxBi2Se3 , and UPt3, are examined and commented on in light of the present theory.

  17. Measurement of the Nodal Precession of WASP-33 b via Doppler Tomography

    NASA Astrophysics Data System (ADS)

    Johnson, Marshall C.; Cochran, William D.; Collier Cameron, Andrew; Bayliss, Daniel

    2015-09-01

    We have analyzed new and archival time series spectra taken six years apart during transits of the hot Jupiter WASP-33 b, and spectroscopically resolved the line profile perturbation caused by the Rossiter-McLaughlin effect. The motion of this line profile perturbation is determined by the path of the planet across the stellar disk, which we show to have changed between the two epochs due to nodal precession of the planetary orbit. We measured rates of change of the impact parameter and the sky-projected spin-orbit misalignment of {db}/{dt}={-0.0228}-0.0018+0.0050 {{yr}}-1 and dλ /{dt}={-0\\buildrel{\\circ}\\over{.} 487}-0.076+0.089 {{yr}}-1, respectively, corresponding to a rate of nodal precession of d{{Ω }}/{dt}=0\\buildrel{\\circ}\\over{.} {373}-0.083+0.031 {{yr}}-1. This is only the second measurement of nodal precession for a confirmed exoplanet transiting a single star. Finally, we used the rate of precession to set limits on the stellar gravitational quadrupole moment of 0.0054≤slant {J}2≤slant 0.035.

  18. Anisotropic density fluctuations, plasmons, and Friedel oscillations in nodal line semimetal

    NASA Astrophysics Data System (ADS)

    Rhim, Jun-Won; Kim, Yong Baek

    2016-04-01

    Motivated by recent experimental efforts on three-dimensional semimetals, we investigate the static and dynamic density response of the nodal line semimetal by computing the polarizability for both undoped and doped cases. The nodal line semimetal in the absence of doping is characterized by a ring-shape zero energy contour in momentum space, which may be considered as a collection of Dirac points. In the doped case, the Fermi surface has a torus shape and two independent processes of the momentum transfer contribute to the singular features of the polarizability even though we only have a single Fermi surface. In the static limit, there exist two independent singularities in the second derivative of the static polarizability. This results in the highly anisotropic Friedel oscillations which show the angle-dependent algebraic power law and the beat phenomena in the oscillatory electron density near a charged impurity. Furthermore, the dynamical polarizability has two singular lines along {\\hslash }ω =γ p and {\\hslash }ω =γ p{sin}η , where η is the angle between the external momentum {p} and the plane where the nodal ring lies. From the dynamical polarizability, we obtain the plasmon modes in the doped case, which show anisotropic dispersions and angle-dependent plasma frequencies. Qualitative differences between the low and high doping regimes are discussed in light of future experiments.

  19. Disappearance of nodal gap across the insulator-superconductor transition in a copper-oxide superconductor.

    PubMed

    Peng, Yingying; Meng, Jianqiao; Mou, Daixiang; He, Junfeng; Zhao, Lin; Wu, Yue; Liu, Guodong; Dong, Xiaoli; He, Shaolong; Zhang, Jun; Wang, Xiaoyang; Peng, Qinjun; Wang, Zhimin; Zhang, Shenjin; Yang, Feng; Chen, Chuangtian; Xu, Zuyan; Lee, T K; Zhou, X J

    2013-01-01

    The parent compound of the copper-oxide high-temperature superconductors is a Mott insulator. Superconductivity is realized by doping an appropriate amount of charge carriers. How a Mott insulator transforms into a superconductor is crucial in understanding the unusual physical properties of high-temperature superconductors and the superconductivity mechanism. Here we report high-resolution angle-resolved photoemission measurement on heavily underdoped Bi₂Sr₂-xLaxCuO(₆+δ) system. The electronic structure of the lightly doped samples exhibit a number of characteristics: existence of an energy gap along the nodal direction, d-wave-like anisotropic energy gap along the underlying Fermi surface, and coexistence of a coherence peak and a broad hump in the photoemission spectra. Our results reveal a clear insulator-superconductor transition at a critical doping level of ~0.10 where the nodal energy gap approaches zero, the three-dimensional antiferromagnetic order disappears, and superconductivity starts to emerge. These observations clearly signal a close connection between the nodal gap, antiferromagnetism and superconductivity.

  20. Formin DAAM1 Organizes Actin Filaments in the Cytoplasmic Nodal Actin Network

    PubMed Central

    Luo, Weiwei; Lieu, Zi Zhao; Manser, Ed; Bershadsky, Alexander D.; Sheetz, Michael P.

    2016-01-01

    A nodal cytoplasmic actin network underlies actin cytoplasm cohesion in the absence of stress fibers. We previously described such a network that forms upon Latrunculin A (LatA) treatment, in which formin DAAM1 was localized at these nodes. Knock down of DAAM1 reduced the mobility of actin nodes but the nodes remained. Here we have investigated DAAM1 containing nodes after LatA washout. DAAM1 was found to be distributed between the cytoplasm and the plasma membrane. The membrane binding likely occurs through an interaction with lipid rafts, but is not required for F-actin assembly. Interesting the forced interaction of DAAM1 with plasma membrane through a rapamycin-dependent linkage, enhanced F-actin assembly at the cell membrane (compared to the cytoplasm) after the LatA washout. However, immediately after addition of both rapamycin and LatA, the cytoplasmic actin nodes formed transiently, before DAAM1 moved to the membrane. This was consistent with the idea that DAAM1 was initially anchored to cytoplasmic actin nodes. Further, photoactivatable tracking of DAAM1 showed DAAM1 was immobilized at these actin nodes. Thus, we suggest that DAAM1 organizes actin filaments into a nodal complex, and such nodal complexes seed actin network recovery after actin depolymerization. PMID:27760153

  1. Extending nodal aberration theory to include mount-induced aberrations with application to freeform surfaces.

    PubMed

    Fuerschbach, Kyle; Rolland, Jannick P; Thompson, Kevin P

    2012-08-27

    This paper introduces the path forward for the integration of freeform optical surfaces, particularly those related to φ-polynomial surfaces, including Zernike polynomial surfaces, with nodal aberration theory. With this formalism, the performance of an optical system throughout the field of view can be anticipated analytically accounting for figure error, mount-induced errors, and misalignment. Previously, only misalignments had been described by nodal aberration theory, with the exception of one special case for figure error. As an example of these new results, three point mounting error that results in a Zernike trefoil deformation is studied for the secondary mirror of a two mirror and three mirror telescope. It is demonstrated that for the case of trefoil deformation applied to a surface not at the stop, there is the anticipated field constant contribution to elliptical coma (also called trefoil) as well as a newly identified field dependent contribution to astigmatism: field linear, field conjugate astigmatism. The magnitude of this astigmatic contribution varies linearly with the field of view; however, it has a unique variation in orientation with field that is described mathematically by a concept that is unique to nodal aberration theory known as the field conjugate vector.

  2. Closed-chest ablation of retrograde conduction in patients with atrioventricular nodal reentrant tachycardia.

    PubMed

    Haissaguerre, M; Warin, J F; Lemetayer, P; Saoudi, N; Guillem, J P; Blanchot, P

    1989-02-16

    We applied a new technique of catheter ablation to treat atrioventricular nodal reentrant tachycardia and preserve anterograde conduction, performing this procedure in 21 patients with repetitive episodes of tachycardia refractory to antiarrhythmic drugs. Using atrial activation in the His-bundle lead as a reference, we selected the optimal site of ablation by positioning an electrode catheter so that atrial activation occurred simultaneously with or earlier than the reference activation during tachycardia. At this site, the His-bundle deflection was completely absent or was present only at a low amplitude (less than 0.1 mV). In the majority of patients, these criteria could be met by withdrawing the catheter 5 to 10 mm from the site of the His-bundle recording (adjacent to the reference catheter). Shocks of 160 or 240 J were delivered at this site (cumulative energy [mean +/- SD], 689 +/- 442 J). Treatment resulted in preferential abolition or impairment of retrograde nodal conduction. Anterograde conduction, although modified, was preserved in 19 patients; complete heart block persisted in 2 patients. Sixteen patients remained free of arrhythmia, without medication or implantation of a pacemaker, for a mean follow-up period of 14 +/- 8 months (range, 7 to 42). Tachycardia was not inducible in 14 patients in a follow-up electrophysiologic study performed 3.6 +/- 6 months after the procedure. We conclude that catheter ablation is an effective alternative for the treatment of atrioventricular nodal tachycardia in patients with drug-resistant tachycardia.

  3. Nonfluoroscopic Imaging as Guidance for Radiofrequency Ablation of Atrioventricular Nodal Reentrant Tachycardia after Mustard Repair

    PubMed Central

    Nguyen, Dinh Q.; Sobczak, Henrik; Brandts, Bodo

    2017-01-01

    Most tachycardias in the pulmonary venous atrium are inaccessible by direct means and require either a retrograde approach or a transseptal approach for ablation. We present a case in which successful radiofrequency ablation of common atrioventricular nodal reentrant tachycardia was accomplished via a retrograde transaortic approach guided by nonfluoroscopic mapping with use of the NavX™ mapping system. The patient was a 49-year-old woman who at the age of 4 years had undergone Mustard repair for complete dextrotransposition of the great arteries. Three-dimensional reconstructions of the ascending aorta, right ventricle, systemic venous atrium, left ventricle, and superior vena cava–inferior vena cava baffle complex were created, and the left-sided His bundle was marked. After a failed attempt at ablation from the systemic venous side, we eliminated the atrioventricular nodal reentrant tachycardia by ablation from the pulmonary venous side. This case is, to our knowledge, the first report of successful radiofrequency ablation of common atrioventricular nodal reentrant tachycardia after Mustard repair for this congenital cardiac malformation in which ablation was guided by 3-dimensional nonfluoroscopic imaging. This imaging technique enabled accurate anatomic location of the ablation catheters in relation to the His bundle marked from the systemic venous side. PMID:28265215

  4. Reticulin and NM23 staining in the interpretation of lymph nodal nevus rests.

    PubMed

    Kanner, William A; Barry, Catherine I; Smart, Chandra N; Frishberg, David P; Binder, Scott W; Wick, Mark R

    2013-06-01

    Melanocytic nevus rests in lymph nodes are a known diagnostic challenge, especially in patients with a history of melanoma. Reticulin and NM23 have been studied in this context. The pattern of reticulin staining in melanomas surrounds groups/nests of melanocytes but individual cells in benign nevi. NM23, a metastasis-suppressor gene, has an association with metastatic potential in melanomas and some carcinomas. Twenty-eight cases (14 cases of metastatic melanoma to lymph nodes and 14 cases of lymph node nevus rests, all confirmed with Melan-A staining) were stained with reticulin and NM23. The pattern of reticulin staining was reported as surrounding groups if staining was noted in approximately 5-10 melanocytes in greater than 50% of the lesion but was otherwise reported as surrounding individual melanocytes. Cytoplasmic staining was considered to represent reactivity for NM23. Reticulin staining around groups of melanocytes was identified in all 14 cases of metastatic melanoma. Regarding nodal nevus rest cases, 12 of 14 cases (86%) demonstrated staining around individual melanocytes, whereas in 2 cases, reticulin surrounded melanocytic groups. NM23 staining was equivocal in all cases. Reticulin staining reliably invests groups of melanocytes in cases of metastatic melanoma, whereas in nodal nevus rests, it predominantly surrounds individual melanocytes. NM23 demonstrated no discriminatory value in this analysis. In cases in which a collection of melanocytes is present within a lymph node, reticulin deposition around individual melanocytes supports a diagnosis of lymph nodal nevus rest.

  5. [Expression of TGFbeta family factors and FGF2 in mouse and human embryonic stem cells maintained in different culture systems].

    PubMed

    Lifantseva, N V; Kol'tsova, A M; Polianskaia, G G; Gordeeva, O F

    2013-01-01

    Mouse and human embryonic stem cells are in different states of pluripotency (naive/ground and primed states). Mechanisms of signaling regulation in cells with ground and primed states of pluripotency are considerably different. In order to understand the contribution of endogenous and exogenous factors in the maintenance of a metastable state of the cells in different phases ofpluripotency, we examined the expression of TGFbeta family factors (ActivinA, Nodal, Leftyl, TGFbeta1, GDF3, BMP4) and FGF2 initiating the appropriate signaling pathways in mouse and human embryonic stem cells (mESCs, hESCs) and supporting feeder cells. Quantitative real-time PCR analysis of gene expression showed that the expression patterns of endogenous factors studied were considerably different in mESCs and hESCs. The most significant differences were found in the levels of endogenous expression of TGFbeta1, BMP4 and ActivinA. The sources of exogenous factors ActivnA, TGFbeta1, and FGF2 for hESCs are feeder cells (mouse and human embryonic fibroblasts) expressing high levels of these factors, as well as low levels of BMP4. Thus, our data demonstrated that the in vitro maintenance of metastable state of undifferentiated pluripotent cells is achieved in mESCs and hESCs using different schemes of the regulations of ActivinA/Nodal/Lefty/Smad2/3BMP/Smad1/5/8 endogenous branches of TGFbeta signaling. The requirement for exogenous stimulation or inhibition of these signaling pathways is due to different patterns of endogenous expression of TGFbeta family factors and FGF2 in the mESCs and hESCs. For the hESCs, enhanced activity of ActivinA/Nodal/Lefty/Smad2/3 signaling by exogenous factor stimulation is necessary to mitigate the effects of BMP/Smadl/5/8 signaling pathways that promote cell differentiation into the extraembryonic structures. Significant differences in endogenous FGF2 expression in the cells in the ground and primary states of pluripotency demonstrate diverse involvement of this

  6. SU-E-J-179: Prediction of Pelvic Nodal Coverage Using Mutual Information Between Cone-Beam and Planning CTs

    SciTech Connect

    Jani, S; Kishan, A; O'Connell, D; King, C; Steinberg, M; Low, D; Lamb, J

    2014-06-01

    Purpose: To investigate if pelvic nodal coverage for prostate patients undergoing intensity modulated radiotherapy (IMRT) can be predicted using mutual image information computed between planning and cone-beam CTs (CBCTs). Methods: Four patients with high-risk prostate adenocarcinoma were treated with IMRT on a Varian TrueBeam. Plans were designed such that 95% of the nodal planning target volume (PTV) received the prescription dose of 45 Gy (N=1) or 50.4 Gy (N=3). Weekly CBCTs (N=25) were acquired and the nodal clinical target volumes and organs at risk were contoured by a physician. The percent nodal volume receiving prescription dose was recorded as a ground truth. Using the recorded shifts performed by the radiation therapists at the time of image acquisition, CBCTs were aligned with the planning kVCT. Mutual image information (MI) was calculated between the CBCT and the aligned planning CT within the contour of the nodal PTV. Due to variable CBCT fields-of-view, CBCT images covering less than 90% of the nodal volume were excluded from the analysis, resulting in the removal of eight CBCTs. Results: A correlation coefficient of 0.40 was observed between the MI metric and the percent of the nodal target volume receiving the prescription dose. One patient's CBCTs had clear outliers from the rest of the patients. Upon further investigation, we discovered image artifacts that were present only in that patient's images. When those four images were excluded, the correlation improved to 0.81. Conclusion: This pilot study shows the potential of predicting pelvic nodal dosimetry by computing the mutual image information between planning CTs and patient setup CBCTs. Importantly, this technique does not involve manual or automatic contouring of the CBCT images. Additional patients and more robust exclusion criteria will help validate our findings.

  7. Infrared inhibition of embryonic hearts

    NASA Astrophysics Data System (ADS)

    Wang, Yves T.; Rollins, Andrew M.; Jenkins, Michael W.

    2016-06-01

    Infrared control is a new technique that uses pulsed infrared lasers to thermally alter electrical activity. Originally developed for nerves, we have applied this technology to embryonic hearts using a quail model, previously demonstrating infrared stimulation and, here, infrared inhibition. Infrared inhibition enables repeatable and reversible block, stopping cardiac contractions for several seconds. Normal beating resumes after the laser is turned off. The block can be spatially specific, affecting propagation on the ventricle or initiation on the atrium. Optical mapping showed that the block affects action potentials and not just calcium or contraction. Increased resting intracellular calcium was observed after a 30-s exposure to the inhibition laser, which likely resulted in reduced mechanical function. Further optimization of the laser illumination should reduce potential damage. Stopping cardiac contractions by disrupting electrical activity with infrared inhibition has the potential to be a powerful tool for studying the developing heart.

  8. Screening the mammalian extracellular proteome for regulators of embryonic human stem cell pluripotency

    PubMed Central

    Gonzalez, Rodolfo; Jennings, Lori L.; Knuth, Mark; Orth, Anthony P.; Klock, Heath E.; Ou, Weija; Feuerhelm, Julie; Hull, Mitchell V.; Koesema, Eric; Wang, Yuping; Zhang, Jia; Wu, Chunlei; Cho, Charles Y.; Su, Andrew I.; Batalov, Serge; Chen, Hong; Johnson, Kristen; Laffitte, Bryan; Nguyen, Deborah G.; Snyder, Evan Y.; Schultz, Peter G.; Harris, Jennifer L.; Lesley, Scott A.

    2010-01-01

    Approximately 3,500 mammalian genes are predicted to be secreted or single-pass transmembrane proteins. The function of the majority of these genes is still unknown, and a number of the encoded proteins might find use as new therapeutic agents themselves or as targets for small molecule or antibody drug development. To analyze the physiological activities of the extracellular proteome, we developed a large-scale, high-throughput protein expression, purification, and screening platform. For this study, the complete human extracellular proteome was analyzed and prioritized based on genome-wide disease association studies to select 529 initial target genes. These genes were cloned into three expression vectors as native sequences and as N-terminal and C-terminal Fc fusions to create an initial collection of 806 purified secreted proteins. To determine its utility, this library was screened in an OCT4-based cellular assay to identify regulators of human embryonic stem-cell self-renewal. We found that the pigment epithelium-derived factor can promote long-term pluripotent growth of human embryonic stem cells without bFGF or TGFβ/Activin/Nodal ligand supplementation. Our results further indicate that activation of the pigment epithelium-derived factor receptor-Erk1/2 signaling pathway by the pigment epithelium-derived factor is sufficient to maintain the self-renewal of pluripotent human embryonic stem cells. These experiments illustrate the potential for discovering novel biological functions by directly screening protein diversity in cell-based phenotypic or reporter assays. PMID:20133595

  9. Chronic ethanol exposure increases goosecoid (GSC) expression in human embryonic carcinoma cell differentiation.

    PubMed

    Halder, Debasish; Park, Ji Hyun; Choi, Mi Ran; Chai, Jin Choul; Lee, Young Seek; Mandal, Chanchal; Jung, Kyoung Hwa; Chai, Young Gyu

    2014-01-01

    Fetal alcohol spectrum disorder (FASD) is a set of developmental malformations caused by excess alcohol consumption during pregnancy. Using an in vitro system, we examined the role that chronic ethanol (EtOH) exposure plays in gene expression changes during the early stage of embryonic differentiation. We demonstrated that EtOH affected the cell morphology, cell cycle progression and also delayed the down-regulation of OCT4 and NANOG during differentiation. Gene expression profiling and pathway analysis demonstrated that EtOH deregulates many genes and pathways that are involved in early embryogenesis. Follow-up analyzes revealed that EtOH exposure to embryoid bodies (EBs) induced the expression of an organizer-specific gene, goosecoid (GSC), in comparison to controls. Moreover, EtOH treatment altered several important genes that are involved in embryonic structure formation, nervous system development, and placental and embryonic vascularization, which are all common processes that FASD can disrupt. Specifically, EtOH treatment let to a reduction in ALDOC, ENO2 and CDH1 expression, whereas EtOH treatment induced the expression of PTCH1, EGLN1, VEGFA and DEC2 in treated EBs. We also found that folic acid (FA) treatment was able to correct the expression of the majority of genes deregulated by EtOH exposure during early embryo development. Finally, the present study identified a gene set including GSC, which was deregulated by EtOH exposure that may contribute to the etiology of fetal alcohol syndrome (FAS). We also reported that EtOH-induced GSC expression is mediated by Nodal signaling, which may provide a new avenue for analyzing the molecular mechanisms behind EtOH teratogenicity in FASD individuals.

  10. Regulation of expression driven by human immunodeficiency virus type 1 and human T-cell leukemia virus type I long terminal repeats in pluripotential human embryonic cells

    SciTech Connect

    Maio, J.; Brown, F.L. )

    1988-04-01

    Human pluripotential embryonic teratocarcinoma cells differentially expressed gene activity controlled by the human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type I (HTLV-I) long terminal repeats (LTRs) when differentiation was induced by the morphogen all-trans retinoic acid. The alterations occurred after commitment and before the appearance of the multiple cell types characteristic of these pluripotential cells. After commitment, gene activity controlled by the HIV-1 LTR markedly increased, whereas that controlled by the HTLV-I LTR decreased. Steady-state mRNA levels and nuclear run-on transcription indicated that the increased HIV-1-directed activity during differentiation occurred posttranscriptionally, whereas the decreased HTLV-I activity was at the transcriptional level. Phorbol esters did not cause commitment but strongly enhanced expression by both viral LTRs at the transcriptional level. Differentiating cells gradually lost the ability to respond to phorbol ester stimulation. Experiments with a deletion mutant of the HIV-1 LTR suggested that this was due to imposition of negative regulation during differentiation that was not reversed by phorbol ester induction. Cycloheximide, with or without phorbol ester, slightly stimulated HIV-1-directed activity at the transcriptional level and massively increased the amounts of steady-state mRNA by posttranscriptional superinduction. It appeared, however, that new nuclear protein synthesis was required for maximal transcriptional stimulation by phorbol esters. Thus, changing cellular regulatory mechanisms influenced human retrovirus expression during human embryonic cell differentiation.

  11. Role of microglia in embryonic neurogenesis

    PubMed Central

    Tong, Chih Kong

    2016-01-01

    Microglia begin colonizing the developing brain as early as embryonic day 9, prior to the emergence of neurons and other glia. Their ontogeny is also distinct from other central nervous system cells, as they derive from yolk sac hematopoietic progenitors and not neural progenitors. In this review, we feature these unique characteristics of microglia and assess the spatiotemporal similarities between microglia colonization of the central nervous system and embryonic neurogenesis. We also infer to existing evidence for microglia function from embryonic through to postnatal neurodevelopment to postulate roles for microglia in neurogenesis. PMID:27555616

  12. Influence of activin A supplementation during human embryonic stem cell derivation on germ cell differentiation potential.

    PubMed

    Duggal, Galbha; Heindryckx, Björn; Warrier, Sharat; O'Leary, Thomas; Van der Jeught, Margot; Lierman, Sylvie; Vossaert, Liesbeth; Deroo, Tom; Deforce, Dieter; Chuva de Sousa Lopes, Susana M; De Sutter, Petra

    2013-12-01

    Human embryonic stem cells (hESCs) are more similar to "primed" mouse epiblast stem cells (mEpiSCs). mEpiSCs, which are derived in Activin A, show an increased propensity to form primordial germ cell (PGC)-like cells in response to bone morphogenic protein 4 (BMP4). Hence, we hypothesized that hESCs derived in the presence of Activin A may be more competent in differentiating towards PGC-like cells after supplementation with BMP4 compared to standard hESC lines. We were able to successfully derive two hESC lines in the presence of Activin A, which were pluripotent and showed higher base levels of STELLA and cKIT compared to standard hESC lines derived without Activin A addition. Furthermore, upon differentiation as embryoid bodies in the presence of BMP4, we observed upregulation of VASA at day 7, both at the transcript and protein level compared to standard hESC lines, which appeared to take longer time for PGC specification. Unlike other hESC lines, nuclear pSMAD2/3 presence confirmed that Activin signalling was switched on in Activin A-derived hESC lines. They were also responsive to BMP4 based on nuclear detection of pSMAD1/5/8 and showed endodermal differentiation as a result of GATA-6 expression. Hence, our results provide novel insights into the impact of hESC derivation in the presence of Activin A and its subsequent influence on germ cell differentiation potential in vitro.

  13. Expression and localization of nodal in bovine oviduct and uterus during different functional stages of oestrus cycle and pregnancy.

    PubMed

    Argañaraz, Martin Eduardo; Apichela, Silvana Andrea; Kenngott, Rebecca; Vermeheren, Margarethe; Rodler, Daniela; Palma, Gustavo Adolfo; Miceli, Dora Cristina; Sinowatz, Fred

    2013-01-01

    Members of TGF-β superfamily play a major role in the endometrial changes involved in the establishment and maintenance of pregnancy. Their deregulated expression and action could lead to absolute or partial failure of embryo implantation. Nonetheless, the precise function and mechanism of many of these cytokines remain unclear. Nodal, a transforming growth factor beta (TGF-β) superfamily member, was characterized in the human and rodent uterus and implicated in the tissue remodeling events during menstruation and embryo implantation. In order to study its possible role in the cattle reproductive process, we have analyzed Nodal expression pattern and localization in the oviduct and uterine horn during the oestrus cycle and early pregnancy (day 20). Nodal was detected both in oviduct and uterus during either the oestrus cycle or pregnancy; however, it shows a differential expression profile in the uterine horn at dioestrus and pregnancy, decreasing 1.5 and 1.4 folds in comparison with oestrus. Nodal immunostaining intensity was observed in stromal and in epithelial cells of the surface and the glandular epithelium. The staining pattern correlates with the RT-qPCR expression profile. This work is the first to evidence the presence of Nodal in the bovine reproductive tract; our data suggest that Nodal is a novel cytokine that would be involved in the remodelling occurring in the endometrium of cattle during the oestrus cycle and in the embryo implantation. The identification of new molecules that participate in endometrium cycling and/or pregnancy may be useful for predicting the ability of the uterine tissue to establish and maintain pregnancy or for detecting the infertility processes. These results highlight Nodal as a possible novel marker of the fertility process, nevertheless further studies should be done to determine its role in the reproductive system.

  14. Interaction between SCO-spondin and low density lipoproteins from embryonic cerebrospinal fluid modulates their roles in early neurogenesis

    PubMed Central

    Vera, América; Recabal, Antonia; Saldivia, Natalia; Stanic, Karen; Torrejón, Marcela; Montecinos, Hernán; Caprile, Teresa

    2015-01-01

    During early stages of development, encephalic vesicles are composed by a layer of neuroepithelial cells surrounding a central cavity filled with embryonic cerebrospinal fluid (eCSF). This fluid contains several morphogens that regulate proliferation and differentiation of neuroepithelial cells. One of these neurogenic factors is SCO-spondin, a giant protein secreted to the eCSF from early stages of development. Inhibition of this protein in vivo or in vitro drastically decreases the neurodifferentiation process. Other important neurogenic factors of the eCSF are low density lipoproteins (LDL), the depletion of which generates a 60% decrease in mesencephalic explant neurodifferentiation. The presence of several LDL receptor class A (LDLrA) domains (responsible for LDL binding in other proteins) in the SCO-spondin sequence suggests a possible interaction between both molecules. This possibility was analyzed using three different experimental approaches: (1) Bioinformatics analyses of the SCO-spondin region, that contains eight LDLrA domains in tandem, and of comparisons with the LDL receptor consensus sequence; (2) Analysis of the physical interactions of both molecules through immunohistochemical colocalization in embryonic chick brains and through the immunoprecipitation of LDL with anti-SCO-spondin antibodies; and (3) Analysis of functional interactions during the neurodifferentiation process when these molecules were added to a culture medium of mesencephalic explants. The results revealed that LDL and SCO-spondin interact to form a complex that diminishes the neurogenic capacities that both molecules have separately. Our work suggests that the eCSF is an active signaling center with a complex regulation system that allows for correct brain development. PMID:26074785

  15. Novel peptides for deciphering structural and signalling functions of E-cadherin in mouse embryonic stem cells

    PubMed Central

    Segal, Joe M.; Ward, Christopher M.

    2017-01-01

    We have previously shown that E-cadherin regulates the naive pluripotent state of mouse embryonic stem cells (mESCs) by enabling LIF-dependent STAT3 phosphorylation, with E-cadherin null mESCs exhibiting over 3000 gene transcript alterations and a switch to Activin/Nodal-dependent pluripotency. However, elucidation of the exact mechanisms associated with E-cadherin function in mESCs is compounded by the difficulty in delineating the structural and signalling functions of this protein. Here we show that mESCs treated with the E-cadherin neutralising antibody DECMA-1 or the E-cadherin binding peptide H-SWELYYPLRANL-NH2 (Epep) exhibit discrete profiles for pluripotent transcripts and NANOG protein expression, demonstrating that the type of E-cadherin inhibitor employed dictates the cellular phenotype of mESCs. Alanine scanning mutation of Epep revealed residues critical for Tbx3, Klf4 and Esrrb transcript repression, cell-cell contact abrogation, cell survival in suspension, STAT3 phosphorylation and water solubility. STAT3 phosphorylation was found to be independent of loss of cell-cell contact and Activin/Nodal-dependent pluripotency and a peptide is described that enhances STAT3 phosphorylation and Nanog transcript and protein expression in mESCs. These peptides represent a useful resource for deciphering the structural and signalling functions of E-cadherin and demonstrate that complete absence of E-cadherin protein is likely required for hierarchical signalling pathway alterations in mESCs. PMID:28169326

  16. Integrated rate-dependent and dual pathway AV nodal functions: principles and assessment framework.

    PubMed

    Billette, Jacques; Tadros, Rafik

    2014-01-15

    The atrioventricular (AV) node conducts slowly and has a long refractory period. These features sustain the filtering of atrial impulses and hence are often modulated to optimize ventricular rate during supraventricular tachyarrhythmias. The AV node is also the site of a clinically common reentrant arrhythmia. Its function is assessed for a variety of purposes from its responses to a premature protocol (S1S2, test beats introduced at different cycle lengths) repeatedly performed at different basic rates and/or to an incremental pacing protocol (increasingly faster rates). Puzzlingly, resulting data and interpretation differ with protocols as well as with chosen recovery and refractory indexes, and are further complicated by the presence of built-in fast and slow pathways. This problem applies to endocavitary investigations of arrhythmias as well as to many experimental functional studies. This review supports an integrated framework of rate-dependent and dual pathway AV nodal function that can account for these puzzling characteristics. The framework was established from AV nodal responses to S1S2S3 protocols that, compared with standard S1S2 protocols, allow for an orderly quantitative dissociation of the different factors involved in changes in AV nodal conduction and refractory indexes under rate-dependent and dual pathway function. Although largely based on data from experimental studies, the proposed framework may well apply to the human AV node. In conclusion, the rate-dependent and dual pathway properties of the AV node can be integrated within a common functional framework the contribution of which to individual responses can be quantitatively determined with properly designed protocols and analytic tools.

  17. Scaling of Harmonic Oscillator Eigenfunctions and Their Nodal Sets Around the Caustic

    NASA Astrophysics Data System (ADS)

    Hanin, Boris; Zelditch, Steve; Zhou, Peng

    2017-03-01

    We study the scaling asymptotics of the eigenspace projection kernels Π_{hbar, E}(x,y) of the isotropic Harmonic Oscillator {hat{H}_{hbar} = - hbar^2 Δ +|x|^2} of eigenvalue {E = hbar(N + d/2)} in the semi-classical limit {hbar to 0} . The principal result is an explicit formula for the scaling asymptotics of Π_{hbar, E}(x,y) for x, y in a {hbar^{2/3}} neighborhood of the caustic C_E as {hbar → 0.} The scaling asymptotics are applied to the distribution of nodal sets of Gaussian random eigenfunctions around the caustic as {hbar to 0} . In previous work we proved that the density of zeros of Gaussian random eigenfunctions of {hat{H}_{hbar}} have different orders in the Planck constant {hbar} in the allowed and forbidden regions: In the allowed region the density is of order {hbar^{-1}} while it is {hbar^{-1/2}} in the forbidden region. Our main result on nodal sets is that the density of zeros is of order {hbar^{-2/3}} in an {hbar^{2/3}} -tube around the caustic. This tube radius is the `critical radius'. For annuli of larger inner and outer radii {hbar^{α}} with {0 < α < 2/3} we obtain density results that interpolate between this critical radius result and our prior ones in the allowed and forbidden region. We also show that the Hausdorff ( d-2)-dimensional measure of the intersection of the nodal set with the caustic is of order {hbar^{- 2/3}}.

  18. Medaka haploid embryonic stem cells.

    PubMed

    Hong, Yunhan

    2010-01-01

    The appearance of diploidy, the presence of two genomes or chromosome sets, is a fundamental hallmark of eukaryotic evolution and bisexual reproduction, because diploidy offers the basis for the bisexual life cycle, allowing for oscillation between diploid and haploid phases. Meiosis produces haploid gametes. At fertilization, male and female gametes fuse to restore diploidy in a zygote, which develops into a new life. At sex maturation, diploid cells enter into meiosis, culminating in the production of haploid gametes. Therefore, diploidy ensures pluripotency, cell proliferation, and functions, whereas haploidy is restricted only to the post-meiotic gamete phase of germline development and represents the end point of cell growth. Diploidy is advantageous for evolution. Haploidy is ideal for genetic analyses, because any recessive mutations of essential genes will show a clear phenotype in the absence of a second gene copy. Recently, my laboratory succeeded in the generation of medaka haploid embryonic stem (ES) cells capable of whole animal production. Therefore, haploidy in a vertebrate is able to support stable cell culture and pluripotency. This finding anticipates the possibility to generate haploid ES cells in other vertebrate species such as zebrafish. These medaka haploid ES cells elegantly combine haploidy and pluripotency, offering a unique yeast-like system for in vitro genetic analyses of molecular, cellular, and developmental events in various cell lineages. This chapter is aimed to describe the strategy of haploid ES cell derivation and their characteristics, and illustrate the perspectives of haploid ES cells for infertility treatment, genetic screens, and analyses.

  19. Embryonic development in Zungaro jahu.

    PubMed

    Marques, Camila; Faustino, Francine; Bertolucci, Bruno; Paes, Maria do Carmo Faria; Silva, Regiane Cristina da; Nakaghi, Laura Satiko Okada

    2017-02-01

    The aim of this study was to characterize the embryonic development of Zungaro jahu, a fresh water teleostei commonly known as 'jaú'. Samples were collected at pre-determined times from oocyte release to larval hatching and analysed under light microscopy, transmission electron microscopy and scanning electron microscopy. At the first collection times, the oocytes and eggs were spherical and yellowish, with an evident micropyle. Embryo development took place at 29.4 ± 1.5°C and was divided into seven stages: zygote, cleavage, morula, blastula, gastrula, organogenesis, and hatching. The differentiation of the animal and vegetative poles occured during the zygote stage, at 10 min post-fertilization (mpf), leading to the development of the egg cell at 15 mpf. From 20 to 75 mpf, successive cleavages resulted in the formation of 2, 4, 8, 16, 32 and 64 blastomeres. The morula stage was observed between 90 and 105 mpf, and the blastula and gastrula stage at 120 and 180 mpf; respectively. The end of the gastrula stage was characterized by the presence of the yolk plug at 360 mpf. Organogenesis followed, with differentiation of the cephalic and caudal regions, elongation of the embryo by the cephalo-caudal axis, and somitogenesis. Hatching occurred at 780 mpf, with mean larval total length of 3.79 ± 0.11 mm.

  20. Comparison between 18F-Fluorodeoxyglucose Positron Emission Tomography and Sentinel Lymph Node Biopsy for Regional Lymph Nodal Staging in Patients with Melanoma: A Review of the Literature

    PubMed Central

    Mirk, Paoletta; Treglia, Giorgio; Salsano, Marco; Basile, Pietro; Giordano, Alessandro; Bonomo, Lorenzo

    2011-01-01

    Aim. to compare 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) to sentinel lymph node biopsy (SLNB) for regional lymph nodal staging in patients with melanoma. Methods. We performed a literature review discussing original articles which compared FDG-PET to SLNB for regional lymph nodal staging in patients with melanoma. Results and Conclusions. There is consensus in the literature that FDG-PET cannot replace SLNB for regional lymph nodal staging in patients with melanoma. PMID:22242204

  1. Embryonal rhabdomyosarcoma: A rare oral tumor

    PubMed Central

    Datta, Sila; Ray, Jay Gopal; Deb, Tushar; Patsa, Santanu

    2016-01-01

    Rhabdomyosarcoma is the malignant neoplasm of striated muscle and a relatively uncommon tumor of the oral cavity. Embryonal variety is the most common subtype, observed in children below 10 years of age but occasionally seen in adolescents and young adults. The present report describes a case of embryonal rhabdomyosarcoma in the left posterior buccal mucosa, with extension in the adjacent alveolus, soft palate, oropharynx and nasopharynx of a 17-year-old female. PMID:27721622

  2. Relativity mission with two counter-orbiting polar satellites. [nodal dragging effect on earth orbiting satellites

    NASA Technical Reports Server (NTRS)

    Van Patten, R. A.; Everitt, C. W. F.

    1975-01-01

    In 1918, J. Lense and H. Thirring calculated that a moon in orbit around a massive rotating planet would experience a nodal dragging effect due to general relativity. We describe an experiment to measure this effect with two counter-orbiting drag-free satellites in polar earth orbit. For a 2 1/2 year experiment, the measurement accuracy should approach 1%. In addition to precision tracking data from existing ground stations, satellite-to-satellite Doppler ranging data are taken at points of passing near the poles. New geophysical information on both earth harmonics and tidal effects is inherent in the polar ranging data.

  3. Light Spectral Quality Effects on the Growth of Potato (Solanum Tuberosum L.) Nodal Cutttings in Vitro

    NASA Technical Reports Server (NTRS)

    Wilson, Deborah A.; Weigel, Russell, C.; Wheeler, Raymond M.; Sager, John C.

    1993-01-01

    The effects of light spectral quality on the growth of in vitro nodal cutting of potato (Solanum tuberosum) cultivars Norland, Superior, Kennebec, and Denali were examined. The different light spectra were provided by Vita-Lite fluorescent (VF) (a white light control), blue fluorescent (BF), red fluorescent (RF), low-pressure sodium (LPS), and a combination of low-pressure sodium plus cool-white fluorescent lamp (LPS/CWF). Results suggested that shoot morphologic development of in vitro grown potato plants can be controlled by controlling irradiant spectral quality.

  4. Evaluation of a Stirling engine heater bypass with the NASA Lewis nodal-analysis performance code

    SciTech Connect

    Sullivan, T.J.

    1986-05-01

    In support of the US Department of Energy's Stirling Engine Highway Vehicle Systems program, the NASA Lewis Research Center investigated whether bypassing the P-40 Stirling engine heater during regenerative cooling would improve the engine thermal efficiency. The investigation was accomplished by using the Lewis nodal-analysis Stirling engine computer model. Bypassing the P-40 Stirling engine heater at full power resulted in a rise in the indicated thermal efficiency from 40.6 to 41.0 percent. For the idealized (some losses not included) heater bypass that was analyzed, this benefit is not considered significant.

  5. Statistics of nodal points of in-plane random waves in elastic media.

    PubMed

    Maksimov, Dmitrii N; Sadreev, Almas F

    2008-05-01

    We consider the nodal points (NPs) u=0 and v=0 of the in-plane vectorial displacements u=(u,v) which obey the Navier-Cauchy equation. Similar to the Berry conjecture of quantum chaos, we present the in-plane eigenstates of chaotic billiards as the real part of the superposition of longitudinal and transverse plane waves with random phases. By an average over random phases we derive the mean density and correlation function of NPs. Consequently we consider the distribution of the nearest distances between NPs.

  6. PoroTomo Subtask 6.3 Nodal Seismometer Earthquake Data

    SciTech Connect

    Kurt Feigl

    2016-03-21

    90-second records of data from 238 three-component nodal seismometer deployed at Bradys geothermal field. The time window catches an earthquake arrival. Earthquake data from USGS online catalog: Magnitude: 4.3 ml ± 0.4 Location: 38.479°N 118.366°W ± 0.7 km Depth: 9.9 km ± 0.7 Date and Time: 2016-03-21 07:37:10.535 UTC http://earthquake.usgs.gov/earthquakes/eventpage/nn00536374#executive

  7. Nodal quasiparticles and the onset of spin-density-wave order in cuprate superconductors.

    PubMed

    Pelissetto, Andrea; Sachdev, Subir; Vicari, Ettore

    2008-07-11

    We present a theory for the onset of spin-density-wave order in the superconducting ground state of the cuprates. We compute the scaling dimensions of allowed perturbations of a "relativistic" fixed point with O4 x O(3) symmetry, including those associated with the fermionic nodal Bogoliubov quasiparticles. Analyses of up to six loops show that all perturbations with square lattice symmetry are likely irrelevant. We demonstrate that the fermion spectral functions are primarily damped by the coupling to fluctuations of a composite field with Ising nematic order. A number of other experimental implications are also discussed.

  8. Nodal promotes the self-renewal of human colon cancer stem cells via an autocrine manner through Smad2/3 signaling pathway.

    PubMed

    Gong, Yuehua; Guo, Ying; Hai, Yanan; Yang, Hao; Liu, Yang; Yang, Shi; Zhang, Zhenzhen; Ma, Meng; Liu, Linhong; Li, Zheng; He, Zuping

    2014-01-01

    Colorectal cancer is one of the most common and fatal tumors. However, molecular mechanisms underlying carcinogenesis of colorectal cancer remain largely undefined. Here, we explored the expression and function of Nodal in colon cancer stem cells (CCSCs). Nodal and its receptors were present in numerous human colorectal cancer cell lines. NODAL and ALK-4 were coexpressed in human colon cancerous tissues, and NODAL, CD24, and CD44, markers for CCSCs, were expressed at higher levels in human colon cancerous tissues than adjacent noncancerous colon tissues. Human CCSCs were isolated by magnetic activated cell sorting using anti-CD24 and anti-CD44. Nodal transcript and protein were hardly detectable in CD44- or CD24-negative human colorectal cancer cell lines, whereas Nodal and its receptors were present in CCSCs. Notably, Nodal facilitated spheroid formation of human CCSCs, and phosphorylation of Smad2 and Smad3 was activated by Nodal in cells of spheres derived from human CCSCs. Collectively, these results suggest that Nodal promotes the self-renewal of human CCSCs and mediate carcinogenesis of human colorectal cancer via an autocrine manner through Smad2/3 pathway. This study provides a novel insight into molecular mechanisms controlling fate of human CCSCs and offers new targets for gene therapy of human colorectal cancer.

  9. Evidence of Topological Nodal-Line Fermions in ZrSiSe and ZrSiTe

    NASA Astrophysics Data System (ADS)

    Hu, Jin; Tang, Zhijie; Liu, Jinyu; Liu, Xue; Zhu, Yanglin; Graf, David; Myhro, Kevin; Tran, Son; Lau, Chun Ning; Wei, Jiang; Mao, Zhiqiang

    2016-07-01

    A Dirac nodal-line semimetal phase, which represents a new quantum state of topological materials, has been experimentally realized only in a few systems, including PbTaSe2 , PtSn4 , and ZrSiS. In this Letter, we report evidence of nodal-line fermions in ZrSiSe and ZrSiTe probed in de Haas-van Alphen quantum oscillations. Although ZrSiSe and ZrSiTe share a similar layered structure with ZrSiS, our studies show the Fermi surface (FS) enclosing a Dirac nodal line has a 2D character in ZrSiTe, in contrast with 3D-like FS in ZrSiSe and ZrSiS. Another important property revealed in our experiment is that the nodal-line fermion density in this family of materials (˜1020 cm-3 ) is much higher than the Dirac fermion density of other topological materials with discrete nodes. In addition, we have demonstrated ZrSiSe and ZrSiTe single crystals can be thinned down to 2D atomic thin layers through microexfoliation, which offers the first platform to explore exotic properties of topological nodal-line fermions in low dimensions.

  10. Evidence of Topological Nodal-Line Fermions in ZrSiSe and ZrSiTe.

    PubMed

    Hu, Jin; Tang, Zhijie; Liu, Jinyu; Liu, Xue; Zhu, Yanglin; Graf, David; Myhro, Kevin; Tran, Son; Lau, Chun Ning; Wei, Jiang; Mao, Zhiqiang

    2016-07-01

    A Dirac nodal-line semimetal phase, which represents a new quantum state of topological materials, has been experimentally realized only in a few systems, including PbTaSe_{2}, PtSn_{4}, and ZrSiS. In this Letter, we report evidence of nodal-line fermions in ZrSiSe and ZrSiTe probed in de Haas-van Alphen quantum oscillations. Although ZrSiSe and ZrSiTe share a similar layered structure with ZrSiS, our studies show the Fermi surface (FS) enclosing a Dirac nodal line has a 2D character in ZrSiTe, in contrast with 3D-like FS in ZrSiSe and ZrSiS. Another important property revealed in our experiment is that the nodal-line fermion density in this family of materials (∼10^{20}  cm^{-3}) is much higher than the Dirac fermion density of other topological materials with discrete nodes. In addition, we have demonstrated ZrSiSe and ZrSiTe single crystals can be thinned down to 2D atomic thin layers through microexfoliation, which offers the first platform to explore exotic properties of topological nodal-line fermions in low dimensions.

  11. Evaluation of intracardiac recordings in diagnosis of impulse formation and concealed conduction in atrioventricular nodal bypass tracts.

    PubMed Central

    Castellanos, A; Agha, A S; Mendoza, I J; Sung, R J

    1977-01-01

    Invasive electrophysiological studies were performed in 2 symptomatic patients with recurrent arrhythmias in which impulse formation presumably occured within atrioventricular nodal bypass tracts. Case 1 had ectopic beats arising within, or close to, the upper end of a left-sided atrioventricular nodal bypass tract of the type described by Brechenmacher. In addition, this conduction was 'concealed' during sinus rhythm and right atrial pacing because the relatively prolonged right-to-left atrial conduction time allowed right atrial impulses to reach the His bundle via the atrioventricular node before they could do so through the atrioventricular nodal bypass tract. Case 2 had ectopic beats arising in a right-sided atrioventricular nodal bypass tract which did not conduct in either forward or retrograde directions, its presence being detected only when initiating impulses. However, it could not be determined whether this tract was an 'abnormal' atrio-His connection or a 'normal' transitional (atrio-atrioventricular nodal) tract. Though intracardiac studies complement body surface recordings, they should be interpreted with knowledge of their inherent limitations. PMID:884022

  12. Neurodegenerative and morphogenic changes in a mouse model of temporal lobe epilepsy do not depend on the expression of the calcium-binding proteins parvalbumin, calbindin, or calretinin.

    PubMed

    Bouilleret, V; Schwaller, B; Schurmans, S; Celio, M R; Fritschy, J M

    2000-01-01

    The functional role of the calcium-binding proteins parvalbumin, calretinin, and calbindin D-28k for epileptogenesis and long-term seizure-related alterations of the hippocampal formation was assessed in single- and double-knockout mice, using a kainate model of mesial temporal lobe epilepsy. The effects of a unilateral intrahippocampal injection of kainic acid were assessed at one day, 30 days, and four months post-injection, using various markers of GABAergic interneurons (GABA-transporter type 1, GABA(A)-receptor alpha1 subunit, calretinin, calbindin D-28k, somatostatin, and neuropeptide Y). Parvalbumin-deficient, parvalbumin/calbindin-deficient, and parvalbumin/calretinin-deficient mice exhibited no difference in cytoarchitecture of the hippocampal formation and in the number, distribution, or morphology of interneurons compared to wild-type mice. Likewise, mutant mice were not more vulnerable to acute kainate-induced excitotoxicity or to long-term effects of recurrent focal seizures, and exhibited the same pattern of neurochemical alterations (e.g., bilateral induction of neuropeptide Y in granule cells) and morphogenic changes (enlargement and dispersion of dentate gyrus granule cells) as wild-type animals. Quantification of interneurons revealed no significant difference in neuronal vulnerability among the genotypes.These results indicate that the calcium-binding proteins investigated here are not essential for determining the neurochemical phenotype of interneurons. Furthermore, they are not protective against kainate-induced excitotoxicity in this model, and do not appear to modulate the overall level of excitability of the hippocampus. Finally, seizure-induced changes in gene expression in granule cells, which normally express high levels of calcium-binding proteins, apparently were not affected by the gene deletions analysed.

  13. Fibroblast growth factor 2 inhibits up-regulation of bone morphogenic proteins and their receptors during osteoblastic differentiation of human mesenchymal stem cells

    SciTech Connect

    Biver, Emmanuel; Soubrier, Anne-Sophie; Thouverey, Cyril; Cortet, Bernard; Broux, Odile; Caverzasio, Joseph; Hardouin, Pierre

    2012-11-02

    Highlights: Black-Right-Pointing-Pointer FGF modulates BMPs pathway in HMSCs by down-regulating BMP/BMPR expression. Black-Right-Pointing-Pointer This effect is mediated by ERK and JNK MAPKs pathways. Black-Right-Pointing-Pointer Crosstalk between FGF and BMPs must be taken into account in skeletal bioengineering. Black-Right-Pointing-Pointer It must also be considered in the use of recombinant BMPs in orthopedic and spine surgeries. -- Abstract: Understanding the interactions between growth factors and bone morphogenic proteins (BMPs) signaling remains a crucial issue to optimize the use of human mesenchymal stem cells (HMSCs) and BMPs in therapeutic perspectives and bone tissue engineering. BMPs are potent inducers of osteoblastic differentiation. They exert their actions via BMP receptors (BMPR), including BMPR1A, BMPR1B and BMPR2. Fibroblast growth factor 2 (FGF2) is expressed by cells of the osteoblastic lineage, increases their proliferation and is secreted during the healing process of fractures or in surgery bone sites. We hypothesized that FGF2 might influence HMSC osteoblastic differentiation by modulating expressions of BMPs and their receptors. BMP2, BMP4, BMPR1A and mainly BMPR1B expressions were up-regulated during this differentiation. FGF2 inhibited HMSCs osteoblastic differentiation and the up-regulation of BMPs and BMPR. This effect was prevented by inhibiting the ERK or JNK mitogen-activated protein kinases which are known to be activated by FGF2. These data provide a mechanism explaining the inhibitory effect of FGF2 on osteoblastic differentiation of HMSCs. These crosstalks between growth and osteogenic factors should be considered in the use of recombinant BMPs in therapeutic purpose of fracture repair or skeletal bioengineering.

  14. Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis

    PubMed Central

    Liu, Yun; Deng, Li-Zhi; Sun, Hai-Peng; Xu, Jia-Yun; Li, Yi-Ming; Xie, Xin; Zhang, Li-Ming; Deng, Fei-Long

    2016-01-01

    Objective To compare the direct osteogenic effect between placental growth factor-2 (PlGF-2) and bone morphogenic protein-2 (BMP-2). Methods Three groups of PlGF-2/BMP-2-loaded heparin–N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) nanocomplexes were prepared: those with 0.5 μg PlGF-2; with 1.0 μg BMP-2; and with 0.5 μg PlGF-2 combined with 1.0 μg BMP-2. The loading efficiencies and release profiles of these growth factors (GFs) in this nanocomplex system were quantified using enzyme-linked immunosorbent assay, their biological activities were evaluated using cell counting kit-8, cell morphology, and cell number counting assays, and their osteogenic activities were quantified using alkaline phosphatase and Alizarin Red S staining assays. Results The loading efficiencies were more than 99% for the nanocomplexes loaded with just PlGF-2 and for those loaded with both PlGF-2 and BMP-2. For the nanocomplex loaded with just BMP-2, the loading efficiency was more than 97%. About 83%–84% of PlGF-2 and 89%–91% of BMP-2 were stably retained on the nanocomplexes for at least 21 days. In in vitro biological assays, PlGF-2 exhibited osteogenic effects comparable to those of BMP-2 despite its dose in the experiments being lower than that of BMP-2. Moreover, the results implied that heparin-based nanocomplexes encapsulating two GFs have enhanced potential in the enhancement of osteoblast function. Conclusion PlGF-2-loaded heparin–HTCC nanocomplexes may constitute a promising system for bone regeneration. Moreover, the dual delivery of PlGF-2 and BMP-2 appears to have greater potential in bone tissue regeneration than the delivery of either GFs alone. PMID:27042064

  15. Bone Morphogenic Protein 4 Mediates NOX1-Dependent eNOS Uncoupling, Endothelial Dysfunction, and COX2 Induction in Type 2 Diabetes Mellitus.

    PubMed

    Youn, Ji-Youn; Zhou, Jun; Cai, Hua

    2015-08-01

    We have recently shown that angiotensin II-mediated uncoupling of endothelial nitric oxide synthase (eNOS) contributes to endothelial dysfunction in streptozotocin-induced type 1 diabetes mellitus. However, it has remained unclear whether and how eNOS uncoupling occurs in type 2 diabetes mellitus (T2DM) and the consequences of such in regulating vascular function. Here we investigated a role of bone morphogenic protein (BMP)-4 in mediating eNOS uncoupling, endothelial dysfunction, and inflammation in db/db mice. Circulating levels of BMP4 were markedly elevated in db/db mice but not in mice with type 1 diabetes mellitus, in which angiotensin II levels were significantly increased. Infusion of BMP4 antagonist noggin into db/db mice (15 μg/kg/day, 4 weeks) abolished eNOS uncoupling activity while restoring tetrahydrobiopterin (H(4)B) bioavailability. The impaired endothelium-dependent vasorelaxation in db/db aortas was significantly improved by noggin infusion. Exposure of aortic endothelial cells to BMP4 (50 ng/mL, 24 hours) resulted in eNOS uncoupling, which was attenuated by H(4)B precursor sepiapterin or small interfering RNA silencing nicotinamide adenine dinucleotide phosphate oxidase isoform 1 (NOX1). Interestingly, BMP4-dependent NOX1 up-regulation was abrogated by sepiapterin, implicating a NOX1-uncoupled eNOS-NOX1 feed-forward loop. BMP4 induction of cyclooxygenase 2 (COX2) expression and vascular cell adhesion protein 1 was found in db/db mice. Consistently, COX2 was up-regulated by BMP4 in endothelial cells, which was attenuated by sepiapterin, implicating an upstream role of eNOS uncoupling in COX2-mediated inflammatory activation. Taken together, our data for the first time reveal a novel role of BMP4 in inducing NOX1-dependent eNOS uncoupling in T2DM, which may promote development of novel therapeutics restoring endothelial function in T2DM.

  16. Oyster Creek cycle 10 nodal model parameter optimization study using PSMS

    SciTech Connect

    Dougher, J.D.

    1987-01-01

    The power shape monitoring system (PSMS) is an on-line core monitoring system that uses a three-dimensional nodal code (NODE-B) to perform nodal power calculations and compute thermal margins. The PSMS contains a parameter optimization function that improves the ability of NODE-B to accurately monitor core power distributions. This functions iterates on the model normalization parameters (albedos and mixing factors) to obtain the best agreement between predicted and measured traversing in-core probe (TIP) reading on a statepoint-by-statepoint basis. Following several statepoint optimization runs, an average set of optimized normalization parameters can be determined and can be implemented into the current or subsequent cycle core model for on-line core monitoring. A statistical analysis of 19 high-power steady-state state-points throughout Oyster Creek cycle 10 operation has shown a consistently poor virgin model performance. The normalization parameters used in the cycle 10 NODE-B model were based on a cycle 8 study, which evaluated only Exxon fuel types. The introduction of General Electric (GE) fuel into cycle 10 (172 assemblies) was a significant fuel/core design change that could have altered the optimum set of normalization parameters. Based on the need to evaluate a potential change in the model normalization parameters for cycle 11 and in an attempt to account for the poor cycle 10 model performance, a parameter optimization study was performed.

  17. Inland waterway ports nodal attraction indices relevant in development strategies on regional level

    NASA Astrophysics Data System (ADS)

    Dinu, O.; Burciu, Ş.; Oprea, C.; Ilie, A.; Rosca, M.

    2016-08-01

    Present paper aims to propose a set of ranking indices and related criteria, concerning mainly spatial analysis, for the inland waterway port, with special view on inland ports of Danube. Commonly, the attraction potential of a certain transport node is assessed by its spatial accessibility indices considering both spatial features of the location provided by the networks that connect into that node and its economic potential defining the level of traffic flows depending on the economic centers of its hinterland. Paper starts with a overview of the critical needs that are required for potential sites to become inland waterway ports and presents nodal functions that coexist at different levels, leading to a port hierarchy from the points of view of: capacity, connection to hinterland, traffic structure and volume. After a brief review of the key inland waterway port ranking criterion, a selection of nodal attraction measures is made. Particular considerations for the Danube inland port case follows proposed methodology concerning indices of performance for network scale and centrality. As expected, the shorter the distance from an inland port to the nearest access point the greater accessibility. Major differences in ranking, dependent on selected criterion, were registered.

  18. Cooperative Wnt-Nodal Signals Regulate the Patterning of Anterior Neuroectoderm

    PubMed Central

    Yaguchi, Junko; Takeda, Noriyo; Inaba, Kazuo; Yaguchi, Shunsuke

    2016-01-01

    When early canonical Wnt is experimentally inhibited, sea urchin embryos embody the concept of a Default Model in vivo because most of the ectodermal cell fates are specified as anterior neuroectoderm. Using this model, we describe here how the combination of orthogonally functioning anteroposterior Wnt and dorsoventral Nodal signals and their targeting transcription factors, FoxQ2 and Homeobrain, regulates the precise patterning of normal neuroectoderm, of which serotonergic neurons are differentiated only at the dorsal/lateral edge. Loss-of-function experiments revealed that ventral Nodal is required for suppressing the serotonergic neural fate in the ventral side of the neuroectoderm through the maintenance of foxQ2 and the repression of homeobrain expression. In addition, non-canonical Wnt suppressed homeobrain in the anterior end of the neuroectoderm, where serotonergic neurons are not differentiated. Canonical Wnt, however, suppresses foxQ2 to promote neural differentiation. Therefore, the three-dimensionally complex patterning of the neuroectoderm is created by cooperative signals, which are essential for the formation of primary and secondary body axes during embryogenesis. PMID:27101101

  19. Misalignment-induced nodal aberration fields in two-mirror astronomical telescopes.

    PubMed

    Schmid, Tobias; Thompson, Kevin P; Rolland, Jannick P

    2010-06-01

    We present the effects of misalignments on the field dependence of the third-order aberration fields of traditional, two-mirror astronomical telescopes in the context of nodal aberration theory, which we believe is the most general and extensible framework for describing and improving on-station performance. While many of the advantages of nodal aberration theory, compared to other, often power series expansion-based descriptions of misalignment effects on aberrations, become particularly important when analyzing telescopes with more than two mirrors, or in the presence of figure errors; this paper aims to provide and demonstrate the fundamental concepts needed to fully describe the state of correction of misaligned two-mirror telescopes. Importantly, it is shown that the assumption that perfect performance on axis ensures a fully aligned telescope is false, and we demonstrate that if Ritchey-Chrétien telescopes are aligned for zero coma on axis as the sole criterion, formidable misalignments will likely remain, leading to image quality degradation, particularly beyond midfield caused by astigmatism with binodal field dependence (i.e., astigmatism goes to zero at two points in the field).

  20. Reflector modelling of small high leakage cores making use of multi-group nodal equivalence theory

    SciTech Connect

    Theron, S. A.; Reitsma, F.

    2012-07-01

    This research focuses on modelling reflectors in typical material testing reactors (MTRs). Equivalence theory is used to homogenise and collapse detailed transport solutions to generate equivalent nodal parameters and albedo boundary conditions for reflectors, for subsequent use in full core nodal diffusion codes. This approach to reflector modelling has been shown to be accurate for two-group large commercial light water reactor (LWR) analysis, but has not been investigated for MTRs. MTRs are smaller, with much larger leakage, environment sensitivity and multi-group spectrum dependencies than LWRs. This study aims to determine if this approach to reflector modelling is an accurate and plausible homogenisation technique for the modelling of small MTR cores. The successful implementation will result in simplified core models, better accuracy and improved efficiency of computer simulations. Codes used in this study include SCALE 6.1, OSCAR-4 and EQUIVA (the last two codes are developed and used at Necsa). The results show a five times reduction in calculational time for the proposed reduced reactor model compared to the traditional explicit model. The calculated equivalent parameters however show some sensitivity to the environment used to generate them. Differences in the results compared to the current explicit model, require more careful investigation including comparisons with a reference result, before its implementation can be recommended. (authors)

  1. Comparison of Nodal Risk Formula and MR Lymphography for Predicting Lymph Node Involvement in Prostate Cancer

    SciTech Connect

    Deserno, Willem M.L.L.G.; Debats, Oscar A.; Rozema, Tom; Fortuin, Ansje S.; Heesakkers, Roel A.M.; Hoogeveen, Yvonne; Peer, Petronella G.M.; Barentsz, Jelle O.; Lin, Emile N.J.T. van

    2011-09-01

    Purpose: To compare the nodal risk formula (NRF) as a predictor for lymph node (LN) metastasis in patients with prostate cancer with magnetic resonance lymphography (MRL) using Ultrasmall Super-Paramagnetic particles of Iron Oxide (USPIO) and with histology as gold standard. Methods and Materials: Logistic regression analysis was performed with the results of histopathological evaluation of the LN as dependent variable and the nodal risk according to the NRF and the result of MRL as independent input variables. Receiver operating characteristic (ROC) analysis was performed to assess the performance of the models. Results: The analysis included 375 patients. In the single-predictor regression models, the NRF and MRL results were both significantly (p <0.001) predictive of the presence of LN metastasis. In the models with both predictors included, NRF was nonsignificant (p = 0.126), but MRL remained significant (p <0.001). For NRF, sensitivity was 0.79 and specificity was 0.38; for MRL, sensitivity was 0.82 and specificity was 0.93. After a negative MRL result, the probability of LN metastasis is 4% regardless of the NRF result. After a positive MRL, the probability of having LN metastasis is 68%. Conclusions: MRL is a better predictor of the presence of LN metastasis than NRF. Using only the NRF can lead to a significant overtreatment on the pelvic LN by radiation therapy. When the MRL result is available, the NRF is no longer of added value.

  2. A generalized framework for nodal first derivative summation-by-parts operators

    NASA Astrophysics Data System (ADS)

    Del Rey Fernández, David C.; Boom, Pieter D.; Zingg, David W.

    2014-06-01

    A generalized framework is presented that extends the classical theory of finite-difference summation-by-parts (SBP) operators to include a wide range of operators, where the main extensions are (i) non-repeating interior point operators, (ii) nonuniform nodal distribution in the computational domain, (iii) operators that do not include one or both boundary nodes. Necessary and sufficient conditions are proven for the existence of nodal approximations to the first derivative with the SBP property. It is proven that the positive-definite norm matrix of each SBP operator must be associated with a quadrature rule; moreover, given a quadrature rule there exists a corresponding SBP operator, where for diagonal-norm SBP operators the weights of the quadrature rule must be positive. The generalized framework gives a straightforward means of posing many known approximations to the first derivative as SBP operators; several are surveyed, such as discontinuous Galerkin discretizations based on the Legendre-Gauss quadrature points, and shown to be SBP operators. Moreover, the new framework provides a method for constructing SBP operators by starting from quadrature rules; this is illustrated by constructing novel SBP operators from known quadrature rules. To demonstrate the utility of the generalization, the Legendre-Gauss and Legendre-Gauss-Radau quadrature points are used to construct SBP operators that do not include one or both boundary nodes.

  3. Successful catheter ablation of a slow AV-nodal pathway from the left posteroseptal region.

    PubMed

    Wieczorek, M; Höltgen, R; Djajadisastra, I

    2005-08-01

    We present the case of a 44 year old woman with recurrent episodes of supraventricular tachycardia due to AV-nodal reentry (AVNRT). She was refractory to conventional medical treatment and referred to our hospital with the view to catheter ablation of the slow AV-nodal pathway. AVNRT of the common type was easily induced performing stimulation from the high right atrium and proximal coronary sinus. Other forms of supraventricular tachycardia were definitely ruled out during further electrophysiologic study. Repetitive RF applications around the right posteroseptal region failed to cure the tachycardia which remained inducible with a typical jump in the AH interval. Extensive RF applications from posteroinferior to the midseptum including the area of the proximal coronary sinus and its os were ineffective as well.AVNRT was transiently but reproducibly eliminated while burns were applied to the high midseptum but AVNRT reoccured within 20 minutes. Finally after retrograde passage of the aortic valve with a 4 mm tip ablation catheter, RF was applied to the left postero to midseptal region. An accelerated junctional rhythm was immediately observed and AVNRT remained non-inducible from that time onwards. It is concluded that an atypical posterior extension of the AV node with predominant leftatrial course might be responsible for this unusual success of slow pathway elimination from left posteroseptal.

  4. Conservation defines functional motifs in the squint/nodal-related 1 RNA dorsal localization element

    PubMed Central

    Gilligan, Patrick C.; Kumari, Pooja; Lim, Shimin; Cheong, Albert; Chang, Alex; Sampath, Karuna

    2011-01-01

    RNA localization is emerging as a general principle of sub-cellular protein localization and cellular organization. However, the sequence and structural requirements in many RNA localization elements remain poorly understood. Whereas transcription factor-binding sites in DNA can be recognized as short degenerate motifs, and consensus binding sites readily inferred, protein-binding sites in RNA often contain structural features, and can be difficult to infer. We previously showed that zebrafish squint/nodal-related 1 (sqt/ndr1) RNA localizes to the future dorsal side of the embryo. Interestingly, mammalian nodal RNA can also localize to dorsal when injected into zebrafish embryos, suggesting that the sequence motif(s) may be conserved, even though the fish and mammal UTRs cannot be aligned. To define potential sequence and structural features, we obtained ndr1 3′-UTR sequences from approximately 50 fishes that are closely, or distantly, related to zebrafish, for high-resolution phylogenetic footprinting. We identify conserved sequence and structural motifs within the zebrafish/carp family and catfish. We find that two novel motifs, a single-stranded AGCAC motif and a small stem-loop, are required for efficient sqt RNA localization. These findings show that comparative sequencing in the zebrafish/carp family is an efficient approach for identifying weak consensus binding sites for RNA regulatory proteins. PMID:21149265

  5. The lunar nodal tide and the distance to tne Moon during the Precambrian era

    NASA Technical Reports Server (NTRS)

    Walker, J. C. G.; Zahnle, K. J.

    1986-01-01

    The origin and early evolution of life on Earth occurred under physical and chemical conditions distinctly different from those of the present day. The broad goal of this research program is to characterize these conditions. One aspect involves the dynamics of the Earth-Moon system, the distance of the Moon from the Earth, and the length of the day. These have evolved during the course of Earth history as a result of the dissipation of tidal energy. As the moon has receded the amplitude of oceanic tides has decreased while the increasing length of the day should have influenced climate and the circulation of atmosphere and ocean. A 23.3 year periodicity preserved in a 2500 million year old banded iron-formation was interpreted as reflecting the climatic influence of the lunar nodal tide. The corresponding lunar distance would then have been approx. 52 Earth radii. The influence of the lunar nodal tide is also apparent in rocks with an age of 680 million years B.P. The derived value for lunar distance 2500 million years ago is the only datum on the dynamics of the Earth-Moon system during the Precambrian era of Earth history. The implied development of Precambrian tidal friction is in accord with more recent paleontological evidence as well as the long term stability of the lunar orbit.

  6. Nodal bilayer-splitting controlled by spin-orbit interactions in underdoped high-Tc cuprates

    PubMed Central

    Harrison, N.; Ramshaw, B. J.; Shekhter, A.

    2015-01-01

    The highest superconducting transition temperatures in the cuprates are achieved in bilayer and trilayer systems, highlighting the importance of interlayer interactions for high Tc. It has been argued that interlayer hybridization vanishes along the nodal directions by way of a specific pattern of orbital overlap. Recent quantum oscillation measurements in bilayer cuprates have provided evidence for a residual bilayer-splitting at the nodes that is sufficiently small to enable magnetic breakdown tunneling at the nodes. Here we show that several key features of the experimental data can be understood in terms of weak spin-orbit interactions naturally present in bilayer systems, whose primary effect is to cause the magnetic breakdown to be accompanied by a spin flip. These features can now be understood to include the equidistant set of three quantum oscillation frequencies, the asymmetry of the quantum oscillation amplitudes in c-axis transport compared to ab-plane transport, and the anomalous magnetic field angle dependence of the amplitude of the side frequencies suggestive of small effective g-factors. We suggest that spin-orbit interactions in bilayer systems can further affect the structure of the nodal quasiparticle spectrum in the superconducting phase. PACS numbers: 71.45.Lr, 71.20.Ps, 71.18.+y PMID:26039222

  7. Clinical target volume delineation including elective nodal irradiation in preoperative and definitive radiotherapy of pancreatic cancer

    PubMed Central

    2012-01-01

    Background Radiotherapy (RT) is widely used in the treatment of pancreatic cancer. Currently, recommendation has been given for the delineation of the clinical target volume (CTV) in adjuvant RT. Based on recently reviewed pathologic data, the aim of this study is to propose criteria for the CTV definition and delineation including elective nodal irradiation (ENI) in the preoperative and definitive treatment of pancreatic cancer. Methods The anatomical structures of interest, as well as the abdominal vasculature were identified on intravenous contrast-enhanced CT scans of two different patients with pancreatic cancer of the head and the body. To delineate the lymph node area, a margin of 10 mm was added to the arteries. Results We proposed a set of guidelines for elective treatment of high-risk nodal areas and CTV delineation. Reference CT images were provided. Conclusions The proposed guidelines could be used for preoperative or definitive RT for carcinoma of the head and body of the pancreas. Further clinical investigations are needed to validate the defined CTVs. PMID:22691275

  8. Nodal bilayer-splitting controlled by spin-orbit interactions in underdoped high-Tc cuprates

    DOE PAGES

    Harrison, N.; Ramshaw, B. J.; Shekhter, A.

    2015-06-03

    The highest superconducting transition temperatures in the cuprates are achieved in bilayer and trilayer systems, highlighting the importance of interlayer interactions for high Tc. It has been argued that interlayer hybridization vanishes along the nodal directions by way of a specific pattern of orbital overlap. Recent quantum oscillation measurements in bilayer cuprates have provided evidence for a residual bilayer-splitting at the nodes that is sufficiently small to enable magnetic breakdown tunneling at the nodes. Here we show that several key features of the experimental data can be understood in terms of weak spin-orbit interactions naturally present in bilayer systems, whosemore » primary effect is to cause the magnetic breakdown to be accompanied by a spin flip. These features can now be understood to include the equidistant set of three quantum oscillation frequencies, the asymmetry of the quantum oscillation amplitudes in c-axis transport compared to ab-plane transport, and the anomalous magnetic field angle dependence of the amplitude of the side frequencies suggestive of small effective g-factors. We suggest that spin-orbit interactions in bilayer systems can further affect the structure of the nodal quasiparticle spectrum in the superconducting phase. PACS numbers: 71.45.Lr, 71.20.Ps, 71.18.+y« less

  9. Observation of topological nodal fermion semimetal phase in ZrSiS

    NASA Astrophysics Data System (ADS)

    Neupane, Madhab; Belopolski, Ilya; Hosen, M. Mofazzel; Sanchez, Daniel S.; Sankar, Raman; Szlawska, Maria; Xu, Su-Yang; Dimitri, Klauss; Dhakal, Nagendra; Maldonado, Pablo; Oppeneer, Peter M.; Kaczorowski, Dariusz; Chou, Fangcheng; Hasan, M. Zahid; Durakiewicz, Tomasz

    2016-05-01

    Unveiling new topological phases of matter is one of the current objectives in condensed matter physics. Recent experimental discoveries of Dirac and Weyl semimetals prompt the search for other exotic phases of matter. Here we present a systematic angle-resolved photoemission spectroscopy study of ZrSiS, a prime topological nodal semimetal candidate. Our wider Brillouin zone (BZ) mapping shows multiple Fermi surface pockets such as the diamond-shaped Fermi surface, elliptical-shaped Fermi surface, and a small electron pocket encircling at the zone center (Γ ) point, the M point, and the X point of the BZ, respectively. We experimentally establish the spinless nodal fermion semimetal phase in ZrSiS, which is supported by our first-principles calculations. Our findings evidence that the ZrSiS-type of material family is a new platform on which to explore exotic states of quantum matter; these materials are expected to provide an avenue for engineering two-dimensional topological insulator systems.

  10. Spin-orbit interaction driven collective electron-hole excitations in a noncentrosymmetric nodal loop Weyl semimetal

    NASA Astrophysics Data System (ADS)

    Ahn, Kyo-Hoon; Lee, Kwan-Woo; Pickett, Warren E.

    2015-09-01

    NbP is one member of a new class of nodal loop semimetals characterized by the cooperative effects of spin-orbit coupling (SOC) and a lack of inversion center. Here transport and spectroscopic properties of NbP are evaluated using density functional theory methods. SOC together with the lack of inversion symmetry splits degeneracies, giving rise to "Russian doll nested" Fermi surfaces containing 4 ×10-4 electron (hole) carriers/f.u. Due to the modest SOC strength in Nb, the Fermi surfaces map out the Weyl nodal loops. Calculated structure around T*≈100 K in transport properties reproduces well the observed transport behavior only when SOC is included, attesting to the precision of the (delicate) calculations and the stoichiometry of the samples. Low-energy collective electron-hole excitations (plasmons) in the 20-60 meV range result from the nodal loop splitting.

  11. Shifting nodal-plane suppressions in high-order-harmonic spectra from diatomic molecules in orthogonally polarized driving fields

    NASA Astrophysics Data System (ADS)

    Das, T.; Figueira de Morisson Faria, C.

    2016-08-01

    We analyze the imprint of nodal planes in high-order-harmonic spectra from aligned diatomic molecules in intense laser fields whose components exhibit orthogonal polarizations. We show that the typical suppression in the spectra associated to nodal planes is distorted, and that this distortion can be employed to map the electron's angle of return to its parent ion. This investigation is performed semianalytically at the single-molecule response and single-active orbital level, using the strong-field approximation and the steepest descent method. We show that the velocity form of the dipole operator is superior to the length form in providing information about this distortion. However, both forms introduce artifacts that are absent in the actual momentum-space wave function. Furthermore, elliptically polarized fields lead to larger distortions in comparison to two-color orthogonally polarized fields. These features are investigated in detail for O2, whose highest occupied molecular orbital provides two orthogonal nodal planes.

  12. Development of a standing-wave fluorescence microscope with high nodal plane flatness.

    PubMed

    Freimann, R; Pentz, S; Hörler, H

    1997-09-01

    This article reports about the development and application of a standing-wave fluorescence microscope (SWFM) with high nodal plane flatness. As opposed to the uniform excitation field in conventional fluorescence microscopes as SWFM uses a standing-wave pattern of laser light. This pattern consists of alternating planar nodes and antinodes. By shifting it along the axis of the microscope a set of different fluorescent structures can be distinguished. Their axial separation may just be a fraction of a wavelength so that an SWFM allows distinction of structures which would appear axially unresolved in a conventional or confocal fluorescence microscope. An SWFM is most powerful when the axial extension of the specimen is comparable to the wavelength of light. Otherwise several planes are illuminated simultaneously and their separation is hardly feasible. The objective of this work was to develop a new SWFM instrument which allows standing-wave fluorescence microscopy with controlled high nodal plane flatness. Earlier SWFMs did not allow such a controlled flatness, which impeded image interpretation and processing. Another design goal was to build a compact, easy-to-use instrument to foster a more widespread use of this new technique. The instrument developed uses a green-emitting helium-neon laser as the light source, a piezoelectric movable beamsplitter to generate two mutually coherent laser beams of variable relative phase and two single-mode fibres to transmit these beams to the microscope. Each beam is passed on to the specimen by a planoconvex lens and an objective lens. The only reflective surface whose residual curvature could cause wavefront deformations is a dichroic beamsplitter. Nodal plane flatness is controlled via interference fringes by a procedure which is similar to the interferometric test of optical surfaces. The performance of the instrument was tested using dried and fluorescently labelled cardiac muscle cells of rats. The SWFM enabled the

  13. Atlas-Based Segmentation Improves Consistency and Decreases Time Required for Contouring Postoperative Endometrial Cancer Nodal Volumes

    SciTech Connect

    Young, Amy V.; Wortham, Angela; Wernick, Iddo; Evans, Andrew; Ennis, Ronald D.

    2011-03-01

    Purpose: Accurate target delineation of the nodal volumes is essential for three-dimensional conformal and intensity-modulated radiotherapy planning for endometrial cancer adjuvant therapy. We hypothesized that atlas-based segmentation ('autocontouring') would lead to time savings and more consistent contours among physicians. Methods and Materials: A reference anatomy atlas was constructed using the data from 15 postoperative endometrial cancer patients by contouring the pelvic nodal clinical target volume on the simulation computed tomography scan according to the Radiation Therapy Oncology Group 0418 trial using commercially available software. On the simulation computed tomography scans from 10 additional endometrial cancer patients, the nodal clinical target volume autocontours were generated. Three radiation oncologists corrected the autocontours and delineated the manual nodal contours under timed conditions while unaware of the other contours. The time difference was determined, and the overlap of the contours was calculated using Dice's coefficient. Results: For all physicians, manual contouring of the pelvic nodal target volumes and editing the autocontours required a mean {+-} standard deviation of 32 {+-} 9 vs. 23 {+-} 7 minutes, respectively (p = .000001), a 26% time savings. For each physician, the time required to delineate the manual contours vs. correcting the autocontours was 30 {+-} 3 vs. 21 {+-} 5 min (p = .003), 39 {+-} 12 vs. 30 {+-} 5 min (p = .055), and 29 {+-} 5 vs. 20 {+-} 5 min (p = .0002). The mean overlap increased from manual contouring (0.77) to correcting the autocontours (0.79; p = .038). Conclusion: The results of our study have shown that autocontouring leads to increased consistency and time savings when contouring the nodal target volumes for adjuvant treatment of endometrial cancer, although the autocontours still required careful editing to ensure that the lymph nodes at risk of recurrence are properly included in the target

  14. Nodal Gap” induced by the incommensurate diagonal spin density modulation in underdoped high- Tc superconductors

    DOE PAGES

    Zhou, Tao; Gao, Yi; Zhu, Jian -Xin

    2015-03-07

    Recenmore » tly it was revealed that the whole Fermi surface is fully gapped for several families of underdoped cuprates. The existence of the finite energy gap along the d-wave nodal lines (nodal gap) contrasts the common understanding of the d-wave pairing symmetry, which challenges the present theories for the high-Tcsuperconductors. Here we propose that the incommensurate diagonal spin-density-wave order can account for the above experimental observation. The Fermi surface and the local density of states are also studied. Our results are in good agreement with many important experiments in high-Tcsuperconductors.« less

  15. Regional Stress Orientations and Slip Compatibility of Earthquake Focal Mechanism Nodal Planes in the New Madrid Seismic Zone

    NASA Astrophysics Data System (ADS)

    Hurd, O.; Zoback, M. D.

    2011-12-01

    In this study we revisit the question of slip on faults in the New Madrid seismic zone in the context of the regional stress field. Specifically, we utilize newly available data to investigate whether fault slip is compatible with the regional stress field and laboratory-determined coefficients of friction (as originally argued by M.D. Zoback and M.L. Zoback, Science, 1981) or if there is evidence for either local sources of stress or anomalously low fault strength. Ten new, well-constrained earthquake focal plane mechanisms from the New Madrid seismic zone are available to update regional stress data and two earthquake focal plane mechanisms originally published in the 1970's have recently been revised. Utilizing these data, we demonstrate that the earthquakes occur on nodal planes which are optimally-oriented for shear failure in the current stress field assuming hydrostatic pore pressure in the brittle crust and coefficients of friction (μ) of about 0.6. The average SHmax orientation inferred from P-axes of the 12 focal mechanisms is N84E +/- 21°, which is consistent with the overall trend of SHmax in the region. In a manner similar to the study by M.L. Zoback (JGR, 1992), which utilized a slightly smaller (and in two cases, less reliable) set of focal mechanisms in this area, we use the orientation of the focal mechanism nodal planes combined with independent stress data to investigate the compatibility of slip on both nodal planes in the current stress field. First, the relative magnitudes of the three principal stresses are calculated from the nodal plane and stress orientations. Next, we utilize Mohr-Coulomb failure criterion to calculate the theoretically-optimal orientation of a fault plane for different coefficients of friction. Lastly, we calculate the difference in orientation between the theoretically-optimal planes and the focal mechanism nodal planes and identify the nodal plane with the smaller difference as the preferred nodal plane. For μ = 0

  16. Performance of a recoverable tug for planetary missions including use of perigee propulsion and corrections for nodal regression

    NASA Technical Reports Server (NTRS)

    Borsody, J.

    1976-01-01

    Mathematical equations are derived by using the Maximum Principle to obtain the maximum payload capability of a reusable tug for planetary missions. The mathematical formulation includes correction for nodal precession of the space shuttle orbit. The tug performs this nodal correction in returning to this precessed orbit. The sample case analyzed represents an inner planet mission as defined by the declination (fixed) and right ascension of the outgoing asymptote and the mission energy. Payload capability is derived for a typical cryogenic tug and the sample case with and without perigee propulsion. Optimal trajectory profiles and some important orbital elements are also discussed.

  17. An analytical discrete ordinates solution for a nodal model of a two-dimensional neutron transport problem

    SciTech Connect

    Filho, J. F. P.

    2013-07-01

    In this work, an analytical discrete ordinates method is used to solve a nodal formulation of a neutron transport problem in x, y-geometry. The proposed approach leads to an important reduction in the order of the associated eigenvalue systems, when combined with the classical level symmetric quadrature scheme. Auxiliary equations are proposed, as usually required for nodal methods, to express the unknown fluxes at the boundary introduced as additional unknowns in the integrated equations. Numerical results, for the problem defined by a two-dimensional region with a spatially constant and isotropically emitting source, are presented and compared with those available in the literature. (authors)

  18. First Case of Automatic His Potential Detection With a Novel Ultra High-density Electroanatomical Mapping System for AV Nodal Ablation

    PubMed Central

    Hilbert, Sebastian; Kosiuk, Jedrzej; John, Silke; Hindricks, Gerhard; Bollmann, Andreas

    2016-01-01

    A 74-year old was considered for atrioventricular (AV) nodal ablation in view of atrial fibrillation (AF) with poorly controlled ventricular rate despite being on amiodarone. Targeted AV nodal ablation was successfully performed after identifying the target site for ablation by reviewing an ultra high-density map of the His region produced by automatic electrogram annotation. PMID:25852249

  19. Scaffolding for Three-Dimensional Embryonic Vasculogenesis

    NASA Astrophysics Data System (ADS)

    Kraehenbuehl, Thomas P.; Aday, Sezin; Ferreira, Lino S.

    Biomaterial scaffolds have great potential to support efficient vascular differentiation of embryonic stem cells. Vascular cell fate-specific biochemical and biophysical cues have been identified and incorporated into three-dimensional (3D) biomaterials to efficiently direct embryonic vasculogenesis. The resulting vascular-like tissue can be used for regenerative medicine applications, further elucidation of biophysical and biochemical cues governing vasculogenesis, and drug discovery. In this chapter, we give an overview on the following: (1) developmental cues for directed differentiation of human embryonic stem cells (hESCs) into vascular cells, (2) 3D vascular differentiation in embryoid bodies (EBs), (3) preparation of 3D scaffolds for the vascular differentiation of hESCs, and (4) the most significant studies combining scaffolding and hESCs for development of vascular-like tissue.

  20. Numerical Solution of Poroelastic Wave Equation Using Nodal Discontinuous Galerkin Finite Element Method

    NASA Astrophysics Data System (ADS)

    Shukla, K.; Wang, Y.; Jaiswal, P.

    2014-12-01

    In a porous medium the seismic energy not only propagates through matrix but also through pore-fluids. The differential movement between sediment grains of the matrix and interstitial fluid generates a diffusive wave which is commonly referred to as the slow P-wave. A combined system of equation which includes both elastic and diffusive phases is known as the poroelasticity. Analyzing seismic data through poroelastic modeling results in accurate interpretation of amplitude and separation of wave modes, leading to more accurate estimation of geomehanical properties of rocks. Despite its obvious multi-scale application, from sedimentary reservoir characterization to deep-earth fractured crust, poroelasticity remains under-developed primarily due to the complex nature of its constituent equations. We present a detail formulation of poroleastic wave equations for isotropic media by combining the Biot's and Newtonian mechanics. System of poroelastic wave equation constitutes for eight time dependent hyperbolic PDEs in 2D whereas in case of 3D number goes up to thirteen. Eigen decomposition of Jacobian of these systems confirms the presence of an additional slow-P wave phase with velocity lower than shear wave, posing stability issues on numerical scheme. To circumvent the issue, we derived a numerical scheme using nodal discontinuous Galerkin approach by adopting the triangular meshes in 2D which is extended to tetrahedral for 3D problems. In our nodal DG approach the basis function over a triangular element is interpolated using Legendre-Gauss-Lobatto (LGL) function leading to a more accurate local solutions than in the case of simple DG. We have tested the numerical scheme for poroelastic media in 1D and 2D case, and solution obtained for the systems offers high accuracy in results over other methods such as finite difference , finite volume and pseudo-spectral. The nodal nature of our approach makes it easy to convert the application into a multi-threaded algorithm

  1. Progressive leukemic non-nodal mantle cell lymphoma associated with deletions of TP53, ATM, and/or 13q14.

    PubMed

    Chapman-Fredricks, Jennifer; Sandoval-Sus, Jose; Vega, Francisco; Lossos, Izidore S

    2014-08-01

    Leukemic, non-nodal mantle cell lymphoma (MCL) is a relatively indolent disease characterized by asymptomatic leukemic presentation, non-nodal disease distribution, and slow disease progression, particularly in comparison to that of classic nodal MCL. We studied 3 cases of leukemic, non-nodal MCL in which TP53, ATM, and/or 13q14 deletions were identified. All three patients had disease progression leading to treatment requirements in two of the patients at 5 and 18 months after initial diagnosis. The third patient also clinically progressed 25 months after initial diagnosis but was lost to follow up despite recommendation for initiation of therapy. We present these cases as potential evidence that while leukemic non-nodal MCL is typically an indolent disease compared to classically defined mantle cell lymphoma, cytogenetic heterogeneity exists and cases with TP53, ATM, and/or 13q14 deletions may have a relatively aggressive clinical course.

  2. Embryonic stem cell patents and human dignity.

    PubMed

    Resnik, David B

    2007-09-01

    This article examines the assertion that human embryonic stem cells patents are immoral because they violate human dignity. After analyzing the concept of human dignity and its role in bioethics debates, this article argues that patents on human embryos or totipotent embryonic stem cells violate human dignity, but that patents on pluripotent or multipotent stem cells do not. Since patents on pluripotent or multipotent stem cells may still threaten human dignity by encouraging people to treat embryos as property, patent agencies should carefully monitor and control these patents to ensure that patents are not inadvertently awarded on embryos or totipotent stem cells.

  3. Embryonic Stem Cell Patents and Human Dignity

    PubMed Central

    Resnik, David B.

    2009-01-01

    This article examines the assertion that human embryonic stem cells patents are immoral because they violate human dignity. After analyzing the concept of human dignity and its role in bioethics debates, this article argues that patents on human embryos or totipotent embryonic stem cells violate human dignity, but that patents on pluripotent or multipotent stem cells do not. Since patents on pluripotent or multipotent stem cells may still threaten human dignity by encouraging people to treat embryos as property, patent agencies should carefully monitor and control these patents to ensure that patents are not inadvertently awarded on embryos or totipotent stem cells. PMID:17922198

  4. Embryonic Stem Cells: Isolation, Characterization and Culture

    NASA Astrophysics Data System (ADS)

    Amit, Michal; Itskovitz-Eldor, Joseph

    Embryonic stem cells are pluripotent cells isolated from the mammalian blastocyst. Traditionally, these cells have been derived and cultured with mouse embryonic fibroblast (MEF) supportive layers, which allow their continuous growth in an undifferentiated state. However, for any future industrial or clinical application hESCs should be cultured in reproducible, defined, and xeno-free culture system, where exposure to animal pathogens is prevented. From their derivation in 1998 the methods for culturing hESCs were significantly improved. This chapter wills discuss hESC characterization and the basic methods for their derivation and maintenance.

  5. Bone Morphogenic Protein 4 Mediates NOX1-Dependent eNOS Uncoupling, Endothelial Dysfunction, and COX2 Induction in Type 2 Diabetes Mellitus

    PubMed Central

    Youn, Ji-Youn; Zhou, Jun

    2015-01-01

    We have recently shown that angiotensin II-mediated uncoupling of endothelial nitric oxide synthase (eNOS) contributes to endothelial dysfunction in streptozotocin-induced type 1 diabetes mellitus. However, it has remained unclear whether and how eNOS uncoupling occurs in type 2 diabetes mellitus (T2DM) and the consequences of such in regulating vascular function. Here we investigated a role of bone morphogenic protein (BMP)-4 in mediating eNOS uncoupling, endothelial dysfunction, and inflammation in db/db mice. Circulating levels of BMP4 were markedly elevated in db/db mice but not in mice with type 1 diabetes mellitus, in which angiotensin II levels were significantly increased. Infusion of BMP4 antagonist noggin into db/db mice (15 μg/kg/day, 4 weeks) abolished eNOS uncoupling activity while restoring tetrahydrobiopterin (H4B) bioavailability. The impaired endothelium-dependent vasorelaxation in db/db aortas was significantly improved by noggin infusion. Exposure of aortic endothelial cells to BMP4 (50 ng/mL, 24 hours) resulted in eNOS uncoupling, which was attenuated by H4B precursor sepiapterin or small interfering RNA silencing nicotinamide adenine dinucleotide phosphate oxidase isoform 1 (NOX1). Interestingly, BMP4-dependent NOX1 up-regulation was abrogated by sepiapterin, implicating a NOX1-uncoupled eNOS-NOX1 feed-forward loop. BMP4 induction of cyclooxygenase 2 (COX2) expression and vascular cell adhesion protein 1 was found in db/db mice. Consistently, COX2 was up-regulated by BMP4 in endothelial cells, which was attenuated by sepiapterin, implicating an upstream role of eNOS uncoupling in COX2-mediated inflammatory activation. Taken together, our data for the first time reveal a novel role of BMP4 in inducing NOX1-dependent eNOS uncoupling in T2DM, which may promote development of novel therapeutics restoring endothelial function in T2DM. PMID:26121233

  6. Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease

    PubMed Central

    Ward-Caviness, Cavin K.; Neas, Lucas M.; Blach, Colette; Haynes, Carol S.; LaRocque-Abramson, Karen; Grass, Elizabeth; Dowdy, Elaine; Devlin, Robert B.; Diaz-Sanchez, David; Cascio, Wayne E.; Lynn Miranda, Marie; Gregory, Simon G.; Shah, Svati H.; Kraus, William E.; Hauser, Elizabeth R.

    2016-01-01

    There is a growing literature indicating that genetic variants modify many of the associations between environmental exposures and clinical outcomes, potentially by increasing susceptibility to these exposures. However, genome-scale investigations of these interactions have been rarely performed particularly in the case of air pollution exposures. We performed race-stratified genome-wide gene-environment interaction association studies on European-American (EA, N = 1623) and African-American (AA, N = 554) cohorts to investigate the joint influence of common single nucleotide polymorphisms (SNPs) and residential exposure to traffic (“traffic exposure”)—a recognized vascular disease risk factor—on peripheral arterial disease (PAD). Traffic exposure was estimated via the distance from the primary residence to the nearest major roadway, defined as the nearest limited access highways or major arterial. The rs755249-traffic exposure interaction was associated with PAD at a genome-wide significant level (P = 2.29x10-8) in European-Americans. Rs755249 is located in the 3’ untranslated region of BMP8A, a member of the bone morphogenic protein (BMP) gene family. Further investigation revealed several variants in BMP genes associated with PAD via an interaction with traffic exposure in both the EA and AA cohorts; this included interactions with non-synonymous variants in BMP2, which is regulated by air pollution exposure. The BMP family of genes is linked to vascular growth and calcification and is a novel gene family for the study of PAD pathophysiology. Further investigation of BMP8A using the Genotype Tissue Expression Database revealed multiple variants with nominally significant (P < 0.05) interaction P-values in our EA cohort were significant BMP8A eQTLs in tissue types highlight relevant for PAD such as rs755249 (tibial nerve, eQTL P = 3.6x10-6) and rs1180341 (tibial artery, eQTL P = 5.3x10-6). Together these results reveal a novel gene, and possibly gene

  7. Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease.

    PubMed

    Ward-Caviness, Cavin K; Neas, Lucas M; Blach, Colette; Haynes, Carol S; LaRocque-Abramson, Karen; Grass, Elizabeth; Dowdy, Elaine; Devlin, Robert B; Diaz-Sanchez, David; Cascio, Wayne E; Lynn Miranda, Marie; Gregory, Simon G; Shah, Svati H; Kraus, William E; Hauser, Elizabeth R

    2016-01-01

    There is a growing literature indicating that genetic variants modify many of the associations between environmental exposures and clinical outcomes, potentially by increasing susceptibility to these exposures. However, genome-scale investigations of these interactions have been rarely performed particularly in the case of air pollution exposures. We performed race-stratified genome-wide gene-environment interaction association studies on European-American (EA, N = 1623) and African-American (AA, N = 554) cohorts to investigate the joint influence of common single nucleotide polymorphisms (SNPs) and residential exposure to traffic ("traffic exposure")-a recognized vascular disease risk factor-on peripheral arterial disease (PAD). Traffic exposure was estimated via the distance from the primary residence to the nearest major roadway, defined as the nearest limited access highways or major arterial. The rs755249-traffic exposure interaction was associated with PAD at a genome-wide significant level (P = 2.29x10-8) in European-Americans. Rs755249 is located in the 3' untranslated region of BMP8A, a member of the bone morphogenic protein (BMP) gene family. Further investigation revealed several variants in BMP genes associated with PAD via an interaction with traffic exposure in both the EA and AA cohorts; this included interactions with non-synonymous variants in BMP2, which is regulated by air pollution exposure. The BMP family of genes is linked to vascular growth and calcification and is a novel gene family for the study of PAD pathophysiology. Further investigation of BMP8A using the Genotype Tissue Expression Database revealed multiple variants with nominally significant (P < 0.05) interaction P-values in our EA cohort were significant BMP8A eQTLs in tissue types highlight relevant for PAD such as rs755249 (tibial nerve, eQTL P = 3.6x10-6) and rs1180341 (tibial artery, eQTL P = 5.3x10-6). Together these results reveal a novel gene, and possibly gene family

  8. High-latitude oceanic variability associated with the 18.6-year nodal tide

    NASA Technical Reports Server (NTRS)

    Royer, Thomas C.

    1993-01-01

    Water column temperature variations which indicate that the upper ocean is responding to 18.6-yr tidal forcing are presented. An enhanced high-latitude response to this forcing is predicted by equilibrium tide theory, and it should be most evident at latitudes poleward of about 50 deg. Critical information on regional climate variations might be found in the subsurface waters of the North Pacific and possibly other high-latitude oceans. The 18.6-yr nodal tidal cycle must be considered in circulation models of the ocean and atmosphere that examine time scales of decades or longer. Because the temperature range associated with the cycle is 0.5-1 C, short-term climate and biological populations could be affected.

  9. Probing the Nodal Structure of Landau Level Wave Functions in Real Space.

    PubMed

    Bindel, J R; Ulrich, J; Liebmann, M; Morgenstern, M

    2017-01-06

    The inversion layer of p-InSb(110) obtained by Cs adsorption of 1.8% of a monolayer is used to probe the Landau level wave functions within smooth potential valleys by scanning tunneling spectroscopy at 14 T. The nodal structure becomes apparent as a double peak structure of each spin polarized first Landau level, while the zeroth Landau level exhibits a single peak per spin level only. The real space data show single rings of the valley-confined drift states for the zeroth Landau level and double rings for the first Landau level. The result is reproduced by a recursive Green function algorithm using the potential landscape obtained experimentally. We show that the result is generic by comparing the local density of states from the Green function algorithm with results from a well-controlled analytic model based on the guiding center approach.

  10. Majorana fermions in spin-singlet nodal superconductors with coexisting non-collinear magnetic order

    NASA Astrophysics Data System (ADS)

    Wang, Ziqiang; Lu, Yuan-Ming

    2013-03-01

    Realizations of Majorana fermions in solid state materials have attracted great interests recently in connection to topological order and quantum information processing. We propose a novel way to create Majorana fermions in superconductors. We show that an incipient non-collinear magnetic order turns a spin-singlet superconductor with nodes into a topological superconductor with a stable Majorana bound state (MBS) in the vortex core or on the edge. Moreover the topologically-stable point defect of non-collinear magnetic order also hosts a zero-energy MBS. We argue that such an exotic non-Abelian phase can be realized in extended t- J models on the triangular and square lattices. Our proposal suggests a new avenue for the search of Majorana fermions in correlated electron materials where nodal superconductivity and magnetism are two common caricatures.

  11. Probing the Nodal Structure of Landau Level Wave Functions in Real Space

    NASA Astrophysics Data System (ADS)

    Bindel, J. R.; Ulrich, J.; Liebmann, M.; Morgenstern, M.

    2017-01-01

    The inversion layer of p -InSb (110 ) obtained by Cs adsorption of 1.8% of a monolayer is used to probe the Landau level wave functions within smooth potential valleys by scanning tunneling spectroscopy at 14 T. The nodal structure becomes apparent as a double peak structure of each spin polarized first Landau level, while the zeroth Landau level exhibits a single peak per spin level only. The real space data show single rings of the valley-confined drift states for the zeroth Landau level and double rings for the first Landau level. The result is reproduced by a recursive Green function algorithm using the potential landscape obtained experimentally. We show that the result is generic by comparing the local density of states from the Green function algorithm with results from a well-controlled analytic model based on the guiding center approach.

  12. Pseudodiffusive transmission of nodal Dirac fermions through a clean d -wave superconductor

    NASA Astrophysics Data System (ADS)

    Asbóth, J. K.; Akhmerov, A. R.; Berceanu, A. C.; Beenakker, C. W. J.

    2009-12-01

    We calculate the transmission of electrons and holes between two normal-metal (N) electrodes, separated over a distance L by an impurity-free superconductor (S) with d -wave symmetry of the order parameter. Nodal lines of vanishing excitation gap form ballistic conduction channels for coupled electron-hole excitations, described by an anisotropic two-dimensional Dirac equation. We find that the transmitted electrical and thermal currents both have the pseudodiffusive 1/L scaling characteristic of massless Dirac fermions—regardless of the presence of tunnel barriers at the NS interfaces. Tunnel barriers reduce the slope of the 1/L scaling in the case of the electrical current while leaving the thermal current unaffected.

  13. Quantum criticality and nodal superconductivity in the FeAs-based superconductor KFe2As2.

    PubMed

    Dong, J K; Zhou, S Y; Guan, T Y; Zhang, H; Dai, Y F; Qiu, X; Wang, X F; He, Y; Chen, X H; Li, S Y

    2010-02-26

    The in-plane resistivity rho and thermal conductivity kappa of the FeAs-based superconductor KFe2As2 single crystal were measured down to 50 mK. We observe non-Fermi-liquid behavior rho(T) approximately T{1.5} at H{c{2}}=5 T, and the development of a Fermi liquid state with rho(T) approximately T{2} when further increasing the field. This suggests a field-induced quantum critical point, occurring at the superconducting upper critical field H{c{2}}. In zero field, there is a large residual linear term kappa{0}/T, and the field dependence of kappa_{0}/T mimics that in d-wave cuprate superconductors. This indicates that the superconducting gaps in KFe2As2 have nodes, likely d-wave symmetry. Such a nodal superconductivity is attributed to the antiferromagnetic spin fluctuations near the quantum critical point.

  14. High critical temperature nodal superconductors as building block for time-reversal invariant topological superconductivity

    NASA Astrophysics Data System (ADS)

    Trani, F.; Campagnano, G.; Tagliacozzo, A.; Lucignano, P.

    2016-10-01

    We study possible applications of high critical temperature nodal superconductors for the search for Majorana bound states in the DIII class. We propose a microscopic analysis of the proximity effect induced by d -wave superconductors on a semiconductor wire with strong spin-orbit coupling. We characterize the induced superconductivity on the wire employing a numerical self-consistent tight-binding Bogoliubov-de Gennes approach, and analytical considerations on the Green's function. The order parameter induced on the wire, the pair correlation function, and the renormalization of the Fermi points are analyzed in detail, as well as the topological phase diagram in the case of weak coupling. We highlight optimal Hamiltonian parameters to access the nontrivial topological phase which could display time-reversal invariant Majorana doublets at the boundaries of the wire.

  15. A study of the radiative transfer equation using a spherical harmonics-nodal collocation method

    NASA Astrophysics Data System (ADS)

    Capilla, M. T.; Talavera, C. F.; Ginestar, D.; Verdú, G.

    2017-03-01

    Optical tomography has found many medical applications that need to know how the photons interact with the different tissues. The majority of the photon transport simulations are done using the diffusion approximation, but this approximation has a limited validity when optical properties of the different tissues present large gradients, when structures near the photons source are studied or when anisotropic scattering has to be taken into account. As an alternative to the diffusion model, the PL equations for the radiative transfer problem are studied. These equations are discretized in a rectangular mesh using a nodal collocation method. The performance of this model is studied by solving different 1D and 2D benchmark problems of light propagation in tissue having media with isotropic and anisotropic scattering.

  16. Field-induced reentrant superconductivity in thin films of nodal superconductors

    NASA Astrophysics Data System (ADS)

    Hachiya, M.; Aoyama, K.; Ikeda, R.

    2013-08-01

    Previous work on nodal d-wave superconductors has shown that a Fulde-Ferrell-Larkin-Ovchinnikov- (FFLO-) like superconducting (SC) state, which is modulated along the film plane, can be realized with no magnetic field when quasiparticles acquire an additional linear term in the wave vector in their dispersion. In the present work, the stability of such a modulated SC state in an artificial film against an applied magnetic field is studied. As a reflection of the presence of two FFLO-like states of different origins, one close to zero field and the other at the high-field end, in a single field vs temperature phase diagram of thin films, the conventional SC state, which is uniform along the film plane, generally tends to appear as a reentrant ordered phase bounded by the normal phase in lower fields.

  17. Lunar nodal tide and distance to the moon during the Precambrian

    NASA Technical Reports Server (NTRS)

    Walker, J. C. G.; Zahnle, K. J.

    1986-01-01

    The first direct determination of the lunar distance in the Precambrian is presented. A 23.3 + or - 0.3 yr periodicity preserved in 2500 Myr BP Australian banded iron formation is interpreted as reflecting the climatic influence of the lunar nodal tide, which has been detected with its modern 18.6-yr periodicity in some modern climate records. The lunar distance at 2500 Myr BP would then have been about 52 earth radii. The implied history of precambrian tidal friction is in accord with both the more recent paleontological evidence and the long-term stability of the lunar orbit. The length of the Milankovitch cycles that modulate the ice ages today also evolve with the earth-moon system. Their detection in the Precambrian sedimentary record would then permit an independent determination of the lunar distance.

  18. Nodal Structure of Quasi-Two-Dimensional Superconductors Probed by a Magnetic Field

    NASA Astrophysics Data System (ADS)

    Vorontsov, A.; Vekhter, I.

    2006-06-01

    We consider a quasi-two-dimensional superconductor with line nodes in the presence of an in-plane magnetic field, and compute the dependence of the specific heat C and the in-plane heat conductivity κ on the angle between the field and the nodal direction in the vortex state. We use a variation of the microscopic Brandt-Pesch-Tewordt method that accounts for the scattering of quasiparticles off vortices, and analyze the signature of the nodes in C and κ. At low to moderate fields the specific heat anisotropy changes sign with increasing temperature. Comparison with measurements of C and κ in CeCoIn5 resolves the contradiction between the two in favor of the dx2-y2 gap.

  19. Diagnosis of non-nodal paratracheobronchial lesions by linear endobronchial ultrasound.

    PubMed

    Lourido, Tamara; Botana, Maribel; Leiro, Virginia; Núñez, Manuel; Fernández-Villar, Alberto

    2013-08-01

    Linear endobronchial ultrasound (EBUS) allows samples of lesions close to the airways to be obtained, as it enables aspiration to be performed under visual control in real time, opening new possibilities for minimally invasive examination of the mediastinum. While there are many publications on its usefulness in the study of mediastinal or hilar lymphadenopathies, there are few that analyse the role of EBUS-guided transbronchial needle aspiration for the diagnosis of other lesions adjacent to the airways or digestive tract. We describe the characteristics and results obtained in a series of 26 cases of non-nodal lesions of different aetiologies studied by EBUS- guided transbronchial needle aspiration through the airways or oesophagus, demonstrating the usefulness and safety of this technique in the diagnosis of these types of lesions.

  20. The HOMO Nodal Arrangement in Polychromophoric Molecules and Assemblies Controls the Interchromophoric Electronic Coupling.

    PubMed

    Talipov, Marat R; Navale, Tushar S; Rathore, Rajendra

    2015-11-23

    Triptycenes spontaneously assemble into two-dimensional networks in which long-range charge transport is facilitated by the extensive electronic coupling through the triptycene framework (intramolecularly) and by cofacial π-stacking (intermolecularly). While designing and synthesizing next-generation triptycenes containing polyaromatic chromophores, the electronic coupling amongst the chromophores was observed to be highly dependent on the nature and position of the substituents. Herein, we demonstrate using hexaalkoxytriptycenes that the electronic coupling amongst the chromophores is switched on and off by a simple repositioning of the substituents, which alters the nodal arrangement of the HOMOs of the individual chromophores. A visual inspection of the HOMOs can thus provide a ready evaluation of the electronic coupling in polychromophoric molecules/assemblies, and will serve as an important tool for the rational design of modern charge-transport materials.

  1. NODAL secreted by male germ cells regulates the proliferation and function of human Sertoli cells from obstructive azoospermia and nonobstructive azoospermia patients

    PubMed Central

    Tian, Ru-Hui; Yang, Shi; Zhu, Zi-Jue; Wang, Jun-Long; Liu, Yun; Yao, Chencheng; Ma, Meng; Guo, Ying; Yuan, Qingqing; Hai, Yanan; Huang, Yi-Ran; He, Zuping; Li, Zheng

    2015-01-01

    This study was designed to explore the regulatory effects of male germ cell secreting factor NODAL on Sertoli cell fate decisions from obstructive azoospermia (OA) and nonobstructive azoospermia (NOA) patients. Human Sertoli cells and male germ cells were isolated using two-step enzymatic digestion and SATPUT from testes of azoospermia patients. Expression of NODAL and its multiple receptors in human Sertoli cells and male germ cells were characterized by reverse transcription-polymerase chain reaction (RT-PCR) and immunochemistry. Human recombinant NODAL and its receptor inhibitor SB431542 were employed to probe their effect on the proliferation of Sertoli cells using the CCK-8 assay. Quantitative PCR and Western blots were utilized to assess the expression of Sertoli cell functional genes and proteins. NODAL was found to be expressed in male germ cells but not in Sertoli cells, whereas its receptors ALK4, ALK7, and ACTR-IIB were detected in Sertoli cells and germ cells, suggesting that NODAL plays a regulatory role in Sertoli cells and germ cells via a paracrine and autocrine pathway, respectively. Human recombinant NODAL could promote the proliferation of human Sertoli cells. The expression of cell cycle regulators, including CYCLIN A, CYCLIN D1 and CYCLIN E, was not remarkably affected by NODAL signaling. NODAL enhanced the expression of essential growth factors, including GDNF, SCF, and BMP4, whereas SB431542 decreased their levels. There was not homogeneity of genes changes by NODAL treatment in Sertoli cells from OA and Sertoli cell-only syndrome (SCO) patients. Collectively, this study demonstrates that NODAL produced by human male germ cells regulates proliferation and numerous gene expression of Sertoli cells. PMID:26289399

  2. Theory of nodal s±-wave pairing symmetry in the Pu-based 115 superconductor family

    SciTech Connect

    Das, Tanmoy; Zhu, Jian -Xin; Graf, Matthias J.

    2015-02-27

    The spin-fluctuation mechanism of superconductivity usually results in the presence of gapless or nodal quasiparticle states in the excitation spectrum. Nodal quasiparticle states are well established in copper-oxide, and heavy-fermion superconductors, but not in iron-based superconductors. Here, we study the pairing symmetry and mechanism of a new class of plutonium-based high-Tc superconductors and predict the presence of a nodal s⁺⁻ wave pairing symmetry in this family. Starting from a density-functional theory (DFT) based electronic structure calculation we predict several three-dimensional (3D) Fermi surfaces in this 115 superconductor family. We identify the dominant Fermi surface “hot-spots” in the inter-band scattering channel, which are aligned along the wavevector Q = (π, π, π), where degeneracy could induce sign-reversal of the pairing symmetry. Our calculation demonstrates that the s⁺⁻ wave pairing strength is stronger than the previously thought d-wave pairing; and more importantly, this pairing state allows for the existence of nodal quasiparticles. Finally, we predict the shape of the momentum- and energy-dependent magnetic resonance spectrum for the identification of this pairing symmetry.

  3. Theory of nodal s±-wave pairing symmetry in the Pu-based 115 superconductor family

    DOE PAGES

    Das, Tanmoy; Zhu, Jian -Xin; Graf, Matthias J.

    2015-02-27

    The spin-fluctuation mechanism of superconductivity usually results in the presence of gapless or nodal quasiparticle states in the excitation spectrum. Nodal quasiparticle states are well established in copper-oxide, and heavy-fermion superconductors, but not in iron-based superconductors. Here, we study the pairing symmetry and mechanism of a new class of plutonium-based high-Tc superconductors and predict the presence of a nodal s⁺⁻ wave pairing symmetry in this family. Starting from a density-functional theory (DFT) based electronic structure calculation we predict several three-dimensional (3D) Fermi surfaces in this 115 superconductor family. We identify the dominant Fermi surface “hot-spots” in the inter-band scattering channel,more » which are aligned along the wavevector Q = (π, π, π), where degeneracy could induce sign-reversal of the pairing symmetry. Our calculation demonstrates that the s⁺⁻ wave pairing strength is stronger than the previously thought d-wave pairing; and more importantly, this pairing state allows for the existence of nodal quasiparticles. Finally, we predict the shape of the momentum- and energy-dependent magnetic resonance spectrum for the identification of this pairing symmetry.« less

  4. Identification and expression of Smads associated with TGF-beta/activin/nodal signaling pathways in the rainbow trout (Oncorhynuchus mykiss)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Smad proteins are essential components of the TGF-beta/activin/nodal family signaling pathway. We report the identification and characterization of transcripts representing 3 receptor Smads (Smad2a, Smad2b, Smad3), 2 common Smads (Smad4a, Smad4b) and one inhibitory Smad (Smad7). Phylogenetic an...

  5. Theory of nodal s±-wave pairing symmetry in the Pu-based 115 superconductor family

    PubMed Central

    Das, Tanmoy; Zhu, Jian-Xin; Graf, Matthias J.

    2015-01-01

    The spin-fluctuation mechanism of superconductivity usually results in the presence of gapless or nodal quasiparticle states in the excitation spectrum. Nodal quasiparticle states are well established in copper-oxide, and heavy-fermion superconductors, but not in iron-based superconductors. Here, we study the pairing symmetry and mechanism of a new class of plutonium-based high-Tc superconductors and predict the presence of a nodal s+− wave pairing symmetry in this family. Starting from a density-functional theory (DFT) based electronic structure calculation we predict several three-dimensional (3D) Fermi surfaces in this 115 superconductor family. We identify the dominant Fermi surface “hot-spots” in the inter-band scattering channel, which are aligned along the wavevector Q = (π, π, π), where degeneracy could induce sign-reversal of the pairing symmetry. Our calculation demonstrates that the s+− wave pairing strength is stronger than the previously thought d-wave pairing; and more importantly, this pairing state allows for the existence of nodal quasiparticles. Finally, we predict the shape of the momentum- and energy-dependent magnetic resonance spectrum for the identification of this pairing symmetry. PMID:25721375

  6. Acute effects of simvastatin to terminate fast reentrant tachycardia through increasing wavelength of atrioventricular nodal reentrant tachycardia circuit.

    PubMed

    Khori, Vahid; Alizadeh, Ali Mohammad; Moheimani, Hamid Reza; Zahedi, Mahdi; Aminolsharieh Najafi, Soroosh; Shakiba, Delaram; Nayebpour, Mohsen

    2015-02-01

    Simvastatin (SV) leads to reduction of ventricular rhythm during atrial fibrillation on rabbit atrioventricular (AV) nodes. The aim of our study was (i) to determine the frequency-dependent effects of SV in a functional model, and (ii) to assess the effects of SV to suppress experimental AV nodal reentrant tachycardia (AVNRT). Selective stimulation protocols were used with two different pacing protocols, His to atrial, and atrial to atrial (AA). An experimental AVNRT model with various cycle lengths was created in three groups of perfused rabbit AV nodal preparations (n = 24) including: SV 3 μm, SV 7 μm, and verapamil 0.1 μm. SV increased nodal conduction time and refractoriness by AA pacing. Different simulated models of slow/fast and fast/slow reentry were induced. SV caused inhibitory effects on the slow anterograde conduction (origin of refractoriness) more than on the fast anterograde conduction time, leading to an increase of tachycardia cycle length, tachycardia wavelength and termination of slow/fast reentrant tachyarrhythmia. Verapamil significantly suppressed the basic and frequency-dependent intrinsic nodal properties. In addition, SV decreased the incidence of gap and echo beats. The present study showed that SV in a concentration and rate-dependent manner increased the AV effective refractory period and reentrant tachycardia wavelength that lead to slowing or termination of experimental fast AVNRT. The direction-dependent inhibitory effect of SV on the anterograde and retrograde dual pathways explains its specific antireentrant actions.

  7. Debunking the lunar nodal tide in sea level data from the Northwest European shelf

    NASA Astrophysics Data System (ADS)

    Schmith, Torben; Thejll, Peter; Nielsen, Jacob W.

    2016-04-01

    In a recent study (Hansen, et al, 2015. Sea-Level Forcing by Synchronization of 56- and 74-Year Oscillations with the Moon's Nodal Tide on the Northwest European Shelf (Eastern North Sea to Central Baltic Sea). Journal of Coastal Research, 31(5), 1041 - 1056, hereafter 'HAK'), the existence of an 18.6 year lunar nodal tide signal of considerable strength and other periodic signals in the North Sea -- Baltic Sea area is claimed. We criticize important aspects of the analysis presented in HAK and thereby cast doubt on their conclusions. HAK claim that 18.6 year variations in sea level are predicted by tidal theory, but this is not the case in general and therefore the existence of such variations must be explicitly shown. We calculate the amplitude spectrum of the annual sea level by harmonic analysis and find no significant peaks at the periods claimed by HAK. Next, we used the results given by HAK to reconstruct their decomposition, and formed the residuals by subtracting the decomposition from the original data. We found that a strong variability near 18.6 years in the residuals, showing that the decomposition by HAK overrepresents the variability at this period. This motivated us to redo HAK's analysis following their prescription and we found a seven times lower amplitude for the 18.6 year periodicity than claimed by HAK. Finally, we discuss HAK's mode selection-criteria, based on correlation coefficients of trending series and find them invalid. Therefore, we perform a significance test based on a Monte Carlo technique and conclude that none of the modes identified by HAK are statistically significant.

  8. Theory of the nematic quantum critical point in a nodal superconductor

    NASA Astrophysics Data System (ADS)

    Kim, Eun-Ah

    2008-03-01

    In the last several years, experimental evidence has accumulated in a variety of highly correlated electronic systems of new quantum phases which (for purely electronic reasons) spontaneously break the rotational (point group) symmetry of the underlying crystal. Such electron ``nematic'' phases have been seen in quantum Hall systems[1], in the metamagnetic metal Sr3Ru2O7[2], and more recently in magnetic neutron scattering studies of the high temperature superconductor, YBCO[3]. In the case of a high Tc superconductor, the quantum dynamics of nematic order parameter naturally couples strongly to quasiparticle (qp) excitations. In this talk, I will discuss our recent results on the effects of the coupling between quantum critical nematic fluctuations and the nodal qp's of a d-wave superconductor in the vicinity of a putative quantum critical point inside the superconducting phase. We solve a model system with N flavors of quasiparticles in the large N limit[4]. To leading order in 1/N, quantum fluctuations enhance the dispersion anisotropy of the nodal excitations, and cause strong scattering which critically broadens the quasiparticle peaks in the spectral function, except in the vicinity of ``the tips of the banana,'' where the qp's remain sharp. We will discuss the possible implications of our results to ARPES and STM experiments. [1] M.P. Lilly, K.B. Cooper, J.P. Eisenstein, L.N. Pfeiffer, and K.W. West, PRL 83, 824 (1999). [2] R. A. Borzi and S. A. Grigera and J. Farrell and R. S. Perry and S. J. S. Lister and S. L. Lee and D. A. Tennant and Y. Maeno and A. P. Mackenzie, Science 315, 214 (2007). [3] V. Hinkov, D. Haug, B. Fauqu'e, P. Bourges, Y. Sidis, A. Ivanov, C. Bernhard, C. T. Lin, B. Keimer, unpublished. [4] E.-A. Kim, M. Lawler, P. Oreto, E. Fradkin, S. Kivelson, cond-mat/0705.4099.

  9. The Association Between Biological Subtype and Isolated Regional Nodal Failure After Breast-Conserving Therapy

    SciTech Connect

    Wo, Jennifer Y.; Taghian, Alphonse G.; Nguyen, Paul L.; Raad, Rita Abi; Sreedhara, Meera B.A.; Bellon, Jennifer R.; Wong, Julia S.; Gadd, Michele A.; Smith, Barbara L.; Harris, Jay R.

    2010-05-01

    Purpose: To evaluate the risk of isolated regional nodal failure (RNF) among women with invasive breast cancer treated with breast-conserving surgery (BCS) and radiation therapy (RT) and to determine factors, including biological subtype, associated with RNF. Methods and Materials: We retrospectively studied 1,000 consecutive women with invasive breast cancer who received breast-conserving surgery and RT from 1997 through 2002. Ninety percent of patients received adjuvant systemic therapy; none received trastuzumab. Sentinel lymph node biopsy was done in 617 patients (62%). Of patients with one to three positive nodes, 34% received regional nodal irradiation (RNI). Biological subtype classification into luminal A, luminal B, HER-2, and basal subtypes was based on estrogen receptor status-, progesterone receptor status-, and HER-2-status of the primary tumor. Results: Median follow-up was 77 months. Isolated RNF occurred in 6 patients (0.6%). On univariate analysis, biological subtype (p = 0.0002), lymph node involvement (p = 0.008), lymphovascular invasion (p = 0.02), and Grade 3 histology (p = 0.01) were associated with significantly higher RNF rates. Compared with luminal A, the HER-2 (p = 0.01) and basal (p = 0.08) subtypes were associated with higher RNF rates. The 5-year RNF rate among patients with one to three positive nodes treated with tangents alone was 2.4%; we could not identify a subset of these patients with a substantial risk of RNF. Conclusions: Isolated RNF is a rare occurrence after breast-conserving therapy. Patients with the HER-2 (not treated with trastuzumab) and basal subtypes appear to be at higher risk of developing RNF although this risk is not high enough to justify the addition of RNI. Low rates of RNF in patients with one to three positive nodes suggest that tangential RT without RNI is reasonable in most patients.

  10. Clinically Apparent Internal Mammary Nodal Metastasis in Patients With Advanced Breast Cancer: Incidence and Local Control

    SciTech Connect

    Zhang Yujing; Oh, Julia L.; Whitman, Gary J.

    2010-07-15

    Purpose: To investigate the incidence and local control of internal mammary lymph node metastases (IMN+) in patients with clinical N2 or N3 locally advanced breast cancer. Methods and Materials: We retrospectively reviewed the records of 809 breast cancer patients diagnosed with advanced nodal disease (clinical N2-3) who received radiation treatment at our institution from January 2000 December 2006. Patients were considered IMN+ on the basis of imaging studies. Results: We identified 112 of 809 patients who presented with IMN+ disease (13.8%) detected on ultrasound, computed tomography (CT), positron emission tomography/CT (PET/CT), and/or magnetic resonance imaging (MRI) studies. All 112 patients with IMN+ disease received anthracycline and taxane-based chemotherapy. Neoadjuvant chemotherapy (NCT) resulted in a complete response (CR) on imaging studies of IMN disease in 72.1% of patients. Excluding 16 patients with progressive disease, 96 patients received adjuvant radiation to the breast or the chest wall and the regional lymphatics including the IMN chain with a median dose of 60 Gy if the internal mammary lymph nodes normalized after chemotherapy and 66 Gy if they did not. The median follow-up of surviving patients was 41 months (8-118 months). For the 96 patients able to complete curative therapy, the actuarial 5-year IMN control rate, locoregional control, overall survival, and disease-free survival were 89%, 80%, 76%, and 56%. Conclusion: Over ten percent of patients with advanced nodal disease will have IMN metastases on imaging studies. Multimodality therapy including IMN irradiation achieves excellent rates of control in the IMN region and a DFS of more than 50% after curative treatment.

  11. The nodal count {0,1,2,3,…} implies the graph is a tree

    PubMed Central

    Band, Ram

    2014-01-01

    Sturm's oscillation theorem states that the nth eigenfunction of a Sturm–Liouville operator on the interval has n−1 zeros (nodes) (Sturm 1836 J. Math. Pures Appl. 1, 106–186; 373–444). This result was generalized for all metric tree graphs (Pokornyĭ et al. 1996 Mat. Zametki 60, 468–470 (doi:10.1007/BF02320380); Schapotschnikow 2006 Waves Random Complex Media 16, 167–178 (doi:10.1080/1745530600702535)) and an analogous theorem was proved for discrete tree graphs (Berkolaiko 2007 Commun. Math. Phys. 278, 803–819 (doi:10.1007/S00220-007-0391-3); Dhar & Ramaswamy 1985 Phys. Rev. Lett. 54, 1346–1349 (doi:10.1103/PhysRevLett.54.1346); Fiedler 1975 Czechoslovak Math. J. 25, 607–618). We prove the converse theorems for both discrete and metric graphs. Namely if for all n, the nth eigenfunction of the graph has n−1 zeros, then the graph is a tree. Our proofs use a recently obtained connection between the graph's nodal count and the magnetic stability of its eigenvalues (Berkolaiko 2013 Anal. PDE 6, 1213–1233 (doi:10.2140/apde.2013.6.1213); Berkolaiko & Weyand 2014 Phil. Trans. R. Soc. A 372, 20120522 (doi:10.1098/rsta.2012.0522); Colin de Verdière 2013 Anal. PDE 6, 1235–1242 (doi:10.2140/apde.2013.6.1235)). In the course of the proof, we show that it is not possible for all (or even almost all, in the metric case) the eigenvalues to exhibit a diamagnetic behaviour. In addition, we develop a notion of ‘discretized’ versions of a metric graph and prove that their nodal counts are related to those of the metric graph. PMID:24344337

  12. Majorana vortex-bound states in three-dimensional nodal noncentrosymmetric superconductors

    NASA Astrophysics Data System (ADS)

    Chang, Po-Yao; Matsuura, Shunji; Schnyder, Andreas P.; Ryu, Shinsei

    2014-11-01

    Noncentrosymmetric superconductors (NCSs), characterized by antisymmetric spin-orbit coupling and a mixture of spin-singlet and spin-triplet pairing components, are promising candidate materials for topological superconductivity. An important hallmark of topological superconductors is the existence of protected zero-energy states at surfaces or in vortex cores. Here we investigate Majorana vortex-bound states in three-dimensional nodal and fully gapped NCSs by combining analytical solutions of Bogoliubov-de Gennes (BdG) equations in the continuum with exact diagonalization of BdG Hamiltonians. We show that depending on the crystal point-group symmetries and the topological properties of the bulk Bogoliubov-quasiparticle wave functions, different types of zero-energy Majorana modes can appear inside the vortex core. We find that for nodal NCSs with tetragonal point group C4 v the vortex states are dispersionless along the vortex line, forming one-dimensional Majorana flat bands, while for NCSs with D4 point-group symmetry the vortex modes are helical Majorana states with a linear dispersion along the vortex line. NCSs with monoclinic point group C2, on the other hand, do not exhibit any zero-energy vortex-bound states. We show that in the case of the C4 v (D4) point group the stability of these Majorana zero modes is guaranteed by a combination of reflection (π rotation), time-reversal, and particle-hole symmetry. Considering continuous deformations of the quasiparticle spectrum in the presence of vortices, we show that the flat-band vortex-bound states of C4 v point-group NCSs can be adiabatically connected to the dispersionless vortex-bound states of time-reversal symmetric Weyl superconductors. Experimental implications of our results for thermal transport and tunneling measurements are discussed.

  13. Asynchronous collision integrators: Explicit treatment of unilateral contact with friction and nodal restraints

    PubMed Central

    Wolff, Sebastian; Bucher, Christian

    2013-01-01

    This article presents asynchronous collision integrators and a simple asynchronous method treating nodal restraints. Asynchronous discretizations allow individual time step sizes for each spatial region, improving the efficiency of explicit time stepping for finite element meshes with heterogeneous element sizes. The article first introduces asynchronous variational integration being expressed by drift and kick operators. Linear nodal restraint conditions are solved by a simple projection of the forces that is shown to be equivalent to RATTLE. Unilateral contact is solved by an asynchronous variant of decomposition contact response. Therein, velocities are modified avoiding penetrations. Although decomposition contact response is solving a large system of linear equations (being critical for the numerical efficiency of explicit time stepping schemes) and is needing special treatment regarding overconstraint and linear dependency of the contact constraints (for example from double-sided node-to-surface contact or self-contact), the asynchronous strategy handles these situations efficiently and robust. Only a single constraint involving a very small number of degrees of freedom is considered at once leading to a very efficient solution. The treatment of friction is exemplified for the Coulomb model. Special care needs the contact of nodes that are subject to restraints. Together with the aforementioned projection for restraints, a novel efficient solution scheme can be presented. The collision integrator does not influence the critical time step. Hence, the time step can be chosen independently from the underlying time-stepping scheme. The time step may be fixed or time-adaptive. New demands on global collision detection are discussed exemplified by position codes and node-to-segment integration. Numerical examples illustrate convergence and efficiency of the new contact algorithm. Copyright © 2013 The Authors. International Journal for Numerical Methods in

  14. Nodal upstaging during lung cancer resection is associated with surgical approach

    PubMed Central

    Martin, Jeremiah T.; Durbin, Eric B.; Chen, Li; Gal, Tamas; Mahan, Angela; Ferraris, Victor; Zwischenberger, Joseph

    2015-01-01

    Background Recent reports demonstrate that thoracoscopic lobectomy for lung cancer may be associated with lower rates of surgical upstaging. We queried a state-wide cancer registry for differences in upstaging rates and survival by surgical approach. Methods The Kentucky Cancer Registry (KCR) collects data, including centralized pathology reporting, on cancer patients treated statewide. We performed a retrospective review from 2010-2012 to examine clinical and pathologic stage. We assessed rates of upstaging and whether or not the surgical approach, thoracotomy (THOR) versus minimally invasive techniques (VATS), had an impact on final pathologic stage and survival. Results The KCR database from 2010 to 2012 contained information on 2830 lung cancer cases, 1964 having THOR and 500 having VATS resections. Preoperatively, 36.4% of THOR were clinically stage 1a vs. 47.4% % VATS (p=0.0002). Of these, final pathologic stage remained stage 1a in 30.5% of THOR and 38.0% of VATS (p=0.0002). The overall nodal upstaging rate for THOR was 9.9% and 4.8% for VATS (p=0.002). There was decreased nodal upstaging with VATS, independent of tumor size and extent of resection (OR 0.6, 95% CI 0.387-0.985, p=0.04). However there was improved survival with VATS compared with THOR (HR 0.733, 95% CI 0.592-0.907, p = 0.0042). Conclusions Consistent with other reports, we demonstrate a lower upstaging rate with VATS. Nevertheless, there is a survival advantage in VATS patients. Although selection bias may play a role in these observed differences, the improved quality of life measures associated with VATS, may explain survival improvement despite lower surgical upstaging. PMID:26428690

  15. Risk factor analysis for central nodal metastasis in papillary thyroid carcinoma.

    PubMed

    Mao, Ling-Na; Wang, Ping; Li, Zhi-Yu; Wang, Yong; Song, Zheng-Ya

    2015-01-01

    Lymph node involvement is associated with recurrence in papillary thyroid carcinoma (PTC). The central neck compartment (level VI) lymph nodes are at the greatest risk of metastases from PTC, but the role of central neck dissection (CND) remains controversial, particularly in PTC without clinical cervical lymph node metastasis (cN0). The present study aimed to identify risk factors of central cervical nodal metastasis and the safety of CND in patients with cN0 PTC. The current study retrospectively investigated 389 patients who had been followed up for 12.0-25.5 months after surgery, and were divided into positive or negative lymph node involvement groups according to the pathological results subsequent to this surgery. Univariate and multivariate analyses were used to study the risk factor of central node involvement. The mean tumor size was 0.71±0.35 cm (range, 0.1-2.0 cm). There was no significant difference in the rate of central lymph node involvement based on age (<45 or ≥45 years) or tumor focality (unifocal or multifocal). However, there were significant differences based on gender, extra-thyroid invasion and tumor size (P<0.05). The incidence of transient hypoparathyroidism and transient vocal cord paralysis following CND was 12.34 and 4.11%, respectively. No patient experienced permanent hypoparathyroidism or vocal cord paralysis. One patient (1/389; 0.23%) experienced disease recurrence during the follow-up. A larger tumor size and the male gender were significantly associated with the central nodal metastasis rate for cN0 PTC with a tumor size of <2.0 cm. CND for cN0 PTC patients was safe and the tumor-associated recurrence rate following CND plus total thyroidectomy was low. The present study suggests that CND should be conducted for male cN0 PTC patients with a larger tumor size (≥0.5 cm).

  16. Embryonic stem cells: testing the germ-cell theory.

    PubMed

    Hochedlinger, Konrad

    2011-10-25

    The exact cellular origin of embryonic stem cells remains elusive. Now a new study provides compelling evidence that embryonic stem cells, established under conventional culture conditions, originate from a transient germ-cell state.

  17. The transcription factor Pitx2 positions the embryonic axis and regulates twinning

    PubMed Central

    Torlopp, Angela; Khan, Mohsin A F; Oliveira, Nidia M M; Lekk, Ingrid; Soto-Jiménez, Luz Mayela; Sosinsky, Alona; Stern, Claudio D

    2014-01-01

    Embryonic polarity of invertebrates, amphibians and fish is specified largely by maternal determinants, which fixes cell fates early in development. In contrast, amniote embryos remain plastic and can form multiple individuals until gastrulation. How is their polarity determined? In the chick embryo, the earliest known factor is cVg1 (homologous to mammalian growth differentiation factor 1, GDF1), a transforming growth factor beta (TGFβ) signal expressed posteriorly before gastrulation. A molecular screen to find upstream regulators of cVg1 in normal embryos and in embryos manipulated to form twins now uncovers the transcription factor Pitx2 as a candidate. We show that Pitx2 is essential for axis formation, and that it acts as a direct regulator of cVg1 expression by binding to enhancers within neighbouring genes. Pitx2, Vg1/GDF1 and Nodal are also key actors in left–right asymmetry, suggesting that the same ancient polarity determination mechanism has been co-opted to different functions during evolution. DOI: http://dx.doi.org/10.7554/eLife.03743.001 PMID:25496870

  18. Axial level-dependent molecular and cellular mechanisms underlying the genesis of the embryonic neural plate.

    PubMed

    Kondoh, Hisato; Takada, Shinji; Takemoto, Tatsuya

    2016-06-01

    The transcription factor gene Sox2, centrally involved in neural primordial regulation, is activated by many enhancers. During the early stages of embryonic development, Sox2 is regulated by the enhancers N2 and N1 in the anterior neural plate (ANP) and posterior neural plate (PNP), respectively. This differential use of the enhancers reflects distinct regulatory mechanisms underlying the genesis of ANP and PNP. The ANP develops directly from the epiblast, triggered by nodal signal inhibition, and via the combined action of TFs SOX2, OTX2, POU3F1, and ZIC2, which promotes the the ANP development and inhibits other cell lineages. In contrast, the PNP is derived from neuromesodermal bipotential axial stem cells that develop into the neural plate when Sox2 is activated by the N1 enhancer, whereas they develop into the paraxial mesoderm when the N1 enhancer is repressed by the action of TBX6. The axial stem cells are maintained by the activity of WNT3a and T (Brachyury). However, at axial levels more anterior to the 8th somites (cervical levels), the development of both the neural plate and somite proceeds in the absence of WNT3a, T, or TBX6. These observations indicate that distinct molecular and cellular mechanisms determine neural plate genesis based on the axial level, and contradict the classical concept of the term "neural induction," which assumes a pan-neural plate mechanism.

  19. Cobalt chloride pretreatment promotes cardiac differentiation of human embryonic stem cells under atmospheric oxygen level.

    PubMed

    Ng, Kwong-Man; Chan, Yau-Chi; Lee, Yee-Ki; Lai, Wing-Hon; Au, Ka-Wing; Fung, Man-Lung; Siu, Chung-Wah; Li, Ronald A; Tse, Hung-Fat

    2011-12-01

    Our previous study demonstrated the direct involvement of the HIF-1α subunit in the promotion of cardiac differentiation of murine embryonic stem cells (ESCs). We report the use of cobalt chloride to induce HIF-1α stabilization in human ESCs to promote cardiac differentiation. Treatment of undifferentiated hES2 human ESCs with 50 μM cobalt chloride markedly increased protein levels of the HIF-1α subunit, and was associated with increased expression of early cardiac specific transcription factors and cardiotrophic factors including NK2.5, vascular endothelial growth factor, and cardiotrophin-1. When pretreated cells were subjected to cardiac differentiation, a notable increase in the occurrence of beating embryoid bodies and sarcomeric actinin-positive cells was observed, along with increased expression of the cardiac-specific markers, MHC-A, MHC-B, and MLC2V. Electrophysiological study revealed increased atrial- and nodal-like cells in the cobalt chloride-pretreated group. Confocal calcium imaging analysis indicated that the maximum upstroke and decay velocities were significantly increased in both noncaffeine and caffeine-induced calcium transient in cardiomyocytes derived from the cobalt chloride-pretreated cells, suggesting these cells were functionally more mature. In conclusion, our study demonstrated that cobalt chloride pretreatment of hES2 human ESCs promotes cardiac differentiation and the maturation of calcium homeostasis of cardiomyocytes derived from ESCs.

  20. Nodal endoplasmic reticulum, a specialized form of endoplasmic reticulum found in gravity-sensing root tip columella cells

    NASA Technical Reports Server (NTRS)

    Zheng, H. Q.; Staehelin, L. A.

    2001-01-01

    The endoplasmic reticulum (ER) of columella root cap cells has been postulated to play a role in gravity sensing. We have re-examined the ultrastructure of columella cells in tobacco (Nicotiana tabacum) root tips preserved by high-pressure freezing/freeze-substitution techniques to gain more precise information about the organization of the ER in such cells. The most notable findings are: the identification of a specialized form of ER, termed "nodal ER," which is found exclusively in columella cells; the demonstration that the bulk of the ER is organized in the form of a tubular network that is confined to a peripheral layer under the plasma membrane; and the discovery that this ER-rich peripheral region excludes Golgi stacks, vacuoles, and amyloplasts but not mitochondria. Nodal ER domains consist of an approximately 100-nm-diameter central rod composed of oblong subunits to which usually seven sheets of rough ER are attached along their margins. These domains form patches at the interface between the peripheral ER network and the ER-free central region of the cells, and they occupy defined positions within central and flanking columella cells. Over one-half of the nodal ER domains are located along the outer tangential walls of the flanking cells. Cytochalasin D and latrunculin A cause an increase in size and a decrease in numbers of nodal ER domains. We postulate that the nodal ER membranes locally modulate the gravisensing signals produced by the sedimenting amyloplasts, and that the confinement of all ER membranes to the cell periphery serves to enhance the sedimentability of the amyloplasts in the central region of columella cells.

  1. Impact of FDG-PET/CT Imaging on Nodal Staging for Head-And-Neck Squamous Cell Carcinoma

    SciTech Connect

    Murakami, Ryuji . E-mail: murakami@kaiju.medic.kumamoto-u.ac.jp; Uozumi, Hideaki; Hirai, Toshinori; Nishimura, Ryuichi; Shiraishi, Shinya; Ota, Kazutoshi D.D.S.; Murakami, Daizo; Tomiguchi, Seiji; Oya, Natsuo; Katsuragawa, Shigehiko; Yamashita, Yasuyuki

    2007-06-01

    Purpose: To evaluate the impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging on nodal staging for head-and-neck squamous cell carcinoma (SCC). Methods and Materials: The study population consisted of 23 patients with head-and-neck SCC who were evaluated with FDG-PET/CT and went on to neck dissection. Two observers consensually determined the lesion size and maximum standardized uptake value (SUV{sub max}) and compared the results with pathologic findings on nodal-level involvement. Two different observers (A and B) independently performed three protocols for clinical nodal staging. Methods 1, 2, and 3 were based on conventional modalities, additional visual information from FDG-PET/CT images, and FDG-PET/CT imaging alone with SUV data, respectively. Results: All primary tumors were visualized with FDG-PET/CT. Pathologically, 19 positive and 93 negative nodal levels were identified. The SUV{sub max} overlapped in negative and positive nodes <15 mm in diameter. According to receiver operating characteristics analysis, the size-based SUV{sub max} cutoff values were 1.9, 2.5, and 3.0 for lymph nodes <10 mm, 10-15 mm, and >15 mm, respectively. These cutoff values yielded 79% sensitivity and 99% specificity for nodal-level staging. For Observer A, the sensitivity and specificity in Methods 1, 2, and 3 were 68% and 94%, 68% and 99%, and 84% and 99%, respectively, and Method 3 yielded significantly higher accuracy than Method 1 (p = 0.0269). For Observer B, Method 3 yielded the highest sensitivity (84%) and specificity (99%); however, the difference among the three protocols was not statistically significant. Conclusion: Imaging with FDG-PET/CT with size-based SUV{sub max} cutoff values is an important modality for radiation therapy planning.

  2. Diffusion-Weighted MRI for Nodal Staging of Head and Neck Squamous Cell Carcinoma: Impact on Radiotherapy Planning

    SciTech Connect

    Dirix, Piet; Vandecaveye, Vincent; De Keyzer, Frederik; Op de beeck, Katya; Poorten, Vincent Vander; Delaere, Pierre; Verbeken, Eric; Hermans, Robert; Nuyts, Sandra

    2010-03-01

    Purpose: To evaluate the use of diffusion-weighted magnetic resonance imaging (DW-MRI) for nodal staging and its impact on radiotherapy (RT) planning. Methods and Materials: Twenty-two patients with locally advanced head and neck squamous cell carcinoma underwent contrast-enhanced computed tomography (CT), as well as MRI (with routine and DW sequences) prior to neck dissection. After topographic correlation, lymph nodes were evaluated microscopically with prekeratin immunostaining. Pathology results were correlated with imaging findings and an RT planning study was performed for these surgically treated patients. One set of target volumes was based on conventional imaging only, and another set was based on the corresponding DW-MRI images. A third reference set was contoured based solely on pathology results. Results: A sensitivity of 89% and a specificity of 97% per lymph node were found for DW-MRI. Nodal staging agreement between imaging and pathology was significantly stronger for DW-MRI (kappa = 0.97; 95% confidence interval [CI], 0.84-1.00) than for conventional imaging (kappa = 0.56; 95% CI, 0.16-0.96; p = 0.019, by McNemar's test). For both imaging modalities, the absolute differences between RT volumes and those obtained by pathology were calculated. Using an exact paired Wilcoxon test, the observed difference was significantly larger for conventional imaging than for DW-MRI for nodal gross tumor volume (p = 0.0013), as well as for nodal clinical target volume (p = 0.0415) delineation. Conclusions: These results suggest that DW-MRI is superior to conventional imaging for preradiotherapy nodal staging of head and neck squamous cell carcinoma, and provides a potential impact on organsparing and tumor control.

  3. Role of Ultrasonography of Regional Nodal Basins in Staging Triple-Negative Breast Cancer and Implications For Local-Regional Treatment

    SciTech Connect

    Shaitelman, Simona F.; Tereffe, Welela; Dogan, Basak E.; Hess, Kenneth R.; Caudle, Abigail S.; Valero, Vicente; Stauder, Michael C.; Krishnamurthy, Savitri; Candelaria, Rosalind P.; Strom, Eric A.; Woodward, Wendy A.; Hunt, Kelly K.; Buchholz, Thomas A.; Whitman, Gary J.

    2015-09-01

    Purpose: We sought to determine the rate at which regional nodal ultrasonography would increase the nodal disease stage in patients with triple-negative breast cancer (TNBC) beyond the clinical stage determined by physical examination and mammography alone, and significantly affect the treatments delivered to these patients. Methods and Materials: We retrospectively reviewed the charts of women with stages I to III TNBC who underwent physical examination, mammography, breast and regional nodal ultrasonography with needle biopsy of abnormal nodes, and definitive local-regional treatment at our institution between 2004 and 2011. The stages of these patients' disease with and without ultrasonography of the regional nodal basins were compared using the Pearson χ{sup 2} test. Definitive treatments of patients whose nodal disease was upstaged on the basis of ultrasonographic findings were compared to those of patients whose disease stage remained the same. Results: A total of 572 women met the study requirements. In 111 (19.4%) of these patients, regional nodal ultrasonography with needle biopsy resulted in an increase in disease stage from the original stage by physical examination and mammography alone. Significantly higher percentages of patients whose nodal disease was upstaged by ultrasonographic findings compared to that in patients whose disease was not upstaged underwent neoadjuvant systemic therapy (91.9% and 51.2%, respectively; P<.0001), axillary lymph node dissection (99.1% and 34.5%, respectively; P<.0001), and radiation to the regional nodal basins (88.2% and 29.1%, respectively; P<.0001). Conclusions: Regional nodal ultrasonography in TNBC frequently changes the initial clinical stage and plays an important role in treatment planning.

  4. Trophic and proliferative effects of Shh on motor neurons in embryonic spinal cord culture from wildtype and G93A SOD1 mice

    PubMed Central

    2013-01-01

    Background The developmental morphogen sonic hedgehog (Shh) may continue to play a trophic role in the support of terminally-differentiated motor neurons, of potential relevance to motor neuron disease. In addition, it may support the proliferation and differentiation of endogenous stem cells along motor neuronal lineages. As such, we have examined the trophic and proliferative effects of Shh supplementation or Shh antagonism in embryonic spinal cord cell cultures derived from wildtype or G93A SOD1 mice, a mouse model of amyotrophic lateral sclerosis. Results Shh supported survival, and stimulated growth of motor neurons, neurite outgrowth, and neurosphere formation in primary culture derived from both G93A SOD1 and WT mice. Shh increased the percentage of ciliated motor neurons, especially in G93A SOD1 culture. Shh-treated cultures showed increased neuronal proliferation compared to controls and especially cyclopamine treated cultures, from G93A SOD1 and WT mice. Moreover, Shh enhanced cell survival and differentiation of motor neuron precursors in WT culture. Conclusions Shh is neurotrophic to motor neurons and has mitogenic effects in WT and mSOD1 G93A culture in vitro. PMID:24119209

  5. Spatiotemporal recapitulation of central nervous system development by murine embryonic stem cell-derived neural stem/progenitor cells.

    PubMed

    Okada, Yohei; Matsumoto, Arifumi; Shimazaki, Takuya; Enoki, Ryosuke; Koizumi, Amane; Ishii, Seiji; Itoyama, Yasuto; Sobue, Gen; Okano, Hideyuki

    2008-12-01

    Neural stem/progenitor cells (NS/PCs) can generate a wide variety of neural cells. However, their fates are generally restricted, depending on the time and location of NS/PC origin. Here we demonstrate that we can recapitulate the spatiotemporal regulation of central nervous system (CNS) development in vitro by using a neurosphere-based culture system of embryonic stem (ES) cell-derived NS/PCs. This ES cell-derived neurosphere system enables the efficient derivation of highly neurogenic fibroblast growth factor-responsive NS/PCs with early temporal identities and high cell-fate plasticity. Over repeated passages, these NS/PCs exhibit temporal progression, becoming epidermal growth factor-responsive gliogenic NS/PCs with late temporal identities; this change is accompanied by an alteration in the epigenetic status of the glial fibrillary acidic protein promoter, similar to that observed in the developing brain. Moreover, the rostrocaudal and dorsoventral spatial identities of the NS/PCs can be successfully regulated by sequential administration of several morphogens. These NS/PCs can differentiate into early-born projection neurons, including cholinergic, catecholaminergic, serotonergic, and motor neurons, that exhibit action potentials in vitro. Finally, these NS/PCs differentiate into neurons that form synaptic contacts with host neurons after their transplantation into wild-type and disease model animals. Thus, this culture system can be used to obtain specific neurons from ES cells, is a simple and powerful tool for investigating the underlying mechanisms of CNS development, and is applicable to regenerative treatment for neurological disorders.

  6. Affinity of the heparin binding motif of Noggin1 to heparan sulfate and its visualization in the embryonic tissues.

    PubMed

    Nesterenko, Alexey M; Orlov, Eugeny E; Ermakova, Galina V; Ivanov, Igor A; Semenyuk, Pavel I; Orlov, Victor N; Martynova, Natalia Y; Zaraisky, Andrey G

    Heparin binding motifs were found in many secreted proteins and it was suggested that they are responsible for retardation of the protein diffusion within the intercellular space due to the binding to heparan sulfate proteoglycanes (HSPG). Here we used synthetic FITC labeled heparin binding motif (HBM peptide) of the Xenopus laevis secreted BMP inhibitor Noggin1 to study its diffusion along the surface of the heparin beads by FRAP method. As a result, we have found out that diffusivity of HBM-labeled FITC was indeed much lesser than those predicted by theoretical calculations even for whole protein of the Noggin size. We also compared by isothermal titration calorimetry the binding affinity of HBM and the control oligolysine peptide to several natural polyanions including heparan sulfate (HS), heparin, the bacterial dextran sulfate and salmon sperm DNA, and demonstrated that HBM significantly exceeds oligolysine peptide in the affinity to HS, heparin and DNA. By contrast, oligolysine peptide bound with higher affinity to dextran sulfate. We speculate that such a difference may ensure specificity of the morphogen binding to HSPG and could be explained by steric constrains imposed by different distribution of the negative charges along a given polymeric molecule. Finally, by using EGFP-HBM recombinant protein we have visualized the natural pattern of the Noggin1 binding sites within the X. laevis gastrula and demonstrated that these sites forms a dorsal-ventral concentration gradient, with a maximum in the dorsal blastopore lip. In sum, our data provide a quantitative basis for modeling the process of Noggin1 diffusion in embryonic tissues, considering its interaction with HSPG.

  7. OCT guided microinjections for mouse embryonic research

    NASA Astrophysics Data System (ADS)

    Larin, Kirill V.; Syed, Saba H.; Coughlin, Andrew J.; Wang, Shang; West, Jennifer L.; Dickinson, Mary E.; Larina, Irina V.

    2013-02-01

    Optical coherence tomography (OCT) is gaining popularity as live imaging tool for embryonic research in animal models. Recently we have demonstrated that OCT can be used for live imaging of cultured early mouse embryos (E7.5-E10) as well as later stage mouse embryos in utero (E12.5 to the end of gestation). Targeted delivery of signaling molecules, drugs, and cells is a powerful approach to study normal and abnormal development, and image guidance is highly important for such manipulations. Here we demonstrate that OCT can be used to guide microinjections of gold nanoshell suspensions in live mouse embryos. This approach can potentially be used for variety of applications such as guided injections of contrast agents, signaling molecules, pharmacological agents, cell transplantation and extraction, as well as other image-guided micromanipulations. Our studies also reveal novel potential for gold nanoshells in embryonic research.

  8. Mechanically patterning the embryonic airway epithelium.

    PubMed

    Varner, Victor D; Gleghorn, Jason P; Miller, Erin; Radisky, Derek C; Nelson, Celeste M

    2015-07-28

    Collections of cells must be patterned spatially during embryonic development to generate the intricate architectures of mature tissues. In several cases, including the formation of the branched airways of the lung, reciprocal signaling between an epithelium and its surrounding mesenchyme helps generate these spatial patterns. Several molecular signals are thought to interact via reaction-diffusion kinetics to create distinct biochemical patterns, which act as molecular precursors to actual, physical patterns of biological structure and function. Here, however, we show that purely physical mechanisms can drive spatial patterning within embryonic epithelia. Specifically, we find that a growth-induced physical instability defines the relative locations of branches within the developing murine airway epithelium in the absence of mesenchyme. The dominant wavelength of this instability determines the branching pattern and is controlled by epithelial growth rates. These data suggest that physical mechanisms can create the biological patterns that underlie tissue morphogenesis in the embryo.

  9. Mechanically patterning the embryonic airway epithelium

    PubMed Central

    Varner, Victor D.; Gleghorn, Jason P.; Miller, Erin; Radisky, Derek C.; Nelson, Celeste M.

    2015-01-01

    Collections of cells must be patterned spatially during embryonic development to generate the intricate architectures of mature tissues. In several cases, including the formation of the branched airways of the lung, reciprocal signaling between an epithelium and its surrounding mesenchyme helps generate these spatial patterns. Several molecular signals are thought to interact via reaction-diffusion kinetics to create distinct biochemical patterns, which act as molecular precursors to actual, physical patterns of biological structure and function. Here, however, we show that purely physical mechanisms can drive spatial patterning within embryonic epithelia. Specifically, we find that a growth-induced physical instability defines the relative locations of branches within the developing murine airway epithelium in the absence of mesenchyme. The dominant wavelength of this instability determines the branching pattern and is controlled by epithelial growth rates. These data suggest that physical mechanisms can create the biological patterns that underlie tissue morphogenesis in the embryo. PMID:26170292

  10. A trade-off between embryonic development rate and immune function of avian offspring is concealed by embryonic temperature

    USGS Publications Warehouse

    Martin, Thomas E.; Arriero, Elena; Majewska, Ania

    2011-01-01

    Long embryonic periods are assumed to reflect slower intrinsic development that are thought to trade off to allow enhanced physiological systems, such as immune function. Yet, the relatively rare studies of this trade-off in avian offspring have not found the expected trade-off. Theory and tests have not taken into account the strong extrinsic effects of temperature on embryonic periods of birds. Here, we show that length of the embryonic period did not explain variation in two measures of immune function when temperature was ignored, based on studies of 34 Passerine species in tropical Venezuela (23 species) and north temperate Arizona (11 species). Variation in immune function was explained when embryonic periods were corrected for average embryonic temperature, in order to better estimate intrinsic rates of development. Immune function of offspring trades off with intrinsic rates of embryonic development once the extrinsic effects of embryonic temperatures are taken into account.

  11. Pou5f3.2-induced proliferative state of embryonic cells during gastrulation of Xenopus laevis embryo.

    PubMed

    Nishitani, Eriko; Li, Chong; Lee, Jaehoon; Hotta, Hiroyo; Katayama, Yuta; Yamaguchi, Masahiro; Kinoshita, Tsutomu

    2015-12-01

    POU class V (POU-V) transcription factors play the important role in maintenance of pluripotency and cell differentiation. Pou5f3.2 (Oct25), one of Xenopus POU-V transcription factors, shows the zygotic expression prior to gastrulation. In order to know the molecular mechanism of pou5f3.2 expression at gastrula stage, we examined a responsiveness of pou5f3.2 to Nodal signaling. Animal cap assay demonstrated that Xnr2 activates the gene expression of pou5f3.2. In comparative analysis of the 5'-flanking region of pou5f3.2 between Xenopus laevis and X. tropicalis, two conserved regions were detected within the flanking region. Reporter analyses showed that one of the conserved regions contained an enhancer region, which had several Smad2/3 and FoxH1 binding motifs. ChIP assay demonstrated that Smad2 binds to the enhancer region. These results suggest that Nodal signaling induces zygotic expression of pou5f3.2 at gastrula stage. To understand a role of pou5f3.2 in gastrula embryos, morpholino oligo DNA of pou5f3.2 was injected into the lateral side of one blastomere at the 2-cell stage. The morphant embryos showed diminution of Xbra1 expression and gastrulation defect in the injection side, suggesting the essential role of pou5f3.2 at the gastrula stage. Xbra1 expression and gastrulation were also inhibited by injecting with the synthesized RNAs of pou5f3.2. Furthermore, in the pou5f3.2-injected embryo, gene expression of p27Xic1 was drastically suppressed, and the number of dividing cells increased in the injection side. These results suggest that one role of pou5f3.2 is to keep the embryonic cells in undifferentiated and proliferative state during gastrulation.

  12. Metabolic circadian rhythms in embryonic turtles.

    PubMed

    Loudon, Fiona Kay; Spencer, Ricky-John; Strassmeyer, Alana; Harland, Karen

    2013-07-01

    Oviparous species are model organisms for investigating embryonic development of endogenous physiological circadian rhythms without the influence of maternal biorhythms. Recent studies have demonstrated that heart rates and metabolic rates of embryonic turtles are not constant or always maximal and can be altered in response to the presence of embryos at a more advanced stage of development within the nest. A first step in understanding the physiological mechanisms underpinning these responses in embryonic ectothermic organisms is to develop metabolic profiles (e.g., heart rate) at different temperatures throughout incubation. Heart beat and rhythmic patterns or changes in development may represent important signals or cues within a nest and may be vital to coordinate synchronous hatching well in advance of the final stages of incubation. We developed baseline embryonic heart-rate profiles of embryos of the short-necked Murray River turtle (Emydura macquarii) to determine the stage of embryogenesis that metabolic circadian rhythms become established, if at all. Eggs were incubated at constant temperatures (26°C and 30°C) and heart rates were monitored at 6-h intervals over 24 h every 7-11 days until hatching. Circadian heart rate rhythms were detected at the mid-gestation period and were maintained until hatching. Heart rates throughout the day varied by up to 20% over 24 h and were not related to time of day. This study demonstrated that endogenous metabolic circadian rhythms in developing embryos in turtle eggs establish earlier in embryogenesis than those documented in other vertebrate taxa during embryogenesis. Early establishment of circadian rhythms in heart rates may be critical for communication among embryos and synchrony in hatching and emergence from the nest.

  13. Do embryonic polar bodies commit suicide?

    PubMed

    Fabian, Dušan; Čikoš, Štefan; Rehák, Pavol; Koppel, Juraj

    2014-02-01

    The extrusion and elimination of unnecessary gametic/embryonic material is one of the key events that determines the success of further development in all living organisms. Oocytes produce the first polar body to fulfill the maturation process just before ovulation, and release the second polar body immediately after fertilization. The aim of this study was to compile a physiological overview of elimination of polar bodies during early preimplantation development in mice. Our results show that three-quarters of the first polar bodies were lost even at the zygotic stage; the 4-cell stage embryos contained only one (second) polar body, and the elimination of second polar bodies proceeded continuously during later development. Both first and second polar bodies showed several typical features of apoptosis: phosphatidylserine redistribution (observed for the first time in the first polar body), specific DNA degradation, condensed nuclear morphology, and inability to exclude cationic dye from the nucleus during the terminal stage of the apoptotic process. Caspase-3 activity was recorded only in the second polar body. From the morphological point of view, mouse polar bodies acted very similarly to damaged embryonic cells which have lost contact with their neighboring blastomeres. In conclusion, polar bodies possess all the molecular equipment necessary for triggering and executing an active suicide process. Furthermore, similarly as in dying embryonic cells, stressing external conditions (culture in vitro) might accelerate and increase the incidence of apoptotic elimination of the polar bodies in embryos.

  14. Informing tendon tissue engineering with embryonic development.

    PubMed

    Glass, Zachary A; Schiele, Nathan R; Kuo, Catherine K

    2014-06-27

    Tendon is a strong connective tissue that transduces muscle-generated forces into skeletal motion. In fulfilling this role, tendons are subjected to repeated mechanical loading and high stress, which may result in injury. Tissue engineering with stem cells offers the potential to replace injured/damaged tissue with healthy, new living tissue. Critical to tendon tissue engineering is the induction and guidance of stem cells towards the tendon phenotype. Typical strategies have relied on adult tissue homeostatic and healing factors to influence stem cell differentiation, but have yet to achieve tissue regeneration. A novel paradigm is to use embryonic developmental factors as cues to promote tendon regeneration. Embryonic tendon progenitor cell differentiation in vivo is regulated by a combination of mechanical and chemical factors. We propose that these cues will guide stem cells to recapitulate critical aspects of tenogenesis and effectively direct the cells to differentiate and regenerate new tendon. Here, we review recent efforts to identify mechanical and chemical factors of embryonic tendon development to guide stem/progenitor cell differentiation toward new tendon formation, and discuss the role this work may have in the future of tendon tissue engineering.

  15. Embryonic development of Pelteobagrus fulvidraco (Richardson, 1846)

    NASA Astrophysics Data System (ADS)

    Wang, Weimin; Abbas, Khalid; Yan, Ansheng

    2006-12-01

    For production enhancement and procedure upgrade, the developmental phases of laboratory-reared eggs of catfish Pelteobagrus fulvidraco were investigated. Twenty mature females and 10 males were collected from Dadongmen wholesale fisheries market in Wuhan City on May 8, 2003. Zygotes were stripped from mature fish after hormone-induced ovulation, fertilized, and incubated through whole embryonic development. The fertilized eggs were stocked in density of 100 eggs/L in white square tanks of 10 L. Incubation water was dechlorinated tap water with continuous aeration. The tanks were lit directly with 60 W fluorescent bulbs with a 12 light: 12 dark photoperiod. Water temperature, dissolved oxygen and pH were 29.0±0.5°C, 6.7±0.4 mg/L and 7.4±2, respectively. The results showed that the eggs of P. fulvidraco were yellow, sticky and contained much yolk. The mean diameter of fertilized eggs was 2.03 mm. At the water temperature of 29.0±0.5°C, the ontogenesis spent about 33 h after fertilization. From fertilization to hatching, the embryonic development can be divided into 30 40 phases, which varies in the emphasis and direction of development. The detailed embryonic movement was also described.

  16. [Heart tissue from embryonic stem cells].

    PubMed

    Zimmermann, W-H

    2008-09-01

    Embryonic stem cells can give rise to all somatic cells, making them an attractive cell source for tissue engineering applications. The propensity of cells to form tissue-like structures in a culture dish has been well documented. We and others made use of this intrinsic property to generate bioartificial heart muscle. First proof-of-concept studies involved immature heart cells mainly from fetal chicken, neonatal rats and mice. They eventually provided evidence that force-generating heart muscle can be engineered in vitro. Recently, the focus shifted to the application of stem cells to eventually enable the generation of human heart muscle and reach following long-term goals: (1) development of a simplified in vitro model of heart muscle development; (2) generation of a human test-bed for drug screening and development; (3) allocation of surrogate heart tissue to myocardial repair applications. This overview will provide the background for cell-based myocardial repair, introduce the main myocardial tissue engineering concepts, discuss the use of embryonic and non-embryonic stem cells, and lays out the potential direct and indirect therapeutic use of human tissue engineered myocardium.

  17. Human embryonic stem cells and lung regeneration.

    PubMed

    Varanou, A; Page, C P; Minger, S L

    2008-10-01

    Human embryonic stem cells are pluripotent cells derived from the inner cell mass of preimplantation stage embryos. Their unique potential to give rise to all differentiated cell types has generated great interest in stem cell research and the potential that it may have in developmental biology, medicine and pharmacology. The main focus of stem cell research has been on cell therapy for pathological conditions with no current methods of treatment, such as neurodegenerative diseases, cardiac pathology, retinal dysfunction and lung and liver disease. The overall aim is to develop methods of application either of pure cell populations or of whole tissue parts to the diseased organ under investigation. In the field of pulmonary research, studies using human embryonic stem cells have succeeded in generating enriched cultures of type II pneumocytes in vitro. On account of their potential of indefinite proliferation in vitro, embryonic stem cells could be a source of an unlimited supply of cells available for transplantation and for use in gene therapy. Uncovering the ability to generate such cell types will expand our understanding of biological processes to such a degree that disease understanding and management could change dramatically.

  18. Mechanical signaling coordinates the embryonic heartbeat

    PubMed Central

    Chiou, Kevin K.; Rocks, Jason W.; Chen, Christina Yingxian; Cho, Sangkyun; Merkus, Koen E.; Rajaratnam, Anjali; Robison, Patrick; Tewari, Manorama; Vogel, Kenneth; Majkut, Stephanie F.; Prosser, Benjamin L.; Discher, Dennis E.; Liu, Andrea J.

    2016-01-01

    In the beating heart, cardiac myocytes (CMs) contract in a coordinated fashion, generating contractile wave fronts that propagate through the heart with each beat. Coordinating this wave front requires fast and robust signaling mechanisms between CMs. The primary signaling mechanism has long been identified as electrical: gap junctions conduct ions between CMs, triggering membrane depolarization, intracellular calcium release, and actomyosin contraction. In contrast, we propose here that, in the early embryonic heart tube, the signaling mechanism coordinating beats is mechanical rather than electrical. We present a simple biophysical model in which CMs are mechanically excitable inclusions embedded within the extracellular matrix (ECM), modeled as an elastic-fluid biphasic material. Our model predicts strong stiffness dependence in both the heartbeat velocity and strain in isolated hearts, as well as the strain for a hydrogel-cultured CM, in quantitative agreement with recent experiments. We challenge our model with experiments disrupting electrical conduction by perfusing intact adult and embryonic hearts with a gap junction blocker, β-glycyrrhetinic acid (BGA). We find this treatment causes rapid failure in adult hearts but not embryonic hearts—consistent with our hypothesis. Last, our model predicts a minimum matrix stiffness necessary to propagate a mechanically coordinated wave front. The predicted value is in accord with our stiffness measurements at the onset of beating, suggesting that mechanical signaling may initiate the very first heartbeats. PMID:27457951

  19. Informing tendon tissue engineering with embryonic development

    PubMed Central

    Glass, Zachary A.; Schiele, Nathan R.; Kuo, Catherine K.

    2014-01-01

    Tendon is a strong connective tissue that transduces muscle-generated forces into skeletal motion. In fulfilling this role, tendons are subjected to repeated mechanical loading and high stress, which may result in injury. Tissue engineering with stem cells offers the potential to replace injured/damaged tissue with healthy, new living tissue. Critical to tendon tissue engineering is the induction and guidance of stem cells towards the tendon phenotype. Typical strategies have relied on adult tissue homeostatic and healing factors to influence stem cell differentiation, but have yet to achieve tissue regeneration. A novel paradigm is to use embryonic developmental factors as cues to promote tendon regeneration. Embryonic tendon progenitor cell differentiation in vivo is regulated by a combination of mechanical and chemical factors. We propose that these cues will guide stem cells to recapitulate critical aspects of tenogenesis and effectively direct the cells to differentiate and regenerate new tendon. Here, we review recent efforts to identify mechanical and chemical factors of embryonic tendon development to guide stem/progenitor cell differentiation toward new tendon formation, and discuss the role this work may have in the future of tendon tissue engineering. PMID:24484642

  20. Embryonic and embryonic-like stem cells in heart muscle engineering.

    PubMed

    Zimmermann, Wolfram-Hubertus

    2011-02-01

    Cardiac muscle engineering is evolving rapidly and may ultimately be exploited to (1) model cardiac development, physiology, and pathology; (2) identify and validate drug targets; (3) assess drug safety and efficacy; and (4) provide therapeutic substitute myocardium. The ultimate success in any of these envisioned applications depends on the utility of human cells and their assembly into myocardial equivalents with structural and functional properties of mature heart muscle. Embryonic stem cells appear as a promising cell source in this respect, because they can be cultured reliably and differentiated robustly into cardiomyocytes. Despite their unambiguous cardiogenicity, data on advanced maturation and seamless myocardial integration of embryonic stem cell-derived cardiomyocytes in vivo are sparse. Additional concerns relate to the limited control over cardiomyogenic specification and cardiomyocyte maturation in vitro as well as the risk of teratocarcinoma formation and immune rejection of stem cell implants in vivo. Through the invent of embryonic-like stem cells - such as parthenogenetic stem cells, male germline stem cells, and induced pluripotent stem cells - some but certainly not all of these issues may be addressed, albeit at the expense of additional concerns. This review will discuss the applicability of embryonic and embryonic-like stem cells in myocardial tissue engineering and address issues that require particular attention before the potential of stem cell-based heart muscle engineering may be fully exploited. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".

  1. Morphology of the embryonic and hatchling American alligator ductus arteriosi and implications for embryonic cardiovascular shunting.

    PubMed

    Jacobs, Kimberley; Goy, Sarah K; Dzialowski, Edward M

    2012-02-01

    The ductus arteriosi (DA) are embryonic blood vessels found in amniotic vertebrates that shunt blood away from the pulmonary artery and lungs and toward the aorta. Here, we examine changes in morphology of the right and left DA (LDA), and right and left aorta (LAo) from embryonic and hatchling alligators. The developing alligator has two-patent DA that join the right and LAo. Both DA exhibit a muscular phenotype composed of an internal smooth muscle layer (2-4 cells thick). At hatching, the lumen diameter of both DA decreases as the vessels begin to close within the first 12 h of posthatch life. Between day 1 and day 12 posthatching, the vessel becomes fully occluded with endothelial and smooth muscle cells filling the lumen. A number of DA from hatchlings contained blood clots along their length. The lumen of the full term alligator DA is reduced in comparison with the full term chicken DA. The developing alligator embryo has an additional right-to-left shunt pathway in the LAo arising from the right ventricle. The embryonic LAo diameter is twice the diameter of either the right DA or LDA, providing a lower resistance pathway for blood leaving the right ventricle. On the basis of these findings, we propose that the paired DA of the embryonic alligator have a reduced role in the embryonic right-to-left shunt of blood from the right ventricle when compared with the avian DA.

  2. Nodal-line pairing with 1D-3D coupled Fermi surfaces: A model motivated by Cr-based superconductors

    NASA Astrophysics Data System (ADS)

    Wachtel, Gideon; Kim, Yong Baek

    2016-09-01

    Motivated by the recent discovery of a new family of chromium-based superconductors, we consider a two-band model, where a band of electrons dispersing only in one direction interacts with a band of electrons dispersing in all three directions. Strong 2 kf density fluctuations in the one-dimensional band induces attractive interactions between the three-dimensional electrons, which, in turn, makes the system superconducting. Solving the associated Eliashberg equations, we obtain a gap function which is peaked at the "poles" of the three-dimensional Fermi sphere, and decreases towards the "equator." When strong enough local repulsion is included, the gap actually changes sign around the equator and nodal rings are formed. These nodal rings manifest themselves in several experimentally observable quantities, some of which resemble unconventional observations in the newly discovered superconductors which motivated this work.

  3. Programming and isolation of highly pure physiologically and pharmacologically functional sinus-nodal bodies from pluripotent stem cells.

    PubMed

    Jung, Julia Jeannine; Husse, Britta; Rimmbach, Christian; Krebs, Stefan; Stieber, Juliane; Steinhoff, Gustav; Dendorfer, Andreas; Franz, Wolfgang-Michael; David, Robert

    2014-05-06

    Therapeutic approaches for "sick sinus syndrome" rely on electrical pacemakers, which lack hormone responsiveness and bear hazards such as infection and battery failure. These issues may be overcome via "biological pacemakers" derived from pluripotent stem cells (PSCs). Here, we show that forward programming of PSCs with the nodal cell inducer TBX3 plus an additional Myh6-promoter-based antibiotic selection leads to cardiomyocyte aggregates consisting of >80% physiologically and pharmacologically functional pacemaker cells. These induced sinoatrial bodies (iSABs) exhibited highly increased beating rates (300-400 bpm), coming close to those found in mouse hearts, and were able to robustly pace myocardium ex vivo. Our study introduces iSABs as highly pure, functional nodal tissue that is derived from PSCs and may be important for future cell therapies and drug testing in vitro.

  4. Programming and Isolation of Highly Pure Physiologically and Pharmacologically Functional Sinus-Nodal Bodies from Pluripotent Stem Cells

    PubMed Central

    Jung, Julia Jeannine; Husse, Britta; Rimmbach, Christian; Krebs, Stefan; Stieber, Juliane; Steinhoff, Gustav; Dendorfer, Andreas; Franz, Wolfgang-Michael; David, Robert

    2014-01-01

    Summary Therapeutic approaches for “sick sinus syndrome” rely on electrical pacemakers, which lack hormone responsiveness and bear hazards such as infection and battery failure. These issues may be overcome via “biological pacemakers” derived from pluripotent stem cells (PSCs). Here, we show that forward programming of PSCs with the nodal cell inducer TBX3 plus an additional Myh6-promoter-based antibiotic selection leads to cardiomyocyte aggregates consisting of >80% physiologically and pharmacologically functional pacemaker cells. These induced sinoatrial bodies (iSABs) exhibited highly increased beating rates (300–400 bpm), coming close to those found in mouse hearts, and were able to robustly pace myocardium ex vivo. Our study introduces iSABs as highly pure, functional nodal tissue that is derived from PSCs and may be important for future cell therapies and drug testing in vitro. PMID:24936448

  5. The 18.6-year lunar nodal cycle and surface temperature variability in the northeast Pacific

    NASA Astrophysics Data System (ADS)

    McKinnell, Stewart M.; Crawford, William R.

    2007-02-01

    The 18.6-year lunar nodal cycle (LNC) is a significant feature of winter (January) air and sea temperatures along the North American west coast over a 400-year period. Yet much of the recent temperature variation can also be explained by wind patterns associated with the PNA teleconnection. At Sitka, Alaska, (57°N) and nearby stations in northern British Columbia, the January PNA index accounts for over 70% of average January air temperatures in lengthy meteorological records. It appears that the LNC signal in January air temperatures in this region is not independent of the PNA, but is a component of it. The Sitka air temperature record, along with SSTs along the British Columbia coast and the PNA index have significant cross-correlations with the LNC that appear at a 2-year lag, LNC leading. The influence of the PNA pattern declines in winter with decreasing latitude but the LNC component does not. It appears as a significant feature of long-term SST variation at Scripps Pier and the California Current System. The LNC also appears over centennial-scales in proxy temperatures along western North America. The linkage of LNC-moderated surface temperatures to processes involving basin-scale teleconnections expands the possibility that the proximate mechanism may be located remotely from its expression in the northeast Pacific. Some of the largest potential sources of a diurnal tidal signal in the atmosphere are located in the western Pacific; the Sea of Okhotsk and the Indonesian archipelago.

  6. High-latitude oceanic variability associated with the 18.6-year nodal tide

    NASA Astrophysics Data System (ADS)

    Royer, Thomas C.

    1993-03-01

    Ocean temperatures in the upper 250 m in the northern North Pacific (60°N, 149°W) increased by more than 1°C from 1972 to 1986 but are now decreasing. Subsurface temperature anomalies are well correlated (˜0.58) with the air temperature anomalies at Sitka, Alaska; hence the coastal air temperatures can be used as a proxy data set to extend the ocean temperature time series back to 1828. Up to 30% of the low-frequency variance can be accounted for with the 18.6-year nodal signal. Additionally, spectral analysis of these air temperature variations indicates a significant low-frequency peak in the range of the 18.6-year signal. Similar low-frequency signals have been reported for Hudson Bay air temperatures since 1700, for sea surface temperatures in the North Atlantic from 1876 to 1939, and for sea level in the high-latitude southern hemisphere. The water column temperature variations presented here are the first evidence that the upper ocean is responding to this very long period tidal forcing. An enhanced high-latitude response to the 18.6-year forcing is predicted by equilibrium tide theory, and it should be most evident at latitudes poleward of about 50°. These low-frequency ocean-atmosphere variations must be considered in high-latitude assessments of global climate change, since they are of the same magnitude as many of the predicted global changes.

  7. CD20-Positive nodal natural killer/T-cell lymphoma with cutaneous involvement.

    PubMed

    Tsai, Yi-Chiun; Chen, Chi-Kuan; Wu, Yu-Hung

    2015-09-01

    CD20-positive natural killer (NK)/T-cell lymphoma is extremely rare. We describe a case of a CD20-positive nodal NK/T-cell lymphoma with cutaneous involvement in a 32-year-old man. The patient presented with fever, night sweats, right inguinal lymphadenopathy and multiple violaceous to erythematous nodules and plaques on the back and bilateral legs. Immunohistochemical analysis showed diffusely and strongly positive staining for CD3, CD3 epsilon, CD43, CD56, TIA-1 and CD20 but negative staining for other B-cell markers, including CD79a and PAX-5 and T-cell markers CD5 and CD7. The tumor cell nuclei were diffusely positive for Epstein-Barr virus-encoded RNA in situ hybridization. A partial clinical response was observed after chemotherapy, indicated by the decreased size of the lymph nodes and skin lesions. It is a diagnostic challenge to deal with lymphoma cells that present with the surface proteins of both T- and B-cells.

  8. Identification of cell-type-specific mutations in nodal T-cell lymphomas

    PubMed Central

    Nguyen, T B; Sakata-Yanagimoto, M; Asabe, Y; Matsubara, D; Kano, J; Yoshida, K; Shiraishi, Y; Chiba, K; Tanaka, H; Miyano, S; Izutsu, K; Nakamura, N; Takeuchi, K; Miyoshi, H; Ohshima, K; Minowa, T; Ogawa, S; Noguchi, M; Chiba, S

    2017-01-01

    Recent genetic analysis has identified frequent mutations in ten-eleven translocation 2 (TET2), DNA methyltransferase 3A (DNMT3A), isocitrate dehydrogenase 2 (IDH2) and ras homolog family member A (RHOA) in nodal T-cell lymphomas, including angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified. We examined the distribution of mutations in these subtypes of mature T-/natural killer cell neoplasms to determine their clonal architecture. Targeted sequencing was performed for 71 genes in tumor-derived DNA of 87 cases. The mutations were then analyzed in a programmed death-1 (PD1)-positive population enriched with tumor cells and CD20-positive B cells purified by laser microdissection from 19 cases. TET2 and DNMT3A mutations were identified in both the PD1+ cells and the CD20+ cells in 15/16 and 4/7 cases, respectively. All the RHOA and IDH2 mutations were confined to the PD1+ cells, indicating that some, including RHOA and IDH2 mutations, being specific events in tumor cells. Notably, we found that all NOTCH1 mutations were detected only in the CD20+ cells. In conclusion, we identified both B- as well as T-cell-specific mutations, and mutations common to both T and B cells. These findings indicate the expansion of a clone after multistep and multilineal acquisition of gene mutations. PMID:28157189

  9. Light Spectral Quality Effects on the Growth of Potato (Solanum Tuberosum L.) Nodal Cuttings in Vitro

    NASA Technical Reports Server (NTRS)

    Wilson, Deborah A.; Weigel, Russell C.; Wheeler, Raymond M.; Sager, John C.

    1993-01-01

    The effects of light spectral quality on the growth of in vitro nodal cuttings of potato (Solanum tuberosum L.) cultivars Norland, Superior, Kennebec, and Denali were examined. The different light spectra were provided by Vita-Lite fluorescent (VF) (a white light control), blue fluorescent (BF), red fluorescent (RF), low-pressure sodium (LPS), and a combination of low-pressure sodium plus cool-white fluorescent lamps (LPS/CWF). For cultivars, stem lengths after 4 wks were longest under LPS, follow by RF, LPS/CWF, VF, and BF (in descending order). Microscopic studies revealed that cells were shortest when cultured in BF or VF environments, and were longest in RF or LPS lamp environments. The highest number axillary branches occurred on plantlets grown with LPS or LPS/CWF, whereas the lowest number occurred with BF. No leaf or stem edema (callus or gall-like growths) occurred iwth LPS or LPS/cwf lighting, and no edema occurred on cv. Norland plantlets, regardless of lighting. Results suggest that shoot morphologic development of in vitro grown potato plants can be controlled by controlling irradiant spectral quality.

  10. Alignment of a three-mirror anastigmatic telescope using nodal aberration theory.

    PubMed

    Gu, Zhiyuan; Yan, Changxiang; Wang, Yang

    2015-09-21

    Most computer-aided alignment methods for optical systems are based on numerical algorithms at present, which omit aberration theory. This paper presents a novel alignment algorithm for three-mirror anastigmatic (TMA) telescopes using Nodal Aberration Theory (NAT). The aberration field decenter vectors and boresight error of misaligned TMA telescopes are derived. Two alignment models based on 3rd and 5th order NAT are established successively and compared in the same alignment example. It is found that the average and the maximum RMS wavefront errors in the whole field of view of 0.3° × 0.15° are 0.063 λ (λ = 1 μm) and 0.068 λ respectively after the 4th alignment action with the 3rd order model, and 0.011 λ and 0.025 λ (nominal values) respectively after the 3rd alignment action with the 5th order model. Monte-Carlo alignment simulations are carried out with the 5th order model. It shows that the 5th order model still has good performance even when the misalignment variables are large (-1 mm≤linear misalignment≤1 mm, -0.1°≤angular misalignment≤0.1°), and multiple iterative alignments are needed when the misalignment variables increase.

  11. Active optical alignment of off-axis telescopes based on nodal aberration theory.

    PubMed

    Zhang, Xiaobin; Zhang, Dong; Xu, Shuyan; Ma, Hongcai

    2016-11-14

    Our paper mainly separates the specific aberration contributions of third-order astigmatism and third-order coma from the total aberration fields, on the framework of the modified nodal aberration theory (NAT), for the perturbed off-axis telescope. Based on the derived aberration functions, two alignment models for the same off-axis two-mirror telescope are established and compared. Among them, one is based on third-order NAT, the other is based on fifth-order NAT. By comparison, it is found that the calculated perturbations based on fifth-order NAT are more accurate. It illustrates that third-order astigmatism and third-order coma contributed from fifth-order aberrations can't be neglected in the alignment process. Then the fifth-order NAT is used for the alignment of off-axis three-mirror telescopes. After simulation, it is found that the perturbed off-axis three-mirror telescope can be perfectly aligned as well. To further demonstrate the application of the alignment method based on fifth-order NAT (simplified as NAT method), Monte-Carlo simulations for both off-axis two-mirror telescope and off-axis three-mirror telescope are conducted in the end. Meantime, a comparison between NAT method and sensitivity table method is also conducted. It is proven that the computation accuracy of NAT method is much higher, especially in poor conditions.

  12. Directed nanoscale self-assembly of molecular wires interconnecting nodal points using Monte Carlo simulations

    SciTech Connect

    Boscoboinik, A. M.; Manzi, S. J.; Tysoe, W. T.; Pereyra, V. D.; Boscoboinik, J. A.

    2015-09-10

    The influence of directing agents in the self-assembly of molecular wires to produce two-dimensional electronic nanoarchitectures is studied here using a Monte Carlo approach to simulate the effect of arbitrarily locating nodal points on a surface, from which the growth of self-assembled molecular wires can be nucleated. This is compared to experimental results reported for the self-assembly of molecular wires when 1,4-phenylenediisocyanide (PDI) is adsorbed on Au(111). The latter results in the formation of (Au-PDI)n organometallic chains, which were shown to be conductive when linked between gold nanoparticles on an insulating substrate. The present study analyzes, by means of stochastic methods, the influence of variables that affect the growth and design of self-assembled conductive nanoarchitectures, such as the distance between nodes, coverage of the monomeric units that leads to the formation of the desired architectures, and the interaction between the monomeric units. As a result, this study proposes an approach and sets the stage for the production of complex 2D nanoarchitectures using a bottom-up strategy but including the use of current state-of-the-art top-down technology as an integral part of the self-assembly strategy.

  13. Directed nanoscale self-assembly of molecular wires interconnecting nodal points using Monte Carlo simulations

    DOE PAGES

    Boscoboinik, A. M.; Manzi, S. J.; Tysoe, W. T.; ...

    2015-09-10

    The influence of directing agents in the self-assembly of molecular wires to produce two-dimensional electronic nanoarchitectures is studied here using a Monte Carlo approach to simulate the effect of arbitrarily locating nodal points on a surface, from which the growth of self-assembled molecular wires can be nucleated. This is compared to experimental results reported for the self-assembly of molecular wires when 1,4-phenylenediisocyanide (PDI) is adsorbed on Au(111). The latter results in the formation of (Au-PDI)n organometallic chains, which were shown to be conductive when linked between gold nanoparticles on an insulating substrate. The present study analyzes, by means of stochasticmore » methods, the influence of variables that affect the growth and design of self-assembled conductive nanoarchitectures, such as the distance between nodes, coverage of the monomeric units that leads to the formation of the desired architectures, and the interaction between the monomeric units. As a result, this study proposes an approach and sets the stage for the production of complex 2D nanoarchitectures using a bottom-up strategy but including the use of current state-of-the-art top-down technology as an integral part of the self-assembly strategy.« less

  14. A "gentle" nodal suspension for measurements of the acoustic attenuation in materials.

    PubMed

    Cesarini, E; Lorenzini, M; Campagna, E; Martelli, F; Piergiovanni, F; Vetrano, F; Losurdo, G; Cagnoli, G

    2009-05-01

    Loss angle measurements in ultralow mechanical loss materials is normally affected by a large systematic error due to the excess losses introduced by the suspension system used to hold the samples. Crystals such as sapphire and silicon or amorphous materials such as fused silica can have loss angles in the range of 10(-10)-10(-7); such materials are of extreme interest in the detection of small displacements as it is required in quantum measurements, frequency stabilization, Micro Electro-Mechanical Systems (MEMS), and gravitational wave research. In the system proposed here the sample is suspended in equilibrium on top of a sphere, touching on one of the nodal points of vibration. The advantage of this system, as compared to others used so far, is twofold: (i) one surface only of the sample is touched and the contact surface is minimized because of the absence of applied forces; (ii) some relevant parameters of the suspension can be measured and eventually varied, giving the experimentalist the possibility to identify whether the measured loss is limited by the suspension system in use or it is an intrinsic property of the sample under investigation. The measurements of a 75 mm diameter and 3 mm thickness disk of Suprasil 311 gave a loss angle phi of 5x10(-8).

  15. Nodal energy weighted transformation: A mistuning projection and its application to FLADE™ turbines

    NASA Astrophysics Data System (ADS)

    Fitzner, Colin; Epureanu, Bogdan I.; Filippi, Sergio

    2014-01-01

    In recent years, several researchers have developed reduced-order models (ROMs) to efficiently and accurately calculate the forced response of blisks with known small mistuning. Small mistuning consists of the small blade-to-blade structural differences which destroy the inherent cyclic symmetry of the structure. This paper presents a nodal energy weighted transformation (NEWT) which can be used to construct ROMs of mistuned blisks and dual flow path systems, such as FLADE™ turbines. The NEWT approach can be interpreted as a hybrid of two existing techniques: component mode mistuning (CMM) and the subset of nominal modes (SNM). Similar to the previous methods, NEWT assumes that the mistuned modes of the system are a linear combination of tuned modes. However, NEWT differs from its predecessors in the blisk substructuring and in the mistuning projection. Numerical results obtained using full order models, CMM, and NEWT are presented and compared over multiple frequency ranges for a finite element model of a blisk and that of a FLADE™ turbine. These results show that ROMs based on NEWT have several attractive features: (a) the accuracy of the ROMs is comparable to ROMs based on CMM, and can be improved by increasing the size of the projection mode subset; (b) no necessary modifications are needed to analyze FLADE™ turbines; and (c) the response of all modes can be predicted well even if they are not blade dominated.

  16. Lunar nodal tide and distance to the Moon during the Precambrian.

    PubMed

    Walker, J C; Zahnle, K J

    1986-04-17

    The pace of tidal evolution for the past approximately 450 Myr implies an Earth/Moon collision some 1,500-2,000 Myr BP, an event for which there is no corroborating evidence. Here we present the first direct determination of the lunar distance in the Precambrian. We interpret a 23.3 +/- 0.3-yr periodicity preserved in a 2,500 Myr BP Australian banded iron formation (BIF) as reflecting the climatic influence of the lunar nodal tide, which has been detected with its modern 18.6-yr periodicity in some modern climate records. The lunar distance at 2,500 Myr BP would then have been about 52 Earth radii. The implied history of Precambrian tidal friction is in accord with both the more recent palaeontological evidence and the long-term stability of the lunar orbit. The length of the Milankovitch cycles that modulate the ice ages today also evolve with the Earth-Moon system. Their detection in the Precambrian sedimentary record would then permit an independent determination of the lunar distance.

  17. Uncompacted Myelin Lamellae and Nodal Ion Channel Disruption in POEMS Syndrome.

    PubMed

    Hashimoto, Rina; Koike, Haruki; Takahashi, Mie; Ohyama, Ken; Kawagashira, Yuichi; Iijima, Masahiro; Sobue, Gen

    2015-12-01

    To elucidate the significance of uncompacted myelin lamellae (UML) and ion channel disruption at the nodes of Ranvier in the polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, we evaluated sural nerve biopsy specimens from 33 patients with POEMS syndrome and from 7 control patients. Uncompacted myelin lamellae distribution was assessed by electron microscopy and immunofluorescence microscopy. In the POEMS patient biopsies, UML were seen more frequently in small versus large myelinated fibers. Paranodes and Schmidt-Lanterman incisures, where normal physiologic UM is located, were frequently associated with UM. Widening of the nodes of Ranvier (i.e. segmental demyelination) was not associated with UML. There was axonal hollowing with neurofilament condensation at Schmidt-Lanterman incisures with abnormal UML, suggesting axonal damage at those sites in the POEMS patient biopsies. Myelin sheath irregularity was conspicuous in large myelinated fibers and was associated with abnormally widened bizarrely shaped Schmidt-Lanterman incisures. Indirect immunofluorescent studies revealed abnormalities of sodium (pan sodium) and potassium (KCNQ2) channels, even at nonwidened nodes of Ranvier. Thus, UML was not apparently associated with segmental demyelination but seemed to be associated with axonal damage. These observations suggest that nodal ion channel disruption may be associated with functional deficits in POEMS syndrome patient nerves.

  18. Anisotropic softening of magnetic excitations along the nodal direction in superconducting cuprates

    NASA Astrophysics Data System (ADS)

    Guarise, M.; Piazza, B. Dalla; Berger, H.; Giannini, E.; Schmitt, T.; Rønnow, H. M.; Sawatzky, G. A.; van den Brink, J.; Altenfeld, D.; Eremin, I.; Grioni, M.

    2014-12-01

    The high-Tc cuprate superconductors are close to antiferromagnetic order. Recent measurements of magnetic excitations have reported an intriguing similarity to the spin waves—magnons—of the antiferromagnetic insulating parent compounds, suggesting that magnons may survive in damped, broadened form throughout the phase diagram. Here we show by resonant inelastic X-ray scattering on Bi2Sr2CaCu2O8+δ (Bi-2212) that the analogy with spin waves is only partial. The magnon-like features collapse along the nodal direction in momentum space and exhibit a photon energy dependence markedly different from the Mott-insulating case. These observations can be naturally described by the continuum of charge and spin excitations of correlated electrons. The persistence of damped magnons could favour scenarios for superconductivity built from quasiparticles coupled to spin fluctuations. However, excitation spectra composed of particle-hole excitations suggest that superconductivity emerges from a coherent treatment of electronic spin and charge in the form of quasiparticles with very strong magnetic correlations.

  19. Atrioventricular nodal ablation versus antiarrhythmic drugs after permanent pacemaker implantation for bradycardia-tachycardia syndrome.

    PubMed

    Nagamoto, Yasutsugu; Inage, Tomohito; Yoshida, Teruhisa; Takeuchi, Tomohiro; Gondo, Takeki; Fukuda, Yujiro; Takii, Eiichi; Murotani, Kenta; Imaizumi, Tsutomu

    2012-03-01

    Patients often require antiarrhythmic drugs to control tachycardia after permanent pacemaker implantation (PMI) for bradycardia-tachycardia syndrome. We compared atrioventricular nodal ablation (AVNA) to antiarrhythmic drugs after PMI for bradycardia-tachycardia syndrome. Twenty-eight symptomatic patients with bradycardia-tachycardia syndrome, all of which had a long pause after termination of paroxysmal atrial fibrillation, underwent PMI with RV lead placement at the mid-septum site. Among these patients, 14 underwent PMI and AVNA (AVNA group). The remaining 14 patients underwent PMI only, and continued to take anti-arrhythmic drugs (drug group). We compared cardiac function (cardio-thoracic ratio on chest X-ray, left atrial diameter, left ventricular end-diastolic dimension, and left ventricular-ejection fraction by echocardiography), exercise tolerance (6-min walking distance), symptoms, and the number of antiarrhythmic drugs just before and 6 months after PMI. Baseline characteristics were similar between the two groups, except for the number of antiarrhythmic drugs. Six months after PMI, cardiac function, exercise tolerance, and symptoms did not differ significantly between the two groups. Compared to the drug group (p < 0.01), the number of antiarrhythmic drugs was significantly smaller in the AVNA group 6 months after PMI. Patients who underwent AVNA concurrently with PMI with RV lead placement at the mid-septum site for bradycardia-tachycardia syndrome were able to reduce the intake of drugs and improve their tachycardia-related symptoms while maintaining cardiac function and exercise tolerance.

  20. A nodal discontinuous Galerkin finite element method for nonlinear elastic wave propagation.

    PubMed

    Bou Matar, Olivier; Guerder, Pierre-Yves; Li, YiFeng; Vandewoestyne, Bart; Van Den Abeele, Koen

    2012-05-01

    A nodal discontinuous Galerkin finite element method (DG-FEM) to solve the linear and nonlinear elastic wave equation in heterogeneous media with arbitrary high order accuracy in space on unstructured triangular or quadrilateral meshes is presented. This DG-FEM method combines the geometrical flexibility of the finite element method, and the high parallelization potentiality and strongly nonlinear wave phenomena simulation capability of the finite volume method, required for nonlinear elastodynamics simulations. In order to facilitate the implementation based on a numerical scheme developed for electromagnetic applications, the equations of nonlinear elastodynamics have been written in a conservative form. The adopted formalism allows the introduction of different kinds of elastic nonlinearities, such as the classical quadratic and cubic nonlinearities, or the quadratic hysteretic nonlinearities. Absorbing layers perfectly matched to the calculation domain of the nearly perfectly matched layers type have been introduced to simulate, when needed, semi-infinite or infinite media. The developed DG-FEM scheme has been verified by means of a comparison with analytical solutions and numerical results already published in the literature for simple geometrical configurations: Lamb's problem and plane wave nonlinear propagation.

  1. High-order nodal discontinuous Galerkin methods for the Maxwell eigenvalue problem.

    PubMed

    Hesthaven, J S; Warburton, T

    2004-03-15

    The Maxwell eigenvalue problem is known to pose difficulties for standard numerical methods, predominantly due to its large null space. As an alternative to the widespread use of Galerkin finite-element methods based on curl-conforming elements, we propose to use high-order nodal elements in a discontinuous element scheme. We consider both two- and three-dimensional problems and show the former to be without problems in a wide range of cases. Numerical experiments suggest the validity of this for general problems. For the three-dimensional eigenproblem, we encounter difficulties with a naive formulation of the scheme and propose minor modifications, intimately related to the discontinuous nature of the formulation, to overcome these concerns. We conclude by connecting the findings to time domain solution of Maxwell's equations. The discussion, analysis, and numerous computational experiments suggest that using discontinuous element schemes for solving Maxwell's equation in the frequency- or time-domain present a high-order accurate, efficient and robust alternative to classical Galerkin finite-element methods.

  2. Intensity-Modulated Radiation Therapy for the Treatment of Squamous Cell Anal Cancer With Para-aortic Nodal Involvement

    SciTech Connect

    Hodges, Joseph C.; Das, Prajnan; Eng, Cathy; Reish, Andrew G.; Beddar, A. Sam; Delclos, Marc E.; Krishnan, Sunil; Crane, Christopher H.

    2009-11-01

    Purpose: To determine the rates of toxicity, locoregional control, distant control, and survival in anal cancer patients with para-aortic nodal involvement, treated with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy at a single institution. Methods and Materials: Between 2001 and 2007, 6 patients with squamous cell anal cancer and para-aortic nodal involvement were treated with IMRT and concurrent infusional 5-fluorouracil and cisplatin. The primary tumor was treated with a median dose of 57.5 Gy (range, 54-60 Gy), involved para-aortic, pelvic, and inguinal lymph nodes were treated with a median dose of 55 Gy (range, 50.5-55 Gy), and noninvolved nodal regions were treated with a median dose of 45 Gy (range, 43.5-45 Gy). Results: After a median follow-up of 25 months, none of the patients had a recurrence at the primary tumor, pelvic/inguinal nodes, or para-aortic nodes, whereas 2 patients developed distant metastases to the liver. Four of the 6 patients are alive. The 3-year actuarial locoregional control, distant control, and overall survival rates were 100%, 56%, and 63%, respectively. Four of the 6 patients developed Grade 3 acute gastrointestinal toxicity during chemoradiation. Conclusions: Intensity-modulated radiotherapy and concurrent chemotherapy could potentially serve as definitive therapy in anal cancer patients with para-aortic nodal involvement. Adjuvant chemotherapy may be indicated in these patients, as demonstrated by the distant failure rates. These patients need to be followed carefully because of the potential for treatment-related toxicities.

  3. Mathematical Formalism for Designing Wide-Field X-Ray Telescopes: Mirror Nodal Positions and Detector Tilts

    NASA Technical Reports Server (NTRS)

    Elsner, R. F.; O'Dell, S. L.; Ramsey, B. D.; Weisskopf, M. C.

    2011-01-01

    We provide a mathematical formalism for optimizing the mirror nodal positions along the optical axis and the tilt of a commonly employed detector configuration at the focus of a x-ray telescope consisting of nested mirror shells with known mirror surface prescriptions. We adopt the spatial resolution averaged over the field-of-view as the figure of merit M. A more complete description appears in our paper in these proceedings.

  4. Prevalence of Common Non-Hodgkin Lymphomas and Subtypes of Hodgkin Lymphoma by Nodal Site of Involvement

    PubMed Central

    Laurent, Camille; Do, Catherine; Gourraud, Pierre-Antoine; de Paiva, Geisilene Russano; Valmary, Séverine; Brousset, Pierre

    2015-01-01

    Abstract Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) represent a heterogeneous group of malignant lymphoid tumors, which have distinct histological and/or biological characteristics with preferential nodal involvement. However, none of the previous studies have assessed the prevalence of common NHL and HL subtypes at each nodal site of involvement. The aim of our study was to determine the prevalence of HL and NHL subtypes depending on their nodal sites of involvement. We conducted a single-center retrospective study of 938 lymphoma cases diagnosed in the Pathology Department of Toulouse Purpan Hospital in France between 2001 and 2008, taking into account the site that corresponded to the diagnostic biopsy. The most frequent sites were cervical lymph nodes (36.8% of all cases), inguinal lymph nodes (16.4%), axillary lymph nodes (11.9%), and supraclavicular lymph nodes (11%). We found an unexpected association between intraparotid nodes and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and between inguinal nodes and follicular lymphoma. The risk of having classical Hodgkin lymphoma (CHL) was 15 times greater in patients with mediastinal lymphoma compared to those with other sites of involvement. Regarding HL, nodal and extranodal mediastinal sites and supraclavicular nodes were more likely to be involved by nodular sclerosis Hodgkin lymphoma (NSCHL). In addition, intra-abdominal lymph nodes were more frequently involved by lymphocyte depleted Hodgkin lymphoma compared to inguinal nodes where NLPHL predominated. Our study shows that some lymph node sites have a disproportionate prevalence of specific subtypes of lymphoma. Identifying these sites may aid to diagnose and better elucidate the pathogenesis of these tumors. PMID:26107683

  5. Early events in xenograft development from the human embryonic stem cell line HS181--resemblance with an initial multiple epiblast formation.

    PubMed

    Gertow, Karin; Cedervall, Jessica; Jamil, Seema; Ali, Rouknuddin; Imreh, Marta P; Gulyas, Miklos; Sandstedt, Bengt; Ahrlund-Richter, Lars

    2011-01-01

    Xenografting is widely used for assessing in vivo pluripotency of human stem cell populations. Here, we report on early to late events in the development of mature experimental teratoma from a well-characterized human embryonic stem cell (HESC) line, HS181. The results show an embryonic process, increasingly chaotic. Active proliferation of the stem cell derived cellular progeny was detected already at day 5, and characterized by the appearance of multiple sites of engraftment, with structures of single or pseudostratified columnar epithelium surrounding small cavities. The striking histological resemblance to developing embryonic ectoderm, and the formation of epiblast-like structures was supported by the expression of the markers OCT4, NANOG, SSEA-4 and KLF4, but a lack of REX1. The early neural marker NESTIN was uniformly expressed, while markers linked to gastrulation, such as BMP-4, NODAL or BRACHYURY were not detected. Thus, observations on day 5 indicated differentiation comparable to the most early transient cell populations in human post implantation development. Confirming and expanding on previous findings from HS181 xenografts, these early events were followed by an increasingly chaotic development, incorporated in the formation of a benign teratoma with complex embryonic components. In the mature HS181 teratomas not all types of organs/tissues were detected, indicating a restricted differentiation, and a lack of adequate spatial developmental cues during the further teratoma formation. Uniquely, a kinetic alignment of rare complex structures was made to human embryos at diagnosed gestation stages, showing minor kinetic deviations between HS181 teratoma and the human counterpart.

  6. Benign nodal lesions mimicking metastases from pediatric renal neoplasms: a report of the National Wilms' Tumor Study Pathology Center.

    PubMed

    Weeks, D A; Beckwith, J B; Mierau, G W

    1990-12-01

    Regional lymph node status is a key factor in the staging of pediatric renal tumors on the National Wilms' Tumor Study (NWTS). A review of cases entered on the NWTS has uncovered a number of cases where benign lymph node findings were mistaken for metastases. Most frequently, this was due to the presence of complexes of epithelial cells and Tamm-Horsfall protein within nodal sinuses. The epithelial cells were derived from damaged nephrons, usually resulting from obstruction by tumor. Another epithelial pseudometastic lesion, intranodal squamous epithelial cells, was found to originate from metaplastic calyceal urothelium. Benign mesothelial or coelomic inclusions similar to those previously described in pelvic and periaortic lymph nodes of adult females were found in nodes of four patients, including two boys, who are, to our knowledge, the first to be described with this finding. Other sources of confusion included protrusion of lymphoid follicles or germinal centers into nodal sinuses, thick endothelial cells of postcapillary venules mimicking epithelial tubules, nodal megakaryocytes resembling anaplastic nuclear changes, and histiocytic granulomas. Immunocytochemical methods were useful in evaluating some of these phenomena. Recognition of these pseudometastatic lesions is essential in order to avoid unnecessary and potentially hazardous therapeutic intensification.

  7. An efficient in vitro regeneration protocol for a natural dye yielding plant, Strobilanthes flaccidifolious Nees., from nodal explants.

    PubMed

    Deb, Chitta Ranjan; Arenmongla, T

    2012-11-01

    Adventitious shoot buds formation from axillary buds of nodal segments of S. flaccidifolious was achieved on MS medium containing sucrose (3%, w/v), and a-naphthalene acetic acid (NAA; 3 microM) and benzyl adenine (3 microM) in combination. The nodal segments were primed on 'Growtak Sieve' for 48 h on MS medium containing sucrose (2%), polyvinyl pyrollidone (200 mgL(-1)) as antioxidant. About 80% of primed nodal segments responded positively and formed approximately 12 adventitious shoot buds per explants from explants collected during October-November months of every year. The shoot buds converted into plantlets on MS medium containing sucrose (3%) and kinetin (3 microM) where approximately 7 micro shoots developed per subculture after 8 weeks of culture. The regenerated micro shoots induced average 14 roots/plant on medium containing NAA (3 microM). The regenerates were hardened for 6-7 weeks on medium with 1/2MS salt solution and sucrose (2%) under normal laboratory condition before transferring to potting mix. About 70% transplants survived after two months of transfer.

  8. [The comparison of biologic character between mouse embryonic fibroblast and human embryonic fibroblast].

    PubMed

    Zhang, Yi; Zhao, Liansan; Wang, Chengxiao; Lei, Binjun

    2003-06-01

    To evaluate the feasibility of using human embryonic fibroblast(HEF) as feeder layer in the culture of human embryonic stem(ES) cells in vitro, we investigated the morphology, the sensitivity to 0.25% trypsin, the growth curve and cell cycle of HEF with DMEM(low glucose) +10% FBS used as culture medium, and then we compared HEF with mouse embryonic fibroblast (MEF). The results showed that both HEF and MEF are adherent cells in vitro, and HEF has longer life span and better growth ability than MEF. In room temperature, HEF is more sensitive to 0.25% trypsin. Our research suggested that HEF can be used as feeder layer in culture of ES cells. HEF has longer service life than MEF and is worthy to be studied further.

  9. Cell cycle regulation of embryonic stem cells and mouse embryonic fibroblasts lacking functional Pax7

    PubMed Central

    Czerwinska, Areta M.; Nowacka, Joanna; Aszer, Magdalena; Fogtman, Anna; Iwanicka-Nowicka, Roksana; Jańczyk-Ilach, Katarzyna; Ciemerych, Maria A.; Grabowska, Iwona

    2016-01-01

    ABSTRACT The transcription factor Pax7 plays a key role during embryonic myogenesis and in adult organisms in that it sustains the proper function of satellite cells, which serve as adult skeletal muscle stem cells. Recently we have shown that lack of Pax7 does not prevent the myogenic differentiation of pluripotent stem cells. In the current work we show that the absence of functional Pax7 in differentiating embryonic stem cells modulates cell cycle facilitating their proliferation. Surprisingly, deregulation of Pax7 function also positively impacts at the proliferation of mouse embryonic fibroblasts. Such phenotypes seem to be executed by modulating the expression of positive cell cycle regulators, such as cyclin E. PMID:27610933

  10. Differential role of Sloan-Kettering Institute (Ski) protein in Nodal and transforming growth factor-beta (TGF-β)-induced Smad signaling in prostate cancer cells.

    PubMed

    Vo, BaoHan T; Cody, Bianca; Cao, Yang; Khan, Shafiq A

    2012-11-01

    Transforming growth factor-beta (TGF-β) signaling pathways contain both tumor suppressor and tumor promoting activities. We have demonstrated that Nodal, another member of the TGF-β superfamily, and its receptors are expressed in prostate cancer cells. Nodal and TGF-β exerted similar biological effects on prostate cells; both inhibited proliferation in WPE, RWPE1 and DU145 cells, whereas neither had any effect on the proliferation of LNCaP or PC3 cells. Interestingly, Nodal and TGF-β induced migration in PC3 cells, but not in DU145 cells. TGF-β induced predominantly phosphorylation of Smad3, whereas Nodal induced phosphorylation of only Smad2. We also determined the expression and differential role of Ski, a corepressor of Smad2/3, in Nodal and TGF-β signaling in prostate cancer cells. Similar levels of Ski mRNA were found in several established prostate cell lines; however, high levels of Ski protein were only detected in prostate cancer cells and prostate cancer tissue samples. Exogenous Nodal and TGF-β had no effects on Ski mRNA levels. On the other hand, TGF-β induced a rapid degradation of Ski protein mediated by the proteasomal pathway, whereas Nodal had no effect on Ski protein. Reduced Ski levels correlated with increased basal and TGF-β-induced Smad2/3 phosphorylation. Knockdown of endogenous Ski reduced proliferation in DU145 cells and enhanced migration of PC3 cells. We conclude that high levels of Ski expression in prostate cancer cells may be responsible for repression of TGF-β and Smad3 signaling, but Ski protein levels do not influence Nodal and Smad2 signaling.

  11. Selective Nodal Irradiation on Basis of {sup 18}FDG-PET Scans in Limited-Disease Small-Cell Lung Cancer: A Prospective Study

    SciTech Connect

    Loon, Judith van; De Ruysscher, Dirk; Wanders, Rinus; Boersma, Liesbeth; Simons, Jean; Oellers, Michel; Dingemans, Anne-Marie C.; Hochstenbag, Monique; Bootsma, Gerben; Geraedts, Wiel; Pitz, Cordula; Teule, Jaap; Rhami, Ali; Thimister, Willy; Snoep, Gabriel; Dehing-Oberije, Cary; Lambin, Philippe

    2010-06-01

    Purpose: To evaluate the results of selective nodal irradiation on basis of {sup 18}F-deoxyglucose positron emission tomography (PET) scans in patients with limited-disease small-cell lung cancer (LD-SCLC) on isolated nodal failure. Methods and Materials: A prospective study was performed of 60 patients with LD-SCLC. Radiotherapy was given to a dose of 45 Gy in twice-daily fractions of 1.5 Gy, concurrent with carboplatin and etoposide chemotherapy. Only the primary tumor and the mediastinal lymph nodes involved on the pretreatment PET scan were irradiated. A chest computed tomography (CT) scan was performed 3 months after radiotherapy completion and every 6 months thereafter. Results: A difference was seen in the involved nodal stations between the pretreatment {sup 18}F-deoxyglucose PET scans and computed tomography scans in 30% of patients (95% confidence interval, 20-43%). Of the 60 patients, 39 (65%; 95% confidence interval [CI], 52-76%) developed a recurrence; 2 patients (3%, 95% CI, 1-11%) experienced isolated regional failure. The median actuarial overall survival was 19 months (95% CI, 17-21). The median actuarial progression-free survival was 14 months (95% CI, 12-16). 12% (95% CI, 6-22%) of patients experienced acute Grade 3 (Common Terminology Criteria for Adverse Events, version 3.0) esophagitis. Conclusion: PET-based selective nodal irradiation for LD-SCLC resulted in a low rate of isolated nodal failures (3%), with a low percentage of acute esophagitis. These findings are in contrast to those from our prospective study of CT-based selective nodal irradiation, which resulted in an unexpectedly high percentage of isolated nodal failures (11%). Because of the low rate of isolated nodal failures and toxicity, we believe that our data support the use of PET-based SNI for LD-SCLC.

  12. [Microglial cells and development of the embryonic central nervous system].

    PubMed

    Legendre, Pascal; Le Corronc, Hervé

    2014-02-01

    Microglia cells are the macrophages of the central nervous system with a crucial function in the homeostasis of the adult brain. However, recent studies showed that microglial cells may also have important functions during early embryonic central nervous system development. In this review we summarize recent works on the extra embryonic origin of microglia, their progenitor niche, the pattern of their invasion of the embryonic central nervous system and on interactions between embryonic microglia and their local environment during invasion. We describe microglial functions during development of embryonic neuronal networks, including their roles in neurogenesis, in angiogenesis and developmental cell death. These recent discoveries open a new field of research on the functions of neural-microglial interactions during the development of the embryonic central nervous system.

  13. A stabilised nodal spectral element method for fully nonlinear water waves

    NASA Astrophysics Data System (ADS)

    Engsig-Karup, A. P.; Eskilsson, C.; Bigoni, D.

    2016-08-01

    We present an arbitrary-order spectral element method for general-purpose simulation of non-overturning water waves, described by fully nonlinear potential theory. The method can be viewed as a high-order extension of the classical finite element method proposed by Cai et al. (1998) [5], although the numerical implementation differs greatly. Features of the proposed spectral element method include: nodal Lagrange basis functions, a general quadrature-free approach and gradient recovery using global L2 projections. The quartic nonlinear terms present in the Zakharov form of the free surface conditions can cause severe aliasing problems and consequently numerical instability for marginally resolved or very steep waves. We show how the scheme can be stabilised through a combination of over-integration of the Galerkin projections and a mild spectral filtering on a per element basis. This effectively removes any aliasing driven instabilities while retaining the high-order accuracy of the numerical scheme. The additional computational cost of the over-integration is found insignificant compared to the cost of solving the Laplace problem. The model is applied to several benchmark cases in two dimensions. The results confirm the high order accuracy of the model (exponential convergence), and demonstrate the potential for accuracy and speedup. The results of numerical experiments are in excellent agreement with both analytical and experimental results for strongly nonlinear and irregular dispersive wave propagation. The benefit of using a high-order - possibly adapted - spatial discretisation for accurate water wave propagation over long times and distances is particularly attractive for marine hydrodynamics applications.

  14. Long term results of fast pathway ablation in atrioventricular nodal reentry tachycardia using a modified technique.

    PubMed Central

    Mehta, D.; Gomes, J. A.

    1995-01-01

    OBJECTIVE--To assess immediate and long term success of "fast" pathway catheter ablation with graded use of radiofrequency energy in patients with classic atrioventricular nodal reentrant tachycardia (AVNRT) and evaluate clinical, procedure related, and electrophysiological features affecting long term results. DESIGN--31 consecutive patients with classic AVNRT at electrophysiological study, who were candidates for radiofrequency ablation. Patients were followed for an average of 24 months after ablation. SETTING--All studies and ablations were performed in an electrophysiological laboratory under fluoroscopic guidance using standard electrophysiological techniques. INTERVENTION--Radiofrequency application was performed at the site of proximal His bundle electrogram with A:V ratio of > 1. It was started at 10 W with increment of 5 W to a maximum of 25 W at 60 s. With the onset of junctional rhythm, atrial pacing was begun in order to monitor the PR interval. Application was terminated prematurely with a non-conducted P wave, continued prolongation of the PR interval beyond 50% of the baseline, or a threefold rise in impedance. RESULTS--Successful ablation was possible in 30/31 patients (97%) with an average of seven applications (range 1-10). It was associated with significant prolongation of PR interval (P < 0.001) and AV Wenckebach cycle length (P = 0.01). Ventriculo-atrial conduction was abolished in 24/30 patients (82%) with successful ablation. Two patients developed transient complete heart block (3 and 12 min) and one persistent right branch block. Four patients had late recurrence. Presence of ventriculo-atrial block was the only electrophysiological index predictive of long term success (P = 0.01). CONCLUSIONS--Graded use of radiofrequency energy and atrial pacing to monitor PR interval decreases the risk of atrioventricular block in patients undergoing fast pathway ablation for AVNRT. Ventriculo-atrial block is predictive of long term success and should

  15. Pediatric-type nodal follicular lymphoma: a biologically distinct lymphoma with frequent MAPK pathway mutations.

    PubMed

    Louissaint, Abner; Schafernak, Kristian T; Geyer, Julia T; Kovach, Alexandra E; Ghandi, Mahmoud; Gratzinger, Dita; Roth, Christine G; Paxton, Christian N; Kim, Sunhee; Namgyal, Chungdak; Morin, Ryan; Morgan, Elizabeth A; Neuberg, Donna S; South, Sarah T; Harris, Marian H; Hasserjian, Robert P; Hochberg, Ephraim P; Garraway, Levi A; Harris, Nancy Lee; Weinstock, David M

    2016-08-25

    Pediatric-type nodal follicular lymphoma (PTNFL) is a variant of follicular lymphoma (FL) characterized by limited-stage presentation and invariably benign behavior despite often high-grade histological appearance. It is important to distinguish PTNFL from typical FL in order to avoid unnecessary treatment; however, this distinction relies solely on clinical and pathological criteria, which may be variably applied. To define the genetic landscape of PTNFL, we performed copy number analysis and exome and/or targeted sequencing of 26 PTNFLs (16 pediatric and 10 adult). The most commonly mutated gene in PTNFL was MAP2K1, encoding MEK1, with a mutation frequency of 43%. All MAP2K1 mutations were activating missense mutations localized to exons 2 and 3, which encode negative regulatory and catalytic domains, respectively. Missense mutations in MAPK1 (2/22) and RRAS (1/22) were identified in cases that lacked MAP2K1 mutations. The second most commonly mutated gene in PTNFL was TNFRSF14, with a mutation frequency of 29%, similar to that seen in limited-stage typical FL (P = .35). PTNFL was otherwise genomically bland and specifically lacked recurrent mutations in epigenetic modifiers (eg, CREBBP, KMT2D). Copy number aberrations affected a mean of only 0.5% of PTNFL genomes, compared with 10% of limited-stage typical FL genomes (P < .02). Importantly, the mutational profiles of PTNFLs in children and adults were highly similar. Together, these findings define PTNFL as a biologically and clinically distinct indolent lymphoma of children and adults characterized by a high prevalence of MAPK pathway mutations and a near absence of mutations in epigenetic modifiers.

  16. Respiratory Organ Motion and Dosimetric Impact on Breast and Nodal Irradiation

    SciTech Connect

    Qi, X. Sharon; White, Julia; Rabinovitch, Rachel; Merrell, Kenneth; Sood, Amit; Bauer, Anderson; Wilson, J. Frank; Miften, Moyed; Li, X. Allen

    2010-10-01

    Purpose: To examine the respiratory motion for target and normal structures during whole breast and nodal irradiation and the resulting dosimetric impact. Methods and Materials: Four-dimensional CT data sets of 18 patients with early-stage breast cancer were analyzed retrospectively. A three-dimensional conformal dosimetric plan designed to irradiate the breast was generated on the basis of CT images at 20% respiratory phase (reference phase). The reference plans were copied to other respiratory phases at 0% (end of inspiration) and 50% (end of expiration) to simulate the effects of breathing motion on whole breast irradiation. Dose-volume histograms, equivalent uniform dose, and normal tissue complication probability were evaluated and compared. Results: Organ motion of up to 8.8 mm was observed during free breathing. A large lung centroid movement was typically associated with a large shift of other organs. The variation of planning target volume coverage during a free breathing cycle is generally within 1%-5% (17 of 18 patients) compared with the reference plan. However, up to 28% of V{sub 45} variation for the internal mammary nodes was observed. Interphase mean dose variations of 2.2%, 1.2%, and 1.4% were observed for planning target volume, ipsilateral lung, and heart, respectively. Dose variations for the axillary nodes and brachial plexus were minimal. Conclusions: The doses delivered to the target and normal structures are different from the planned dose based on the reference phase. During normal breathing, the dosimetric impact of respiratory motion is clinically insignificant with the exception of internal mammary nodes. However, noticeable degradation in dosimetric plan quality may be expected for the patients with large respiratory motion.

  17. Pediatric-type nodal follicular lymphoma: a biologically distinct lymphoma with frequent MAPK pathway mutations

    PubMed Central

    Schafernak, Kristian T.; Geyer, Julia T.; Kovach, Alexandra E.; Ghandi, Mahmoud; Gratzinger, Dita; Roth, Christine G.; Paxton, Christian N.; Kim, Sunhee; Namgyal, Chungdak; Morin, Ryan; Morgan, Elizabeth A.; Neuberg, Donna S.; South, Sarah T.; Harris, Marian H.; Hasserjian, Robert P.; Hochberg, Ephraim P.; Garraway, Levi A.; Harris, Nancy Lee; Weinstock, David M.

    2016-01-01

    Pediatric-type nodal follicular lymphoma (PTNFL) is a variant of follicular lymphoma (FL) characterized by limited-stage presentation and invariably benign behavior despite often high-grade histological appearance. It is important to distinguish PTNFL from typical FL in order to avoid unnecessary treatment; however, this distinction relies solely on clinical and pathological criteria, which may be variably applied. To define the genetic landscape of PTNFL, we performed copy number analysis and exome and/or targeted sequencing of 26 PTNFLs (16 pediatric and 10 adult). The most commonly mutated gene in PTNFL was MAP2K1, encoding MEK1, with a mutation frequency of 43%. All MAP2K1 mutations were activating missense mutations localized to exons 2 and 3, which encode negative regulatory and catalytic domains, respectively. Missense mutations in MAPK1 (2/22) and RRAS (1/22) were identified in cases that lacked MAP2K1 mutations. The second most commonly mutated gene in PTNFL was TNFRSF14, with a mutation frequency of 29%, similar to that seen in limited-stage typical FL (P = .35). PTNFL was otherwise genomically bland and specifically lacked recurrent mutations in epigenetic modifiers (eg, CREBBP, KMT2D). Copy number aberrations affected a mean of only 0.5% of PTNFL genomes, compared with 10% of limited-stage typical FL genomes (P < .02). Importantly, the mutational profiles of PTNFLs in children and adults were highly similar. Together, these findings define PTNFL as a biologically and clinically distinct indolent lymphoma of children and adults characterized by a high prevalence of MAPK pathway mutations and a near absence of mutations in epigenetic modifiers. PMID:27325104

  18. Maternal diet programs embryonic kidney gene expression.

    PubMed

    Welham, Simon J M; Riley, Paul R; Wade, Angie; Hubank, Mike; Woolf, Adrian S

    2005-06-16

    Human epidemiological data associating birth weight with adult disease suggest that organogenesis is "programmed" by maternal diet. In rats, protein restriction in pregnancy produces offspring with fewer renal glomeruli and higher systemic blood pressures than controls. We tested the hypothesis that maternal diet alters gene expression in the metanephros, the precursor of the definitive mammalian kidney. We demonstrated that maternal low-protein diet initiated when pregnancy starts and maintained to embryonic day 13, when the metanephros consists of mesenchyme surrounding a once-branched ureteric bud, is sufficient to significantly reduce glomerular numbers in offspring by about 20%. As assessed by representational difference analyses and real-time quantitative polymerase chain reactions, low-protein diet modulated gene expression in embryonic day 13 metanephroi. In particular, levels of prox-1, the ortholog of Drosophila transcription factor prospero, and cofilin-1, a regulator of the actin cytoskeleton, were reduced. During normal metanephrogenesis, prox-1 protein was first detected in mesenchymal cells around the ureteric tree and thereafter in nascent nephron epithelia, whereas cofilin-1 immunolocalized to bud derivatives and condensing mesenchyme. Previously, we reported that low-protein diets increased mesenchymal apoptosis cells when metanephrogenesis began and thereafter reduced numbers of precursor cells. Collectively, these studies prove that the maternal diet programs the embryonic kidney, altering cell turnover and gene expression at a time when nephrons and glomeruli have yet to form. The human implication is that the maternal diet ingested between conception and 5- 6-wk gestation contributes to the variation in glomerular numbers that are known to occur between healthy and hypertensive populations.

  19. Embryonic in vivo electroporation in the mouse.

    PubMed

    Saito, Tetsuichiro

    2010-01-01

    Electroporation combined with surgery is a quick and highly efficient method to transfect nucleic acids into various embryonic tissues in a spatiotemporally restricted manner. Forceps-type electrodes facilitate transfection by delivering electric pulses from outside of the embryo. Many electroporated embryos survive in the pregnant mouse, are born, and are reared. The developing central nervous system (CNS) is a good target for transfection, because there are many neural progenitors adjacent to the ventricle, into which nucleic acids are relatively easily injected. The expression of transfected genes persists in neurons for months.

  20. [Ethical aspects of embryonic stem cell research].

    PubMed

    Kostka, U

    2002-11-01

    Research using embryonic stem cells raises a variety of ethical questions, which will be explored in this article. At the core of the ethical controversy is the question of the status of the embryo and its availability for research. A range of countries have approved the use of "supernumerous" embryos from in-vitro fertilization. But ethical problems also arise in reproduction medicine, the informed consent of affected couples, and the targeted production of embryos and egg cell donation for research. The author discuss some of these neglected issues and develops suggestions for comprehensive ethical reflection.

  1. Imaging embryonic morphogenesis in C. elegans.

    PubMed

    Hardin, Jeff

    2011-01-01

    The Caenorhabditis elegans embryo is well suited to morphogenetic analysis via modern microscopy, due to its short generation time, transparency, invariant lineage, and the ability to generate transgenic embryos expressing various fluorescent proteins. This chapter provides an overview of microscopy techniques for imaging embryonic morphogenesis, including making agar mounts, capturing four-dimensional (4D) data using Nomarski microscopy, imaging of actin in embryos, factors important for optimizing 4D fluorescence microscopy, and recent techniques that leverage fluorescence microscopy for intracellular imaging of cellular components during morphogenesis.

  2. A deuterostome origin of the Spemann organiser suggested by Nodal and ADMPs functions in Echinoderms

    PubMed Central

    Lapraz, François; Haillot, Emmanuel; Lepage, Thierry

    2015-01-01

    During development of chordates, establishment of the body plan relies on the activity of an organizing centre located on the dorsal side of the embryo that patterns the embryo and induces neural tissue. Intriguingly, the evolutionary origin of this crucial signalling centre remains unclear and whether analogous organizers regulate D/V patterning in other deuterostome or protostome phyla is not known. Here we provide evidence that the ventral ectoderm of the sea urchin embryo is a long-range organizing centre that shares several fundamental properties with the Spemann organizer: the ability to induce duplicated embryonic axes when ectopically induced, the ability to induce neural fate in neighbouring tissues and the ability to finely regulate the level of BMP signalling by using an autoregulatory expansion–repression mechanism. These findings suggest that the evolutionary origin of the Spemann organizer is more ancient than previously thought and that it may possibly be traced back to the common ancestor of deuterostomes. PMID:26423516

  3. A deuterostome origin of the Spemann organiser suggested by Nodal and ADMPs functions in Echinoderms.

    PubMed

    Lapraz, François; Haillot, Emmanuel; Lepage, Thierry

    2015-10-01

    During development of chordates, establishment of the body plan relies on the activity of an organizing centre located on the dorsal side of the embryo that patterns the embryo and induces neural tissue. Intriguingly, the evolutionary origin of this crucial signalling centre remains unclear and whether analogous organizers regulate D/V patterning in other deuterostome or protostome phyla is not known. Here we provide evidence that the ventral ectoderm of the sea urchin embryo is a long-range organizing centre that shares several fundamental properties with the Spemann organizer: the ability to induce duplicated embryonic axes when ectopically induced, the ability to induce neural fate in neighbouring tissues and the ability to finely regulate the level of BMP signalling by using an autoregulatory expansion-repression mechanism. These findings suggest that the evolutionary origin of the Spemann organizer is more ancient than previously thought and that it may possibly be traced back to the common ancestor of deuterostomes.

  4. Estimation of cellular fabric in embryonic epithelia.

    PubMed

    Iles, Peter J W; Brodland, G Wayne; Clausi, David A; Puddister, Shannon M

    2007-02-01

    Recent computational and analytical studies have shown that cellular fabric-as embodied by average cell size, aspect ratio and orientation-is a key indicator of the stresses acting in an embryonic epithelium. Cellular fabric in real embryonic tissues could not previously be measured automatically because the cell boundaries tend to be poorly defined, significant lighting and cell pigmentation differences occur and tissues contain a variety of cell geometries. To overcome these difficulties, four algorithms were developed: least squares ellipse fitting (LSEF), area moments (AM), correlation and axes search (CAS) and Gabor filters (GF). The AM method was found to be the most reliable of these methods, giving typical cell size, aspect ratio and orientation errors of 18%, 0.10 and 7.4 degrees, respectively, when evaluated against manually segmented images. The power of the AM algorithm to provide new insights into the mechanics of morphogenesis is demonstrated through a brief investigation of gastrulation, where fabric data suggest that key gastrulation movements are driven by epidermal tensions circumferential to the blastopore.

  5. Organotypic slice culture of embryonic brain tissue.

    PubMed

    Daza, Ray A M; Englund, Chris; Hevner, Robert F

    2007-12-01

    INTRODUCTIONThis protocol describes how to dissect, assemble, and cultivate mouse embryonic (E) brain tissue from age E11.5 to E18.5 (days) for organotypic slice culture. These preparations can be used for a variety of assays and studies including coculture of different brain regions, cell migration assays, axon guidance assays, and DNA electroporation experiments. During electroporation, an electric current is applied to the surface of a specific target area of the brain slice in order to open holes in the plasma membrane and introduce a plasmid of coding DNA. The floating slice-on-membrane construct helps to preserve the structural integrity of the brain slices, while maintaining easy experimental access and optimal viability. Experiments can be monitored in living slices (e.g., with confocal imaging), and further studies can be completed using slices that have been fixed and cryosectioned at the end of the experiment. Any region of embryonic brain or spinal tissue can be used in this protocol.

  6. Embryonic paratesticular rhabdomyosarcoma: a case report

    PubMed Central

    2013-01-01

    Introduction An embryonic paratesticular rhabdomyosarcoma is a very rare mesenchymal tumor. It is an intrascrotal tumor that is localized in paratesticular structures such as the epididymis or spermatic cord. Rhabdomyosarcoma is most often observed in children and adolescents, presenting as a painless scrotal mass. Case presentation Our patient was an 18-year-old Moroccan man who presented with a painless left scrotal mass that had evolved over four months. An inguinal orchiectomy was performed. A histological examination of the excised tissue revealed an embryonic rhabdomyosarcoma. Our patient had three sessions of chemotherapy with vincristine, actinomycin C and cyclophosphamide. Each chemotherapy session was conducted over five days, with a cycle of 21 days. Our patient was assessed two months after the last chemotherapy session and demonstrated good clinical improvement. Conclusion Paratesticular rhabdomyosarcoma is a rare aggressive tumor manifesting in children and very young adults. Localized forms have a good prognosis whereas metastatic tumors show very poor results. A well-defined treatment based on surgery and chemotherapy yields good results. PMID:23561643

  7. Embryonic stem cells: from markers to market.

    PubMed

    Deb, Kaushik Dilip; Jayaprakash, Anitha Devi; Sharma, Vijay; Totey, Satish

    2008-02-01

    ABSTRACT Embryonic stem cells are considered the mother of all kinds of tissues and cells and it is envisioned as the holy grail of regenerative medicine. However, their use in cell replacement therapies (CRT) has so far been limited and their potentials are yet to be fully realized. The use of human embryonic stem cells (hESC) involves many safety issues pertaining to culture conditions and epigenetic changes. The role and importance of an epigenomic signature in derivation and maintenance of hESC are discussed. We provide a list of important epigenetic markers, which should be studied for evaluation of safety in hESC-based cell replacement therapies. These genes also need to be screened to determine an epigenetic signature for pluripotency in the hESCs. Finally a comprehensive list of all known stemness signature genes and the marker genes for different germ line lineages are presented. This review aims at summing up most of the intriguing molecules that can play a role in the maintenance of pluripotency and can help in determining hESC differentiation to various lineages. Extensive understanding of these markers will eventually help the researchers to transform the hESC research from bench to the bedside. The use of hESCs in CRTs is still in its infancy; much effort is warranted to turn them into the much dreamed about magic wand of regenerative medicine.

  8. Human embryonic stem cells and cardiac repair.

    PubMed

    Zhu, Wei-Zhong; Hauch, Kip D; Xu, Chunhui; Laflamme, Michael A

    2009-01-01

    The muscle lost after a myocardial infarction is replaced with noncontractile scar tissue, often initiating heart failure. Whole-organ cardiac transplantation is the only currently available clinical means of replacing the lost muscle, but this option is limited by the inadequate supply of donor hearts. Thus, cell-based cardiac repair has attracted considerable interest as an alternative means of ameliorating cardiac injury. Because of their tremendous capacity for expansion and unquestioned cardiac potential, pluripotent human embryonic stem cells (hESCs) represent an attractive candidate cell source for obtaining cardiomyocytes and other useful mesenchymal cell types for such therapies. Human embryonic stem cell-derived cardiomyocytes exhibit a committed cardiac phenotype and robust proliferative capacity, and recent testing in rodent infarct models indicates that they can partially remuscularize injured hearts and improve contractile function. Although the latter successes give good reason for optimism, considerable challenges remain in the successful application of hESCs to cardiac repair, including the need for preparations of high cardiac purity, improved methods of delivery, and approaches to overcome immune rejection and other causes of graft cell death. This review will describe the phenotype of hESC-derived cardiomyocytes and preclinical experience with these cells and will consider strategies to overcoming the aforementioned challenges.

  9. Mechanical signaling coordinates the embryonic heart

    NASA Astrophysics Data System (ADS)

    Chiou, Kevin; Rocks, Jason; Prosser, Benjamin; Discher, Dennis; Liu, Andrea

    The heart is an active material which relies on robust signaling mechanisms between cells in order to produce well-timed, coordinated beats. Heart tissue is composed primarily of active heart muscle cells (cardiomyocytes) embedded in a passive extracellular matrix. During a heartbeat, cardiomyocyte contractions are coordinated across the heart to form a wavefront that propagates through the tissue to pump blood. In the adult heart, this contractile wave is coordinated via intercellular electrical signaling.Here we present theoretical and experimental evidence for mechanical coordination of embryonic heartbeats. We model cardiomyocytes as mechanically excitable Eshelby inclusions embedded in an overdamped elastic-fluid biphasic medium. For physiological parameters, this model replicates recent experimental measurements of the contractile wavefront which are not captured by electrical signaling models. We additionally challenge our model by pharmacologically blocking gap junctions, inhibiting electrical signaling between myocytes. We find that while adult hearts stop beating almost immediately after gap junctions are blocked, embryonic hearts continue beating even at significantly higher concentrations, providing strong support for a mechanical signaling mechanism.

  10. Proteome analysis of chick embryonic cerebrospinal fluid.

    PubMed

    Parada, Carolina; Gato, Angel; Aparicio, Mariano; Bueno, David

    2006-01-01

    During early stages of embryo development, the brain cavity is filled with embryonic cerebrospinal fluid (E-CSF), a complex fluid containing different protein fractions that contributes to the regulation of the survival, proliferation and neurogenesis of the neuroectodermal stem cells. Using 2-DE, protein sequencing and database searches, we identified and analyzed the proteome of the E-CSF from chick embryos (Gallus gallus). We identified 26 different gene products, including proteins related to the extracellular matrix, proteins associated with the regulation of osmotic pressure and metal transport, proteins related to cell survival, MAP kinase activators, proteins involved in the transport of retinol and vitamin D, antioxidant and antimicrobial proteins, intracellular proteins and some unknown proteins. Most of these gene products are involved in the regulation of developmental processes during embryogenesis in systems other than E-CSF. Interestingly, 14 of them are also present in adult human CSF proteome, and it has been reported that they are altered in the CSF of patients suffering neurodegenerative diseases and/or neurological disorders. Understanding these molecules and the mechanisms they control during embryonic neurogenesis is a key contribution to the general understanding of CNS development, and may also contribute to greater knowledge of these human diseases.

  11. Gene signature of the embryonic meniscus.

    PubMed

    Pazin, Dorothy E; Gamer, Laura W; Capelo, Luciane P; Cox, Karen A; Rosen, Vicki

    2014-01-01

    The meniscus is a fibrocartilagenous disc in the knee that protects the joint from damage. Meniscal injuries are common, however repair efforts are largely unsuccessful and are not able to prevent the degenerative changes that result in development of osteoarthritis. Tissue regeneration in adults often recapitulates events of embryonic development, suggesting the regulatory pathways controlling morphogenesis are candidate repair signals. Here we use laser capture microdissection to collect mouse embryonic day 16 (E16) meniscus, articular cartilage, and cruciate ligaments. RNA isolated from these tissues was then used to perform genome-wide microarray analysis. We found 38 genes were differentially expressed between E16 meniscus and articular cartilage and 43 genes were differentially expressed between E16 meniscus and cruciate ligaments. Included in our data set were extracellular matrix proteins, transcription factors, and growth factors, including TGF-β modulators (Lox, Dpt) and IGF-1 pathway members (Igf-1, Igfbp2, Igfbp3, Igfbp5). Ingenuity Pathway Analysis revealed that IGF-1 signaling was enriched in the meniscus compared to the other joint structures, while qPCR showed that Igf-1, Igfbp2, and Igfbp3 expression declined with age. We also found that several meniscus-enriched genes were expressed either in the inner or outer meniscus, establishing that regionalization of the meniscus occurs early in development.

  12. Disseminated Cerebrospinal Embryonal Tumor in the Adult

    PubMed Central

    Armocida, Daniele; Caporlingua, Federico; Lapadula, Gennaro; Elefante, Grazia Maria; Antonelli, Manila; Salvati, Maurizio

    2016-01-01

    Introduction. According to the 2016 World Health Organization classification of Tumors of the Central Nervous System, the term Primitive Neuroectodermal Tumor has been replaced by the term Embryonal Tumor (ET). We present a case of disseminated cerebrospinal ET presenting in an adult patient. Illustrative Case. A 49-year-old male presenting with low back pain, dysuria, and hypoesthesia of the lower extremities referred to our emergency department. Brain and whole spine contrast-enhanced MRI documented a diffusively disseminated heterogeneous neoplasm with intradural extra- and intramedullary involvement of the cervicothoracic tract and cauda equina. A primary biopsy of the lumbosacral localization was performed through L5 bilateral laminectomy. Histologic diagnosis was Embryonal Tumor Not Otherwise Specified. The patient underwent chemotherapy with postoperative adjuvant alternating Vincristine-Doxorubicin-Ifosfamide (VAI) and Ifosfamide-Etoposide (IE). Discussion. Spinal ETs are exceedingly rare especially when presenting in the adult patient. Neurosurgical and oncologic management is still unclear. When feasible, surgical removal should always be performed to obtain a histologic diagnosis. Postoperative adjuvant therapy might entail both chemo- and radiotherapy; however a consensus on this matter is still lacking. PMID:27818821

  13. A multivariate Bayesian model for embryonic growth.

    PubMed

    Willemsen, Sten P; Eilers, Paul H C; Steegers-Theunissen, Régine P M; Lesaffre, Emmanuel

    2015-04-15

    Most longitudinal growth curve models evaluate the evolution of each of the anthropometric measurements separately. When applied to a 'reference population', this exercise leads to univariate reference curves against which new individuals can be evaluated. However, growth should be evaluated in totality, that is, by evaluating all body characteristics jointly. Recently, Cole et al. suggested the Superimposition by Translation and Rotation (SITAR) model, which expresses individual growth curves by three subject-specific parameters indicating their deviation from a flexible overall growth curve. This model allows the characterization of normal growth in a flexible though compact manner. In this paper, we generalize the SITAR model in a Bayesian way to multiple dimensions. The multivariate SITAR model allows us to create multivariate reference regions, which is advantageous for prediction. The usefulness of the model is illustrated on longitudinal measurements of embryonic growth obtained in the first semester of pregnancy, collected in the ongoing Rotterdam Predict study. Further, we demonstrate how the model can be used to find determinants of embryonic growth.

  14. Induced pluripotent stem cells from pigs and other ungulate species: an alternative to embryonic stem cells?

    PubMed

    Ezashi, T; Telugu, B P V L; Roberts, R M

    2012-08-01

    Robust embryonic stem cell (ESC) lines from livestock species have been difficult to derive and maintain, and unlike mouse ESC, have not contributed to our ability to understand directed differentiation in vitro. Nor have such cells yet provided a simpler means than pronuclear injection to manipulate the genomes of agriculturally important species, such as cattle, sheep and pigs. Induced pluripotent stem cells (iPSC) generated by reprogramming somatic cells, such as fibroblasts, with a set of stemness genes, most usually but not exclusively POU5F1, SOX2, KLF4 and c-MYC, offer an alternative to ESC in these regards, as they exhibit a pluripotent phenotype resembling that of ESC, yet are readily generated in the laboratory. Accordingly, such cells, in association with cloning technologies, may be useful for introducing complex genetic changes into livestock, although this potential has yet to be demonstrated. Porcine iPSC may be especially valuable because the pig is a prime biomedical model for tissue transplantation. In general, iPSC from livestock, like those from humans, are of the epiblast type and depend upon FGF2 and activin/nodal signalling systems to maintain their pluripotency and growth. Recent experiments, in which newly reprogrammed porcine and bovine cells were selected on a LIF-based medium in presence of specific protein kinase inhibitors, have allowed iPSC cells of the naïve type, resembling the more amenable blastocyst-derived mouse ESC and iPSC to be isolated. However, hurdles still remain if such cells are to achieve their biotechnological promise.

  15. A microfluidic processor for gene expression profiling of single human embryonic stem cells.

    PubMed

    Zhong, Jiang F; Chen, Yan; Marcus, Joshua S; Scherer, Axel; Quake, Stephen R; Taylor, Clive R; Weiner, Leslie P

    2008-01-01

    The gene expression of human embryonic stem cells (hESC) is a critical aspect for understanding the normal and pathological development of human cells and tissues. Current bulk gene expression assays rely on RNA extracted from cell and tissue samples with various degree of cellular heterogeneity. These 'cell population averaging' data are difficult to interpret, especially for the purpose of understanding the regulatory relationship of genes in the earliest phases of development and differentiation of individual cells. Here, we report a microfluidic approach that can extract total mRNA from individual single-cells and synthesize cDNA on the same device with high mRNA-to-cDNA efficiency. This feature makes large-scale single-cell gene expression profiling possible. Using this microfluidic device, we measured the absolute numbers of mRNA molecules of three genes (B2M, Nodal and Fzd4) in a single hESC. Our results indicate that gene expression data measured from cDNA of a cell population is not a good representation of the expression levels in individual single cells. Within the G0/G1 phase pluripotent hESC population, some individual cells did not express all of the 3 interrogated genes in detectable levels. Consequently, the relative expression levels, which are broadly used in gene expression studies, are very different between measurements from population cDNA and single-cell cDNA. The results underscore the importance of discrete single-cell analysis, and the advantages of a microfluidic approach in stem cell gene expression studies.

  16. Porcine induced pluripotent stem cells analogous to naïve and primed embryonic stem cells of the mouse.

    PubMed

    Telugu, Bhanu Prakash V L; Ezashi, Toshihiko; Roberts, R Michael

    2010-01-01

    Authentic or naïve embryonic stem cells (ESC) have probably never been derived from the inner cell mass (ICM) of pig blastocysts, despite over 25 years of effort. Recently, several groups, including ours, have reported induced pluripotent stem cells (iPSC) from swine by reprogramming somatic cells with a combination of four factors, OCT4 (POU5F1)/SOX2/KLF4/c-MYC delivered by retroviral transduction. The porcine (p) iPSC resembled human (h) ESC and the mouse "Epiblast stem cells" (EpiSC) in their colony morphology and expression of pluripotent genes, and are likely dependent on FGF2/ACTIVIN/NODAL signaling, therefore representing a primed ESC state. These cells are likely to advance swine as a model in biomedical research, since grafts could potentially be matched to the animal that donated the cells for re-programming. The objective of the present work has been to develop naïve piPSC. Employing a combination of seven reprogramming factors assembled on episomal vectors, we successfully reprogrammed porcine embryonic fibroblasts on a modified LIF-medium supplemented with two kinase inhibitors; CHIR99021, which inhibits GSK-3beta, and PD0325901, a MEK inhibitor. The derived piPSC bear a striking resemblance to naïve mESC in colony morphology, are dependent on LIF to maintain an undifferentiated phenotype, and express markers consistent with pluripotency. They exhibit high telomerase activity, a short cell cycle interval, and a normal karyotype, and are able to generate teratomas. Currently, the competence of these lines for contributing to germ-line chimeras is being tested.

  17. The multifaceted role of the embryonic gene Cripto-1 in cancer, stem cells and epithelial-mesenchymal transition

    PubMed Central

    Klauzinska, Malgorzata; Castro, Nadia P.; Rangel, Maria Cristina; Spike, Benjamin T.; Gray, Peter C.; Bertolette, Daniel; Cuttitta, Frank; Salomon, David

    2014-01-01

    Cripto-1 (CR-1)/Teratocarcinoma-derived growth factor1 (TDGF-1) is a cell surface glycosylphosphatidylinositol (GPI)-linked glycoprotein that can function either in cis (autocrine) or in trans (paracrine). The cell membrane cis form is found in lipid rafts and endosomes while the trans acting form lacking the GPI anchor is soluble. As a member of the epidermal growth factor (EGF)/Cripto-1-FRL-1-Cryptic (CFC) family, CR-1 functions as an obligatory co-receptor for the transforming growth factor-β (TGF-β) family members, Nodal and growth and differentiation factors 1 and 3 (GDF1/3) by activating Alk4/Alk7 signaling pathways that involve Smads 2, 3 and 4. In addition, CR-1 can activate non-Smad-dependent signaling elements such as PI3K, Akt and MAPK. Both of these pathways depend upon the 78 kDa glucose regulated protein (GRP78). Finally, CR-1 can facilitate signaling through the canonical Wnt/β-catenin and Notch/Cbf-1 pathways by functioning as a chaperone protein for LRP5/6 and Notch, respectively. CR-1 is essential for early embryonic development and maintains embryonic stem cell pluripotentiality. CR-1 performs an essential role in the etiology and progression of several types of human tumors where it is expressed in a population of cancer stem cells (CSCs) and facilitates epithelial-mesenchymal transition (EMT). In this context, CR-1 can significantly enhance tumor cell migration, invasion and angiogenesis. Collectively, these facts suggest that CR-1 may be an attractive target in the diagnosis, prognosis and therapy of several types of human cancer. PMID:25153355

  18. Embryonal Rhabdomyosarcoma Occurring on Mandibular Gingiva in an Adult

    PubMed Central

    Patil, Gururaj; Halawar, Sangamesh; Sagari, Shitalkumar; Babannavar, Roopa; Purohit, Sharad

    2013-01-01

    An embryonal rhabdomyosarcoma (ERMS) is a primitive, malignant, soft tissue sarcoma that recapitulates the phenotypic and biological features of embryonic skeletal muscles. Occurrence of intraoral ERMS in adults is extremely rare. This unique case report highlights the clinical, radiographic, histopathological and immunohistochemical findings of an intraoral ERMS. PMID:24179953

  19. Paraxial left-sided nodal expression and the start of left-right patterning in the early chick embryo.

    PubMed

    Tsikolia, Nikoloz; Schröder, Silke; Schwartz, Peter; Viebahn, Christoph

    2012-12-01

    A common element during early left-right patterning of the vertebrate body is left-sided nodal expression in the early-somite stage lateral plate mesoderm. Leftward cell movements near the node of the gastrulating chick embryo recently offered a plausible mechanism for breaking the presomite-stage molecular symmetry in those vertebrates which lack rotating cilia on the notochord or equivalent tissues. However, the temporal and functional relationships between generation of the known morphological node asymmetry, onset of leftward cell movements and establishment of stable molecular asymmetry in the chick remain unresolved. This study uses high-resolution light microscopy and in situ gene expression analysis to show that intranodal cell rearrangement during the phase of counter-clockwise node torsion at stage 4+ is immediately followed by symmetry loss and rearrangement of shh and fgf8 expression in node epiblast between stages 5- and 5+. Surprisingly, left-sided nodal expression starts at stage 5-, too, but lies in the paraxial mesoderm next to the forming notochordal plate, and can be rendered symmetrical by minimal mechanical disturbance of distant tissue integrity at stage 4. The "premature" paraxial nodal expression together with morphological and molecular asymmetries in, and near, midline compartments occurring at defined substages of early gastrulation help to identify a new narrow time window for early steps in left-right patterning in the chick and support the concept of a causal relationship between a-still enigmatic-chiral (motor) protein, cell movements and incipient left-right asymmetry in the amniote embryo.

  20. Involvement of both sodium influx and potassium efflux in ciguatoxin-induced nodal swelling of frog myelinated axons.

    PubMed

    Mattei, César; Molgó, Jordi; Benoit, Evelyne

    2014-10-01

    Ciguatoxins, mainly produced by benthic dinoflagellate Gambierdiscus species, are responsible for a complex human poisoning known as ciguatera. Previous pharmacological studies revealed that these toxins activate voltage-gated Na+ channels. In frog nodes of Ranvier, ciguatoxins induce spontaneous and repetitive action potentials (APs) and increase axonal volume that may explain alterations of nerve functioning in intoxicated humans. The present study aimed determining the ionic mechanisms involved in Pacific ciguatoxin-1B (P-CTX-1B)-induced membrane hyperexcitability and subsequent volume increase in frog nodes of Ranvier, using electrophysiology and confocal microscopy. The results reveal that P-CTX-1B action is not dependent on external Cl- ions since it was not affected by substituting Cl- by methylsulfate ions. In contrast, substitution of external Na+ by Li+ ions suppressed spontaneous APs and prevented nodal swelling. This suggests that P-CTX-1B-modified Na+ channels are not selective to Li+ ions and/or are blocked by these ions, and that Na+ influx through Na+ channels opened during spontaneous APs is required for axonal swelling. The fact that the K+ channel blocker tetraethylammonium modified, but did not suppress, spontaneous APs and greatly reduced nodal swelling induced by P-CTX-1B indicates that K+ efflux might also be involved. This is supported by the fact that P-CTX-1B, when tested in the presence of both tetraethylammonium and the K+ ionophore valinomycin, produced the characteristic nodal swelling. It is concluded that, during the action of P-CTX-1B, water movements responsible for axonal swelling depend on both Na+ influx and K+ efflux. These results pave the way for further studies regarding ciguatera treatment.

  1. Cranial location of level II lymph nodes in laryngeal cancer: Implications for elective nodal target volume delineation

    SciTech Connect

    Braam, Petra M. . E-mail: P.M.Braam@umcutrecht.nl; Raaijmakers, Cornelis P.J.; Terhaard, Chris

    2007-02-01

    Purpose: To analyze the cranial distribution of level II lymph nodes in patients with laryngeal cancer to optimize the elective radiation nodal target volume delineation. Methods and Materials: The most cranially located metastatic lymph node was delineated in 67 diagnostic CT data sets. The minimum distance from the base of the skull (BOS) to the lymph node was determined. Results: A total of 98 lymph nodes were delineated including 62 ipsilateral and 36 contralateral lymph nodes. The mean ipsilateral and contralateral distance from the top of the most cranial metastatic lymph node to the BOS was 36 mm (range, -9-120; standard deviation [SD], 17.9) and 35 mm (range, 14-78; SD 15.0), respectively. Only 5% and 12% of the ipsilateral and 3% and 9% of the contralateral metastatic lymph nodes were located within 15 mm and 20 mm below the BOS, respectively. No significant differences were found between patients with only ipsilateral metastatic lymph nodes and patients with bilateral metastatic lymph nodes. Between tumors that do cross the midline and those that do not, no significant difference was found in the distance of the most cranial lymph node to the BOS and the occurrence ipsilateral or contralateral. Conclusions: Setting the cranial border of the nodal target volume 1.5 cm below the base of the skull covers 95% of the lymph nodes and should be considered in elective nodal irradiation for laryngeal cancer. Bilateral neck irradiation is mandatory, including patients with unilateral laryngeal cancer, when elective irradiation is advised.

  2. JAM-C promotes lymphangiogenesis and nodal metastasis in non-small cell lung cancer.

    PubMed

    Hao, SongNan; Yang, YanMei; Liu, Yan; Yang, ShuCai; Wang, Geng; Xiao, JianBing; Liu, HuiDong

    2014-06-01

    This study aims to investigate lymphatic metastasis-related genes in non-small cell lung carcinomas (NSCLC). NSCLC tissue was analyzed for expression of junctional adhesion molecule-C (JAM-C) protein. Our data revealed novel associations between JAM-C overexpression in primary tumors and lymphatic microvessel density (LMVD), lymph node metastasis, and poorer overall survival and recurrence-free survival. We used the highly metastatic human lung adenocarcinoma cell line Anip973 and its parental line AGZY83-a, which has a low metastatic capacity, in vivo and vitro. We found that JAM-C played an important role in different metastasis capacity of lymph node. JAM-C affected tumor growth, LNM, JAM-C, VEGF-C, vasculature, and ERK1/2 phosphorylation (p-ERK1/2). β1 integrin was involved in lymph node metastasis. Moreover, JAM-C knockdown in highly metastatic Anip973 decreased cell migration in scratch-wound assays. The JAM-C knockdown in Anip973 cells and JAM-C cDNA in AGZY83-a cells regulated the vascular endothelial growth factor C (VEGF-C) expression. Immunofluorescence showed that blocked VEGF-C expression in JAM-C shRNA Anip973 cells were restored after JAM-C treatment. JAM-C-induced VEGF-C in JAM-C cDNA AGZY83-a cells was also effectively inhibited by treatment with an antibody specifically against JAM-C. Use of media from Anip973 cells, AGZY83-a, and A549cells lung cancer cells that overexpressed or downregulated JAM-C was demonstrated to affect activity of VEGF-C-induced β1 integrin subunit or ERK activity in human dermal lymphatic endothelial cells (HDLEC) treated with VEGF-C or inhibitory antibody to JAM-C. Overall, these results indicate that JAM-C could mediate metastasis as it contributes to VEGF-C expression in cancer cells. JAM-C affects β1and ERK activation in HDLEC, thus promoting lymphangiogenesis and nodal metastasis. Our findings indicate that JAM-C may be a therapeutic target for preventing and treating lymphatic metastases.

  3. Anatomical Variations in the Sinoatrial Nodal Artery: A Meta-Analysis and Clinical Considerations

    PubMed Central

    Roy, Joyeeta; Ramakrishnan, Piravin Kumar; Hsieh, Wan Chin; Walocha, Jerzy A.; Tomaszewski, Krzysztof A.

    2016-01-01

    Background and Objective The sinoatrial nodal artery (SANa) is a highly variable vessel which supplies blood to the sinoatrial node (SAN). Due to its variability and susceptibility to iatrogenic injury, our study aimed to assess the anatomy of the SANa and determine the prevalence of its anatomical variations. Study Design An extensive search of major electronic databases was performed to identify all articles reporting anatomical data on the SANa. No lower date limit or language restrictions were applied. Anatomical data regarding the artery were extracted and pooled into a meta-analysis. Results Sixty-six studies (n = 21455 hearts) were included in the meta-analysis. The SANa usually arose as a single vessel with a pooled prevalence of 95.5% (95%CI:93.6–96.9). Duplication and triplication of the artery were also observed with pooled prevalence of 4.3% (95%CI:2.8–6.0) and 0.3% (95%CI:0–0.7), respectively. The most common origin of the SANa was from the right coronary artery (RCA), found in 68.0% (95%CI:55.6–68.9) of cases, followed by origin from the left circumflex artery, and origin from the left coronary artery with pooled prevalence of 22.1% (95%CI:15.0–26.2) and 2.7 (95%CI:0.7–5.2), respectively. A retrocaval course of the SANa was the most common course of the artery with a pooled prevalence of 47.1% (95%CI:36.0–55.5). The pooled prevalence of an S-shaped SANa was 7.6% (95%CI:2.9–14.1). Conclusions The SANa is most commonly reported as a single vessel, originating from the RCA, and taking a retrocaval course to reach the SAN. Knowledge of high risk anatomical variants of the SANa, such as an S-shaped artery, must be taken into account by surgeons to prevent iatrogenic injuries. Specifically, interventional or cardiosurgical procedures, such as the Cox maze procedure for atrial fibrillation, open heart surgeries through the right atrium or intraoperative cross-clamping or dissection procedures during mitral valve surgery using the septal

  4. Cervical nodal necrosis is an independent survival predictor in nasopharyngeal carcinoma: an observational cohort study

    PubMed Central

    Luo, Yangkun; Ren, Jing; Zhou, Peng; Gao, Yang; Yang, Guangquan; Lang, Jinyi

    2016-01-01

    Purpose Most nasopharyngeal carcinoma (NPC) patients present with locoregionally advanced disease at the time of diagnosis; however, there is a lack of consensus on specific prognostic factors potentially improving overall survival, especially in late-stage disease. Herein, we conducted a retrospective study to evaluate various potential prognostic factors in order to provide useful information for clinical treatment of T3/T4-stage NPC. Patients and methods A total of 189 previously untreated NPC patients were enrolled in the current study. All patients received intensity-modulated radiotherapy. Survival, death, relapse-free survival (both local and regional), and metastasis were recorded during follow-up. Factors affecting patient survival were assessed by using univariate and multivariate analyses. Results The median follow-up time was 69 months. The 5-year local-regional recurrence-free survival, distant metastasis-free survival, progression-free survival (PFS), and overall survival (OS) of the entire group were 89.8%, 71.5%, 66.3%, and 68.9%, respectively. Univariate analysis revealed significant differences in the 5-year PFS (58.5% vs 72.5%, P=0.015) and OS (59.5% vs 75.8%, P=0.033) rates of patients with and without cervical nodal necrosis (CNN). Subgroup analyses revealed that CNN was associated with poorer distant metastasis-free survival and PFS among patients with N2 stage (P=0.046 and P=0.005) and with poorer PFS among patients with T3 or III stage (all P=0.022). Multivariate analysis revealed CNN to be an independent prognostic factor for PFS and OS (PFS: adjusted hazard ratio, 1.860; 95% CI: 1.134–3.051; P=0.014; OS: adjusted hazard ratio, 1.754; 95% CI: 1.061–2.899; P=0.028). Conclusion CNN is a potential independent negative prognostic factor in NPC patients. Our results suggest that stratification of NPC patients based on their CNN status should be considered as part of NPC disease management. PMID:27843328

  5. Evidence for 18.6-year lunar nodal drought in Western North America during the past millennium

    NASA Astrophysics Data System (ADS)

    Currie, Robert G.

    1984-02-01

    Analysis of 38 tree ring chronologies yields evidence for enhanced drought conditions every 18.6 years in the North American interior for the past millenium. Cross spectra between a drought area index and 26 temperature records confirm the analysis of Currie (1979, 1981d) as regards a lunar nodal MN term in these data. Discussion of the MN tidal constituent, which appreciably modulate amplitude and phase of four main constituents (M2, K1, O1, Mf), is presented, and implications for agriculture are surveyed.

  6. Global Performance Characterization of the Three Burn Trans-Earth Injection Maneuver Sequence over the Lunar Nodal Cycle

    NASA Technical Reports Server (NTRS)

    Williams, Jacob; Davis, Elizabeth C.; Lee, David E.; Condon, Gerald L.; Dawn, Tim

    2009-01-01

    The Orion spacecraft will be required to perform a three-burn trans-Earth injection (TEI) maneuver sequence to return to Earth from low lunar orbit. The origin of this approach lies in the Constellation Program requirements for access to any lunar landing site location combined with anytime lunar departure. This paper documents the development of optimized databases used to rapidly model the performance requirements of the TEI three-burn sequence for an extremely large number of mission cases. It also discusses performance results for lunar departures covering a complete 18.6 year lunar nodal cycle as well as general characteristics of the optimized three-burn TEI sequence.

  7. An incidental finding of a nodal recurrence of cutaneous malignant melanoma after a 45-year disease-free period.

    PubMed

    Goodenough, Jenny; Cozon, Caroline Louise; Liew, Se Hwang

    2014-06-03

    We report the case of an 84-year-old woman who had a nodal recurrence of melanoma 45 years after the primary diagnosis of an extremity cutaneous melanoma. It is believed to be the longest disease-free latency period reported between primary melanoma diagnosis and recurrence to date. Late recurrences of melanoma are rare and recurrence after four decades extremely rare. This article suggests melanoma is a disease with a potentially lifelong risk of recurrence and thus clinicians and patients must be vigilant and aware of this risk, particularly if late recurrences are to be recognised early and management optimised.

  8. Extra-nodal Diffuse Large B-cell Lymphoma (Germinal Center Type) Manifesting as Non-healing Extraction Socket

    PubMed Central

    Basavarajappa, Manjunath Anekonda; Pathan, Sana; Raheem, Ahmed Mujib Bangalore; Godavarthy, Divyasri

    2016-01-01

    Lymphomas occurring in the oral cavity are rare. They account only for about 2% of extra-nodal sites. Most of the lymphomas occur in the lymph nodes and in the oral cavity, the most commonly affected region is the Waldeyer’s ring. Its occurrence in the mandibular gingiva is rare. Here, we describe a case of Diffuse Large B-cell Lymphoma manifested as a non-healing extraction socket in the mandibular right posterior region in a 62-year-old male patient. PMID:27656575

  9. Nodal Stage of Surgically Resected Non-Small Cell Lung Cancer and Its Effect on Recurrence Patterns and Overall Survival

    SciTech Connect

    Varlotto, John M.; Yao, Aaron N.; DeCamp, Malcolm M.; Ramakrishna, Satvik; Recht, Abe; Flickinger, John; Andrei, Adin; Reed, Michael F.; Toth, Jennifer W.; Fizgerald, Thomas J.; Higgins, Kristin; Zheng, Xiao; Shelkey, Julie; and others

    2015-03-15

    Purpose: Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. Methods and Materials: A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. Results: The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95% CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum. Conclusions: Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence. Prospective

  10. 4D embryonic cardiography using gated optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Jenkins, M. W.; Rothenberg, F.; Roy, D.; Nikolski, V. P.; Hu, Z.; Watanabe, M.; Wilson, D. L.; Efimov, I. R.; Rollins, A. M.

    2006-01-01

    Simultaneous imaging of very early embryonic heart structure and function has technical limitations of spatial and temporal resolution. We have developed a gated technique using optical coherence tomography (OCT) that can rapidly image beating embryonic hearts in four-dimensions (4D), at high spatial resolution (10-15 μm), and with a depth penetration of 1.5 - 2.0 mm that is suitable for the study of early embryonic hearts. We acquired data from paced, excised, embryonic chicken and mouse hearts using gated sampling and employed image processing techniques to visualize the hearts in 4D and measure physiologic parameters such as cardiac volume, ejection fraction, and wall thickness. This technique is being developed to longitudinally investigate the physiology of intact embryonic hearts and events that lead to congenital heart defects.

  11. MicroRNA-29b/Tet1 regulatory axis epigenetically modulates mesendoderm differentiation in mouse embryonic stem cells

    PubMed Central

    Tu, Jiajie; Ng, Shuk Han; Shui Luk, Alfred Chun; Liao, Jinyue; Jiang, Xiaohua; Feng, Bo; Lun Mak, Kingston King; Rennert, Owen M.; Chan, Wai-Yee; Lee, Tin-Lap

    2015-01-01

    Ten eleven translocation (Tet) family-mediated DNA oxidation on 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) represents a novel epigenetic modification that regulates dynamic gene expression during embryonic stem cells (ESCs) differentiation. Through the role of Tet on 5hmC regulation in stem cell development is relatively defined, how the Tet family is regulated and impacts on ESCs lineage development remains elusive. In this study, we show non-coding RNA regulation on Tet family may contribute to epigenetic regulation during ESCs differentiation, which is suggested by microRNA-29b (miR-29b) binding sites on the Tet1 3′ untranslated region (3′ UTR). We demonstrate miR-29b increases sharply after embyoid body (EB) formation, which causes Tet1 repression and reduction of cellular 5hmC level during ESCs differentiation. Importantly, we show this miR-29b/Tet1 regulatory axis promotes the mesendoderm lineage formation both in vitro and in vivo by inducing the Nodal signaling pathway and repressing the key target of the active demethylation pathway, Tdg. Taken together, our findings underscore the contribution of small non-coding RNA mediated regulation on DNA demethylation dynamics and the differential expressions of key mesendoderm regulators during ESCs lineage specification. MiR-29b could potentially be applied to enrich production of mesoderm and endoderm derivatives and be further differentiated into desired organ-specific cells. PMID:26130713

  12. Sept6 is required for ciliogenesis in Kupffer's vesicle, the pronephros, and the neural tube during early embryonic development.

    PubMed

    Zhai, Gang; Gu, Qilin; He, Jiangyan; Lou, Qiyong; Chen, Xiaowen; Jin, Xia; Bi, Erfei; Yin, Zhan

    2014-04-01

    Septins are conserved filament-forming GTP-binding proteins that act as cellular scaffolds or diffusion barriers in a number of cellular processes. However, the role of septins in vertebrate development remains relatively obscure. Here, we show that zebrafish septin 6 (sept6) is first expressed in the notochord and then in nearly all of the ciliary organs, including Kupffer's vesicle (KV), the pronephros, eye, olfactory bulb, and neural tube. Knockdown of sept6 in zebrafish embryos results in reduced numbers and length of cilia in KV. Consequently, cilium-related functions, such as the left-right patterning of internal organs and nodal/spaw signaling, are compromised. Knockdown of sept6 also results in aberrant cilium formation in the pronephros and neural tube, leading to cilium-related defects in pronephros development and Sonic hedgehog (Shh) signaling. We further demonstrate that SEPT6 associates with acetylated α-tubulin in vivo and localizes along the axoneme in the cilia of zebrafish pronephric duct cells as well as cultured ZF4 cells. Our study reveals a novel role of sept6 in ciliogenesis during early embryonic development in zebrafish.

  13. Activin A Modulates CRIPTO-1/HNF4α+ Cells to Guide Cardiac Differentiation from Human Embryonic Stem Cells

    PubMed Central

    Duelen, Robin; Gilbert, Guillaume; Patel, Abdulsamie; de Schaetzen, Nathalie; De Waele, Liesbeth; Roderick, Llewelyn; Sipido, Karin R.; Verfaillie, Catherine M.; Buyse, Gunnar M.

    2017-01-01

    The use of human pluripotent stem cells in basic and translational cardiac research requires efficient differentiation protocols towards cardiomyocytes. In vitro differentiation yields heterogeneous populations of ventricular-, atrial-, and nodal-like cells hindering their potential applications in regenerative therapies. We described the effect of the growth factor Activin A during early human embryonic stem cell fate determination in cardiac differentiation. Addition of high levels of Activin A during embryoid body cardiac differentiation augmented the generation of endoderm derivatives, which in turn promoted cardiomyocyte differentiation. Moreover, a dose-dependent increase in the coreceptor expression of the TGF-β superfamily member CRIPTO-1 was observed in response to Activin A. We hypothesized that interactions between cells derived from meso- and endodermal lineages in embryoid bodies contributed to improved cell maturation in early stages of cardiac differentiation, improving the beating frequency and the percentage of contracting embryoid bodies. Activin A did not seem to affect the properties of cardiomyocytes at later stages of differentiation, measuring action potentials, and intracellular Ca2+ dynamics. These findings are relevant for improving our understanding on human heart development, and the proposed protocol could be further explored to obtain cardiomyocytes with functional phenotypes, similar to those observed in adult cardiac myocytes. PMID:28163723

  14. A clinical series and literature review of the management of inguinal nodal metastases in patients with primary extramammary Paget disease of the scrotum.

    PubMed

    Koh, Ye Xin; Tay, Timothy Kwang Yong; Xu, Sheng; Lee, Chee Meng; Teo, Melissa Ching Ching

    2015-01-01

    We describe a series of five patients with extramammary Paget disease of the scrotum with inguinal nodal metastases. These patients underwent combined groin dissection. All patients experienced invasion to the dermis. One patient had invasion of the dartos muscle, another had tumor invading into the skeletal muscle and femoral vein. Four patients had positive Cloquet node involvement on frozen section and formal histology, but only one patient had positive pelvic nodal disease. Another patient with pelvic nodal metastases seen on computed tomography scan had no Cloquet node identified intraoperatively but had positive pelvic nodal metastases. The mean disease-free survival and the overall survival were 28.6 months (range: 2-60 months) and 33.4 months (range: 2-60 months), respectively, for all patients. Three patients developed distant metastases and two patients were disease free to date. No locoregional recurrences were observed. Aggressive lymphadenectomy in selected cases can provide a long-term survival benefit. The use of Cloquet node in the prediction of pelvic nodal disease should be considered. Based on the literature review, sentinel lymph node biopsy can potentially diagnose occult metastases in otherwise nonenlarged nodes.

  15. Efficient introduction of specific TP53 mutations into mouse embryonic fibroblasts and embryonic stem cells.

    PubMed

    Wei, Quan-Xiang; van der Hoeven, Franciscus; Hollstein, Monica; Odell, Adam F

    2012-05-17

    This protocol describes a rapid, precise method for generating sets of embryonic stem (ES) cells or mouse embryonic fibroblasts (MEFs) harboring point mutations in the p53 tumor suppressor gene (officially known as Trp53). The strategy uses cells from the