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Sample records for neural cell-fate determination

  1. Dlx proteins position the neural plate border and determine adjacent cell fates.

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    Woda, Juliana M; Pastagia, Julie; Mercola, Mark; Artinger, Kristin Bruk

    2003-01-01

    The lateral border of the neural plate is a major source of signals that induce primary neurons, neural crest cells and cranial placodes as well as provide patterning cues to mesodermal structures such as somites and heart. Whereas secreted BMP, FGF and Wnt proteins influence the differentiation of neural and non-neural ectoderm, we show here that members of the Dlx family of transcription factors position the border between neural and non-neural ectoderm and are required for the specification of adjacent cell fates. Inhibition of endogenous Dlx activity in Xenopus embryos with an EnR-Dlx homeodomain fusion protein expands the neural plate into non-neural ectoderm tissue whereas ectopic activation of Dlx target genes inhibits neural plate differentiation. Importantly, the stereotypic pattern of border cell fates in the adjacent ectoderm is re-established only under conditions where the expanded neural plate abuts Dlx-positive non-neural ectoderm. Experiments in which presumptive neural plate was grafted to ventral ectoderm reiterate induction of neural crest and placodal lineages and also demonstrate that Dlx activity is required in non-neural ectoderm for the production of signals needed for induction of these cells. We propose that Dlx proteins regulate intercellular signaling across the interface between neural and non-neural ectoderm that is critical for inducing and patterning adjacent cell fates.

  2. New roles for Nanos in neural cell fate determination revealed by studies in a cnidarian.

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    Kanska, Justyna; Frank, Uri

    2013-07-15

    Nanos is a pan-metazoan germline marker, important for germ cell development and maintenance. In flies, Nanos also acts in posterior and neural development, but these functions have not been demonstrated experimentally in other animals. Using the cnidarian Hydractinia we have uncovered novel roles for Nanos in neural cell fate determination. Ectopic expression of Nanos2 increased the numbers of embryonic stinging cell progenitors, but decreased the numbers of neurons. Downregulation of Nanos2 had the opposite effect. Furthermore, Nanos2 blocked maturation of committed, post-mitotic nematoblasts. Hence, Nanos2 acts as a switch between two differentiation pathways, increasing the numbers of nematoblasts at the expense of neuroblasts, but preventing nematocyte maturation. Nanos2 ectopic expression also caused patterning defects, but these were not associated with deregulation of Wnt signaling, showing that the basic anterior-posterior polarity remained intact, and suggesting that numerical imbalance between nematocytes and neurons might have caused these defects, affecting axial patterning only indirectly. We propose that the functions of Nanos in germ cells and in neural development are evolutionarily conserved, but its role in posterior patterning is an insect or arthropod innovation.

  3. The neural stem cell fate determinant TLX promotes tumorigenesis and genesis of cells resembling glioma stem cells.

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    Park, Hyo-Jung; Kim, Jun-Kyum; Jeon, Hye-Min; Oh, Se-Yeong; Kim, Sung-Hak; Nam, Do-Hyun; Kim, Hyunggee

    2010-11-01

    A growing body of evidence indicates that deregulation of stem cell fate determinants is a hallmark of many types of malignancies. The neural stem cell fate determinant TLX plays a pivotal role in neurogenesis in the adult brain by maintaining neural stem cells. Here, we report a tumorigenic role of TLX in brain tumor initiation and progression. Increased TLX expression was observed in a number of glioma cells and glioma stem cells, and correlated with poor survival of patients with gliomas. Ectopic expression of TLX in the U87MG glioma cell line and Ink4a/Arf-deficient mouse astrocytes (Ink4a/Arf(-/-) astrocytes) induced cell proliferation with a concomitant increase in cyclin D expression, and accelerated foci formation in soft agar and tumor formation in in vivo transplantation assays. Furthermore, overexpression of TLX in Ink4a/Arf(-/-) astrocytes inhibited cell migration and invasion and promoted neurosphere formation and Nestin expression, which are hallmark characteristics of glioma stem cells, under stem cell culture conditions. Our results indicate that TLX is involved in glioma stem cell genesis and represents a potential therapeutic target for this type of malignancy.

  4. Hydrogel formulation determines cell fate of fetal and adult neural progenitor cells

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    Emily R. Aurand

    2014-01-01

    Full Text Available Hydrogels provide a unique tool for neural tissue engineering. These materials can be customized for certain functions, i.e. to provide cell/drug delivery or act as a physical scaffold. Unfortunately, hydrogel complexities can negatively impact their biocompatibility, resulting in unintended consequences. These adverse effects may be combated with a better understanding of hydrogel chemical, physical, and mechanical properties, and how these properties affect encapsulated neural cells. We defined the polymerization and degradation rates and compressive moduli of 25 hydrogels formulated from different concentrations of hyaluronic acid (HA and poly(ethylene glycol (PEG. Changes in compressive modulus were driven primarily by the HA concentration. The in vitro biocompatibility of fetal-derived (fNPC and adult-derived (aNPC neural progenitor cells was dependent on hydrogel formulation. Acute survival of fNPC benefited from hydrogel encapsulation. NPC differentiation was divergent: fNPC differentiated into mostly glial cells, compared with neuronal differentiation of aNPC. Differentiation was influenced in part by the hydrogel mechanical properties. This study indicates that there can be a wide range of HA and PEG hydrogels compatible with NPC. Additionally, this is the first study comparing hydrogel encapsulation of NPC derived from different aged sources, with data suggesting that fNPC and aNPC respond dissimilarly within the same hydrogel formulation.

  5. Regulatory Role of Redox Balance in Determination of Neural Precursor Cell Fate

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    Mohamed Ariff Iqbal

    2017-01-01

    Full Text Available In 1990s, reports of discovery of a small group of cells capable of proliferation and contribution to formation of new neurons in the central nervous system (CNS reversed a century-old concept on lack of neurogenesis in the adult mammalian brain. These cells are found in all stages of human life and contribute to normal cellular turnover of the CNS. Therefore, the identity of regulating factors that affect their proliferation and differentiation is a highly noteworthy issue for basic scientists and their clinician counterparts for therapeutic purposes. The cues for such control are embedded in developmental and environmental signaling through a highly regulated tempo-spatial expression of specific transcription factors. Novel findings indicate the importance of reactive oxygen species (ROS in the regulation of this signaling system. The elusive nature of ROS signaling in many vital processes from cell proliferation to cell death creates a complex literature in this field. Here, we discuss the emerging thoughts on the importance of redox regulation of proliferation and maintenance in mammalian neural stem and progenitor cells under physiological and pathological conditions. The current knowledge on ROS-mediated changes in redox-sensitive proteins that govern the molecular mechanisms in proliferation and differentiation of these cells is reviewed.

  6. Cell fate determination dynamics in bacteria

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    Kuchina, Anna; Espinar, Lorena; Cagatay, Tolga; Garcia-Ojalvo, Jordi; Suel, Gurol

    2010-03-01

    The fitness of an organism depends on many processes that serve the purpose to adapt to changing environment in a robust and coordinated fashion. One example of such process is cellular fate determination. In the presence of a variety of alternative responses each cell adopting a particular fate represents a ``choice'' that must be tightly regulated to ensure the best survival strategy for the population taking into account the broad range of possible environmental challenges. We investigated this problem in the model organism B.Subtilis which under stress conditions differentiates terminally into highly resistant spores or initiates an alternative transient state of competence. The dynamics underlying cell fate choice remains largely unknown. We utilize quantitative fluorescent microscopy to track the activities of genes involved in these responses on a single-cell level. We explored the importance of temporal interactions between competing cell fates by re- engineering the differentiation programs. I will discuss how the precise dynamics of cellular ``decision-making'' governed by the corresponding biological circuits may enable cells to adjust to diverse environments and determine survival.

  7. Cell fate determination in the Caenorhabditis elegans epidermal lineages

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    Soete, G.A.J.

    2007-01-01

    The starting point for this work was to use the hypodermal seam of C. elegans as a model system to study cell fate determination. Even though the seam is a relatively simple developmental system, the mechanisms that control cell fate determination in the seam lineages are connected in a highly

  8. A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination.

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    Zhao, Chunnian; Sun, GuoQiang; Li, Shengxiu; Shi, Yanhong

    2009-04-01

    MicroRNAs have been implicated as having important roles in stem cell biology. MicroRNA-9 (miR-9) is expressed specifically in neurogenic areas of the brain and may be involved in neural stem cell self-renewal and differentiation. We showed previously that the nuclear receptor TLX is an essential regulator of neural stem cell self-renewal. Here we show that miR-9 suppresses TLX expression to negatively regulate neural stem cell proliferation and accelerate neural differentiation. Introducing a TLX expression vector that is not prone to miR-9 regulation rescued miR-9-induced proliferation deficiency and inhibited precocious differentiation. In utero electroporation of miR-9 in embryonic brains led to premature differentiation and outward migration of the transfected neural stem cells. Moreover, TLX represses expression of the miR-9 pri-miRNA. By forming a negative regulatory loop with TLX, miR-9 provides a model for controlling the balance between neural stem cell proliferation and differentiation.

  9. Cell fate determination in zebrafish embryonic and adult muscle development

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    Tee, J.M.

    2010-01-01

    We are interested in how the genetic basis of muscle precursor cells determines the outcome of the muscle cell fate, and thus leading to disruption in muscle formation and maintenance. We utilized the zebrafish carrying mutations in both Axin1 and Apc1, resulting in overactivation of the

  10. Regulation of spindle orientation and neural stem cell fate in the Drosophila optic lobe

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    Brand Andrea H

    2007-01-01

    Full Text Available Abstract Background The choice of a stem cell to divide symmetrically or asymmetrically has profound consequences for development and disease. Unregulated symmetric division promotes tumor formation, whereas inappropriate asymmetric division affects organ morphogenesis. Despite its importance, little is known about how spindle positioning is regulated. In some tissues cell fate appears to dictate the type of cell division, whereas in other tissues it is thought that stochastic variation in spindle position dictates subsequent sibling cell fate. Results Here we investigate the relationship between neural progenitor identity and spindle positioning in the Drosophila optic lobe. We use molecular markers and live imaging to show that there are two populations of progenitors in the optic lobe: symmetrically dividing neuroepithelial cells and asymmetrically dividing neuroblasts. We use genetically marked single cell clones to show that neuroepithelial cells give rise to neuroblasts. To determine if a change in spindle orientation can trigger a neuroepithelial to neuroblast transition, we force neuroepithelial cells to divide along their apical/basal axis by misexpressing Inscuteable. We find that this does not induce neuroblasts, nor does it promote premature neuronal differentiation. Conclusion We show that symmetrically dividing neuroepithelial cells give rise to asymmetrically dividing neuroblasts in the optic lobe, and that regulation of spindle orientation and division symmetry is a consequence of cell type specification, rather than a mechanism for generating cell type diversity.

  11. Antagonism between the transcription factors NANOG and OTX2 specifies rostral or caudal cell fate during neural patterning transition.

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    Su, Zhenghui; Zhang, Yanqi; Liao, Baojian; Zhong, Xiaofen; Chen, Xin; Wang, Haitao; Guo, Yiping; Shan, Yongli; Wang, Lihui; Pan, Guangjin

    2018-03-23

    During neurogenesis, neural patterning is a critical step during which neural progenitor cells differentiate into neurons with distinct functions. However, the molecular determinants that regulate neural patterning remain poorly understood. Here we optimized the "dual SMAD inhibition" method to specifically promote differentiation of human pluripotent stem cells (hPSCs) into forebrain and hindbrain neural progenitor cells along the rostral-caudal axis. We report that neural patterning determination occurs at the very early stage in this differentiation. Undifferentiated hPSCs expressed basal levels of the transcription factor orthodenticle homeobox 2 (OTX2) that dominantly drove hPSCs into the "default" rostral fate at the beginning of differentiation. Inhibition of glycogen synthase kinase 3β (GSK3β) through CHIR99021 application sustained transient expression of the transcription factor NANOG at early differentiation stages through Wnt signaling. Wnt signaling and NANOG antagonized OTX2 and, in the later stages of differentiation, switched the default rostral cell fate to the caudal one. Our findings have uncovered a mutual antagonism between NANOG and OTX2 underlying cell fate decisions during neural patterning, critical for the regulation of early neural development in humans. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Twist1 Controls a Cell-Specification Switch Governing Cell Fate Decisions within the Cardiac Neural Crest

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    Vincentz, Joshua W.; Firulli, Beth A.; Lin, Andrea; Spicer, Douglas B.; Howard, Marthe J.; Firulli, Anthony B.

    2013-01-01

    Neural crest cells are multipotent progenitor cells that can generate both ectodermal cell types, such as neurons, and mesodermal cell types, such as smooth muscle. The mechanisms controlling this cell fate choice are not known. The basic Helix-loop-Helix (bHLH) transcription factor Twist1 is expressed throughout the migratory and post-migratory cardiac neural crest. Twist1 ablation or mutation of the Twist-box causes differentiation of ectopic neuronal cells, which molecularly resemble sympathetic ganglia, in the cardiac outflow tract. Twist1 interacts with the pro-neural factor Sox10 via its Twist-box domain and binds to the Phox2b promoter to repress transcriptional activity. Mesodermal cardiac neural crest trans-differentiation into ectodermal sympathetic ganglia-like neurons is dependent upon Phox2b function. Ectopic Twist1 expression in neural crest precursors disrupts sympathetic neurogenesis. These data demonstrate that Twist1 functions in post-migratory neural crest cells to repress pro-neural factors and thereby regulate cell fate determination between ectodermal and mesodermal lineages. PMID:23555309

  13. Concentration Sensing by the Moving Nucleus in Cell Fate Determination: A Computational Analysis.

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    Varun Aggarwal

    Full Text Available During development of the vertebrate neuroepithelium, the nucleus in neural progenitor cells (NPCs moves from the apex toward the base and returns to the apex (called interkinetic nuclear migration at which point the cell divides. The fate of the resulting daughter cells is thought to depend on the sampling by the moving nucleus of a spatial concentration profile of the cytoplasmic Notch intracellular domain (NICD. However, the nucleus executes complex stochastic motions including random waiting and back and forth motions, which can expose the nucleus to randomly varying levels of cytoplasmic NICD. How nuclear position can determine daughter cell fate despite the stochastic nature of nuclear migration is not clear. Here we derived a mathematical model for reaction, diffusion, and nuclear accumulation of NICD in NPCs during interkinetic nuclear migration (INM. Using experimentally measured trajectory-dependent probabilities of nuclear turning, nuclear waiting times and average nuclear speeds in NPCs in the developing zebrafish retina, we performed stochastic simulations to compute the nuclear trajectory-dependent probabilities of NPC differentiation. Comparison with experimentally measured nuclear NICD concentrations and trajectory-dependent probabilities of differentiation allowed estimation of the NICD cytoplasmic gradient. Spatially polarized production of NICD, rapid NICD cytoplasmic consumption and the time-averaging effect of nuclear import/export kinetics are sufficient to explain the experimentally observed differentiation probabilities. Our computational studies lend quantitative support to the feasibility of the nuclear concentration-sensing mechanism for NPC fate determination in zebrafish retina.

  14. The influence of immunosuppressive drugs on neural stem/progenitor cell fate in vitro

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    Skardelly, Marco, E-mail: Marco.Skardelly@med.uni-tuebingen.de [Department of Neurosurgery, University Hospital, Leipzig (Germany); Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig (Germany); Glien, Anja; Groba, Claudia; Schlichting, Nadine [Department of Neurosurgery, University Hospital, Leipzig (Germany); Kamprad, Manja [Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Leipzig (Germany); Meixensberger, Juergen [Department of Neurosurgery, University Hospital, Leipzig (Germany); Milosevic, Javorina [Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig (Germany)

    2013-12-10

    In allogenic and xenogenic transplantation, adequate immunosuppression plays a major role in graft survival, especially over the long term. The effect of immunosuppressive drugs on neural stem/progenitor cell fate has not been sufficiently explored. The focus of this study is to systematically investigate the effects of the following four different immunotherapeutic strategies on human neural progenitor cell survival/death, proliferation, metabolic activity, differentiation and migration in vitro: (1) cyclosporine A (CsA), a calcineurin inhibitor; (2) everolimus (RAD001), an mTOR-inhibitor; (3) mycophenolic acid (MPA, mycophenolate), an inhibitor of inosine monophosphate dehydrogenase and (4) prednisolone, a steroid. At the minimum effective concentration (MEC), we found a prominent decrease in hNPCs' proliferative capacity (BrdU incorporation), especially for CsA and MPA, and an alteration of the NAD(P)H-dependent metabolic activity. Cell death rate, neurogenesis, gliogenesis and cell migration remained mostly unaffected under these conditions for all four immunosuppressants, except for apoptotic cell death, which was significantly increased by MPA treatment. - Highlights: • Four immunosuppresants (ISs) were tested in human neural progenitor cells in vitro. • Cyclosporine A and mycophenolic acid showed a prominent anti-proliferative activity • Mycophenolic acid exhibited a significant pro-apoptotic effect. • NAD(P)H-dependent metabolic activity was occasionally induced by ISs. • Neuronal differentiation and migration potential remained unaffected by ISs treatment.

  15. Reconstructing the regulatory circuit of cell fate determination in yeast mating response.

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    Shao, Bin; Yuan, Haiyu; Zhang, Rongfei; Wang, Xuan; Zhang, Shuwen; Ouyang, Qi; Hao, Nan; Luo, Chunxiong

    2017-07-01

    Massive technological advances enabled high-throughput measurements of proteomic changes in biological processes. However, retrieving biological insights from large-scale protein dynamics data remains a challenging task. Here we used the mating differentiation in yeast Saccharomyces cerevisiae as a model and developed integrated experimental and computational approaches to analyze the proteomic dynamics during the process of cell fate determination. When exposed to a high dose of mating pheromone, the yeast cell undergoes growth arrest and forms a shmoo-like morphology; however, at intermediate doses, chemotropic elongated growth is initialized. To understand the gene regulatory networks that control this differentiation switch, we employed a high-throughput microfluidic imaging system that allows real-time and simultaneous measurements of cell growth and protein expression. Using kinetic modeling of protein dynamics, we classified the stimulus-dependent changes in protein abundance into two sources: global changes due to physiological alterations and gene-specific changes. A quantitative framework was proposed to decouple gene-specific regulatory modes from the growth-dependent global modulation of protein abundance. Based on the temporal patterns of gene-specific regulation, we established the network architectures underlying distinct cell fates using a reverse engineering method and uncovered the dose-dependent rewiring of gene regulatory network during mating differentiation. Furthermore, our results suggested a potential crosstalk between the pheromone response pathway and the target of rapamycin (TOR)-regulated ribosomal biogenesis pathway, which might underlie a cell differentiation switch in yeast mating response. In summary, our modeling approach addresses the distinct impacts of the global and gene-specific regulation on the control of protein dynamics and provides new insights into the mechanisms of cell fate determination. We anticipate that our

  16. Role of Geminin in cell fate determination of hematopoietic stem cells (HSCs).

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    Yasunaga, Shin'ichiro; Ohno, Yoshinori; Shirasu, Naoto; Zhang, Bo; Suzuki-Takedachi, Kyoko; Ohtsubo, Motoaki; Takihara, Yoshihiro

    2016-09-01

    Geminin exerts two distinct molecular roles. Geminin negatively regulates DNA replication licensing through the direct interaction with Cdt1 to prevent re-replication in proliferating cells. Geminin also regulates chromatin remodeling through the direct interaction with Brahma/Brg1 to maintain undifferentiated states of stem cells. We previously uncovered that Polycomb-group complex 1 and Hoxb4/Hoxa9, well-known intrinsic factors that are essential for maintaining the hematopoietic stem cell (HSC) activity, alternatively act as ubiquitin-proteasome systems for Geminin protein to reduce the protein expression level, and sustain the HSC activity. Thus, Geminin is presumed to play an important role in determining cell fate, i.e., turning on and off cellular quiescence and proliferation/differentiation, in HSCs. We recently generated recombinant cell-penetrating Geminin (CP-Geminin), enabling rapid incorporation and withdraw of Geminin protein in cells. CP-Geminin may be useful in regulating the cell cycle and chromatin configuration. In this article, we summarize current information on the molecular functions of Geminin and the regulatory system for Geminin protein expression, and argue for the molecular role of Geminin in cell fate determination of HSCs, and future perspective of a new technology for manipulating the activities of HSCs and cancer stem cells (CSCs).

  17. Stem Cell Fate Determination during Development and Regeneration of Ectodermal Organs

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    Jiménez-Rojo, Lucía; Granchi, Zoraide; Graf, Daniel; Mitsiadis, Thimios A.

    2012-01-01

    The development of ectoderm-derived appendages results in a large variety of highly specialized organs such as hair follicles, mammary glands, salivary glands, and teeth. Despite varying in number, shape, and function, all these ectodermal organs develop through continuous and reciprocal epithelial–mesenchymal interactions, sharing common morphological and molecular features especially during their embryonic development. Diseases such as ectodermal dysplasias can affect simultaneously these organs, suggesting that they may arise from common multipotent precursors residing in the embryonic ectoderm. During embryogenesis, these putative ectodermal stem cells may adopt different fates and consequently be able to generate a variety of tissue-specific stem cells, which are the sources for the various cell lineages that form the diverse organs. The specification of those common epithelial precursors, as well as their further lineage commitment to tissue-specific stem cells, might be controlled by specific signals. It has been well documented that Notch, Wnt, bone morphogenetic protein, and fibroblast growth factor signaling pathways regulate cell fate decisions during the various stages of ectodermal organ development. However, the in vivo spatial and temporal dynamics of these signaling pathways are not yet well understood. Improving the current knowledge on the mechanisms involved in stem cell fate determination during organogenesis and homeostasis of ectodermal organs is crucial to develop effective stem cell-based therapies in order to regenerate or replace pathological and damaged tissues. PMID:22539926

  18. Selected microRNAs define cell fate determination of murine central memory CD8 T cells.

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    Gonzalo Almanza

    2010-06-01

    Full Text Available During an immune response T cells enter memory fate determination, a program that divides them into two main populations: effector memory and central memory T cells. Since in many systems protection appears to be preferentially mediated by T cells of the central memory it is important to understand when and how fate determination takes place. To date, cell intrinsic molecular events that determine their differentiation remains unclear. MicroRNAs are a class of small, evolutionarily conserved RNA molecules that negatively regulate gene expression, causing translational repression and/or messenger RNA degradation. Here, using an in vitro system where activated CD8 T cells driven by IL-2 or IL-15 become either effector memory or central memory cells, we assessed the role of microRNAs in memory T cell fate determination. We found that fate determination to central memory T cells is under the balancing effects of a discrete number of microRNAs including miR-150, miR-155 and the let-7 family. Based on miR-150 a new target, KChIP.1 (K (+ channel interacting protein 1, was uncovered, which is specifically upregulated in developing central memory CD8 T cells. Our studies indicate that cell fate determination such as surface phenotype and self-renewal may be decided at the pre-effector stage on the basis of the balancing effects of a discrete number of microRNAs. These results may have implications for the development of T cell vaccines and T cell-based adoptive therapies.

  19. Cell fate in the Arabidopsis root meristem determined by directional signalling.

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    van den Berg, C; Willemsen, V; Hage, W; Weisbeek, P; Scheres, B

    1995-11-02

    Postembryonic development in plants is achieved by apical meristems. Surgical studies and clonal analysis have revealed indirectly that cells in shoot meristems have no predictable destiny and that position is likely to play a role in the acquisition of cell identity. In contrast to animal systems, there has been no direct evidence for inductive signalling in plants until now. Here we present evidence for such signalling using laser ablation of cells in the root meristem of Arabidopsis thaliana. Although these cells show rigid clonal relationships, we now demonstrate that it is positional control that is most important in the determination of cell fate. Positional signals can be perpetuated from more mature to initial cells to guide the pattern of meristem cell differentiation. This offers an alternative to the general opinion that meristems are the source of patterning information.

  20. Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells

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    Dontu, Gabriela; Jackson, Kyle W; McNicholas, Erin; Kawamura, Mari J; Abdallah, Wissam M; Wicha, Max S

    2004-01-01

    Notch signaling has been implicated in the regulation of cell-fate decisions such as self-renewal of adult stem cells and differentiation of progenitor cells along a particular lineage. Moreover, depending on the cellular and developmental context, the Notch pathway acts as a regulator of cell survival and cell proliferation. Abnormal expression of Notch receptors has been found in different types of epithelial metaplastic lesions and neoplastic lesions, suggesting that Notch may act as a proto-oncogene. The vertebrate Notch1 and Notch4 homologs are involved in normal development of the mammary gland, and mutated forms of these genes are associated with development of mouse mammary tumors. In order to determine the role of Notch signaling in mammary cell-fate determination, we have utilized a newly described in vitro system in which mammary stem/progenitor cells can be cultured in suspension as nonadherent 'mammospheres'. Notch signaling was activated using exogenous ligands, or was inhibited using previously characterized Notch signaling antagonists. Utilizing this system, we demonstrate that Notch signaling can act on mammary stem cells to promote self-renewal and on early progenitor cells to promote their proliferation, as demonstrated by a 10-fold increase in secondary mammosphere formation upon addition of a Notch-activating DSL peptide. In addition to acting on stem cells, Notch signaling is also able to act on multipotent progenitor cells, facilitating myoepithelial lineage-specific commitment and proliferation. Stimulation of this pathway also promotes branching morphogenesis in three-dimensional Matrigel cultures. These effects are completely inhibited by a Notch4 blocking antibody or a gamma secretase inhibitor that blocks Notch processing. In contrast to the effects of Notch signaling on mammary stem/progenitor cells, modulation of this pathway has no discernable effect on fully committed, differentiated, mammary epithelial cells. These studies

  1. High glucose alters the expression of genes involved in proliferation and cell-fate specification of embryonic neural stem cells.

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    Fu, J; Tay, S S W; Ling, E A; Dheen, S T

    2006-05-01

    Maternal diabetes induces neural tube defects during embryogenesis. Since the neural tube is derived from neural stem cells (NSCs), it is hypothesised that in diabetic pregnancy neural tube defects result from altered expression of developmental control genes, leading to abnormal proliferation and cell-fate choice of NSCs. Cell viability, proliferation index and apoptosis of NSCs and differentiated cells from mice exposed to physiological or high glucose concentration medium were examined by a tetrazolium salt assay, 5-bromo-2'-deoxyuridine incorporation, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling and immunocytochemistry. Expression of developmental genes, including sonic hedgehog (Shh), bone morphogenetic protein 4 (Bmp4), neurogenin 1/2 (Neurog1/2), achaete-scute complex-like 1 (Ascl1), oligodendrocyte transcription factor 1 (Olig1), oligodendrocyte lineage transcription factor 2 (Olig2), hairy and enhancer of split 1/5 (Hes1/5) and delta-like 1 (Dll1), was analysed by real-time RT-PCR. Proliferation index and neuronal specification in the forebrain of embryos at embryonic day 11.5 were examined histologically. High glucose decreased the proliferation of NSCs and differentiated cells. The incidence of apoptosis was increased in NSCs treated with high glucose, but not in the differentiated cells. High glucose also accelerated neuronal and glial differentiation from NSCs. The decreased proliferation index and early differentiation of neurons were evident in the telencephalon of embryos derived from diabetic mice. Exposure to high glucose altered the mRNA expression levels of Shh, Bmp4, Neurog1/2, Ascl1, Hes1, Dll1 and Olig1 in NSCs and Shh, Dll1, Neurog1/2 and Hes5 in differentiated cells. The changes in proliferation and differentiation of NSCs exposed to high glucose are associated with altered expression of genes that are involved in cell-cycle progression and cell-fate specification during neurulation. These changes may form the

  2. Structural and biochemical characterization of the cell fate determining nucleotidyltransferase fold protein MAB21L1.

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    de Oliveira Mann, Carina C; Kiefersauer, Reiner; Witte, Gregor; Hopfner, Karl-Peter

    2016-06-08

    The exceptionally conserved metazoan MAB21 proteins are implicated in cell fate decisions and share considerable sequence homology with the cyclic GMP-AMP synthase. cGAS is the major innate immune sensor for cytosolic DNA and produces the second messenger 2'-5', 3'-5' cyclic GMP-AMP. Little is known about the structure and biochemical function of other proteins of the cGAS-MAB21 subfamily, such as MAB21L1, MAB21L2 and MAB21L3. We have determined the crystal structure of human full-length MAB21L1. Our analysis reveals high structural conservation between MAB21L1 and cGAS but also uncovers important differences. Although monomeric in solution, MAB21L1 forms a highly symmetric double-pentameric oligomer in the crystal, raising the possibility that oligomerization could be a feature of MAB21L1. In the crystal, MAB21L1 is in an inactive conformation requiring a conformational change - similar to cGAS - to develop any nucleotidyltransferase activity. Co-crystallization with NTP identified a putative ligand binding site of MAB21 proteins that corresponds to the DNA binding site of cGAS. Finally, we offer a structure-based explanation for the effects of MAB21L2 mutations in patients with eye malformations. The underlying residues participate in fold-stabilizing interaction networks and mutations destabilize the protein. In summary, we provide a first structural framework for MAB21 proteins.

  3. CHD1 regulates cell fate determination by activation of differentiation-induced genes.

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    Baumgart, Simon J; Najafova, Zeynab; Hossan, Tareq; Xie, Wanhua; Nagarajan, Sankari; Kari, Vijayalakshmi; Ditzel, Nicholas; Kassem, Moustapha; Johnsen, Steven A

    2017-07-27

    The coordinated temporal and spatial activation of gene expression is essential for proper stem cell differentiation. The Chromodomain Helicase DNA-binding protein 1 (CHD1) is a chromatin remodeler closely associated with transcription and nucleosome turnover downstream of the transcriptional start site (TSS). In this study, we show that CHD1 is required for the induction of osteoblast-specific gene expression, extracellular-matrix mineralization and ectopic bone formation in vivo. Genome-wide occupancy analyses revealed increased CHD1 occupancy around the TSS of differentiation-activated genes. Furthermore, we observed that CHD1-dependent genes are mainly induced during osteoblast differentiation and are characterized by higher levels of CHD1 occupancy around the TSS. Interestingly, CHD1 depletion resulted in increased pausing of RNA Polymerase II (RNAPII) and decreased H2A.Z occupancy close to the TSS, but not at enhancer regions. These findings reveal a novel role for CHD1 during osteoblast differentiation and provide further insights into the intricacies of epigenetic regulatory mechanisms controlling cell fate determination. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. Prolonged Mitosis of Neural Progenitors Alters Cell Fate in the Developing Brain.

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    Pilaz, Louis-Jan; McMahon, John J; Miller, Emily E; Lennox, Ashley L; Suzuki, Aussie; Salmon, Edward; Silver, Debra L

    2016-01-06

    Embryonic neocortical development depends on balanced production of progenitors and neurons. Genetic mutations disrupting progenitor mitosis frequently impair neurogenesis; however, the link between altered mitosis and cell fate remains poorly understood. Here we demonstrate that prolonged mitosis of radial glial progenitors directly alters neuronal fate specification and progeny viability. Live imaging of progenitors from a neurogenesis mutant, Magoh(+/-), reveals that mitotic delay significantly correlates with preferential production of neurons instead of progenitors, as well as apoptotic progeny. Independently, two pharmacological approaches reveal a causal relationship between mitotic delay and progeny fate. As mitotic duration increases, progenitors produce substantially more apoptotic progeny or neurons. We show that apoptosis, but not differentiation, is p53 dependent, demonstrating that these are distinct outcomes of mitotic delay. Together our findings reveal that prolonged mitosis is sufficient to alter fates of radial glia progeny and define a new paradigm to understand how mitosis perturbations underlie brain size disorders such as microcephaly. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Differential PKA activation and AKAP association determines cell fate in cancer cells

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    2013-01-01

    cytoplasmic pathways dependent upon the same enzymatic activity with opposite effects on cell fate in terms of life and death. Understanding the specific mechanistic functions of IGF1R with respect to determining the PKA survival functions would have potential for impact upon the development of new therapeutic strategies by exploiting the IGF1R/cAMP-PKA survival signaling in cancer. PMID:24083380

  6. Genomic DISC1 Disruption in hiPSCs Alters Wnt Signaling and Neural Cell Fate

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    Priya Srikanth

    2015-09-01

    Full Text Available Genetic and clinical association studies have identified disrupted in schizophrenia 1 (DISC1 as a candidate risk gene for major mental illness. DISC1 is interrupted by a balanced chr(1;11 translocation in a Scottish family in which the translocation predisposes to psychiatric disorders. We investigate the consequences of DISC1 interruption in human neural cells using TALENs or CRISPR-Cas9 to target the DISC1 locus. We show that disruption of DISC1 near the site of the translocation results in decreased DISC1 protein levels because of nonsense-mediated decay of long splice variants. This results in an increased level of canonical Wnt signaling in neural progenitor cells and altered expression of fate markers such as Foxg1 and Tbr2. These gene expression changes are rescued by antagonizing Wnt signaling in a critical developmental window, supporting the hypothesis that DISC1-dependent suppression of basal Wnt signaling influences the distribution of cell types generated during cortical development.

  7. Piezo type mechanosensitive ion channel component 1 functions as a regulator of the cell fate determination of mesenchymal stem cells.

    Science.gov (United States)

    Sugimoto, Asuna; Miyazaki, Aya; Kawarabayashi, Keita; Shono, Masayuki; Akazawa, Yuki; Hasegawa, Tomokazu; Ueda-Yamaguchi, Kimiko; Kitamura, Takamasa; Yoshizaki, Keigo; Fukumoto, Satoshi; Iwamoto, Tsutomu

    2017-12-18

    The extracellular environment regulates the dynamic behaviors of cells. However, the effects of hydrostatic pressure (HP) on cell fate determination of mesenchymal stem cells (MSCs) are not clearly understood. Here, we established a cell culture chamber to control HP. Using this system, we found that the promotion of osteogenic differentiation by HP is depend on bone morphogenetic protein 2 (BMP2) expression regulated by Piezo type mechanosensitive ion channel component 1 (PIEZO1) in MSCs. The PIEZO1 was expressed and induced after HP loading in primary MSCs and MSC lines, UE7T-13 and SDP11. HP and Yoda1, an activator of PIEZO1, promoted BMP2 expression and osteoblast differentiation, whereas inhibits adipocyte differentiation. Conversely, PIEZO1 inhibition reduced osteoblast differentiation and BMP2 expression. Furthermore, Blocking of BMP2 function by noggin inhibits HP induced osteogenic maker genes expression. In addition, in an in vivo model of medaka with HP loading, HP promoted caudal fin ray development whereas inhibition of piezo1 using GsMTx4 suppressed its development. Thus, our results suggested that PIEZO1 is responsible for HP and could functions as a factor for cell fate determination of MSCs by regulating BMP2 expression.

  8. Mitogen-activated protein kinase (MAPK) dynamics determine cell fate in the yeast mating response.

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    Li, Yang; Roberts, Julie; AkhavanAghdam, Zohreh; Hao, Nan

    2017-12-15

    In the yeast Saccharomyces cerevisiae , the exposure to mating pheromone activates a prototypic mitogen-activated protein kinase (MAPK) cascade and triggers a dose-dependent differentiation response. Whereas a high pheromone dose induces growth arrest and formation of a shmoo-like morphology in yeast cells, lower pheromone doses elicit elongated cell growth. Previous population-level analysis has revealed that the MAPK Fus3 plays an important role in mediating this differentiation switch. To further investigate how Fus3 controls the fate decision process at the single-cell level, we developed a specific translocation-based reporter for monitoring Fus3 activity in individual live cells. Using this reporter, we observed strikingly different dynamic patterns of Fus3 activation in single cells differentiated into distinct fates. Cells committed to growth arrest and shmoo formation exhibited sustained Fus3 activation. In contrast, most cells undergoing elongated growth showed either a delayed gradual increase or pulsatile dynamics of Fus3 activity. Furthermore, we found that chemically perturbing Fus3 dynamics with a specific inhibitor could effectively redirect the mating differentiation, confirming the causative role of Fus3 dynamics in driving cell fate decisions. MAPKs mediate proliferation and differentiation signals in mammals and are therapeutic targets in many cancers. Our results highlight the importance of MAPK dynamics in regulating single-cell responses and open up the possibility that MAPK signaling dynamics could be a pharmacological target in therapeutic interventions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Ascorbic acid alters cell fate commitment of human neural progenitors in a WNT/β-catenin/ROS signaling dependent manner.

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    Rharass, Tareck; Lantow, Margareta; Gbankoto, Adam; Weiss, Dieter G; Panáková, Daniela; Lucas, Stéphanie

    2017-10-16

    Improving the neuronal yield from in vitro cultivated neural progenitor cells (NPCs) is an essential challenge in transplantation therapy in neurological disorders. In this regard, Ascorbic acid (AA) is widely used to expand neurogenesis from NPCs in cultures although the mechanisms of its action remain unclear. Neurogenesis from NPCs is regulated by the redox-sensitive WNT/β-catenin signaling pathway. We therefore aimed to investigate how AA interacts with this pathway and potentiates neurogenesis. Effects of 200 μM AA were compared with the pro-neurogenic reagent and WNT/β-catenin signaling agonist lithium chloride (LiCl), and molecules with antioxidant activities i.e. N-acetyl-L-cysteine (NAC) and ruthenium red (RuR), in differentiating neural progenitor ReNcell VM cells. Cells were supplemented with reagents for two periods of treatment: a full period encompassing the whole differentiation process versus an early short period that is restricted to the cell fate commitment stage. Intracellular redox balance and reactive oxygen species (ROS) metabolism were examined by flow cytometry using redox and ROS sensors. Confocal microscopy was performed to assess cell viability, neuronal yield, and levels of two proteins: Nucleoredoxin (NXN) and the WNT/β-catenin signaling component Dishevelled 2 (DVL2). TUBB3 and MYC gene responses were evaluated by quantitative real-time PCR. DVL2-NXN complex dissociation was measured by fluorescence resonance energy transfer (FRET). In contrast to NAC which predictably exhibited an antioxidant effect, AA treatment enhanced ROS metabolism with no cytotoxic induction. Both drugs altered ROS levels only at the early stage of the differentiation as no changes were held beyond the neuronal fate commitment stage. FRET studies showed that AA treatment accelerated the redox-dependent release of the initial pool of DVL2 from its sequestration by NXN, while RuR treatment hampered the dissociation of the two proteins. Accordingly, AA

  10. A specific box switches the cell fate determining activity of XOTX2 and XOTX5b in the Xenopus retina

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    He Rong-Qiao

    2007-06-01

    Full Text Available Abstract Background Otx genes, orthologues of the Drosophila orthodenticle gene (otd, play crucial roles in vertebrate brain development. In the Xenopus eye, Xotx2 and Xotx5b promote bipolar and photoreceptor cell fates, respectively. The molecular basis of their differential action is not completely understood, though the carboxyl termini of the two proteins seem to be crucial. To define the molecular domains that make the action of these proteins so different, and to determine whether their retinal abilities are shared by Drosophila OTD, we performed an in vivo molecular dissection of their activity by transfecting retinal progenitors with several wild-type, deletion and chimeric constructs of Xotx2, Xotx5b and otd. Results We identified a small 8–10 amino acid divergent region, directly downstream of the homeodomain, that is crucial for the respective activities of XOTX2 and XOTX5b. In lipofection experiments, the exchange of this 'specificity box' completely switches the retinal activity of XOTX5b into that of XOTX2 and vice versa. Moreover, the insertion of this box into Drosophila OTD, which has no effect on retinal cell fate, endows it with the specific activity of either XOTX protein. Significantly, in cell transfection experiments, the diverse ability of XOTX2 and XOTX5b to synergize with NRL, a cofactor essential for vertebrate rod development, to transactivate the rhodopsin promoter is also switched depending on the box. We also show by GST-pull down that XOTX2 and XOTX5b differentially interact with NRL, though this property is not strictly dependent on the box. Conclusion Our data provide molecular evidence on how closely related homeodomain gene products can differentiate their functions to regulate distinct cell fates. A small 'specificity box' is both necessary and sufficient to confer on XOTX2 and XOTX5b their distinct activities in the developing frog retina and to convert the neutral orthologous OTD protein of Drosophila

  11. Termination factor Rho: From the control of pervasive transcription to cell fate determination in Bacillus subtilis

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    Nicolas, Pierre; Repoila, Francis; Bardowski, Jacek; Aymerich, Stéphane

    2017-01-01

    In eukaryotes, RNA species originating from pervasive transcription are regulators of various cellular processes, from the expression of individual genes to the control of cellular development and oncogenesis. In prokaryotes, the function of pervasive transcription and its output on cell physiology is still unknown. Most bacteria possess termination factor Rho, which represses pervasive, mostly antisense, transcription. Here, we investigate the biological significance of Rho-controlled transcription in the Gram-positive model bacterium Bacillus subtilis. Rho inactivation strongly affected gene expression in B. subtilis, as assessed by transcriptome and proteome analysis of a rho–null mutant during exponential growth in rich medium. Subsequent physiological analyses demonstrated that a considerable part of Rho-controlled transcription is connected to balanced regulation of three mutually exclusive differentiation programs: cell motility, biofilm formation, and sporulation. In the absence of Rho, several up-regulated sense and antisense transcripts affect key structural and regulatory elements of these differentiation programs, thereby suppressing motility and biofilm formation and stimulating sporulation. We dissected how Rho is involved in the activity of the cell fate decision-making network, centered on the master regulator Spo0A. We also revealed a novel regulatory mechanism of Spo0A activation through Rho-dependent intragenic transcription termination of the protein kinase kinB gene. Altogether, our findings indicate that distinct Rho-controlled transcripts are functional and constitute a previously unknown built-in module for the control of cell differentiation in B. subtilis. In a broader context, our results highlight the recruitment of the termination factor Rho, for which the conserved biological role is probably to repress pervasive transcription, in highly integrated, bacterium-specific, regulatory networks. PMID:28723971

  12. Cell fate after mitotic arrest in different tumor cells is determined by the balance between slippage and apoptotic threshold

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    Galán-Malo, Patricia; Vela, Laura; Gonzalo, Oscar; Calvo-Sanjuán, Rubén; Gracia-Fleta, Lucía; Naval, Javier; Marzo, Isabel, E-mail: imarzo@unizar.es

    2012-02-01

    Microtubule poisons and other anti-mitotic drugs induce tumor death but the molecular events linking mitotic arrest to cell death are still not fully understood. We have analyzed cell fate after mitotic arrest produced by the microtubule-destabilizing drug vincristine in a panel of human tumor cell lines showing different response to vincristine. In Jurkat, RPMI 8226 and HeLa cells, apoptosis was triggered shortly after vincristine-induced mitotic arrest. However, A549 cells, which express a great amount of Bcl-x{sub L} and undetectable amounts of Bak, underwent mitotic slippage prior to cell death. However, when Bcl-x{sub L} gene was silenced in A549 cells, vincristine induced apoptosis during mitotic arrest. Another different behavior was found in MiaPaca2 cells, where vincristine caused death by mitotic catastrophe that switched to apoptosis when cyclin B1 degradation was prevented by proteasome inhibition. Overexpression of Bcl-x{sub L} or silencing Bax and Bak expression delayed the onset of apoptosis in Jurkat and RPMI 8226 cells, enabling mitotic slippage and endoreduplication. In HeLa cells, overexpression of Bcl-x{sub L} switched cell death from apoptosis to mitotic catastrophe. Mcl-1 offered limited protection to vincristine-induced cell death and Mcl-1 degradation was not essential for vincristine-induced death. All these results, taken together, indicate that the Bcl-x{sub L}/Bak ratio and the ability to degrade cyclin B1 determine cell fate after mitotic arrest in the different tumor cell types. Highlights: ► Vincristine induces cell death by apoptosis or mitotic catastrophe. ► Apoptosis-proficient cells die by apoptosis during mitosis upon vincristine treatment. ► p53wt apoptosis-deficient cells undergo apoptosis from a G1-like tetraploid state. ► p53mt apoptosis-deficient cells can survive and divide giving rise to 8N cells.

  13. The mir-279/996 cluster represses receptor tyrosine kinase signaling to determine cell fates in the Drosophila eye.

    Science.gov (United States)

    Duan, Hong; de Navas, Luis F; Hu, Fuqu; Sun, Kailiang; Mavromatakis, Yannis E; Viets, Kayla; Zhou, Cyrus; Kavaler, Joshua; Johnston, Robert J; Tomlinson, Andrew; Lai, Eric C

    2018-04-09

    Photoreceptors in the crystalline Drosophila eye are recruited by receptor tyrosine kinase (RTK)/Ras signaling mediated by Epidermal growth factor receptor (EGFR) and the Sevenless (Sev) receptor. Analyses of an allelic deletion series of the mir-279/996 locus, along with a panel of modified genomic rescue transgenes, show that Drosophila eye patterning depends on both miRNAs. Transcriptional reporter and activity sensor transgenes reveal expression and function of miR-279/996 in non-neural cells of the developing eye. Moreover, mir-279/996 mutants exhibit substantial numbers of ectopic photoreceptors, particularly of R7, and cone cell loss. These miRNAs restrict RTK signaling in the eye, since mir-279/996 nulls are dominantly suppressed by positive components of the EGFR pathway and enhanced by heterozygosity for an EGFR repressor. miR-279/996 limit photoreceptor recruitment by targeting multiple positive RTK/Ras signaling components that promote photoreceptor/R7 specification. Strikingly, deletion of mir-279/996 sufficiently derepresses RTK/Ras signaling so as to rescue a population of R7 cells in R7-specific RTK null mutants boss and sev , which otherwise completely lack this cell fate. Altogether, we reveal a rare setting of developmental cell specification that involves substantial miRNA control. © 2018. Published by The Company of Biologists Ltd.

  14. Modeling reveals bistability and low-pass filtering in the network module determining blood stem cell fate.

    Directory of Open Access Journals (Sweden)

    Jatin Narula

    2010-05-01

    Full Text Available Combinatorial regulation of gene expression is ubiquitous in eukaryotes with multiple inputs converging on regulatory control elements. The dynamic properties of these elements determine the functionality of genetic networks regulating differentiation and development. Here we propose a method to quantitatively characterize the regulatory output of distant enhancers with a biophysical approach that recursively determines free energies of protein-protein and protein-DNA interactions from experimental analysis of transcriptional reporter libraries. We apply this method to model the Scl-Gata2-Fli1 triad-a network module important for cell fate specification of hematopoietic stem cells. We show that this triad module is inherently bistable with irreversible transitions in response to physiologically relevant signals such as Notch, Bmp4 and Gata1 and we use the model to predict the sensitivity of the network to mutations. We also show that the triad acts as a low-pass filter by switching between steady states only in response to signals that persist for longer than a minimum duration threshold. We have found that the auto-regulation loops connecting the slow-degrading Scl to Gata2 and Fli1 are crucial for this low-pass filtering property. Taken together our analysis not only reveals new insights into hematopoietic stem cell regulatory network functionality but also provides a novel and widely applicable strategy to incorporate experimental measurements into dynamical network models.

  15. GSK3 as a Sensor Determining Cell Fate in the Brain.

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    Cole, Adam R

    2012-01-01

    Glycogen synthase kinase 3 (GSK3) is an unusual serine/threonine kinase that controls many neuronal functions, including neurite outgrowth, synapse formation, neurotransmission, and neurogenesis. It mediates these functions by phosphorylating a wide range of substrates involved in gene transcription, metabolism, apoptosis, cytoskeletal dynamics, signal transduction, lipid membrane dynamics, and trafficking, amongst others. This complicated list of diverse substrates generally follow a more simple pattern: substrates negatively regulated by GSK3-mediated phosphorylation favor a proliferative/survival state, while substrates positively regulated by GSK3 favor a more differentiated/functional state. Accordingly, GSK3 activity is higher in differentiated cells than undifferentiated cells and physiological (Wnt, growth factors) and pharmacological inhibitors of GSK3 promote the proliferative capacity of embryonic stem cells. In the brain, the level of GSK3 activity influences neural progenitor cell proliferation/differentiation in neuroplasticity and repair, as well as efficient neurotransmission in differentiated adult neurons. While defects in GSK3 activity are unlikely to be the primary cause of neurodegenerative diseases, therapeutic regulation of its activity to promote a proliferative/survival versus differentiated/mature functional environment in the brain could be a powerful strategy for treatment of neurodegenerative and other mental disorders.

  16. GSK3 as a sensor determining cell fate in the brain

    Directory of Open Access Journals (Sweden)

    Adam R Cole

    2012-02-01

    Full Text Available Glycogen synthase kinase 3 (GSK3 is an unusual serine/threonine kinase that controls many neuronal functions, including neurite outgrowth, synapse formation, neurotransmission and neurogenesis. It mediates these functions by phosphorylating a wide range of substrates involved in gene transcription, metabolism, apoptosis, cytoskeletal dynamics, signal transduction, lipid membrane dynamics and trafficking, amongst others. This complicated list of diverse substrates generally follow a more simple pattern: substrates negatively regulated by GSK3-mediated phosphorylation favour a proliferative/survival state, while substrates positively regulated by GSK3 favour a more differentiated/functional state. Accordingly, GSK3 activity is higher in differentiated cells than undifferentiated cells and physiological (Wnt, growth factors and pharmacological inhibitors of GSK3 promote the proliferative capacity of embryonic stem cells. In the brain, the level of GSK3 activity influences neural progenitor cell proliferation/differentiation in neuroplasticity and repair, as well as efficient neurotransmission in differentiated adult neurons. While defects in GSK3 activity are unlikely to be the primary cause of neurodegenerative diseases, therapeutic regulation of its activity to promote a proliferative/survival versus differentiated/mature functional environment in the brain could be a powerful strategy for treatment of neurodegenerative and other mental disorders.

  17. The role of cell cycle in retinal development: cyclin-dependent kinase inhibitors co-ordinate cell-cycle inhibition, cell-fate determination and differentiation in the developing retina.

    Science.gov (United States)

    Bilitou, Aikaterini; Ohnuma, Shin-ichi

    2010-03-01

    The mature retina is formed through multi-step developmental processes, including eye field specification, optic vesicle evagination, and cell-fate determination. Co-ordination of these developmental events with cell-proliferative activity is essential to achieve formation of proper retinal structure and function. In particular, the molecular and cellular dynamics of the final cell cycle significantly influence the identity that a cell acquires, since cell fate is largely determined at the final cell cycle for the production of postmitotic cells. This review summarizes our current understanding of the cellular mechanisms that underlie the co-ordination of cell-cycle and cell-fate determination, and also describes a molecular role of cyclin-dependent kinase inhibitors (CDKIs) as co-ordinators of cell-cycle arrest, cell-fate determination and differentiation. Copyright (c) 2010 Wiley-Liss, Inc.

  18. Morphogen and community effects determine cell fates in response to BMP4 signaling in human embryonic stem cells.

    Science.gov (United States)

    Nemashkalo, Anastasiia; Ruzo, Albert; Heemskerk, Idse; Warmflash, Aryeh

    2017-09-01

    Paracrine signals maintain developmental states and create cell fate patterns in vivo and influence differentiation outcomes in human embryonic stem cells (hESCs) in vitro Systematic investigation of morphogen signaling is hampered by the difficulty of disentangling endogenous signaling from experimentally applied ligands. Here, we grow hESCs in micropatterned colonies of 1-8 cells ('µColonies') to quantitatively investigate paracrine signaling and the response to external stimuli. We examine BMP4-mediated differentiation in µColonies and standard culture conditions and find that in µColonies, above a threshold concentration, BMP4 gives rise to only a single cell fate, contrary to its role as a morphogen in other developmental systems. Under standard culture conditions BMP4 acts as a morphogen but this requires secondary signals and particular cell densities. We find that a 'community effect' enforces a common fate within µColonies, both in the state of pluripotency and when cells are differentiated, and that this effect allows a more precise response to external signals. Using live cell imaging to correlate signaling histories with cell fates, we demonstrate that interactions between neighbors result in sustained, homogenous signaling necessary for differentiation. © 2017. Published by The Company of Biologists Ltd.

  19. Spatio-temporal Model of Endogenous ROS and Raft-Dependent WNT/Beta-Catenin Signaling Driving Cell Fate Commitment in Human Neural Progenitor Cells

    Science.gov (United States)

    Haack, Fiete; Lemcke, Heiko; Ewald, Roland; Rharass, Tareck; Uhrmacher, Adelinde M.

    2015-01-01

    Canonical WNT/β-catenin signaling is a central pathway in embryonic development, but it is also connected to a number of cancers and developmental disorders. Here we apply a combined in-vitro and in-silico approach to investigate the spatio-temporal regulation of WNT/β-catenin signaling during the early neural differentiation process of human neural progenitors cells (hNPCs), which form a new prospect for replacement therapies in the context of neurodegenerative diseases. Experimental measurements indicate a second signal mechanism, in addition to canonical WNT signaling, being involved in the regulation of nuclear β-catenin levels during the cell fate commitment phase of neural differentiation. We find that the biphasic activation of β-catenin signaling observed experimentally can only be explained through a model that combines Reactive Oxygen Species (ROS) and raft dependent WNT/β-catenin signaling. Accordingly after initiation of differentiation endogenous ROS activates DVL in a redox-dependent manner leading to a transient activation of down-stream β-catenin signaling, followed by continuous auto/paracrine WNT signaling, which crucially depends on lipid rafts. Our simulation studies further illustrate the elaborate spatio-temporal regulation of DVL, which, depending on its concentration and localization, may either act as direct inducer of the transient ROS/β-catenin signal or as amplifier during continuous auto-/parcrine WNT/β-catenin signaling. In addition we provide the first stochastic computational model of WNT/β-catenin signaling that combines membrane-related and intracellular processes, including lipid rafts/receptor dynamics as well as WNT- and ROS-dependent β-catenin activation. The model’s predictive ability is demonstrated under a wide range of varying conditions for in-vitro and in-silico reference data sets. Our in-silico approach is realized in a multi-level rule-based language, that facilitates the extension and modification of the

  20. Neural cell fate in rca1 and cycA mutants: the roles of intrinsic and extrinsic factors in asymmetric division in the Drosophila central nervous system.

    Science.gov (United States)

    Lear, B C; Skeath, J B; Patel, N H

    1999-11-01

    In the central nervous system (CNS) of Drosophila embryos lacking regulator of cyclin A (rca1) or cyclin A, we observe that several ganglion mother cells (GMCs) fail to divide. Whereas GMCs normally produce two sibling neurons that acquire different fates ('A/B'), non-dividing GMCs differentiate exclusively in the manner of one of their progeny ('B'). In zygotic numb mutants, sibling neuron fate alterations ('A/B' to 'A/A') occur infrequently or do not occur in some sibling pairs; we have determined that depletion of both maternal and zygotic numb causes sibling neurons to acquire equalized fates ('A/A') with near-complete expressivity. In rca1, numb mutant embryos, we observe binary cell fate changes ('B' to 'A') in several GMCs as well. Finally, we have demonstrated that expression of Delta in the mesoderm is sufficient to attain both sibling fates. Our results indicate that the intrinsic determinant Numb is absolutely required to attain differential sibling neuron fates. While the extrinsic factors Notch and Delta are also required to attain both fates, our results indicate that Delta signal can be received from outside the sibling pair.

  1. Cyclin D2 in the basal process of neural progenitors is linked to non-equivalent cell fates

    Science.gov (United States)

    Tsunekawa, Yuji; Britto, Joanne M; Takahashi, Masanori; Polleux, Franck; Tan, Seong-Seng; Osumi, Noriko

    2012-01-01

    Asymmetric cell division plays an indispensable role during corticogenesis for producing new neurons while maintaining a self-renewing pool of apical progenitors. The cellular and molecular determinants favouring asymmetric division are not completely understood. Here, we identify a novel mechanism for generating cellular asymmetry through the active transportation and local translation of Cyclin D2 mRNA in the basal process. This process is regulated by a unique cis-regulatory sequence found in the 3′ untranslated region (3′UTR) of the mRNA. Unequal inheritance of Cyclin D2 protein to the basally positioned daughter cell with the basal process confers renewal of the apical progenitor after asymmetric division. Conversely, depletion of Cyclin D2 in the apically positioned daughter cell results in terminal neuronal differentiation. We demonstrate that Cyclin D2 is also expressed in the developing human cortex within similar domains, thus indicating that its role as a fate determinant is ancient and conserved. PMID:22395070

  2. Cell fate control in the developing central nervous system

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    Guérout, Nicolas; Li, Xiaofei; Barnabé-Heider, Fanie, E-mail: Fanie.Barnabe-Heider@ki.se

    2014-02-01

    The principal neural cell types forming the mature central nervous system (CNS) are now understood to be diverse. This cellular subtype diversity originates to a large extent from the specification of the earlier proliferating progenitor populations during development. Here, we review the processes governing the differentiation of a common neuroepithelial cell progenitor pool into mature neurons, astrocytes, oligodendrocytes, ependymal cells and adult stem cells. We focus on studies performed in mice and involving two distinct CNS structures: the spinal cord and the cerebral cortex. Understanding the origin, specification and developmental regulators of neural cells will ultimately impact comprehension and treatments of neurological disorders and diseases. - Highlights: • Similar mechanisms regulate cell fate in different CNS cell types and structures. • Cell fate regulators operate in a spatial–temporal manner. • Different neural cell types rely on the generation of a diversity of progenitor cells. • Cell fate decision is dictated by the integration of intrinsic and extrinsic signals.

  3. Cell fate control in the developing central nervous system

    International Nuclear Information System (INIS)

    Guérout, Nicolas; Li, Xiaofei; Barnabé-Heider, Fanie

    2014-01-01

    The principal neural cell types forming the mature central nervous system (CNS) are now understood to be diverse. This cellular subtype diversity originates to a large extent from the specification of the earlier proliferating progenitor populations during development. Here, we review the processes governing the differentiation of a common neuroepithelial cell progenitor pool into mature neurons, astrocytes, oligodendrocytes, ependymal cells and adult stem cells. We focus on studies performed in mice and involving two distinct CNS structures: the spinal cord and the cerebral cortex. Understanding the origin, specification and developmental regulators of neural cells will ultimately impact comprehension and treatments of neurological disorders and diseases. - Highlights: • Similar mechanisms regulate cell fate in different CNS cell types and structures. • Cell fate regulators operate in a spatial–temporal manner. • Different neural cell types rely on the generation of a diversity of progenitor cells. • Cell fate decision is dictated by the integration of intrinsic and extrinsic signals

  4. A threshold model for receptor tyrosine kinase signaling specificity and cell fate determination [version 1; referees: 4 approved

    Directory of Open Access Journals (Sweden)

    Allen Zinkle

    2018-06-01

    Full Text Available Upon ligand engagement, the single-pass transmembrane receptor tyrosine kinases (RTKs dimerize to transmit qualitatively and quantitatively different intracellular signals that alter the transcriptional landscape and thereby determine the cellular response. The molecular mechanisms underlying these fundamental events are not well understood. Considering recent insights into the structural biology of fibroblast growth factor signaling, we propose a threshold model for RTK signaling specificity in which quantitative differences in the strength/longevity of ligand-induced receptor dimers on the cell surface lead to quantitative differences in the phosphorylation of activation loop (A-loop tyrosines as well as qualitative differences in the phosphorylation of tyrosines mediating substrate recruitment. In this model, quantitative differences on A-loop tyrosine phosphorylation result in gradations in kinase activation, leading to the generation of intracellular signals of varying amplitude/duration. In contrast, qualitative differences in the pattern of tyrosine phosphorylation on the receptor result in the recruitment/activation of distinct substrates/intracellular pathways. Commensurate with both the dynamics of the intracellular signal and the types of intracellular pathways activated, unique transcriptional signatures are established. Our model provides a framework for engineering clinically useful ligands that can tune receptor dimerization stability so as to bias the cellular transcriptome to achieve a desired cellular output.

  5. Specifying pancreatic endocrine cell fates.

    Science.gov (United States)

    Collombat, Patrick; Hecksher-Sørensen, Jacob; Serup, Palle; Mansouri, Ahmed

    2006-07-01

    Cell replacement therapy could represent an attractive alternative to insulin injections for the treatment of diabetes. However, this approach requires a thorough understanding of the molecular switches controlling the specification of the different pancreatic cell-types in vivo. These are derived from an apparently identical pool of cells originating from the early gut endoderm, which are successively specified towards the pancreatic, endocrine, and hormone-expressing cell lineages. Numerous studies have outlined the crucial roles exerted by transcription factors in promoting the cell destiny, defining the cell identity and maintaining a particular cell fate. This review focuses on the mechanisms regulating the morphogenesis of the pancreas with particular emphasis on recent findings concerning the transcription factor hierarchy orchestrating endocrine cell fate allocation.

  6. MicroRNA let-7d regulates the TLX/microRNA-9 cascade to control neural cell fate and neurogenesis.

    Science.gov (United States)

    Zhao, Chunnian; Sun, GuoQiang; Ye, Peng; Li, Shengxiu; Shi, Yanhong

    2013-01-01

    MicroRNAs have important functions in the nervous system through post-transcriptional regulation of neurogenesis genes. Here we show that microRNA let-7d, which has been implicated in cocaine addiction and other neurological disorders, targets the neural stem cell regulator TLX. Overexpression of let-7d in vivo reduced neural stem cell proliferation and promoted premature neuronal differentiation and migration, a phenotype similar to those induced by TLX knockdown or overexpression of its negatively-regulated target, microRNA-9. We found a let-7d binding sequence in the tlx 3' UTR and demonstrated that let-7d reduced TLX expression levels in neural stem cells, which in turn, up-regulated miR-9 expression. Moreover, co-expression of let-7d and TLX lacking its 3' UTR in vivo restored neural stem cell proliferation and reversed the premature neuronal differentiation and migration. Therefore, manipulating let-7d and its downstream targets could be a novel strategy to unravel neurogenic signaling pathways and identify potential interventions for relevant neurological disorders.

  7. BTG interacts with retinoblastoma to control cell fate in Dictyostelium.

    Directory of Open Access Journals (Sweden)

    Daniele Conte

    Full Text Available BACKGROUND: In the genesis of many tissues, a phase of cell proliferation is followed by cell cycle exit and terminal differentiation. The latter two processes overlap: genes involved in the cessation of growth may also be important in triggering differentiation. Though conceptually distinct, they are often causally related and functional interactions between the cell cycle machinery and cell fate control networks are fundamental to coordinate growth and differentiation. A switch from proliferation to differentiation may also be important in the life cycle of single-celled organisms, and genes which arose as regulators of microbial differentiation may be conserved in higher organisms. Studies in microorganisms may thus contribute to understanding the molecular links between cell cycle machinery and the determination of cell fate choice networks. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that in the amoebozoan D. discoideum, an ortholog of the metazoan antiproliferative gene btg controls cell fate, and that this function is dependent on the presence of a second tumor suppressor ortholog, the retinoblastoma-like gene product. Specifically, we find that btg-overexpressing cells preferentially adopt a stalk cell (and, more particularly, an Anterior-Like Cell fate. No btg-dependent preference for ALC fate is observed in cells in which the retinoblastoma-like gene has been genetically inactivated. Dictyostelium btg is the only example of non-metazoan member of the BTG family characterized so far, suggesting that a genetic interaction between btg and Rb predated the divergence between dictyostelids and metazoa. CONCLUSIONS/SIGNIFICANCE: While the requirement for retinoblastoma function for BTG antiproliferative activity in metazoans is known, an interaction of these genes in the control of cell fate has not been previously documented. Involvement of a single pathway in the control of mutually exclusive processes may have relevant implication in the

  8. Astrocytes Can Adopt Endothelial Cell Fates in a p53-Dependent Manner.

    Science.gov (United States)

    Brumm, Andrew J; Nunez, Stefanie; Doroudchi, Mehdi M; Kawaguchi, Riki; Duan, Jinhzu; Pellegrini, Matteo; Lam, Larry; Carmichael, S Thomas; Deb, Arjun; Hinman, Jason D

    2017-08-01

    Astrocytes respond to a variety of CNS injuries by cellular enlargement, process outgrowth, and upregulation of extracellular matrix proteins that function to prevent expansion of the injured region. This astrocytic response, though critical to the acute injury response, results in the formation of a glial scar that inhibits neural repair. Scar-forming cells (fibroblasts) in the heart can undergo mesenchymal-endothelial transition into endothelial cell fates following cardiac injury in a process dependent on p53 that can be modulated to augment cardiac repair. Here, we sought to determine whether astrocytes, as the primary scar-forming cell of the CNS, are able to undergo a similar cellular phenotypic transition and adopt endothelial cell fates. Serum deprivation of differentiated astrocytes resulted in a change in cellular morphology and upregulation of endothelial cell marker genes. In a tube formation assay, serum-deprived astrocytes showed a substantial increase in vessel-like morphology that was comparable to human umbilical vein endothelial cells and dependent on p53. RNA sequencing of serum-deprived astrocytes demonstrated an expression profile that mimicked an endothelial rather than astrocyte transcriptome and identified p53 and angiogenic pathways as specifically upregulated. Inhibition of p53 with genetic or pharmacologic strategies inhibited astrocyte-endothelial transition. Astrocyte-endothelial cell transition could also be modulated by miR-194, a microRNA downstream of p53 that affects expression of genes regulating angiogenesis. Together, these studies demonstrate that differentiated astrocytes retain a stimulus-dependent mechanism for cellular transition into an endothelial phenotype that may modulate formation of the glial scar and promote injury-induced angiogenesis.

  9. Cell fate regulation in the shoot meristem.

    Science.gov (United States)

    Laux, T; Mayer, K F

    1998-04-01

    The shoot meristem is a proliferative centre containing pluripotent stem cells that are the ultimate source of all cells and organs continuously added to the growing shoot. The progeny of the stem cells have two developmental options, either to renew the stem cell population or to leave the meristem and to differentiate, possibly according to signals from more mature tissue. The destiny of each cell depends on its position within the dynamic shoot meristem. Genetic data suggest a simple model in which graded positional information is provided by antagonistic gene functions and is interpreted by genes which regulate cell fate.

  10. Synthetic RNA Controllers for Programming Mammalian Cell Fate and Function

    Science.gov (United States)

    2015-11-04

    Final report for “Synthetic RNA controllers for programming mammalian cell fate and function” Principal Investigator: Christina D. Smolke...SUBTITLE Synthetic RNA controllers for programming mammalian cell fate and function 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18   2 Synthetic RNA controllers for programming mammalian cell fate and function Task 1

  11. Connecting Mitochondria, Metabolism, and Stem Cell Fate

    Science.gov (United States)

    Wanet, Anaïs; Arnould, Thierry; Najimi, Mustapha

    2015-01-01

    As sites of cellular respiration and energy production, mitochondria play a central role in cell metabolism. Cell differentiation is associated with an increase in mitochondrial content and activity and with a metabolic shift toward increased oxidative phosphorylation activity. The opposite occurs during reprogramming of somatic cells into induced pluripotent stem cells. Studies have provided evidence of mitochondrial and metabolic changes during the differentiation of both embryonic and somatic (or adult) stem cells (SSCs), such as hematopoietic stem cells, mesenchymal stem cells, and tissue-specific progenitor cells. We thus propose to consider those mitochondrial and metabolic changes as hallmarks of differentiation processes. We review how mitochondrial biogenesis, dynamics, and function are directly involved in embryonic and SSC differentiation and how metabolic and sensing pathways connect mitochondria and metabolism with cell fate and pluripotency. Understanding the basis of the crosstalk between mitochondria and cell fate is of critical importance, given the promising application of stem cells in regenerative medicine. In addition to the development of novel strategies to improve the in vitro lineage-directed differentiation of stem cells, understanding the molecular basis of this interplay could lead to the identification of novel targets to improve the treatment of degenerative diseases. PMID:26134242

  12. Choose your destiny: Make a cell fate decision with COUP-TFII.

    Science.gov (United States)

    Wu, San-Pin; Yu, Cheng-Tai; Tsai, Sophia Y; Tsai, Ming-Jer

    2016-03-01

    Cell fate specification is a critical process to generate cells with a wide range of characteristics from stem and progenitor cells. Emerging evidence demonstrates that the orphan nuclear receptor COUP-TFII serves as a key regulator in determining the cell identity during embryonic development. The present review summarizes our current knowledge on molecular mechanisms by which COUP-TFII employs to define the cell fates, with special emphasis on cardiovascular and renal systems. These novel insights pave the road for future studies of regenerative medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Cell volume change through water efflux impacts cell stiffness and stem cell fate

    NARCIS (Netherlands)

    Guo, Ming; Pegoraro, Adrian F.; Mao, Angelo; Zhou, Enhua H.; Arany, Praveen R.; Han, Yulong; Burnette, Dylan T.; Jensen, Mikkel H.; Kasza, Karen E.; Moore, Jeffrey R.; Mackintosh, Frederick C.; Fredberg, Jeffrey J.; Mooney, David J.; Lippincott-Schwartz, Jennifer; Weitz, David A.

    2017-01-01

    Cells alter their mechanical properties in response to their local microenvironment; this plays a role in determining cell function and can even influence stem cell fate. Here, we identify a robust and unified relationship between cell stiffness and cell volume. As a cell spreads on a substrate, its

  14. Synergic Functions of miRNAs Determine Neuronal Fate of Adult Neural Stem Cells

    Directory of Open Access Journals (Sweden)

    Meritxell Pons-Espinal

    2017-04-01

    Full Text Available Summary: Adult neurogenesis requires the precise control of neuronal versus astrocyte lineage determination in neural stem cells. While microRNAs (miRNAs are critically involved in this step during development, their actions in adult hippocampal neural stem cells (aNSCs has been unclear. As entry point to address that question we chose DICER, an endoribonuclease essential for miRNA biogenesis and other RNAi-related processes. By specific ablation of Dicer in aNSCs in vivo and in vitro, we demonstrate that miRNAs are required for the generation of new neurons, but not astrocytes, in the adult murine hippocampus. Moreover, we identify 11 miRNAs, of which 9 have not been previously characterized in neurogenesis, that determine neurogenic lineage fate choice of aNSCs at the expense of astrogliogenesis. Finally, we propose that the 11 miRNAs sustain adult hippocampal neurogenesis through synergistic modulation of 26 putative targets from different pathways. : In this article, the authors demonstrate that Dicer-dependent miRNAs are required for the generation of new neurons, but not astrocytes, in the adult hippocampus in vivo and in vitro. The authors identify a new set of 11 miRNAs that synergistically converge on multiple targets in different pathways to sustain neurogenic lineage fate commitment in aNSCs. Keywords: mouse, hippocampus, neural stem cells, fate choice, adult neurogenesis, astrogliogenesis, DICER, microRNAs, synergy

  15. Nuclear envelope and genome interactions in cell fate

    Science.gov (United States)

    Talamas, Jessica A.; Capelson, Maya

    2015-01-01

    The eukaryotic cell nucleus houses an organism’s genome and is the location within the cell where all signaling induced and development-driven gene expression programs are ultimately specified. The genome is enclosed and separated from the cytoplasm by the nuclear envelope (NE), a double-lipid membrane bilayer, which contains a large variety of trans-membrane and associated protein complexes. In recent years, research regarding multiple aspects of the cell nucleus points to a highly dynamic and coordinated concert of efforts between chromatin and the NE in regulation of gene expression. Details of how this concert is orchestrated and how it directs cell differentiation and disease are coming to light at a rapid pace. Here we review existing and emerging concepts of how interactions between the genome and the NE may contribute to tissue specific gene expression programs to determine cell fate. PMID:25852741

  16. Redox regulation of plant stem cell fate.

    Science.gov (United States)

    Zeng, Jian; Dong, Zhicheng; Wu, Haijun; Tian, Zhaoxia; Zhao, Zhong

    2017-10-02

    Despite the importance of stem cells in plant and animal development, the common mechanisms of stem cell maintenance in both systems have remained elusive. Recently, the importance of hydrogen peroxide (H 2 O 2 ) signaling in priming stem cell differentiation has been extensively studied in animals. Here, we show that different forms of reactive oxygen species (ROS) have antagonistic roles in plant stem cell regulation, which were established by distinct spatiotemporal patterns of ROS-metabolizing enzymes. The superoxide anion (O2·-) is markedly enriched in stem cells to activate WUSCHEL and maintain stemness, whereas H 2 O 2 is more abundant in the differentiating peripheral zone to promote stem cell differentiation. Moreover, H 2 O 2 negatively regulates O2·- biosynthesis in stem cells, and increasing H 2 O 2 levels or scavenging O2·- leads to the termination of stem cells. Our results provide a mechanistic framework for ROS-mediated control of plant stem cell fate and demonstrate that the balance between O2·- and H 2 O 2 is key to stem cell maintenance and differentiation. © 2017 The Authors.

  17. Glioma cell fate decisions mediated by Dll1-Jag1-Fringe in Notch1 signaling pathway.

    Science.gov (United States)

    Shi, Xiaofei; Wang, Ruiqi

    2017-09-21

    The Notch family of proteins plays a vital role in determining cell fates, such as proliferation, differentiation, and apoptosis. It has been shown that Notch1 and its ligands, Dll1 and Jag1, are overexpressed in many glioma cell lines and primary human gliomas. The roles of Notch1 in some cancers have been firmly established, and recent data implicate that it plays important roles in glioma cell fate decisions. This paper focuses on devising a specific theoretical framework that incorporates Dll1, Jag1, and Fringe in Notch1 signaling pathway to explore their functional roles of these proteins in glioma cells in the tumorigenesis and progression of human gliomas, and to study how glioma cell fate decisions are modulated by both trans-activation and cis-inhibition. This paper presents a computational model for Notch1 signaling pathway in glioma cells. Based on the bifurcation analysis of the model, we show that how the glioma cell fate decisions are modulated by both trans-activation and cis-inhibition mediated by the Fringe protein, providing insight into the design and control principles of the Notch signaling system and the gliomas. This paper presents a computational model for Notch1 signaling pathway in glioma cells based on intertwined dynamics with cis-inhibition and trans-activation involving the proteins Notch1, Dll1, Jag1, and Fringe. The results show that how the glioma cell fate transitions are performed by the Notch1 signaling. Transition from grade III ∼ IV with significantly high Notch1 to grade I ∼ II with high Notch1, and then to normal cells by repressing the Fringe levels or decreasing the strength of enhancement induced by Fringe.

  18. Msx2 alters the timing of retinal ganglion cells fate commitment and differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Shao-Yun, E-mail: jiangshaoyun@yahoo.com [School of Dentistry, Tianjin Medical University, 12 Qi Xiang Tai Street, Tianjin 300070 (China); Wang, Jian-Tao, E-mail: wangjiantao65@hotmail.com [Eye Center, Tianjin Medical University, 64 Tongan Road, Tianjin 300070 (China); Dohney Eye Institute, Keck School of Medicine, University of Southern California, 1355 San Pablo Street, DOH 314, Los Angeles, CA 90033 (United States)

    2010-05-14

    Timing of cell fate commitment determines distinct retinal cell types, which is believed to be controlled by a tightly coordinated regulatory program of proliferation, cell cycle exit and differentiation. Although homeobox protein Msx2 could induce apoptosis of optic vesicle, it is unclear whether Msx2 regulates differentiation and cell fate commitment of retinal progenitor cells (RPCs) to retinal ganglion cells (RGCs). In this study, we show that overexpression of Msx2 transiently suppressed the expression of Cyclin D1 and blocked cell proliferation. Meanwhile, overexpression of Msx2 delayed the expression of RGC-specific differentiation markers (Math5 and Brn3b), which showed that Msx2 could affect the timing of RGCs fate commitment and differentiation by delaying the timing of cell cycle exit of retinal progenitors. These results indicate Msx2 possesses dual regulatory functions in controlling cell cycle progression of retinal RPCs and timing of RGCs differentiation.

  19. Reactive Oxygen Species and Mitochondrial Homeostasis as Regulators of Stem Cell Fate and Function.

    Science.gov (United States)

    Tan, Darren Q; Suda, Toshio

    2018-07-10

    The precise role and impact of reactive oxygen species (ROS) in stem cells, which are essential for lifelong tissue homeostasis and regeneration, remain of significant interest to the field. The long-term regenerative potential of a stem cell compartment is determined by the delicate balance between quiescence, self-renewal, and differentiation, all of which can be influenced by ROS levels. Recent Advances: The past decade has seen a growing appreciation for the importance of ROS and redox homeostasis in various stem cell compartments, particularly those of hematopoietic, neural, and muscle tissues. In recent years, the importance of proteostasis and mitochondria in relation to stem cell biology and redox homeostasis has garnered considerable interest. Here, we explore the reciprocal relationship between ROS and stem cells, with significant emphasis on mitochondria as a core component of redox homeostasis. We discuss how redox signaling, involving cell-fate determining protein kinases and transcription factors, can control stem cell function and fate. We also address the impact of oxidative stress on stem cells, especially oxidative damage of lipids, proteins, and nucleic acids. We further discuss ROS management in stem cells, and present recent evidence supporting the importance of mitochondrial activity and its modulation (via mitochondrial clearance, biogenesis, dynamics, and distribution [i.e., segregation and transfer]) in stem cell redox homeostasis. Therefore, elucidating the intricate links between mitochondria, cellular metabolism, and redox homeostasis is envisioned to be critical for our understanding of ROS in stem cell biology and its therapeutic relevance in regenerative medicine. Antioxid. Redox Signal. 00, 000-000.

  20. Logic programming to predict cell fate patterns and retrodict genotypes in organogenesis.

    Science.gov (United States)

    Hall, Benjamin A; Jackson, Ethan; Hajnal, Alex; Fisher, Jasmin

    2014-09-06

    Caenorhabditis elegans vulval development is a paradigm system for understanding cell differentiation in the process of organogenesis. Through temporal and spatial controls, the fate pattern of six cells is determined by the competition of the LET-23 and the Notch signalling pathways. Modelling cell fate determination in vulval development using state-based models, coupled with formal analysis techniques, has been established as a powerful approach in predicting the outcome of combinations of mutations. However, computing the outcomes of complex and highly concurrent models can become prohibitive. Here, we show how logic programs derived from state machines describing the differentiation of C. elegans vulval precursor cells can increase the speed of prediction by four orders of magnitude relative to previous approaches. Moreover, this increase in speed allows us to infer, or 'retrodict', compatible genomes from cell fate patterns. We exploit this technique to predict highly variable cell fate patterns resulting from dig-1 reduced-function mutations and let-23 mosaics. In addition to the new insights offered, we propose our technique as a platform for aiding the design and analysis of experimental data. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  1. Mammalian aPKC/Par polarity complex mediated regulation of epithelial division orientation and cell fate

    Energy Technology Data Exchange (ETDEWEB)

    Vorhagen, Susanne; Niessen, Carien M., E-mail: carien.niessen@uni-koeln.de

    2014-11-01

    Oriented cell division is a key regulator of tissue architecture and crucial for morphogenesis and homeostasis. Balanced regulation of proliferation and differentiation is an essential property of tissues not only to drive morphogenesis but also to maintain and restore homeostasis. In many tissues orientation of cell division is coupled to the regulation of differentiation producing daughters with similar (symmetric cell division, SCD) or differential fate (asymmetric cell division, ACD). This allows the organism to generate cell lineage diversity from a small pool of stem and progenitor cells. Division orientation and/or the ratio of ACD/SCD need to be tightly controlled. Loss of orientation or an altered ratio can promote overgrowth, alter tissue architecture and induce aberrant differentiation, and have been linked to morphogenetic diseases, cancer and aging. A key requirement for oriented division is the presence of a polarity axis, which can be established through cell intrinsic and/or extrinsic signals. Polarity proteins translate such internal and external cues to drive polarization. In this review we will focus on the role of the polarity complex aPKC/Par3/Par6 in the regulation of division orientation and cell fate in different mammalian epithelia. We will compare the conserved function of this complex in mitotic spindle orientation and distribution of cell fate determinants and highlight common and differential mechanisms in which this complex is used by tissues to adapt division orientation and cell fate to the specific properties of the epithelium.

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

    Directory of Open Access Journals (Sweden)

    Samantha Hughes

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

  3. Chemicals as the Sole Transformers of Cell Fate.

    Science.gov (United States)

    Ebrahimi, Behnam

    2016-05-30

    Forced expression of lineage-specific transcription factors in somatic cells can result in the generation of different cell types in a process named direct reprogramming, bypassing the pluripotent state. However, the introduction of transgenes limits the therapeutic applications of the produced cells. Numerous small-molecules have been introduced in the field of stem cell biology capable of governing self-renewal, reprogramming, transdifferentiation and regeneration. These chemical compounds are versatile tools for cell fate conversion toward desired outcomes. Cell fate conversion using small-molecules alone (chemical reprogramming) has superiority over arduous traditional genetic techniques in several aspects. For instance, rapid, transient, and reversible effects in activation and inhibition of functions of specific proteins are of the profits of small-molecules. They are cost-effective, have a long half-life, diversity on structure and function, and allow for temporal and flexible regulation of signaling pathways. Additionally, their effects could be adjusted by fine-tuning concentrations and combinations of different small-molecules. Therefore, chemicals are powerful tools in cell fate conversion and study of stem cell and chemical biology in vitro and in vivo. Moreover, transgene-free and chemical-only transdifferentiation approaches provide alternative strategies for the generation of various cell types, disease modeling, drug screening, and regenerative medicine. The current review gives an overview of the recent findings concerning transdifferentiation by only small-molecules without the use of transgenes.

  4. An adaptive molecular timer in p53-meidated cell fate decision

    Science.gov (United States)

    Zhang, Xiao-Peng; Wang, Ping; Liu, Feng; Wang, Wei

    The tumor suppressor p53 decides cellular outcomes in the DNA damage response. It is intriguing to explore the link between p53 dynamics and cell fates. We developed a theoretical model of p53 signaling network to clarify the mechanism of cell fate decision mediated by its dynamics. We found that the interplay between p53-Mdm2 negative feedback loop and p53-PTEN-Mdm2 positive feedback loop shapes p53 dynamics. Depending on the intensity of DNA damage, p53 shows three modes of dynamics: persistent pulses, two-phase dynamics with pulses followed by sustained high levels and straightforward high levels. Especially, p53 shows two-phase dynamics upon moderated damage and the required number of p53 pulses before apoptosis induction decreases with increasing DNA damage. Our results suggested there exists an adaptive molecular timer that determines whether and when the apoptosis switch should be triggered. We clarified the mechanism behind the switching of p53 dynamical modes by bifurcation analysis. Moreover, we reproduced the experimental results that drug additions alter p53 pulses to sustained p53 activation and leads to senescence. Our work may advance the understanding the significance of p53 dynamics in tumor suppression. This work was supported by National Natural Science Foundation of China (Nos. 11175084, 11204126 and 31361163003).

  5. Metabolism and the Control of Cell Fate Decisions and Stem Cell Renewal

    Science.gov (United States)

    Ito, Kyoko; Ito, Keisuke

    2016-01-01

    Although the stem cells of various tissues remain in the quiescent state to maintain their undifferentiated state, they also undergo cell divisions as required, and if necessary, even a single stem cell is able to provide for lifelong tissue homeostasis. Stem cell populations are precisely controlled by the balance between their symmetric and asymmetric divisions, with their division patterns determined by whether the daughter cells involved retain their self-renewal capacities. Recent studies have reported that metabolic pathways and the distribution of mitochondria are regulators of the division balance of stem cells and that metabolic defects can shift division balance toward symmetric commitment, which leads to stem cell exhaustion. It has also been observed that in asymmetric division, old mitochondria, which are central metabolic organelles, are segregated to the daughter cell fated to cell differentiation, whereas in symmetric division, young and old mitochondria are equally distributed between both daughter cells. Thus, metabolism and mitochondrial biology play important roles in stem cell fate decisions. As these decisions directly affect tissue homeostasis, understanding their regulatory mechanisms in the context of cellular metabolism is critical. PMID:27482603

  6. α6-Integrin alternative splicing: distinct cytoplasmic variants in stem cell fate specification and niche interaction.

    Science.gov (United States)

    Zhou, Zijing; Qu, Jing; He, Li; Peng, Hong; Chen, Ping; Zhou, Yong

    2018-05-02

    α6-Integrin subunit (also known as CD49f) is a stemness signature that has been found on the plasma membrane of more than 30 stem cell populations. A growing body of studies have focused on the critical role of α6-containing integrins (α6β1 and α6β4) in the regulation of stem cell properties, lineage-specific differentiation, and niche interaction. α6-Integrin subunit can be alternatively spliced at the post-transcriptional level, giving rise to divergent isoforms which differ in the cytoplasmic and/or extracellular domains. The cytoplasmic domain of integrins is an important functional part of integrin-mediated signals. Structural changes in the cytoplasmic domain of α6 provide an efficient means for the regulation of stem cell responses to biochemical stimuli and/or biophysical cues in the stem cell niche, thus impacting stem cell fate determination. In this review, we summarize the current knowledge on the structural variants of the α6-integrin subunit and spatiotemporal expression of α6 cytoplasmic variants in embryonic and adult stem/progenitor cells. We highlight the roles of α6 cytoplasmic variants in stem cell fate decision and niche interaction, and discuss the potential mechanisms involved. Understanding of the distinct functions of α6 splicing variants in stem cell biology may inform the rational design of novel stem cell-based therapies for a range of human diseases.

  7. Putting things in place for fertilization: discovering roles for importin proteins in cell fate and spermatogenesis

    Directory of Open Access Journals (Sweden)

    Kate L. Loveland

    2015-01-01

    Full Text Available Importin proteins were originally characterized for their central role in protein transport through the nuclear pores, the only intracellular entry to the nucleus. This vital function must be tightly regulated to control access by transcription factors and other nuclear proteins to genomic DNA, to achieve appropriate modulation of cellular behaviors affecting cell fate. Importin-mediated nucleocytoplasmic transport relies on their specific recognition of cargoes, with each importin binding to distinct and overlapping protein subsets. Knowledge of importin function has expanded substantially in regard to three key developmental systems: embryonic stem cells, muscle cells and the germ line. In the decade since the potential for regulated nucleocytoplasmic transport to contribute to spermatogenesis was proposed, we and others have shown that the importins that ferry transcription factors into the nucleus perform additional roles, which control cell fate. This review presents key findings from studies of mammalian spermatogenesis that reveal potential new pathways by which male fertility and infertility arise. These studies of germline genesis illuminate new ways in which importin proteins govern cellular differentiation, including via directing proteins to distinct intracellular compartments and by determining cellular stress responses.

  8. Dendritic cell fate is determined by BCL11A

    Science.gov (United States)

    Ippolito, Gregory C.; Dekker, Joseph D.; Wang, Yui-Hsi; Lee, Bum-Kyu; Shaffer, Arthur L.; Lin, Jian; Wall, Jason K.; Lee, Baeck-Seung; Staudt, Louis M.; Liu, Yong-Jun; Iyer, Vishwanath R.; Tucker, Haley O.

    2014-01-01

    The plasmacytoid dendritic cell (pDC) is vital to the coordinated action of innate and adaptive immunity. pDC development has not been unequivocally traced, nor has its transcriptional regulatory network been fully clarified. Here we confirm an essential requirement for the BCL11A transcription factor in fetal pDC development, and demonstrate this lineage-specific requirement in the adult organism. Furthermore, we identify BCL11A gene targets and provide a molecular mechanism for its action in pDC commitment. Embryonic germ-line deletion of Bcl11a revealed an absolute cellular, molecular, and functional absence of pDCs in fetal mice. In adults, deletion of Bcl11a in hematopoietic stem cells resulted in perturbed yet continued generation of progenitors, loss of downstream pDC and B-cell lineages, and persisting myeloid, conventional dendritic, and T-cell lineages. Challenge with virus resulted in a marked reduction of antiviral response in conditionally deleted adults. Genome-wide analyses of BCL11A DNA binding and expression revealed that BCL11A regulates transcription of E2-2 and other pDC differentiation modulators, including ID2 and MTG16. Our results identify BCL11A as an essential, lineage-specific factor that regulates pDC development, supporting a model wherein differentiation into pDCs represents a primed “default” pathway for common dendritic cell progenitors. PMID:24591644

  9. Neural crest cells: from developmental biology to clinical interventions.

    Science.gov (United States)

    Noisa, Parinya; Raivio, Taneli

    2014-09-01

    Neural crest cells are multipotent cells, which are specified in embryonic ectoderm in the border of neural plate and epiderm during early development by interconnection of extrinsic stimuli and intrinsic factors. Neural crest cells are capable of differentiating into various somatic cell types, including melanocytes, craniofacial cartilage and bone, smooth muscle, and peripheral nervous cells, which supports their promise for cell therapy. In this work, we provide a comprehensive review of wide aspects of neural crest cells from their developmental biology to applicability in medical research. We provide a simplified model of neural crest cell development and highlight the key external stimuli and intrinsic regulators that determine the neural crest cell fate. Defects of neural crest cell development leading to several human disorders are also mentioned, with the emphasis of using human induced pluripotent stem cells to model neurocristopathic syndromes. © 2014 Wiley Periodicals, Inc.

  10. The Unfolded Protein Response and Cell Fate Control.

    Science.gov (United States)

    Hetz, Claudio; Papa, Feroz R

    2018-01-18

    The secretory capacity of a cell is constantly challenged by physiological demands and pathological perturbations. To adjust and match the protein-folding capacity of the endoplasmic reticulum (ER) to changing secretory needs, cells employ a dynamic intracellular signaling pathway known as the unfolded protein response (UPR). Homeostatic activation of the UPR enforces adaptive programs that modulate and augment key aspects of the entire secretory pathway, whereas maladaptive UPR outputs trigger apoptosis. Here, we discuss recent advances into how the UPR integrates information about the intensity and duration of ER stress stimuli in order to control cell fate. These findings are timely and significant because they inform an evolving mechanistic understanding of a wide variety of human diseases, including diabetes mellitus, neurodegeneration, and cancer, thus opening up the potential for new therapeutic modalities to treat these diverse diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Engineering Cell Fate for Tissue Regeneration by In Vivo Transdifferentiation.

    Science.gov (United States)

    de Lázaro, I; Kostarelos, K

    2016-02-01

    Changes in cell identity occur in adult mammalian organisms but are rare and often linked to disease. Research in the last few decades has thrown light on how to manipulate cell fate, but the conversion of a particular cell type into another within a living organism (also termed in vivo transdifferentiation) has only been recently achieved in a limited number of tissues. Although the therapeutic promise of this strategy for tissue regeneration and repair is exciting, important efficacy and safety concerns will need to be addressed before it becomes a reality in the clinical practice. Here, we review the most relevant in vivo transdifferentiation studies in adult mammalian animal models, offering a critical assessment of this potentially powerful strategy for regenerative medicine.

  12. Spatially patterned matrix elasticity directs stem cell fate

    Science.gov (United States)

    Yang, Chun; DelRio, Frank W.; Ma, Hao; Killaars, Anouk R.; Basta, Lena P.; Kyburz, Kyle A.; Anseth, Kristi S.

    2016-08-01

    There is a growing appreciation for the functional role of matrix mechanics in regulating stem cell self-renewal and differentiation processes. However, it is largely unknown how subcellular, spatial mechanical variations in the local extracellular environment mediate intracellular signal transduction and direct cell fate. Here, the effect of spatial distribution, magnitude, and organization of subcellular matrix mechanical properties on human mesenchymal stem cell (hMSCs) function was investigated. Exploiting a photodegradation reaction, a hydrogel cell culture substrate was fabricated with regions of spatially varied and distinct mechanical properties, which were subsequently mapped and quantified by atomic force microscopy (AFM). The variations in the underlying matrix mechanics were found to regulate cellular adhesion and transcriptional events. Highly spread, elongated morphologies and higher Yes-associated protein (YAP) activation were observed in hMSCs seeded on hydrogels with higher concentrations of stiff regions in a dose-dependent manner. However, when the spatial organization of the mechanically stiff regions was altered from a regular to randomized pattern, lower levels of YAP activation with smaller and more rounded cell morphologies were induced in hMSCs. We infer from these results that irregular, disorganized variations in matrix mechanics, compared with regular patterns, appear to disrupt actin organization, and lead to different cell fates; this was verified by observations of lower alkaline phosphatase (ALP) activity and higher expression of CD105, a stem cell marker, in hMSCs in random versus regular patterns of mechanical properties. Collectively, this material platform has allowed innovative experiments to elucidate a novel spatial mechanical dosing mechanism that correlates to both the magnitude and organization of spatial stiffness.

  13. The linear interplay of intrinsic and extrinsic noises ensures a high accuracy of cell fate selection in budding yeast

    Science.gov (United States)

    Li, Yongkai; Yi, Ming; Zou, Xiufen

    2014-01-01

    To gain insights into the mechanisms of cell fate decision in a noisy environment, the effects of intrinsic and extrinsic noises on cell fate are explored at the single cell level. Specifically, we theoretically define the impulse of Cln1/2 as an indication of cell fates. The strong dependence between the impulse of Cln1/2 and cell fates is exhibited. Based on the simulation results, we illustrate that increasing intrinsic fluctuations causes the parallel shift of the separation ratio of Whi5P but that increasing extrinsic fluctuations leads to the mixture of different cell fates. Our quantitative study also suggests that the strengths of intrinsic and extrinsic noises around an approximate linear model can ensure a high accuracy of cell fate selection. Furthermore, this study demonstrates that the selection of cell fates is an entropy-decreasing process. In addition, we reveal that cell fates are significantly correlated with the range of entropy decreases. PMID:25042292

  14. Dll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis

    OpenAIRE

    Kawaguchi, Daichi; Furutachi, Shohei; Kawai, Hiroki; Hozumi, Katsuto; Gotoh, Yukiko

    2013-01-01

    Stem cells often divide asymmetrically to produce one stem cell and one differentiating cell, thus maintaining the stem cell pool. Although neural stem cells (NSCs) in the adult mouse subventricular zone have been suggested to divide asymmetrically, intrinsic cell fate determinants for asymmetric NSC division are largely unknown. Stem cell niches are important for stem cell maintenance, but the niche for the maintenance of adult quiescent NSCs has remained obscure. Here we show that the Notch...

  15. Cellular Programming and Reprogramming: Sculpting Cell Fate for the Production of Dopamine Neurons for Cell Therapy

    Directory of Open Access Journals (Sweden)

    Julio C. Aguila

    2012-01-01

    success of clinical applications depends on our ability to steer pluripotent stem cells towards the right neuronal identity. In Parkinson disease, the loss of dopamine neurons is more pronounced in the ventrolateral population that projects to the sensorimotor striatum. Because synapses are highly specific, only neurons with this precise identity will contribute, upon transplantation, to the synaptic reconstruction of the dorsal striatum. Thus, understanding the developmental cell program of the mesostriatal dopamine neurons is critical for the identification of the extrinsic signals and cell-intrinsic factors that instruct and, ultimately, determine cell identity. Here, we review how extrinsic signals and transcription factors act together during development to shape midbrain cell fates. Further, we discuss how these same factors can be applied in vitro to induce, select, and reprogram cells to the mesostriatal dopamine fate.

  16. Cellular programming and reprogramming: sculpting cell fate for the production of dopamine neurons for cell therapy.

    Science.gov (United States)

    Aguila, Julio C; Hedlund, Eva; Sanchez-Pernaute, Rosario

    2012-01-01

    Pluripotent stem cells are regarded as a promising cell source to obtain human dopamine neurons in sufficient amounts and purity for cell replacement therapy. Importantly, the success of clinical applications depends on our ability to steer pluripotent stem cells towards the right neuronal identity. In Parkinson disease, the loss of dopamine neurons is more pronounced in the ventrolateral population that projects to the sensorimotor striatum. Because synapses are highly specific, only neurons with this precise identity will contribute, upon transplantation, to the synaptic reconstruction of the dorsal striatum. Thus, understanding the developmental cell program of the mesostriatal dopamine neurons is critical for the identification of the extrinsic signals and cell-intrinsic factors that instruct and, ultimately, determine cell identity. Here, we review how extrinsic signals and transcription factors act together during development to shape midbrain cell fates. Further, we discuss how these same factors can be applied in vitro to induce, select, and reprogram cells to the mesostriatal dopamine fate.

  17. Posttranscriptional (Re)programming of Cell Fate: Examples in Stem Cells, Progenitor, and Differentiated Cells.

    Science.gov (United States)

    Kanellopoulou, Chrysi; Muljo, Stefan A

    2018-01-01

    How a single genome can give rise to many different transcriptomes and thus all the different cell lineages in the human body is a fundamental question in biology. While signaling pathways, transcription factors, and chromatin architecture, to name a few determinants, have been established to play critical roles, recently, there is a growing appreciation of the roles of non-coding RNAs and RNA-binding proteins in controlling cell fates posttranscriptionally. Thus, it is vital that these emerging players are also integrated into models of gene regulatory networks that underlie programs of cellular differentiation. Sometimes, we can leverage knowledge about such posttranscriptional circuits to reprogram patterns of gene expression in meaningful ways. Here, we review three examples from our work.

  18. System and method for determining stability of a neural system

    Science.gov (United States)

    Curtis, Steven A. (Inventor)

    2011-01-01

    Disclosed are methods, systems, and computer-readable media for determining stability of a neural system. The method includes tracking a function world line of an N element neural system within at least one behavioral space, determining whether the tracking function world line is approaching a psychological stability surface, and implementing a quantitative solution that corrects instability if the tracked function world line is approaching the psychological stability surface.

  19. Nanomaterials for regulating cancer and stem cell fate

    Science.gov (United States)

    Shah, Birju P.

    The realm of nanomedicine has grown exponentially over the past few decades. However, there are several obstacles that need to be overcome, prior to the wide-spread clinical applications of these nanoparticles, such as (i) developing well-defined nanoparticles of varying size, morphology and composition to enable various clinical applications; (ii) overcome various physiological barriers encountered in order to deliver the therapeutics to the target location; and (iii) real-time monitoring of the nano-therapeutics within the human body for tracking their uptake, localization and effect. Hence, this dissertation focuses on developing multimodal nanotechnology-based approaches to overcome the above-mentioned challenges and thus enable regulation of cancer and stem cell fate. The initial part of this dissertation describes the development of multimodal magnetic core-shell nanoparticles (MCNPs), comprised of a highly magnetic core surrounded by a thin gold shell, thus combining magnetic and plasmonic properties. These nanoparticles were utilized for mainly two applications: (i) Magnetically-facilitated delivery of siRNA and plasmid DNA for effective stem cell differentiation and imaging and (ii) Combined hyperthermia and targeted delivery of a mitochondria-targeting peptide for enhancing apoptosis in cancer cells. The following part of this dissertation presents the generation of a multi-functional cyclodextrin-conjugated polymeric delivery platform (known as DexAMs), for co-delivery of anticancer drugs and siRNAs in a target-specific manner to brain tumor cells. This combined delivery of chemotherapeutics and siRNA resulted in a synergistic effect on the apoptosis of brain tumor cells, as compared to the individual treatments. The final part of this thesis presents development of stimuli-responsive uorescence resonance energy transfer (FRET)-based mesoporous silica nanoparticles for real-time monitoring of drug release in cells. The stimuli-responsive behavior of

  20. Cell fate reprogramming by control of intracellular network dynamics

    Science.gov (United States)

    Zanudo, Jorge G. T.; Albert, Reka

    Identifying control strategies for biological networks is paramount for practical applications that involve reprogramming a cell's fate, such as disease therapeutics and stem cell reprogramming. Although the topic of controlling the dynamics of a system has a long history in control theory, most of this work is not directly applicable to intracellular networks. Here we present a network control method that integrates the structural and functional information available for intracellular networks to predict control targets. Formulated in a logical dynamic scheme, our control method takes advantage of certain function-dependent network components and their relation to steady states in order to identify control targets, which are guaranteed to drive any initial state to the target state with 100% effectiveness and need to be applied only transiently for the system to reach and stay in the desired state. We illustrate our method's potential to find intervention targets for cancer treatment and cell differentiation by applying it to a leukemia signaling network and to the network controlling the differentiation of T cells. We find that the predicted control targets are effective in a broad dynamic framework. Moreover, several of the predicted interventions are supported by experiments. This work was supported by NSF Grant PHY 1205840.

  1. Parathyroid Hormone Directs Bone Marrow Mesenchymal Cell Fate.

    Science.gov (United States)

    Fan, Yi; Hanai, Jun-Ichi; Le, Phuong T; Bi, Ruiye; Maridas, David; DeMambro, Victoria; Figueroa, Carolina A; Kir, Serkan; Zhou, Xuedong; Mannstadt, Michael; Baron, Roland; Bronson, Roderick T; Horowitz, Mark C; Wu, Joy Y; Bilezikian, John P; Dempster, David W; Rosen, Clifford J; Lanske, Beate

    2017-03-07

    Intermittent PTH administration builds bone mass and prevents fractures, but its mechanism of action is unclear. We genetically deleted the PTH/PTHrP receptor (PTH1R) in mesenchymal stem cells using Prx1Cre and found low bone formation, increased bone resorption, and high bone marrow adipose tissue (BMAT). Bone marrow adipocytes traced to Prx1 and expressed classic adipogenic markers and high receptor activator of nuclear factor kappa B ligand (Rankl) expression. RANKL levels were also elevated in bone marrow supernatant and serum, but undetectable in other adipose depots. By cell sorting, Pref1 + RANKL + marrow progenitors were twice as great in mutant versus control marrow. Intermittent PTH administration to control mice reduced BMAT significantly. A similar finding was noted in male osteoporotic patients. Thus, marrow adipocytes exhibit osteogenic and adipogenic characteristics, are uniquely responsive to PTH, and secrete RANKL. These studies reveal an important mechanism for PTH's therapeutic action through its ability to direct mesenchymal cell fate. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Extracellular Matrix as a Regulator of Epidermal Stem Cell Fate.

    Science.gov (United States)

    Chermnykh, Elina; Kalabusheva, Ekaterina; Vorotelyak, Ekaterina

    2018-03-27

    Epidermal stem cells reside within the specific anatomic location, called niche, which is a microenvironment that interacts with stem cells to regulate their fate. Regulation of many important processes, including maintenance of stem cell quiescence, self-renewal, and homeostasis, as well as the regulation of division and differentiation, are common functions of the stem cell niche. As it was shown in multiple studies, extracellular matrix (ECM) contributes a lot to stem cell niches in various tissues, including that of skin. In epidermis, ECM is represented, primarily, by a highly specialized ECM structure, basement membrane (BM), which separates the epidermal and dermal compartments. Epidermal stem cells contact with BM, but when they lose the contact and migrate to the overlying layers, they undergo terminal differentiation. When considering all of these factors, ECM is of fundamental importance in regulating epidermal stem cells maintenance, proper mobilization, and differentiation. Here, we summarize the remarkable progress that has recently been made in the research of ECM role in regulating epidermal stem cell fate, paying special attention to the hair follicle stem cell niche. We show that the destruction of ECM components impairs epidermal stem cell morphogenesis and homeostasis. A deep understanding of ECM molecular structure as well as the development of in vitro system for stem cell maintaining by ECM proteins may bring us to developing new approaches for regenerative medicine.

  3. The Melanocyte Fate in Neural Crest is Triggered by Myb Proteins through Activation of c-kit

    Czech Academy of Sciences Publication Activity Database

    Karafiát, Vít; Dvořáková, Marta; Pajer, Petr; Čermák, Vladimír; Dvořák, Michal

    2007-01-01

    Roč. 64, č. 21 (2007), s. 2975-2984 ISSN 1420-682X R&D Projects: GA MŠk(CZ) LC06061; GA ČR GA204/06/1728 Institutional research plan: CEZ:AV0Z50520514 Keywords : c-myb proto-oncogene * v-mybAMV oncogene * neural crest * cell fate determination * melanocytes * c-kit signal Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.239, year: 2007

  4. Determining the confidence levels of sensor outputs using neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Broten, G S; Wood, H C [Saskatchewan Univ., Saskatoon, SK (Canada). Dept. of Electrical Engineering

    1996-12-31

    This paper describes an approach for determining the confidence level of a sensor output using multi-sensor arrays, sensor fusion and artificial neural networks. The authors have shown in previous work that sensor fusion and artificial neural networks can be used to learn the relationships between the outputs of an array of simulated partially selective sensors and the individual analyte concentrations in a mixture of analyses. Other researchers have shown that an array of partially selective sensors can be used to determine the individual gas concentrations in a gaseous mixture. The research reported in this paper shows that it is possible to extract confidence level information from an array of partially selective sensors using artificial neural networks. The confidence level of a sensor output is defined as a numeric value, ranging from 0% to 100%, that indicates the confidence associated with a output of a given sensor. A three layer back-propagation neural network was trained on a subset of the sensor confidence level space, and was tested for its ability to generalize, where the confidence level space is defined as all possible deviations from the correct sensor output. A learning rate of 0.1 was used and no momentum terms were used in the neural network. This research has shown that an artificial neural network can accurately estimate the confidence level of individual sensors in an array of partially selective sensors. This research has also shown that the neural network`s ability to determine the confidence level is influenced by the complexity of the sensor`s response and that the neural network is able to estimate the confidence levels even if more than one sensor is in error. The fundamentals behind this research could be applied to other configurations besides arrays of partially selective sensors, such as an array of sensors separated spatially. An example of such a configuration could be an array of temperature sensors in a tank that is not in

  5. Deubiquitylating enzyme UBP64 controls cell fate through stabilization of the transcriptional repressor tramtrack

    NARCIS (Netherlands)

    P.K. Bajpe (Prashanth Kumar); J.A. van der Knaap (Jan); J.A.A. Demmers (Jeroen); K. Bezstarosti (Karel); A. Bassett (Andrew); H.M.M. van Beusekom (Heleen); A.A. Travers (Andrew); C.P. Verrijzer (Peter)

    2008-01-01

    textabstractProtein ubiquitylation plays a central role in multiple signal transduction pathways. However, the substrate specificity and potential developmental roles of deubiquitylating enzymes remain poorly understood. Here, we show that the Drosophila ubiquitin protease UBP64 controls cell fate

  6. Impact parameter determination in experimental analysis using neural network

    International Nuclear Information System (INIS)

    Haddad, F.; David, C.; Freslier, M.; Aichelin, J.; Haddad, F.; Hagel, K.; Li, J.; Mdeiwayeh, N.; Natowitz, J.B.; Wada, R.; Xiao, B.

    1997-01-01

    A neural network is used to determine the impact parameter in 40 Ca + 40 Ca reactions. The effect of the detection efficiency as well as the model dependence of the training procedure have been studied carefully. An overall improvement of the impact parameter determination of 25 % is obtained using this technique. The analysis of Amphora 40 Ca+ 40 Ca data at 35 MeV per nucleon using a neural network shows two well separated classes of events among the selected 'complete' events. (authors)

  7. Optical neural network system for pose determination of spinning satellites

    Science.gov (United States)

    Lee, Andrew; Casasent, David

    1990-01-01

    An optical neural network architecture and algorithm based on a Hopfield optimization network are presented for multitarget tracking. This tracker utilizes a neuron for every possible target track, and a quadratic energy function of neural activities which is minimized using gradient descent neural evolution. The neural net tracker is demonstrated as part of a system for determining position and orientation (pose) of spinning satellites with respect to a robotic spacecraft. The input to the system is time sequence video from a single camera. Novelty detection and filtering are utilized to locate and segment novel regions from the input images. The neural net multitarget tracker determines the correspondences (or tracks) of the novel regions as a function of time, and hence the paths of object (satellite) parts. The path traced out by a given part or region is approximately elliptical in image space, and the position, shape and orientation of the ellipse are functions of the satellite geometry and its pose. Having a geometric model of the satellite, and the elliptical path of a part in image space, the three-dimensional pose of the satellite is determined. Digital simulation results using this algorithm are presented for various satellite poses and lighting conditions.

  8. Neural network determination of parton distributions: the nonsinglet case

    International Nuclear Information System (INIS)

    Del Debbio, Luigi; Forte, Stefano; Latorre, Jose I.; Piccione, Andrea; Rojo, Joan

    2007-01-01

    We provide a determination of the isotriplet quark distribution from available deep-inelastic data using neural networks. We give a general introduction to the neural network approach to parton distributions, which provides a solution to the problem of constructing a faithful and unbiased probability distribution of parton densities based on available experimental information. We discuss in detail the techniques which are necessary in order to construct a Monte Carlo representation of the data, to construct and evolve neural parton distributions, and to train them in such a way that the correct statistical features of the data are reproduced. We present the results of the application of this method to the determination of the nonsinglet quark distribution up to next-to-next-to-leading order, and compare them with those obtained using other approaches

  9. A polynomial based model for cell fate prediction in human diseases.

    Science.gov (United States)

    Ma, Lichun; Zheng, Jie

    2017-12-21

    Cell fate regulation directly affects tissue homeostasis and human health. Research on cell fate decision sheds light on key regulators, facilitates understanding the mechanisms, and suggests novel strategies to treat human diseases that are related to abnormal cell development. In this study, we proposed a polynomial based model to predict cell fate. This model was derived from Taylor series. As a case study, gene expression data of pancreatic cells were adopted to test and verify the model. As numerous features (genes) are available, we employed two kinds of feature selection methods, i.e. correlation based and apoptosis pathway based. Then polynomials of different degrees were used to refine the cell fate prediction function. 10-fold cross-validation was carried out to evaluate the performance of our model. In addition, we analyzed the stability of the resultant cell fate prediction model by evaluating the ranges of the parameters, as well as assessing the variances of the predicted values at randomly selected points. Results show that, within both the two considered gene selection methods, the prediction accuracies of polynomials of different degrees show little differences. Interestingly, the linear polynomial (degree 1 polynomial) is more stable than others. When comparing the linear polynomials based on the two gene selection methods, it shows that although the accuracy of the linear polynomial that uses correlation analysis outcomes is a little higher (achieves 86.62%), the one within genes of the apoptosis pathway is much more stable. Considering both the prediction accuracy and the stability of polynomial models of different degrees, the linear model is a preferred choice for cell fate prediction with gene expression data of pancreatic cells. The presented cell fate prediction model can be extended to other cells, which may be important for basic research as well as clinical study of cell development related diseases.

  10. Using function approximation to determine neural network accuracy

    International Nuclear Information System (INIS)

    Wichman, R.F.; Alexander, J.

    2013-01-01

    Many, if not most, control processes demonstrate nonlinear behavior in some portion of their operating range and the ability of neural networks to model non-linear dynamics makes them very appealing for control. Control of high reliability safety systems, and autonomous control in process or robotic applications, however, require accurate and consistent control and neural networks are only approximators of various functions so their degree of approximation becomes important. In this paper, the factors affecting the ability of a feed-forward back-propagation neural network to accurately approximate a non-linear function are explored. Compared to pattern recognition using a neural network for function approximation provides an easy and accurate method for determining the network's accuracy. In contrast to other techniques, we show that errors arising in function approximation or curve fitting are caused by the neural network itself rather than scatter in the data. A method is proposed that provides improvements in the accuracy achieved during training and resulting ability of the network to generalize after training. Binary input vectors provided a more accurate model than with scalar inputs and retraining using a small number of the outlier x,y pairs improved generalization. (author)

  11. Determining the confidence levels of sensor outputs using neural networks

    International Nuclear Information System (INIS)

    Broten, G.S.; Wood, H.C.

    1995-01-01

    This paper describes an approach for determining the confidence level of a sensor output using multi-sensor arrays, sensor fusion and artificial neural networks. The authors have shown in previous work that sensor fusion and artificial neural networks can be used to learn the relationships between the outputs of an array of simulated partially selective sensors and the individual analyte concentrations in a mixture of analyses. Other researchers have shown that an array of partially selective sensors can be used to determine the individual gas concentrations in a gaseous mixture. The research reported in this paper shows that it is possible to extract confidence level information from an array of partially selective sensors using artificial neural networks. The confidence level of a sensor output is defined as a numeric value, ranging from 0% to 100%, that indicates the confidence associated with a output of a given sensor. A three layer back-propagation neural network was trained on a subset of the sensor confidence level space, and was tested for its ability to generalize, where the confidence level space is defined as all possible deviations from the correct sensor output. A learning rate of 0.1 was used and no momentum terms were used in the neural network. This research has shown that an artificial neural network can accurately estimate the confidence level of individual sensors in an array of partially selective sensors. This research has also shown that the neural network's ability to determine the confidence level is influenced by the complexity of the sensor's response and that the neural network is able to estimate the confidence levels even if more than one sensor is in error. The fundamentals behind this research could be applied to other configurations besides arrays of partially selective sensors, such as an array of sensors separated spatially. An example of such a configuration could be an array of temperature sensors in a tank that is not in

  12. Superficial physicochemical properties of polyurethane biomaterials as osteogenic regulators in human mesenchymal stem cells fates.

    Science.gov (United States)

    Shahrousvand, Mohsen; Sadeghi, Gity Mir Mohamad; Shahrousvand, Ehsan; Ghollasi, Marzieh; Salimi, Ali

    2017-08-01

    All of the cells' interactions are done through their surfaces. Evaluation of surface physicochemical scaffolds along with other factors is important and determines the fate of stem cells. In this work, biodegradable and biocompatible polyester/polyether based polyurethanes (PUs) were synthesized by polycaprolactone diol (PCL) and poly (tetra methylene ether) glycol (PTMEG) as the soft segment. To assess better the impact of surface parameters such as stiffness and roughness effects on osteogenic differentiation of the human mesenchymal stem cell (hMSC), the dimension effect of substrates was eliminated and two-dimensional membranes were produced by synthesized polyurethane. Surface and bulk properties of prepared 2D membranes such as surface chemistry, roughness, stiffness and tensile behavior were evaluated by Attenuated total reflectance Fourier transform infrared (ATR-FTIR), atomic force microscopy (AFM) and tensile behavior. The prepared 2D PU films had suitable hydrophilicity, biodegradability, water absorption, surface roughness and bulk strength. The hMSCs showed greater osteogenesis expression in PU substrates with more roughness and stiffness than others. The results demonstrated that surface parameters along with other differentiation cues have a synergistic effect on stem cells fates. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Relationship between nanotopographical alignment and stem cell fate with live imaging and shape analysis

    Science.gov (United States)

    Newman, Peter; Galenano-Niño, Jorge Luis; Graney, Pamela; Razal, Joselito M.; Minett, Andrew I.; Ribas, João; Ovalle-Robles, Raquel; Biro, Maté; Zreiqat, Hala

    2016-12-01

    The topography of a biomaterial regulates cellular interactions and determine stem cell fate. A complete understanding of how topographical properties affect cell behavior will allow the rational design of material surfaces that elicit specified biological functions once placed in the body. To this end, we fabricate substrates with aligned or randomly organized fibrous nanostructured topographies. Culturing adipose-derived stem cells (ASCs), we explore the dynamic relationship between the alignment of topography, cell shape and cell differentiation to osteogenic and myogenic lineages. We show aligned topographies differentiate cells towards a satellite cell muscle progenitor state - a distinct cell myogenic lineage responsible for postnatal growth and repair of muscle. We analyze cell shape between the different topographies, using fluorescent time-lapse imaging over 21 days. In contrast to previous work, this allows the direct measurement of cell shape at a given time rather than defining the morphology of the underlying topography and neglecting cell shape. We report quantitative metrics of the time-based morphological behaviors of cell shape in response to differing topographies. This analysis offers insights into the relationship between topography, cell shape and cell differentiation. Cells differentiating towards a myogenic fate on aligned topographies adopt a characteristic elongated shape as well as the alignment of cells.

  14. Modeling bistable cell-fate choices in the Drosophila eye: qualitative and quantitative perspectives

    Science.gov (United States)

    Graham, Thomas G. W.; Tabei, S. M. Ali; Dinner, Aaron R.; Rebay, Ilaria

    2010-01-01

    A major goal of developmental biology is to understand the molecular mechanisms whereby genetic signaling networks establish and maintain distinct cell types within multicellular organisms. Here, we review cell-fate decisions in the developing eye of Drosophila melanogaster and the experimental results that have revealed the topology of the underlying signaling circuitries. We then propose that switch-like network motifs based on positive feedback play a central role in cell-fate choice, and discuss how mathematical modeling can be used to understand and predict the bistable or multistable behavior of such networks. PMID:20570936

  15. Diethylstilbestrol induces vaginal adenosis by disrupting SMAD/RUNX1-mediated cell fate decision in the Müllerian duct epithelium

    Science.gov (United States)

    Laronda, Monica M.; Unno, Kenji; Ishi, Kazutomo; Serna, Vanida A.; Butler, Lindsey M.; Mills, Alea A.; Orvis, Grant D.; Behringer, Richard R.; Deng, Chuxia; Sinha, Satrajit; Kurita, Takeshi

    2013-01-01

    Women exposed to diethylstilbestrol (DES) in utero frequently develop vaginal adenosis, from which clear cell adenocarcinoma can arise. Despite decades of extensive investigation, the molecular pathogenesis of DES-associated vaginal adenosis remains elusive. Here we report that DES induces vaginal adenosis by inhibiting the BMP4/Activin A-regulated vaginal cell fate decision through a downregulation of RUNX1. BMP4 and Activin A produced by vaginal mesenchyme synergistically activated the expression of ΔNp63, thus deciding vaginal epithelial cell fate in the Müllerian duct epithelial cells (MDECs) via direct binding of SMADs on the highly conserved 5′sequence of ΔNp63. Therefore, mice in which Smad4 was deleted in MDECs failed to express ΔNp63 in vaginal epithelium and developed adenosis. This SMAD-dependent ΔNp63 activation required RUNX1, a binding partner of SMADs. Conditional deletion of Runx1 in the MDECs induced adenosis in the cranial portion of vagina, which mimicked the effect of developmental DES-exposure. Furthermore, neonatal DES exposure downregulated RUNX1 in the fornix of the vagina, where DES-associated adenosis is frequently found. This observation strongly suggests that the downregulation of RUNX1 is the cause of vaginal adenosis. However, once cell fate was determined, the BMP/Activin-SMAD/RUNX1 signaling pathway became dispensable for the maintenance of ΔNp63 expression in vaginal epithelium. Instead, the activity of the ΔNp63 locus in vaginal epithelium was maintained by a ΔNp63-dependent mechanism. This is the first demonstration of a molecular mechanism through which developmental chemical exposure causes precancerous lesions by altering cell fate. PMID:23830984

  16. Amplification of neural stem cell proliferation by intermediate progenitor cells in Drosophila brain development

    Directory of Open Access Journals (Sweden)

    Bello Bruno C

    2008-02-01

    Full Text Available Abstract Background In the mammalian brain, neural stem cells divide asymmetrically and often amplify the number of progeny they generate via symmetrically dividing intermediate progenitors. Here we investigate whether specific neural stem cell-like neuroblasts in the brain of Drosophila might also amplify neuronal proliferation by generating symmetrically dividing intermediate progenitors. Results Cell lineage-tracing and genetic marker analysis show that remarkably large neuroblast lineages exist in the dorsomedial larval brain of Drosophila. These lineages are generated by brain neuroblasts that divide asymmetrically to self renew but, unlike other brain neuroblasts, do not segregate the differentiating cell fate determinant Prospero to their smaller daughter cells. These daughter cells continue to express neuroblast-specific molecular markers and divide repeatedly to produce neural progeny, demonstrating that they are proliferating intermediate progenitors. The proliferative divisions of these intermediate progenitors have novel cellular and molecular features; they are morphologically symmetrical, but molecularly asymmetrical in that key differentiating cell fate determinants are segregated into only one of the two daughter cells. Conclusion Our findings provide cellular and molecular evidence for a new mode of neurogenesis in the larval brain of Drosophila that involves the amplification of neuroblast proliferation through intermediate progenitors. This type of neurogenesis bears remarkable similarities to neurogenesis in the mammalian brain, where neural stem cells as primary progenitors amplify the number of progeny they generate through generation of secondary progenitors. This suggests that key aspects of neural stem cell biology might be conserved in brain development of insects and mammals.

  17. Control of flowering and cell fate by LIF2, an RNA binding partner of the polycomb complex component LHP1.

    Directory of Open Access Journals (Sweden)

    David Latrasse

    Full Text Available Polycomb Repressive Complexes (PRC modulate the epigenetic status of key cell fate and developmental regulators in eukaryotes. The chromo domain protein like heterochromatin protein1 (LHP1 is a subunit of a plant PRC1-like complex in Arabidopsis thaliana and recognizes histone H3 lysine 27 trimethylation, a silencing epigenetic mark deposited by the PRC2 complex. We have identified and studied an LHP1-Interacting Factor2 (LIF2. LIF2 protein has RNA recognition motifs and belongs to the large hnRNP protein family, which is involved in RNA processing. LIF2 interacts in vivo, in the cell nucleus, with the LHP1 chromo shadow domain. Expression of LIF2 was detected predominantly in vascular and meristematic tissues. Loss-of-function of LIF2 modifies flowering time, floral developmental homeostasis and gynoecium growth determination. lif2 ovaries have indeterminate growth and produce ectopic inflorescences with severely affected flowers showing proliferation of ectopic stigmatic papillae and ovules in short-day conditions. To look at how LIF2 acts relative to LHP1, we conducted transcriptome analyses in lif2 and lhp1 and identified a common set of deregulated genes, which showed significant enrichment in stress-response genes. By comparing expression of LHP1 targets in lif2, lhp1 and lif2 lhp1 mutants we showed that LIF2 can either antagonize or act with LHP1. Interestingly, repression of the FLC floral transcriptional regulator in lif2 mutant is accompanied by an increase in H3K27 trimethylation at the locus, without any change in LHP1 binding, suggesting that LHP1 is targeted independently from LIF2 and that LHP1 binding does not strictly correlate with gene expression. LIF2, involved in cell identity and cell fate decision, may modulate the activity of LHP1 at specific loci, during specific developmental windows or in response to environmental cues that control cell fate determination. These results highlight a novel link between plant RNA

  18. Determination of the Corona model parameters with artificial neural networks

    International Nuclear Information System (INIS)

    Ahmet, Nayir; Bekir, Karlik; Arif, Hashimov

    2005-01-01

    Full text : The aim of this study is to calculate new model parameters taking into account the corona of electrical transmission line wires. For this purpose, a neural network modeling proposed for the corona frequent characteristics modeling. Then this model was compared with the other model developed at the Polytechnic Institute of Saint Petersburg. The results of development of the specified corona model for calculation of its influence on the wave processes in multi-wires line and determination of its parameters are submitted. Results of obtained calculation equations are brought for electrical transmission line with allowance for superficial effect in the ground and wires with reference to developed corona model

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

    Science.gov (United States)

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

    2016-02-01

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

  20. Putative oncogene Brachyury (T) is essential to specify cell fate but dispensable for notochord progenitor proliferation and EMT.

    Science.gov (United States)

    Zhu, Jianjian; Kwan, Kin Ming; Mackem, Susan

    2016-04-05

    The transcription factor Brachyury (T) gene is expressed throughout primary mesoderm (primitive streak and notochord) during early embryonic development and has been strongly implicated in the genesis of chordoma, a sarcoma of notochord cell origin. Additionally, T expression has been found in and proposed to play a role in promoting epithelial-mesenchymal transition (EMT) in various other types of human tumors. However, the role of T in normal mammalian notochord development and function is still not well-understood. We have generated an inducible knockdown model to efficiently and selectively deplete T from notochord in mouse embryos. In combination with genetic lineage tracing, we show that T function is essential for maintaining notochord cell fate and function. Progenitors adopt predominantly a neural fate in the absence of T, consistent with an origin from a common chordoneural progenitor. However, T function is dispensable for progenitor cell survival, proliferation, and EMT, which has implications for the therapeutic targeting of T in chordoma and other cancers.

  1. Muscle Stem Cell Fate Is Controlled by the Cell-Polarity Protein Scrib

    Directory of Open Access Journals (Sweden)

    Yusuke Ono

    2015-02-01

    Full Text Available Satellite cells are resident skeletal muscle stem cells that supply myonuclei for homeostasis, hypertrophy, and repair in adult muscle. Scrib is one of the major cell-polarity proteins, acting as a potent tumor suppressor in epithelial cells. Here, we show that Scrib also controls satellite-cell-fate decisions in adult mice. Scrib is undetectable in quiescent cells but becomes expressed during activation. Scrib is asymmetrically distributed in dividing daughter cells, with robust accumulation in cells committed to myogenic differentiation. Low Scrib expression is associated with the proliferative state and preventing self-renewal, whereas high Scrib levels reduce satellite cell proliferation. Satellite-cell-specific knockout of Scrib in mice causes a drastic and insurmountable defect in muscle regeneration. Thus, Scrib is a regulator of tissue stem cells, controlling population expansion and self-renewal with Scrib expression dynamics directing satellite cell fate.

  2. Analyzing cell fate control by cytokines through continuous single cell biochemistry.

    Science.gov (United States)

    Rieger, Michael A; Schroeder, Timm

    2009-10-01

    Cytokines are important regulators of cell fates with high clinical and commercial relevance. However, despite decades of intense academic and industrial research, it proved surprisingly difficult to describe the biological functions of cytokines in a precise and comprehensive manner. The exact analysis of cytokine biology is complicated by the fact that individual cytokines control many different cell fates and activate a multitude of intracellular signaling pathways. Moreover, although activating different molecular programs, different cytokines can be redundant in their biological effects. In addition, cytokines with different biological effects can activate overlapping signaling pathways. This prospect article will outline the necessity of continuous single cell biochemistry to unravel the biological functions of molecular cytokine signaling. It focuses on potentials and limitations of recent technical developments in fluorescent time-lapse imaging and single cell tracking allowing constant long-term observation of molecules and behavior of single cells. (c) 2009 Wiley-Liss, Inc.

  3. Controlling destiny through chemistry: small-molecule regulators of cell fate.

    Science.gov (United States)

    Firestone, Ari J; Chen, James K

    2010-01-15

    Controlling cell fate is essential for embryonic development, tissue regeneration, and the prevention of human disease. With each cell in the human body sharing a common genome, achieving the appropriate spectrum of stem cells and their differentiated lineages requires the selective activation of developmental signaling pathways, the expression of specific target genes, and the maintenance of these cellular states through epigenetic mechanisms. Small molecules that target these regulatory processes are therefore valuable tools for probing and manipulating the molecular mechanisms by which stem cells self-renew, differentiate, and arise from somatic cell reprogramming. Pharmacological modulators of cell fate could also help remediate human diseases caused by dysregulated cell proliferation or differentiation, heralding a new era in molecular therapeutics.

  4. Differentiation state determines neural effects on microvascular endothelial cells

    International Nuclear Information System (INIS)

    Muffley, Lara A.; Pan, Shin-Chen; Smith, Andria N.; Ga, Maricar; Hocking, Anne M.; Gibran, Nicole S.

    2012-01-01

    Growing evidence indicates that nerves and capillaries interact paracrinely in uninjured skin and cutaneous wounds. Although mature neurons are the predominant neural cell in the skin, neural progenitor cells have also been detected in uninjured adult skin. The aim of this study was to characterize differential paracrine effects of neural progenitor cells and mature sensory neurons on dermal microvascular endothelial cells. Our results suggest that neural progenitor cells and mature sensory neurons have unique secretory profiles and distinct effects on dermal microvascular endothelial cell proliferation, migration, and nitric oxide production. Neural progenitor cells and dorsal root ganglion neurons secrete different proteins related to angiogenesis. Specific to neural progenitor cells were dipeptidyl peptidase-4, IGFBP-2, pentraxin-3, serpin f1, TIMP-1, TIMP-4 and VEGF. In contrast, endostatin, FGF-1, MCP-1 and thrombospondin-2 were specific to dorsal root ganglion neurons. Microvascular endothelial cell proliferation was inhibited by dorsal root ganglion neurons but unaffected by neural progenitor cells. In contrast, microvascular endothelial cell migration in a scratch wound assay was inhibited by neural progenitor cells and unaffected by dorsal root ganglion neurons. In addition, nitric oxide production by microvascular endothelial cells was increased by dorsal root ganglion neurons but unaffected by neural progenitor cells. -- Highlights: ► Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell proliferation. ► Neural progenitor cells, not dorsal root ganglion neurons, regulate microvascular endothelial cell migration. ► Neural progenitor cells and dorsal root ganglion neurons do not effect microvascular endothelial tube formation. ► Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell production of nitric oxide. ► Neural progenitor cells and dorsal root

  5. The Tumor Suppressor Hace1 Is a Critical Regulator of TNFR1-Mediated Cell Fate

    Directory of Open Access Journals (Sweden)

    Luigi Tortola

    2016-05-01

    Full Text Available Summary: The HECT domain E3 ligase HACE1 has been identified as a tumor suppressor in multiple cancers. Here, we report that HACE1 is a central gatekeeper of TNFR1-induced cell fate. Genetic inactivation of HACE1 inhibits TNF-stimulated NF-κB activation and TNFR1-NF-κB-dependent pathogen clearance in vivo. Moreover, TNF-induced apoptosis was impaired in hace1 mutant cells and knockout mice in vivo. Mechanistically, HACE1 is essential for the ubiquitylation of the adaptor protein TRAF2 and formation of the apoptotic caspase-8 effector complex. Intriguingly, loss of HACE1 does not impair TNFR1-mediated necroptotic cell fate via RIP1 and RIP3 kinases. Loss of HACE1 predisposes animals to colonic inflammation and carcinogenesis in vivo, which is markedly alleviated by genetic inactivation of RIP3 kinase and TNFR1. Thus, HACE1 controls TNF-elicited cell fate decisions and exerts tumor suppressor and anti-inflammatory activities via a TNFR1-RIP3 kinase-necroptosis pathway. : Tortola et al. report that the E3 ubiquitin ligase HACE1 is a gatekeeper of TNFR1-mediated cell fate. Hace1 deficiency impairs TNF-driven NF-κB activation and apoptosis and predisposes cells to necroptosis. Consequently, hace1–/– mice show enhanced colitis and colon cancer, which can be reverted by inactivation of pro-necroptotic kinase RIP3 and TNFR1.

  6. Transcriptional control of stem cell fate by E2Fs and pocket proteins

    Science.gov (United States)

    Julian, Lisa M.; Blais, Alexandre

    2015-01-01

    E2F transcription factors and their regulatory partners, the pocket proteins (PPs), have emerged as essential regulators of stem cell fate control in a number of lineages. In mammals, this role extends from both pluripotent stem cells to those encompassing all embryonic germ layers, as well as extra-embryonic lineages. E2F/PP-mediated regulation of stem cell decisions is highly evolutionarily conserved, and is likely a pivotal biological mechanism underlying stem cell homeostasis. This has immense implications for organismal development, tissue maintenance, and regeneration. In this article, we discuss the roles of E2F factors and PPs in stem cell populations, focusing on mammalian systems. We discuss emerging findings that position the E2F and PP families as widespread and dynamic epigenetic regulators of cell fate decisions. Additionally, we focus on the ever expanding landscape of E2F/PP target genes, and explore the possibility that E2Fs are not simply regulators of general ‘multi-purpose’ cell fate genes but can execute tissue- and cell type-specific gene regulatory programs. PMID:25972892

  7. Transcriptional control of stem cell fate by E2Fs and Pocket Proteins

    Directory of Open Access Journals (Sweden)

    Lisa Marie Julian

    2015-04-01

    Full Text Available E2F transcription factors and their regulatory partners, the pocket proteins (PPs, have emerged as essential regulators of stem cell fate control in a number of lineages. In mammals, this role extends from both pluripotent stem cells to those encompassing all embryonic germ layers, as well as extra-embryonic lineages. E2F/PP-mediated regulation of stem cell decisions is highly evolutionarily conserved, and is likely a pivotal biological mechanism underlying stem cell homeostasis. This has immense implications for organismal development, tissue maintenance and regeneration. In this article, we discuss the roles of E2F factors and PPs in stem cell populations, focusing on mammalian systems. We discuss emerging findings that position the E2F and PP families as widespread and dynamic epigenetic regulators of cell fate decisions. Additionally, we focus on the ever expanding landscape of E2F/PP target genes, and explore the possibility that E2Fs are not simply regulators of general ‘multi-purpose’ cell fate genes but can execute tissue- and cell type-specific gene regulatory programs.

  8. Conversion of neurons and glia to external-cell fates in the external sensory organs of Drosophila hamlet mutants by a cousin-cousin cell-type respecification.

    Science.gov (United States)

    Moore, Adrian W; Roegiers, Fabrice; Jan, Lily Y; Jan, Yuh-Nung

    2004-03-15

    The Drosophila external sensory organ forms in a lineage elaborating from a single precursor cell via a stereotypical series of asymmetric divisions. HAMLET transcription factor expression demarcates the lineage branch that generates two internal cell types, the external sensory neuron and thecogen. In HAMLET mutant organs, these internal cells are converted to external cells via an unprecedented cousin-cousin cell-fate respecification event. Conversely, ectopic HAMLET expression in the external cell branch leads to internal cell production. The fate-determining signals NOTCH and PAX2 act at multiple stages of lineage elaboration and HAMLET acts to modulate their activity in a branch-specific manner.

  9. Modulated DISP3/PTCHD2 expression influences neural stem cell fate decisions

    Czech Academy of Sciences Publication Activity Database

    Konířová, Jana; Oltová, Jana; Corlett, Alicia; Kopycinska, Justyna; Kolář, Michal; Bartůněk, Petr; Zíková, Martina

    2017-01-01

    Roč. 7, JAN (2017), č. článku 41597. ISSN 2045-2322 R&D Projects: GA ČR GAP301/12/1478; GA MŠk LO1419 Institutional support: RVO:68378050 Keywords : lemli-opitz-syndrome * sterol-sensing domain * binding-protein 7 * diacylglycerol-kinase * growth-factor * in-vitro * poor-prognosis * self-renewal * differentiation * neurons Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 4.259, year: 2016

  10. Endoplasmic Reticulum Stress, Unfolded Protein Response, and Cancer Cell Fate

    Directory of Open Access Journals (Sweden)

    Marco Corazzari

    2017-04-01

    Full Text Available Perturbation of endoplasmic reticulum (ER homeostasis results in a stress condition termed “ER stress” determining the activation of a finely regulated program defined as unfolded protein response (UPR and whose primary aim is to restore this organelle’s physiological activity. Several physiological and pathological stimuli deregulate normal ER activity causing UPR activation, such as hypoxia, glucose shortage, genome instability, and cytotoxic compounds administration. Some of these stimuli are frequently observed during uncontrolled proliferation of transformed cells, resulting in tumor core formation and stage progression. Therefore, it is not surprising that ER stress is usually induced during solid tumor development and stage progression, becoming an hallmark of such malignancies. Several UPR components are in fact deregulated in different tumor types, and accumulating data indicate their active involvement in tumor development/progression. However, although the UPR program is primarily a pro-survival process, sustained and/or prolonged stress may result in cell death induction. Therefore, understanding the mechanism(s regulating the cell survival/death decision under ER stress condition may be crucial in order to specifically target tumor cells and possibly circumvent or overcome tumor resistance to therapies. In this review, we discuss the role played by the UPR program in tumor initiation, progression and resistance to therapy, highlighting the recent advances that have improved our understanding of the molecular mechanisms that regulate the survival/death switch.

  11. Cell Fate and Differentiation of Bone Marrow Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Shoichiro Kokabu

    2016-01-01

    Full Text Available Osteoblasts and bone marrow adipocytes originate from bone marrow mesenchymal stem cells (BMMSCs and there appears to be a reciprocal relationship between adipogenesis and osteoblastogenesis. Alterations in the balance between adipogenesis and osteoblastogenesis in BMMSCs wherein adipogenesis is increased relative to osteoblastogenesis are associated with decreased bone quality and quantity. Several proteins have been reported to regulate this reciprocal relationship but the exact nature of the signals regulating the balance between osteoblast and adipocyte formation within the bone marrow space remains to be determined. In this review, we focus on the role of Transducin-Like Enhancer of Split 3 (TLE3, which was recently reported to regulate the balance between osteoblast and adipocyte formation from BMMSCs. We also discuss evidence implicating canonical Wnt signalling, which plays important roles in both adipogenesis and osteoblastogenesis, in regulating TLE3 expression. Currently, there is demand for new effective therapies that target the stimulation of osteoblast differentiation to enhance bone formation. We speculate that reducing TLE3 expression or activity in BMMSCs could be a useful approach towards increasing osteoblast numbers and reducing adipogenesis in the bone marrow environment.

  12. Integrative modelling of the influence of MAPK network on cancer cell fate decision.

    Directory of Open Access Journals (Sweden)

    Luca Grieco

    2013-10-01

    Full Text Available The Mitogen-Activated Protein Kinase (MAPK network consists of tightly interconnected signalling pathways involved in diverse cellular processes, such as cell cycle, survival, apoptosis and differentiation. Although several studies reported the involvement of these signalling cascades in cancer deregulations, the precise mechanisms underlying their influence on the balance between cell proliferation and cell death (cell fate decision in pathological circumstances remain elusive. Based on an extensive analysis of published data, we have built a comprehensive and generic reaction map for the MAPK signalling network, using CellDesigner software. In order to explore the MAPK responses to different stimuli and better understand their contributions to cell fate decision, we have considered the most crucial components and interactions and encoded them into a logical model, using the software GINsim. Our logical model analysis particularly focuses on urinary bladder cancer, where MAPK network deregulations have often been associated with specific phenotypes. To cope with the combinatorial explosion of the number of states, we have applied novel algorithms for model reduction and for the compression of state transition graphs, both implemented into the software GINsim. The results of systematic simulations for different signal combinations and network perturbations were found globally coherent with published data. In silico experiments further enabled us to delineate the roles of specific components, cross-talks and regulatory feedbacks in cell fate decision. Finally, tentative proliferative or anti-proliferative mechanisms can be connected with established bladder cancer deregulations, namely Epidermal Growth Factor Receptor (EGFR over-expression and Fibroblast Growth Factor Receptor 3 (FGFR3 activating mutations.

  13. Is autophagy the key mechanism by which the sphingolipid rheostat controls the cell fate decision?

    Science.gov (United States)

    Lavieu, Gregory; Scarlatti, Francesca; Sala, Giusy; Levade, Thierry; Ghidoni, Riccardo; Botti, Joëlle; Codogno, Patrice

    2007-01-01

    Sphingolipids are major constituents of biological membrane and some of them behave as second messengers involved in the cell fate decision. Ceramide and sphingosine 1-phosphate (S1P) constitute a rheostat system in which ceramide promotes cell death and S1P increases cell survival. We have shown that both sphingolipids are able to trigger autophagy with opposing outcomes on cell survival. Here we discuss and speculate on the diverging functions of the autophagic pathways induced by ceramide and S1P, respectively.

  14. Human mammary progenitor cell fate decisions are productsof interactions with combinatorial microenvironments

    DEFF Research Database (Denmark)

    LaBarge, Mark A.; Nelson, Celeste M.; Villadsen, René

    2009-01-01

    factors, ECM, and other cells, as well as physical properties of the ECM. To understand regulation of fate decisions, therefore, would require a means of understanding carefully choreographed combinatorial interactions. Here we used microenvironment protein microarrays to functionally identify...... combinations of cell-extrinsic mammary gland proteins and ECM molecules that imposed specific cell fates on bipotent human mammary progenitor cells.Micropatterned cell culture surfaces were fabricated to distinguish between the instructive effects of cell-cell versus cell-ECM interactions, as well...

  15. ¬Mesenchymal Stem Cell Fate: Applying Biomaterials for Control of Stem Cell Behaviour

    Directory of Open Access Journals (Sweden)

    Hilary Jane Anderson

    2016-05-01

    Full Text Available Mesenchymal Stem Cell Fate: Applying Biomaterials for Control of Stem Cell BehaviourHilary J Anderson1, Jugal Kishore Sahoo2, Rein V Ulijn2,3, Matthew J Dalby1*1 Centre for Cell Engineering, University of Glasgow, Glasgow, UK.2 Technology and Innovation centre, Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow, UK. 3 Advanced Science Research Centre (ASRC and Hunter College, City University of New York, NY 10031, NY, USA. Correspondence:*Hilary Andersonh.anderson.1@research.gla.ac.ukKeywords: mesenchymal stem cells, bioengineering, materials synthesis, nanotopography, stimuli responsive material□AbstractThe materials pipeline for biomaterials and tissue engineering applications is under continuous development. Specifically, there is great interest in the use of designed materials in the stem cell arena as materials can be used to manipulate the cells providing control of behaviour. This is important as the ability to ‘engineer’ complexity and subsequent in vitro growth of tissues and organs is a key objective for tissue engineers. This review will describe the nature of the materials strategies, both static and dynamic, and their influence specifically on mesenchymal stem cell fate.

  16. Notch signaling and ghost cell fate in the calcifying cystig odontogenic tumor

    Directory of Open Access Journals (Sweden)

    Siar CH

    2011-11-01

    Full Text Available Abstract Notch signaling is an evolutionarily conserved mechanism that enables adjacent cells to adopt different fates. Ghost cells (GCs are anucleate cells with homogeneous pale eosinophilic cytoplasm and very pale to clear central areas (previous nucleus sites. Although GCs are present in a variety of odontogenic lesions notably the calcifying cystic odontogenic tumor (GCOT, their nature and process of formation remains elusive. The aim of this study was to investigate the role of Notch signaling in the cell fate specification of GCs in CCOT. Immunohistochemical staining for four Notch receptors (Notch1, Notch2, Notch3 and Notch4 and three ligands (Jagged1, Jagged2 and Delta1 was performed on archival tissues of five CCOT cases. Level of positivity was quantified as negative (0, mild (+, moderate (2+ and strong (3+. Results revealed that GCs demonstrated overexpression for Notch1 and Jagged1 suggesting that Notch1Jagged1 signaling might serve as the main transduction mechanism in cell fate decision for GCs in CCOT. Protein localizations were largely membranous and/or cytoplasmic. Mineralized GCs also stained positive implicating that the calcification process might be associated with upregulation of these molecules. The other Notch receptors and ligands were weak to absent in GCs and tumoral epithelium. Stromal endothelium and fibroblasts were stained variably positive.

  17. Crosstalk between Bcl-2 family and Ras family small GTPases: potential cell fate regulation?

    International Nuclear Information System (INIS)

    Kang, Jia; Pervaiz, Shazib

    2013-01-01

    Cell fate regulation is a function of diverse cell signaling pathways that promote cell survival and or inhibit cell death execution. In this regard, the role of the Bcl-2 family in maintaining a tight balance between cell death and cell proliferation has been extensively studied. The conventional dogma links cell fate regulation by the Bcl-2 family to its effect on mitochondrial permeabilization and apoptosis amplification. However, recent evidence provide a novel mechanism for death regulation by the Bcl-2 family via modulating cellular redox metabolism. For example overexpression of Bcl-2 has been shown to contribute to a pro-oxidant intracellular milieu and down-regulation of cellular superoxide levels enhanced death sensitivity of Bcl-2 overexpressing cells. Interestingly, gene knockdown of the small GTPase Rac1 or pharmacological inhibition of its activity also reverted death phenotype in Bcl-2 expressing cells. This appears to be a function of an interaction between Bcl-2 and Rac1. Similar functional associations have been described between the Bcl-2 family and other members of the Ras superfamily. These interactions at the mitochondria provide novel opportunities for strategic therapeutic targeting of drug-resistant cancers.

  18. Prostaglandin E2 Regulates Liver versus Pancreas Cell Fate Decisions and Endodermal Outgrowth

    Science.gov (United States)

    Nissim, Sahar; Sherwood, Richard I.; Wucherpfennig, Julia; Saunders, Diane; Harris, James M.; Esain, Virginie; Carroll, Kelli J.; Frechette, Gregory M.; Kim, Andrew J.; Hwang, Katie L.; Cutting, Claire C.; Elledge, Susanna; North, Trista E.; Goessling, Wolfram

    2014-01-01

    SUMMARY The liver and pancreas arise from common endodermal progenitors. How these distinct cell fates are specified is poorly understood. Here, we describe prostaglandin E2 (PGE2) as a regulator of endodermal fate specification during development. Modulating PGE2 activity has opposing effects on liver-versus-pancreas specification in zebrafish embryos as well as mouse endodermal progenitors. The PGE2 synthetic enzyme cox2a and receptor ep2a are patterned such that cells closest to PGE2 synthesis acquire a liver fate whereas more distant cells acquire a pancreas fate. PGE2 interacts with the bmp2b pathway to regulate fate specification. At later stages of development, PGE2 acting via the ep4a receptor promotes outgrowth of both the liver and pancreas. PGE2 remains important for adult organ growth, as it modulates liver regeneration. This work provides in vivo evidence that PGE2 may act as a morphogen to regulate cell fate decisions and outgrowth of the embryonic endodermal anlagen. PMID:24530296

  19. Pak2 Controls Acquisition of NKT Cell Fate by Regulating Expression of the Transcription Factors PLZF and Egr2

    Science.gov (United States)

    O’Hagan, Kyle L.; Zhao, Jie; Pryshchep, Olga; Wang, Chyung-Ru

    2015-01-01

    NKT cells constitute a small population of T cells developed in the thymus that produce large amounts of cytokines and chemokines in response to lipid Ags. Signaling through the Vα14-Jα18 TCR instructs commitment to the NKT cell lineage, but the precise signaling mechanisms that instruct their lineage choice are unclear. In this article, we report that the cytoskeletal remodeling protein, p21-activated kinase 2 (Pak2), was essential for NKT cell development. Loss of Pak2 in T cells reduced stage III NKT cells in the thymus and periphery. Among different NKT cell subsets, Pak2 was necessary for the generation and function of NKT1 and NKT2 cells, but not NKT17 cells. Mechanistically, expression of Egr2 and promyelocytic leukemia zinc finger (PLZF), two key transcription factors for acquiring the NKT cell fate, were markedly diminished in the absence of Pak2. Diminished expression of Egr2 and PLZF were not caused by aberrant TCR signaling, as determined using a Nur77-GFP reporter, but were likely due to impaired induction and maintenance of signaling lymphocyte activation molecule 6 expression, a TCR costimulatory receptor required for NKT cell development. These data suggest that Pak2 controls thymic NKT cell development by providing a signal that links Egr2 to induce PLZF, in part by regulating signaling lymphocyte activation molecule 6 expression. PMID:26519537

  20. Pak2 Controls Acquisition of NKT Cell Fate by Regulating Expression of the Transcription Factors PLZF and Egr2.

    Science.gov (United States)

    O'Hagan, Kyle L; Zhao, Jie; Pryshchep, Olga; Wang, Chyung-Ru; Phee, Hyewon

    2015-12-01

    NKT cells constitute a small population of T cells developed in the thymus that produce large amounts of cytokines and chemokines in response to lipid Ags. Signaling through the Vα14-Jα18 TCR instructs commitment to the NKT cell lineage, but the precise signaling mechanisms that instruct their lineage choice are unclear. In this article, we report that the cytoskeletal remodeling protein, p21-activated kinase 2 (Pak2), was essential for NKT cell development. Loss of Pak2 in T cells reduced stage III NKT cells in the thymus and periphery. Among different NKT cell subsets, Pak2 was necessary for the generation and function of NKT1 and NKT2 cells, but not NKT17 cells. Mechanistically, expression of Egr2 and promyelocytic leukemia zinc finger (PLZF), two key transcription factors for acquiring the NKT cell fate, were markedly diminished in the absence of Pak2. Diminished expression of Egr2 and PLZF were not caused by aberrant TCR signaling, as determined using a Nur77-GFP reporter, but were likely due to impaired induction and maintenance of signaling lymphocyte activation molecule 6 expression, a TCR costimulatory receptor required for NKT cell development. These data suggest that Pak2 controls thymic NKT cell development by providing a signal that links Egr2 to induce PLZF, in part by regulating signaling lymphocyte activation molecule 6 expression. Copyright © 2015 by The American Association of Immunologists, Inc.

  1. Determination of Liquefaction Potential using Artificial Neural Networks

    DEFF Research Database (Denmark)

    Farrokhzad, F; Choobbasti, A.J; Barari, Amin

    2011-01-01

    The authors propose an alternative general regression model based on neural networks, which enables analysis of summary data obtained by liquefaction analysis according to usual methods. For that purpose, the data from some thirty boreholes made during field investigations in Babol, in the Iranian...

  2. Histone Methylation and microRNA-dependent Regulation of Epigenetic Activities in Neural Progenitor Self-Renewal and Differentiation.

    Science.gov (United States)

    Cacci, Emanuele; Negri, Rodolfo; Biagioni, Stefano; Lupo, Giuseppe

    2017-01-01

    Neural stem/progenitor cell (NSPC) self-renewal and differentiation in the developing and the adult brain are controlled by extra-cellular signals and by the inherent competence of NSPCs to produce appropriate responses. Stage-dependent responsiveness of NSPCs to extrinsic cues is orchestrated at the epigenetic level. Epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNA-mediated regulation control crucial aspects of NSPC development and function, and are also implicated in pathological conditions. While their roles in the regulation of stem cell fate have been largely explored in pluripotent stem cell models, the epigenetic signature of NSPCs is also key to determine their multipotency as well as their progressive bias towards specific differentiation outcomes. Here we review recent developments in this field, focusing on the roles of histone methylation marks and the protein complexes controlling their deposition in NSPCs of the developing cerebral cortex and the adult subventricular zone. In this context, we describe how bivalent promoters, carrying antagonistic epigenetic modifications, feature during multiple steps of neural development, from neural lineage specification to neuronal differentiation. Furthermore, we discuss the emerging cross-talk between epigenetic regulators and microRNAs, and how the interplay between these different layers of regulation can finely tune the expression of genes controlling NSPC maintenance and differentiation. In particular, we highlight recent advances in the identification of astrocyte-enriched microRNAs and their function in cell fate choices of NSPCs differentiating towards glial lineages.

  3. Impact parameter determination for 40Ca + 40Ca reactions using a neural network

    International Nuclear Information System (INIS)

    Haddad, F.; Hagel, K.; Li, J.; Mdeiwayeh, N.; Natowitz, J.B.; Wada, R.; Xiao, B.; David, C.; Freslier, M.; Aichelin, J.

    1995-01-01

    A neural network is used for the impact parameter determination in 40 Ca + 40 Ca reactions at energies between 35 and 70 AMeV. A special attention is devoted to the effect of experimental constraints such as the detection efficiency. An overall improvement of the impact parameter determination of 25% is obtained with the neural network. The neural network technique is then used in the analysis of the Ca+Ca data at 35 AMeV and allows separation of three different class of events among the selected 'complete' events. (authors). 8 refs., 5 figs

  4. Landslide Susceptibility Index Determination Using Aritificial Neural Network

    Science.gov (United States)

    Kawabata, D.; Bandibas, J.; Urai, M.

    2004-12-01

    The occurrence of landslide is the result of the interaction of complex and diverse environmental factors. The geomorphic features, rock types and geologic structure are especially important base factors of the landslide occurrence. Generating landslide susceptibility index by defining the relationship between landslide occurrence and that base factors using conventional mathematical and statistical methods is very difficult and inaccurate. This study focuses on generating landslide susceptibility index using artificial neural networks in Southern Japanese Alps. The training data are geomorphic (e.g. altitude, slope and aspect) and geologic parameters (e.g. rock type, distance from geologic boundary and geologic dip-strike angle) and landslides. Artificial neural network structure and training scheme are formulated to generate the index. Data from areas with and without landslide occurrences are used to train the network. The network is trained to output 1 when the input data are from areas with landslides and 0 when no landslide occurred. The trained network generates an output ranging from 0 to 1 reflecting the possibility of landslide occurrence based on the inputted data. Output values nearer to 1 means higher possibility of landslide occurrence. The artificial neural network model is incorporated into the GIS software to generate a landslide susceptibility map.

  5. Nonsense-Mediated RNA Decay Influences Human Embryonic Stem Cell Fate

    Directory of Open Access Journals (Sweden)

    Chih-Hong Lou

    2016-06-01

    Full Text Available Nonsense-mediated RNA decay (NMD is a highly conserved pathway that selectively degrades specific subsets of RNA transcripts. Here, we provide evidence that NMD regulates early human developmental cell fate. We found that NMD factors tend to be expressed at higher levels in human pluripotent cells than in differentiated cells, raising the possibility that NMD must be downregulated to permit differentiation. Loss- and gain-of-function experiments in human embryonic stem cells (hESCs demonstrated that, indeed, NMD downregulation is essential for efficient generation of definitive endoderm. RNA-seq analysis identified NMD target transcripts induced when NMD is suppressed in hESCs, including many encoding signaling components. This led us to test the role of TGF-β and BMP signaling, which we found NMD acts through to influence definitive endoderm versus mesoderm fate. Our results suggest that selective RNA decay is critical for specifying the developmental fate of specific human embryonic cell lineages.

  6. The Yin and Yang of chromatin dynamics in adult stem cell fate selection

    Science.gov (United States)

    Adam, Rene C.; Fuchs, Elaine

    2015-01-01

    Adult organisms rely on tissue stem cells for maintenance and repair. During homeostasis, the concerted action of local niche signals and epigenetic regulators establish stable gene expression patterns to ensure that stem cells are not lost over time. However, stem cells also provide host tissues with a remarkable plasticity to respond to perturbations. How adult stem cells choose and acquire new fates is unknown, but the genome-wide mapping of epigenetic landscapes suggests a critical role for chromatin remodeling in these processes. Here, we explore the emerging role of chromatin modifiers and pioneer transcription factors in adult stem cell fate decisions and plasticity, which ensure that selective lineage choices are only made when environmentally cued. PMID:26689127

  7. Sensitivity analysis of intracellular signaling pathway kinetics predicts targets for stem cell fate control.

    Directory of Open Access Journals (Sweden)

    Alborz Mahdavi

    2007-07-01

    Full Text Available Directing stem cell fate requires knowledge of how signaling networks integrate temporally and spatially segregated stimuli. We developed and validated a computational model of signal transducer and activator of transcription-3 (Stat3 pathway kinetics, a signaling network involved in embryonic stem cell (ESC self-renewal. Our analysis identified novel pathway responses; for example, overexpression of the receptor glycoprotein-130 results in reduced pathway activation and increased ESC differentiation. We used a systematic in silico screen to identify novel targets and protein interactions involved in Stat3 activation. Our analysis demonstrates that signaling activation and desensitization (the inability to respond to ligand restimulation is regulated by balancing the activation state of a distributed set of parameters including nuclear export of Stat3, nuclear phosphatase activity, inhibition by suppressor of cytokine signaling, and receptor trafficking. This knowledge was used to devise a temporally modulated ligand delivery strategy that maximizes signaling activation and leads to enhanced ESC self-renewal.

  8. Roles of Notch1 Signaling in Regulating Satellite Cell Fates Choices and Postnatal Skeletal Myogenesis.

    Science.gov (United States)

    Shan, Tizhong; Xu, Ziye; Wu, Weiche; Liu, Jiaqi; Wang, Yizhen

    2017-11-01

    Adult skeletal muscle stem cells, also called satellite cells, are indispensable for the growth, maintenance, and regeneration of the postnatal skeletal muscle. Satellite cells, predominantly quiescent in mature resting muscles, are activated after skeletal muscle injury or degeneration. Notch1 signaling is an evolutionarily conserved pathway that plays crucial roles in satellite cells homeostasis and postnatal skeletal myogenesis and regeneration. Activation of Notch1 signaling promotes the muscle satellite cells quiescence and proliferation, but inhibits differentiation of muscle satellite cells. Notably, the new roles of Notch1 signaling during late-stage of skeletal myogenesis including in post-differentiation myocytes and post-fusion myotubes have been recently reported. Here, we mainly review and discuss the regulatory roles of Notch1 in regulating satellite cell fates choices and skeletal myogenesis. J. Cell. Physiol. 232: 2964-2967, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Differentially activated macrophages orchestrate myogenic precursor cell fate during human skeletal muscle regeneration

    DEFF Research Database (Denmark)

    Saclier, Marielle; Yacoub-Youssef, Houda; Mackey, Abigail

    2013-01-01

    , we explored both in vitro and in vivo, in human, the interactions of differentially activated MPs with myogenic precursor cells (MPCs) during adult myogenesis and skeletal muscle regeneration. We showed in vitro that through the differential secretion of cytokines and growth factors, proinflammatory...... anti-inflammatory markers. These data demonstrate for the first time in human that MPs sequentially orchestrate adult myogenesis during regeneration of damaged skeletal muscle. These results support the emerging concept that inflammation, through MP activation, controls stem cell fate and coordinates......Macrophages (MPs) exert either beneficial or deleterious effects on tissue repair, depending on their activation/polarization state. They are crucial for adult skeletal muscle repair, notably by acting on myogenic precursor cells. However, these interactions have not been fully characterized. Here...

  10. Synthetic Substrata to Instruct Human Pluripotent Stem Cell Fate: From Novel Ligands to Functional Biomaterials

    Science.gov (United States)

    Musah, Samira

    Human pluripotent stem (hPS) cells have the remarkable capacity to self-renew indefinitely and differentiate into desired cell types. They can serve as a virtually unlimited supply of cells for applications ranging from drug screening to cell therapies to understanding human development. Reaping the promise of hPS cells hinges on effective defined culture and differentiation conditions. Efforts to generate chemically-defined environments for hPS cell propagation and directed differentiation have been hindered by access to only a handful of ligands to target hPS cells. Additionally, progress has been limited also by lack of knowledge regarding the relevant functional properties of the cell culture substratum. To address these problems, I first employed forward-chemical-genetics coupled with self-assembled monolayer technology to identify novel peptides that bind to hPS cell-surface receptors. I then developed a controlled synthesis of hydrogels with tailored peptide display and mechanical properties. This approach yielded synthetic hydrogels with specific mechanical properties that function in a defined medium to robustly support hPS cell self-renewal. Finally, by starting from molecular level understanding that matrix elasticity regulates developmental pathways, I generated a highly efficient hydrogel platform that restricts hPS cell differentiation to neurons, even without soluble inductive factors. These results indicate that insoluble cues can be important information conduits to guide hPS cell fate decisions. I envision that the blueprint provided by this work can be utilized to devise new materials to guide hPS cell fate.

  11. Macrophage-derived Wnt opposes notch signaling to specify hepatic progenitor cell fate in chronic liver disease

    NARCIS (Netherlands)

    Boulter, L.; Govaere, O.; Bird, T.G.; Radulescu, S.; Ramachandran, P.; Pellicoro, A.; Ridgway, R.; Seo, S.S.; Spee, B.|info:eu-repo/dai/nl/304830925; van Rooijen, N.; Sansom, O.J.; Iredale, J.P.; Lowell, S.; Roskams, T.A.; Forbes, S.J.

    2012-01-01

    Nat Med. 2012 Mar 4;18(4):572-9. doi: 10.1038/nm.2667. Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease. Boulter L, Govaere O, Bird TG, Radulescu S, Ramachandran P, Pellicoro A, Ridgway RA, Seo SS, Spee B, Van Rooijen N, Sansom OJ,

  12. The selector gene Pax7 dictates alternate pituitary cell fates through its pioneer action on chromatin remodeling

    NARCIS (Netherlands)

    Budry, L.; Balsalobre, A.; Gauthier, Y.; Khetchoumian, K.; L'Honore, A.; Vallette-Kasic, S.; Brue, T; Figarella-Branger, D.; Meij, B.P.; Drouin, J.

    2012-01-01

    Genes Dev. 2012 Oct 15;26(20):2299-310. doi: 10.1101/gad.200436.112. The selector gene Pax7 dictates alternate pituitary cell fates through its pioneer action on chromatin remodeling. Budry L, Balsalobre A, Gauthier Y, Khetchoumian K, L'honoré A, Vallette S, Brue T, Figarella-Branger D, Meij B,

  13. Magnesium degradation as determined by artificial neural networks.

    Science.gov (United States)

    Willumeit, Regine; Feyerabend, Frank; Huber, Norbert

    2013-11-01

    Magnesium degradation under physiological conditions is a highly complex process in which temperature, the use of cell culture growth medium and the presence of CO2, O2 and proteins can influence the corrosion rate and the composition of the resulting corrosion layer. Due to the complexity of this process it is almost impossible to predict the parameters that are most important and whether some parameters have a synergistic effect on the corrosion rate. Artificial neural networks are a mathematical tool that can be used to approximate and analyse non-linear problems with multiple inputs. In this work we present the first analysis of corrosion data obtained using this method, which reveals that CO2 and the composition of the buffer system play a crucial role in the corrosion of magnesium, whereas O2, proteins and temperature play a less prominent role. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  14. Cell-type-specific predictive network yields novel insights into mouse embryonic stem cell self-renewal and cell fate.

    Directory of Open Access Journals (Sweden)

    Karen G Dowell

    Full Text Available Self-renewal, the ability of a stem cell to divide repeatedly while maintaining an undifferentiated state, is a defining characteristic of all stem cells. Here, we clarify the molecular foundations of mouse embryonic stem cell (mESC self-renewal by applying a proven Bayesian network machine learning approach to integrate high-throughput data for protein function discovery. By focusing on a single stem-cell system, at a specific developmental stage, within the context of well-defined biological processes known to be active in that cell type, we produce a consensus predictive network that reflects biological reality more closely than those made by prior efforts using more generalized, context-independent methods. In addition, we show how machine learning efforts may be misled if the tissue specific role of mammalian proteins is not defined in the training set and circumscribed in the evidential data. For this study, we assembled an extensive compendium of mESC data: ∼2.2 million data points, collected from 60 different studies, under 992 conditions. We then integrated these data into a consensus mESC functional relationship network focused on biological processes associated with embryonic stem cell self-renewal and cell fate determination. Computational evaluations, literature validation, and analyses of predicted functional linkages show that our results are highly accurate and biologically relevant. Our mESC network predicts many novel players involved in self-renewal and serves as the foundation for future pluripotent stem cell studies. This network can be used by stem cell researchers (at http://StemSight.org to explore hypotheses about gene function in the context of self-renewal and to prioritize genes of interest for experimental validation.

  15. Defined spatiotemporal features of RAS-ERK signals dictate cell fate in MCF-7 mammary epithelial cells.

    Science.gov (United States)

    Herrero, Ana; Casar, Berta; Colón-Bolea, Paula; Agudo-Ibáñez, Lorena; Crespo, Piero

    2016-06-15

    Signals conveyed through the RAS-ERK pathway are essential for the determination of cell fate. It is well established that signal variability is achieved in the different microenvironments in which signals unfold. It is also known that signal duration is critical for decisions concerning cell commitment. However, it is unclear how RAS-ERK signals integrate time and space in order to elicit a given biological response. To investigate this, we used MCF-7 cells, in which EGF-induced transient ERK activation triggers proliferation, whereas sustained ERK activation in response to heregulin leads to adipocytic differentiation. We found that both proliferative and differentiating signals emanate exclusively from plasma membrane-disordered microdomains. Of interest, the EGF signal can be transformed into a differentiating stimulus by HRAS overexpression, which prolongs ERK activation, but only if HRAS localizes at disordered membrane. On the other hand, HRAS signals emanating from the Golgi complex induce apoptosis and can prevent heregulin-induced differentiation. Our results indicate that within the same cellular context, RAS can exert different, even antagonistic, effects, depending on its sublocalization. Thus cell destiny is defined by the ability of a stimulus to activate RAS at the appropriate sublocalization for an adequate period while avoiding switching on opposing RAS signals. © 2016 Herrero et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  16. Phyllotactic pattern and stem cell fate are determined by the Arabidopsis homeobox gene BELLRINGER

    Science.gov (United States)

    Mary E. Byrne; Andrew T. Groover; Joseph R. Fontana; Robert A. Martienssen

    2003-01-01

    Lateral organs in plants arise from the meristem in a stereotypical pattern known as phyllotaxy. Spiral patterns result from initiation of successive organs at a fixed angle of divergence but variable patterns of physical contact. Such patterns ultimately give rise to individual leaves and flowers at positions related to each other by consecutive terms in the...

  17. CHD1 regulates cell fate determination by activation of differentiation-induced genes

    DEFF Research Database (Denmark)

    Baumgart, Simon J; Najafova, Zeynab; Hossan, Tareq

    2017-01-01

    The coordinated temporal and spatial activation of gene expression is essential for proper stem cell differentiation. The Chromodomain Helicase DNA-binding protein 1 (CHD1) is a chromatin remodeler closely associated with transcription and nucleosome turnover downstream of the transcriptional start...... site (TSS). In this study, we show that CHD1 is required for the induction of osteoblast-specific gene expression, extracellular-matrix mineralization and ectopic bone formation in vivo. Genome-wide occupancy analyses revealed increased CHD1 occupancy around the TSS of differentiation-activated genes....... Furthermore, we observed that CHD1-dependent genes are mainly induced during osteoblast differentiation and are characterized by higher levels of CHD1 occupancy around the TSS. Interestingly, CHD1 depletion resulted in increased pausing of RNA Polymerase II (RNAPII) and decreased H2A.Z occupancy close...

  18. Continuous-time modeling of cell fate determination in Arabidopsis flowers

    Directory of Open Access Journals (Sweden)

    Angenent Gerco C

    2010-07-01

    Full Text Available Abstract Background The genetic control of floral organ specification is currently being investigated by various approaches, both experimentally and through modeling. Models and simulations have mostly involved boolean or related methods, and so far a quantitative, continuous-time approach has not been explored. Results We propose an ordinary differential equation (ODE model that describes the gene expression dynamics of a gene regulatory network that controls floral organ formation in the model plant Arabidopsis thaliana. In this model, the dimerization of MADS-box transcription factors is incorporated explicitly. The unknown parameters are estimated from (known experimental expression data. The model is validated by simulation studies of known mutant plants. Conclusions The proposed model gives realistic predictions with respect to independent mutation data. A simulation study is carried out to predict the effects of a new type of mutation that has so far not been made in Arabidopsis, but that could be used as a severe test of the validity of the model. According to our predictions, the role of dimers is surprisingly important. Moreover, the functional loss of any dimer leads to one or more phenotypic alterations.

  19. Asymmetric cell division and its role in cell fate determination in the green alga Tetraselmis indica

    Digital Repository Service at National Institute of Oceanography (India)

    Arora, M.; Anil, A.C.; Burgess, K.; Delany, J.E.; Mesbahi, E.

    is a mechanism to ensure survival upon exposure to stress. Int. J. Food Microbiol. 78 19-30 De Smet I and Beeckman T 2011 Asymmetric cell division in land plants and algae: the driving force for differentiation. Nature Rev. Mol. Cell Biol. 12 177... of Prasinophytes, but are as evolved as any other green alga or land plant. These organisms share several ultrastructural features with the other core Chlorophytes (Trebouxiophyceae, Ulvophyceae and Chlorophyceae). However, the role of Chlorodendrophycean algae...

  20. Cell fate in the Arabidopsis root meristem determined by directional signalling

    NARCIS (Netherlands)

    Berg, C. van den; Willemsen, V.; Hage, W.; Weisbeek, P.; Scheres, B.J.G.

    1995-01-01

    Postembryonic development in plants is achieved by apical meristems. Surgical studies and clonal analysis have revealed indirectly that cells in shoot meristems have no predictable destiny and that position is likely to play a role in the acquisition of cell identity . In contrast to animal

  1. Asymmetric cell division and its role in cell fate determination in the ...

    Indian Academy of Sciences (India)

    Supplementary figure 1. Light micrograph of an asymmetrically dividing T. indica cell at various time intervals. Progress over a 12 hr period, showing that the larger component does not undergo further division. (A) 0 h, cell division at an early stage. (B) 5 h, lower half of cell undergoing further division. (C) 12 h, differentiated ...

  2. Sigma factors, asymmetry, and the determination of cell fate in Bacillus subtilis.

    OpenAIRE

    Lewis, P J; Partridge, S R; Errington, J

    1994-01-01

    Soon after the initiation of sporulation, Bacillus subtilis divides asymmetrically to produce sister cells that have very different developmental fates. Recently, it has been proposed that the differential gene expression which begins soon after this division is due to cell-specific activation of the transcription factors sigma F and sigma E in the prespore and the mother cell, respectively. We describe the use of a method for the localization of gene expression in individual sporulating cell...

  3. Asymmetric cell division and its role in cell fate determination in the ...

    Indian Academy of Sciences (India)

    2015-12-04

    Dec 4, 2015 ... F/2 media (Guillard and Ryther 1962) without silicates, at. 25°C, photon flux ... transmission electron microscope and digital images were collected .... UK Department for Education and Skills (DfES), Office of. Science and ...

  4. Mediator Med23 deficiency enhances neural differentiation of murine embryonic stem cells through modulating BMP signaling.

    Science.gov (United States)

    Zhu, Wanqu; Yao, Xiao; Liang, Yan; Liang, Dan; Song, Lu; Jing, Naihe; Li, Jinsong; Wang, Gang

    2015-02-01

    Unraveling the mechanisms underlying early neural differentiation of embryonic stem cells (ESCs) is crucial to developing cell-based therapies of neurodegenerative diseases. Neural fate acquisition is proposed to be controlled by a 'default' mechanism, for which the molecular regulation is not well understood. In this study, we investigated the functional roles of Mediator Med23 in pluripotency and lineage commitment of murine ESCs. Unexpectedly, we found that, despite the largely unchanged pluripotency and self-renewal of ESCs, Med23 depletion rendered the cells prone to neural differentiation in different differentiation assays. Knockdown of two other Mediator subunits, Med1 and Med15, did not alter the neural differentiation of ESCs. Med15 knockdown selectively inhibited endoderm differentiation, suggesting the specificity of cell fate control by distinctive Mediator subunits. Gene profiling revealed that Med23 depletion attenuated BMP signaling in ESCs. Mechanistically, MED23 modulated Bmp4 expression by controlling the activity of ETS1, which is involved in Bmp4 promoter-enhancer communication. Interestingly, med23 knockdown in zebrafish embryos also enhanced neural development at early embryogenesis, which could be reversed by co-injection of bmp4 mRNA. Taken together, our study reveals an intrinsic, restrictive role of MED23 in early neural development, thus providing new molecular insights for neural fate determination. © 2015. Published by The Company of Biologists Ltd.

  5. Egg cell signaling by the secreted peptide ZmEAL1 controls antipodal cell fate.

    Science.gov (United States)

    Krohn, Nadia Graciele; Lausser, Andreas; Juranić, Martina; Dresselhaus, Thomas

    2012-07-17

    Unlike in animals, female gametes of flowering plants are not the direct products of meiosis but develop from a functional megaspore after three rounds of free mitotic divisions. After nuclei migration and positioning, the eight-nucleate syncytium differentiates into the embryo sac, which contains two female gametes as well as accessory cells at the micropylar and chalazal pole, respectively. We report that an egg-cell-specific gene, ZmEAL1, is activated at the micropylar pole of the eight-nucleate syncytium. ZmEAL1 translation is restricted to the egg cell, resulting in the generation of peptide-containing vesicles directed toward its chalazal pole. RNAi knockdown studies show that ZmEAL1 is required for robust expression of the proliferation-regulatory gene IG1 at the chalazal pole of the embryo sac in antipodal cells. We further show that ZmEAL1 is required to prevent antipodal cells from adopting central cell fate. These findings show how egg cells orchestrate differentiation of the embryo sac. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Host–virus dynamics and subcellular controls of cell fate in a natural coccolithophore population

    Science.gov (United States)

    Vardi, Assaf; Haramaty, Liti; Van Mooy, Benjamin A. S.; Fredricks, Helen F.; Kimmance, Susan A.; Larsen, Aud; Bidle, Kay D.

    2012-01-01

    Marine viruses are major evolutionary and biogeochemical drivers in marine microbial foodwebs. However, an in-depth understanding of the cellular mechanisms and the signal transduction pathways mediating host–virus interactions during natural bloom dynamics has remained elusive. We used field-based mesocosms to examine the “arms race” between natural populations of the coccolithophore Emiliania huxleyi and its double-stranded DNA-containing coccolithoviruses (EhVs). Specifically, we examined the dynamics of EhV infection and its regulation of cell fate over the course of bloom development and demise using a diverse suite of molecular tools and in situ fluorescent staining to target different levels of subcellular resolution. We demonstrate the concomitant induction of reactive oxygen species, caspase-specific activity, metacaspase expression, and programmed cell death in response to the accumulation of virus-derived glycosphingolipids upon infection of natural E. huxleyi populations. These subcellular responses to viral infection simultaneously resulted in the enhanced production of transparent exopolymer particles, which can facilitate aggregation and stimulate carbon flux. Our results not only corroborate the critical role for glycosphingolipids and programmed cell death in regulating E. huxleyi–EhV interactions, but also elucidate promising molecular biomarkers and lipid-based proxies for phytoplankton host–virus interactions in natural systems. PMID:23134731

  7. Metabolism of murine TH 17 cells: Impact on cell fate and function.

    Science.gov (United States)

    Wang, Ran; Solt, Laura A

    2016-04-01

    An effective adaptive immune response relies on the ability of lymphocytes to rapidly act upon a variety of insults. In T lymphocytes, this response includes cell growth, clonal expansion, differentiation, and cytokine production, all of which place a significant energy burden on the cell. Recent evidence shows that T-cell metabolic reprogramming is an essential component of the adaptive immune response and specific metabolic pathways dictate T-cell fate decisions, including the development of TH 17 versus T regulatory (Treg) cells. TH 17 cells have garnered significant attention due to their roles in the pathology of immune-mediated inflammatory diseases. Attempts to characterize TH 17 cells have demonstrated that they are highly dynamic, adjusting their function to environmental cues, which dictate their metabolic program. In this review, we highlight recent data demonstrating the impact of cellular metabolism on the TH 17/Treg balance and present factors that mediate TH 17-cell metabolism. Some examples of these include the differential impact of the mTOR signaling complexes on T-helper-cell differentiation, hypoxia inducible factor 1 alpha (HIF1α) promotion of glycolysis to favor TH 17-cell development, and ACC1-dependent de novo fatty acid synthesis favoring TH 17-cell development over Treg cells. Finally, we discuss the potential therapeutic options and the implications of modulating TH 17-cell metabolism for the treatment of TH 17-mediated diseases. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Physical constraints in cell fate specification. A case in point: Microgravity and phenotypes differentiation.

    Science.gov (United States)

    Masiello, Maria Grazia; Verna, Roberto; Cucina, Alessandra; Bizzarri, Mariano

    2018-05-01

    Data obtained by studying mammalian cells in absence of gravity strongly support the notion that cell fate specification cannot be understood according to the current molecular model. A paradigmatic case in point is provided by studying cell populations growing in absence of gravity. When the physical constraint (gravity) is 'experimentally removed', cells spontaneously allocate into two morphologically different phenotypes. Such phenomenon is likely enacted by the intrinsic stochasticity, which, in turn, is successively 'canalized' by a specific gene regulatory network. Both phenotypes are thermodynamically and functionally 'compatibles' with the new, modified environment. However, when the two cell subsets are reseeded into the 1g gravity field the two phenotypes collapse into one. Gravity constraints the system in adopting only one phenotype, not by selecting a pre-existing configuration, but more precisely shaping it de-novo through the modification of the cytoskeleton three-dimensional structure. Overall, those findings highlight how macro-scale features are irreducible to lower-scale explanations. The identification of macroscale control parameters - as those depending on the field (gravity, electromagnetic fields) or emerging from the cooperativity among the field's components (tissue stiffness, cell-to-cell connectivity) - are mandatory for assessing boundary conditions for models at lower scales, thus providing a concrete instantiation of top-down effects. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Jagged2a-notch signaling mediates cell fate choice in the zebrafish pronephric duct.

    Directory of Open Access Journals (Sweden)

    Ming Ma

    2007-01-01

    Full Text Available Pronephros, a developmental model for adult mammalian kidneys (metanephros and a functional kidney in early teleosts, consists of glomerulus, tubule, and duct. These structural and functional elements are responsible for different kidney functions, e.g., blood filtration, waste extraction, salt recovery, and water balance. During pronephros organogenesis, cell differentiation is a key step in generating different cell types in specific locations to accomplish designated functions. However, it is poorly understood what molecules regulate the differentiation of different cell types in different parts of the kidney. Two types of epithelial cells, multi-cilia cells and principal cells, are found in the epithelia of the zebrafish distal pronephric duct. While the former is characterized by at least 15 apically localized cilia and expresses centrin2 and rfx2, the latter is characterized by a single primary cilium and sodium pumps. Multi-cilia cells and principal cells differentiate from 17.5 hours post-fertilization onwards in a mosaic pattern. Jagged2a-Notch1a/Notch3-Her9 is responsible for specification and patterning of these two cell types through a lateral inhibition mechanism. Furthermore, multi-cilia cell hyperplasia was observed in mind bomb mutants and Mind bomb was shown to interact with Jagged2a and facilitate its internalization. Taken together, our findings add a new paradigm of Notch signaling in kidney development, namely, that Jagged2a-Notch signaling modulates cell fate choice in a nephric segment, the distal pronephric duct.

  10. Human mammary progenitor cell fate decisions are products of interactions with combinatorial microenvironments

    Energy Technology Data Exchange (ETDEWEB)

    LaBarge, Mark A; Nelson, Celeste M; Villadsen, Rene; Fridriksdottir, Agla; Ruth, Jason R; Stampfer, Martha R; Petersen, Ole W; Bissell, Mina J

    2008-09-19

    In adult tissues, multi-potent progenitor cells are some of the most primitive members of the developmental hierarchies that maintain homeostasis. That progenitors and their more mature progeny share identical genomes, suggests that fate decisions are directed by interactions with extrinsic soluble factors, ECM, and other cells, as well as physical properties of the ECM. To understand regulation of fate decisions, therefore, would require a means of understanding carefully choreographed combinatorial interactions. Here we used microenvironment protein microarrays to functionally identify combinations of cell-extrinsic mammary gland proteins and ECM molecules that imposed specific cell fates on bipotent human mammary progenitor cells. Micropatterned cell culture surfaces were fabricated to distinguish between the instructive effects of cell-cell versus cell-ECM interactions, as well as constellations of signaling molecules; and these were used in conjunction with physiologically relevant 3 dimensional human breast cultures. Both immortalized and primary human breast progenitors were analyzed. We report on the functional ability of those proteins of the mammary gland that maintain quiescence, maintain the progenitor state, and guide progenitor differentiation towards myoepithelial and luminal lineages.

  11. Phosphorylated DegU Manipulates Cell Fate Differentiation in the Bacillus subtilis Biofilm

    Science.gov (United States)

    Marlow, Victoria L.; Porter, Michael; Hobley, Laura; Kiley, Taryn B.; Swedlow, Jason R.; Davidson, Fordyce A.

    2014-01-01

    Cell differentiation is ubiquitous and facilitates division of labor and development. Bacteria are capable of multicellular behaviors that benefit the bacterial community as a whole. A striking example of bacterial differentiation occurs throughout the formation of a biofilm. During Bacillus subtilis biofilm formation, a subpopulation of cells differentiates into a specialized population that synthesizes the exopolysaccharide and the TasA amyloid components of the extracellular matrix. The differentiation process is indirectly controlled by the transcription factor Spo0A that facilitates transcription of the eps and tapA (tasA) operons. DegU is a transcription factor involved in regulating biofilm formation. Here, using a combination of genetics and live single-cell cytological techniques, we define the mechanism of biofilm inhibition at high levels of phosphorylated DegU (DegU∼P) by showing that transcription from the eps and tapA promoter regions is inhibited. Data demonstrating that this is not a direct regulatory event are presented. We demonstrate that DegU∼P controls the frequency with which cells activate transcription from the operons needed for matrix biosynthesis in favor of an off state. Subsequent experimental analysis led us to conclude that DegU∼P functions to increase the level of Spo0A∼P, driving cell fate differentiation toward the terminal developmental process of sporulation. PMID:24123822

  12. A Blueprint for a Synthetic Genetic Feedback Controller to Reprogram Cell Fate.

    Science.gov (United States)

    Del Vecchio, Domitilla; Abdallah, Hussein; Qian, Yili; Collins, James J

    2017-01-25

    To artificially reprogram cell fate, experimentalists manipulate the gene regulatory networks (GRNs) that maintain a cell's phenotype. In practice, reprogramming is often performed by constant overexpression of specific transcription factors (TFs). This process can be unreliable and inefficient. Here, we address this problem by introducing a new approach to reprogramming based on mathematical analysis. We demonstrate that reprogramming GRNs using constant overexpression may not succeed in general. Instead, we propose an alternative reprogramming strategy: a synthetic genetic feedback controller that dynamically steers the concentration of a GRN's key TFs to any desired value. The controller works by adjusting TF expression based on the discrepancy between desired and actual TF concentrations. Theory predicts that this reprogramming strategy is guaranteed to succeed, and its performance is independent of the GRN's structure and parameters, provided that feedback gain is sufficiently high. As a case study, we apply the controller to a model of induced pluripotency in stem cells. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Sox17-Mediated XEN Cell Conversion Identifies Dynamic Networks Controlling Cell-Fate Decisions in Embryo-Derived Stem Cells

    Directory of Open Access Journals (Sweden)

    Angela C.H. McDonald

    2014-10-01

    Full Text Available Little is known about the gene regulatory networks (GRNs distinguishing extraembryonic endoderm (ExEn stem (XEN cells from those that maintain the extensively characterized embryonic stem cell (ESC. An intriguing network candidate is Sox17, an essential transcription factor for XEN derivation and self-renewal. Here, we show that forced Sox17 expression drives ESCs toward ExEn, generating XEN cells that contribute to ExEn when placed back into early mouse embryos. Transient Sox17 expression is sufficient to drive this fate change during which time cells transit through distinct intermediate states prior to the generation of functional XEN-like cells. To orchestrate this conversion process, Sox17 acts in autoregulatory and feedforward network motifs, regulating dynamic GRNs directing cell fate. Sox17-mediated XEN conversion helps to explain the regulation of cell-fate changes and reveals GRNs regulating lineage decisions in the mouse embryo.

  14. Adaptive online state-of-charge determination based on neuro-controller and neural network

    Energy Technology Data Exchange (ETDEWEB)

    Shen Yanqing, E-mail: network_hawk@126.co [Department of Automation, Chongqing Industry Polytechnic College, Jiulongpo District, Chongqing 400050 (China)

    2010-05-15

    This paper presents a novel approach using adaptive artificial neural network based model and neuro-controller for online cell State of Charge (SOC) determination. Taking cell SOC as model's predictive control input unit, radial basis function neural network, which can adjust its structure to prediction error with recursive least square algorithm, is used to simulate battery system. Besides that, neuro-controller based on Back-Propagation Neural Network (BPNN) and modified PID controller is used to decide the control input of battery system, i.e., cell SOC. Finally this algorithm is applied for the SOC determination of lead-acid batteries, and results of lab tests on physical cells, compared with model prediction, are presented. Results show that the ANN based battery system model adaptively simulates battery system with great accuracy, and the predicted SOC simultaneously converges to the real value quickly within the error of +-1 as time goes on.

  15. The use of skewness, kurtosis and neural networks for determining corrosion mechanism from electrochemical noise data

    International Nuclear Information System (INIS)

    Reid, S.; Bell, G.E.C.; Edgemon, G.L.

    1998-01-01

    This paper describes the work undertaken to de-skill the complex procedure of determining corrosion mechanisms derived from electrochemical noise data. The use of neural networks is discussed and applied to the real time generated electrochemical noise data files with the purpose of determining characteristics particular to individual types of corrosion mechanisms. The electrochemical noise signals can have a wide dynamic range and various methods of raw data pre-processing prior to neural network analysis were investigated. Normalized data were ultimately used as input to the final network analysis. Various network schemes were designed, trained and tested. Factors such as the network learning schedule and network design were considered before a final network was implemented to achieve a solution. Neural networks trained using general and localized corrosion data from various material environment systems were used to analyze data from simulated nuclear waste tank environments with favorable results

  16. Neural and behavioral associations of manipulated determination facial expressions.

    Science.gov (United States)

    Price, Tom F; Hortensius, Ruud; Harmon-Jones, Eddie

    2013-09-01

    Past research associated relative left frontal cortical activity with positive affect and approach motivation, or the urge to move toward a stimulus. Less work has examined relative left frontal activity and positive emotions ranging from low to high approach motivation, to test whether positive affects that differ in approach motivational intensity influence relative left frontal cortical activity. Participants in the present experiment adopted determination (high approach positive), satisfaction (low approach positive), or neutral facial expressions while electroencephalographic (EEG) activity was recorded. Next, participants completed a task measuring motivational persistence behavior and then they completed self-report emotion questionnaires. Determination compared to satisfaction and neutral facial expressions caused greater relative left frontal activity relative to baseline EEG recordings. Facial expressions did not directly influence task persistence. However, relative left frontal activity correlated positively with persistence on insolvable tasks in the determination condition. These results extend embodiment theories and motivational interpretations of relative left frontal activity. Published by Elsevier B.V.

  17. Essential role of Bmp signaling and its positive feedback loop in the early cell fate evolution of chordates

    Czech Academy of Sciences Publication Activity Database

    Kozmiková, Iryna; Candiani, S.; Fabian, Peter; Gurská, Daniela; Kozmik, Zbyněk

    2013-01-01

    Roč. 382, č. 2 (2013), s. 538-554 ISSN 0012-1606 R&D Projects: GA ČR GCP305/10/J064; GA MŠk EE2.3.30.0027 Institutional support: RVO:68378050 Keywords : Bmp signaling * axial patterning * cell fate * chordates * evolution Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.637, year: 2013

  18. Redundant mechanisms are involved in suppression of default cell fates during embryonic mesenchyme and notochord induction in ascidians.

    Science.gov (United States)

    Kodama, Hitoshi; Miyata, Yoshimasa; Kuwajima, Mami; Izuchi, Ryoichi; Kobayashi, Ayumi; Gyoja, Fuki; Onuma, Takeshi A; Kumano, Gaku; Nishida, Hiroki

    2016-08-01

    During embryonic induction, the responding cells invoke an induced developmental program, whereas in the absence of an inducing signal, they assume a default uninduced cell fate. Suppression of the default fate during the inductive event is crucial for choice of the binary cell fate. In contrast to the mechanisms that promote an induced cell fate, those that suppress the default fate have been overlooked. Upon induction, intracellular signal transduction results in activation of genes encoding key transcription factors for induced tissue differentiation. It is elusive whether an induced key transcription factor has dual functions involving suppression of the default fates and promotion of the induced fate, or whether suppression of the default fate is independently regulated by other factors that are also downstream of the signaling cascade. We show that during ascidian embryonic induction, default fates were suppressed by multifold redundant mechanisms. The key transcription factor, Twist-related.a, which is required for mesenchyme differentiation, and another independent transcription factor, Lhx3, which is dispensable for mesenchyme differentiation, sequentially and redundantly suppress the default muscle fate in induced mesenchyme cells. Similarly in notochord induction, Brachyury, which is required for notochord differentiation, and other factors, Lhx3 and Mnx, are likely to suppress the default nerve cord fate redundantly. Lhx3 commonly suppresses the default fates in two kinds of induction. Mis-activation of the autonomously executed default program in induced cells is detrimental to choice of the binary cell fate. Multifold redundant mechanisms would be required for suppression of the default fate to be secure. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Asymmetric Localization of Cdx2 mRNA during the First Cell-Fate Decision in Early Mouse Development

    Directory of Open Access Journals (Sweden)

    Maria Skamagki

    2013-02-01

    Full Text Available A longstanding question in mammalian development is whether the divisions that segregate pluripotent progenitor cells for the future embryo from cells that differentiate into extraembryonic structures are asymmetric in cell-fate instructions. The transcription factor Cdx2 plays a key role in the first cell-fate decision. Here, using live-embryo imaging, we show that localization of Cdx2 transcripts becomes asymmetric during development, preceding cell lineage segregation. Cdx2 transcripts preferentially localize apically at the late eight-cell stage and become inherited asymmetrically during divisions that set apart pluripotent and differentiating cells. Asymmetric localization depends on a cis element within the coding region of Cdx2 and requires cell polarization as well as intact microtubule and actin cytoskeletons. Failure to enrich Cdx2 transcripts apically results in a significant decrease in the number of pluripotent cells. We discuss how the asymmetric localization and segregation of Cdx2 transcripts could contribute to multiple mechanisms that establish different cell fates in the mouse embryo.

  20. Applying of neural networks in determination of replacement cycle of spare parts

    International Nuclear Information System (INIS)

    Saric, Tomislav; Majdandzic; Niko; Lujic, Roberto

    2003-01-01

    The article shows neural networks applicability to determine expected working time of equipment components before the damage. The results based on measure - simulated values of suggested model have been presented. Advantages of suggested model have been analyzed compared to traditional way of replacement of spare parts and components. Implementation possibility of suggested model in Management Information Maintenance System has been described. (author)

  1. Dynamic analysis of the combinatorial regulation involving transcription factors and microRNAs in cell fate decisions.

    Science.gov (United States)

    Yan, Fang; Liu, Haihong; Liu, Zengrong

    2014-01-01

    P53 and E2F1 are critical transcription factors involved in the choices between different cell fates including cell differentiation, cell cycle arrest or apoptosis. Recent experiments have shown that two families of microRNAs (miRNAs), p53-responsive miR34 (miRNA-34 a, b and c) and E2F1-inducible miR449 (miRNA-449 a, b and c) are potent inducers of these different fates and might have an important role in sensitizing cancer cells to drug treatment and tumor suppression. Identifying the mechanisms responsible for the combinatorial regulatory roles of these two transcription factors and two miRNAs is an important and challenging problem. Here, based in part on the model proposed in Tongli Zhang et al. (2007), we developed a mathematical model of the decision process and explored the combinatorial regulation between these two transcription factors and two miRNAs in response to DNA damage. By analyzing nonlinear dynamic behaviors of the model, we found that p53 exhibits pulsatile behavior. Moreover, a comparison is given to reveal the subtle differences of the cell fate decision process between regulation and deregulation of miR34 on E2F1. It predicts that miR34 plays a critical role in promoting cell cycle arrest. In addition, a computer simulation result also predicts that the miR449 is necessary for apoptosis in response to sustained DNA damage. In agreement with experimental observations, our model can account for the intricate regulatory relationship between these two transcription factors and two miRNAs in the cell fate decision process after DNA damage. These theoretical results indicate that miR34 and miR449 are effective tumor suppressors and play critical roles in cell fate decisions. The work provides a dynamic mechanism that shows how cell fate decisions are coordinated by two transcription factors and two miRNAs. This article is part of a Special Issue entitled: Computational Proteomics, Systems Biology and Clinical Implications. Guest Editor: Yudong Cai

  2. miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells.

    Science.gov (United States)

    Sun, GuoQiang; Ye, Peng; Murai, Kiyohito; Lang, Ming-Fei; Li, Shengxiu; Zhang, Heying; Li, Wendong; Fu, Chelsea; Yin, Jason; Wang, Allen; Ma, Xiaoxiao; Shi, Yanhong

    2011-11-08

    miR-137 is a brain-enriched microRNA. Its role in neural development remains unknown. Here we show that miR-137 has an essential role in controlling embryonic neural stem cell fate determination. miR-137 negatively regulates cell proliferation and accelerates neural differentiation of embryonic neural stem cells. In addition, we show that the histone lysine-specific demethylase 1 (LSD1), a transcriptional co-repressor of nuclear receptor TLX, is a downstream target of miR-137. In utero electroporation of miR-137 in embryonic mouse brains led to premature differentiation and outward migration of the transfected cells. Introducing a LSD1 expression vector lacking the miR-137 recognition site rescued miR-137-induced precocious differentiation. Furthermore, we demonstrate that TLX, an essential regulator of neural stem cell self-renewal, represses the expression of miR-137 by recruiting LSD1 to the genomic regions of miR-137. Thus, miR-137 forms a feedback regulatory loop with TLX and LSD1 to control the dynamics between neural stem cell proliferation and differentiation during neural development.

  3. Engineering the human pluripotent stem cell microenvironment to direct cell fate.

    Science.gov (United States)

    Hazeltine, Laurie B; Selekman, Joshua A; Palecek, Sean P

    2013-11-15

    Human pluripotent stem cells (hPSCs), including both embryonic stem cells and induced pluripotent stem cells, offer a potential cell source for research, drug screening, and regenerative medicine applications due to their unique ability to self-renew or differentiate to any somatic cell type. Before the full potential of hPSCs can be realized, robust protocols must be developed to direct their fate. Cell fate decisions are based on components of the surrounding microenvironment, including soluble factors, substrate or extracellular matrix, cell-cell interactions, mechanical forces, and 2D or 3D architecture. Depending on their spatio-temporal context, these components can signal hPSCs to either self-renew or differentiate to cell types of the ectoderm, mesoderm, or endoderm. Researchers working at the interface of engineering and biology have identified various factors which can affect hPSC fate, often based on lessons from embryonic development, and they have utilized this information to design in vitro niches which can reproducibly direct hPSC fate. This review highlights culture systems that have been engineered to promote self-renewal or differentiation of hPSCs, with a focus on studies that have elucidated the contributions of specific microenvironmental cues in the context of those culture systems. We propose the use of microsystem technologies for high-throughput screening of spatial-temporal presentation of cues, as this has been demonstrated to be a powerful approach for differentiating hPSCs to desired cell types. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Determination of daily solar ultraviolet radiation using statistical models and artificial neural networks

    Directory of Open Access Journals (Sweden)

    F. J. Barbero

    2006-09-01

    Full Text Available In this study, two different methodologies are used to develop two models for estimating daily solar UV radiation. The first is based on traditional statistical techniques whereas the second is based on artificial neural network methods. Both models use daily solar global broadband radiation as the only measured input. The statistical model is derived from a relationship between the daily UV and the global clearness indices but modulated by the relative optical air mass. The inputs to the neural network model were determined from a large number of radiometric and atmospheric parameters using the automatic relevance determination method, although only the daily solar global irradiation, daily global clearness index and relative optical air mass were shown to be the optimal input variables. Both statistical and neural network models were developed using data measured at Almería (Spain, a semiarid and coastal climate, and tested against data from Table Mountain (Golden, CO, USA, a mountainous and dry environment. Results show that the statistical model performs adequately in both sites for all weather conditions, especially when only snow-free days at Golden were considered (RMSE=4.6%, MBE= –0.1%. The neural network based model provides the best overall estimates in the site where it has been trained, but presents an inadequate performance for the Golden site when snow-covered days are included (RMSE=6.5%, MBE= –3.0%. This result confirms that the neural network model does not adequately respond on those ranges of the input parameters which were not used for its development.

  5. The feasibility of using neural networks for determination of control rod elevation in a PWR

    International Nuclear Information System (INIS)

    Garis, N.S.; Temesvari, E.; Pazsit, I.

    1996-08-01

    This paper presents the results of a preliminary study on using neural networks for determination of the axial position of control rods in PWRs. The method is based on the dependence of the axial flux profile on control rod elevation in a reactor. This flux profile can be measured by e.g. a moveable detector in an operating plant. However, in this preliminary study the flux profile is only calculated using an advanced core code for several axial positions of a partially inserted control rod. The calculated fluxes with corresponding positions of the control rod are used for training a neural network. Using the trained network it is then possible to determine the unknown axial position of a control rod elevation from the corresponding axial flux profile. 10 refs

  6. Dll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis.

    Science.gov (United States)

    Kawaguchi, Daichi; Furutachi, Shohei; Kawai, Hiroki; Hozumi, Katsuto; Gotoh, Yukiko

    2013-01-01

    Stem cells often divide asymmetrically to produce one stem cell and one differentiating cell, thus maintaining the stem cell pool. Although neural stem cells (NSCs) in the adult mouse subventricular zone have been suggested to divide asymmetrically, intrinsic cell fate determinants for asymmetric NSC division are largely unknown. Stem cell niches are important for stem cell maintenance, but the niche for the maintenance of adult quiescent NSCs has remained obscure. Here we show that the Notch ligand Delta-like 1 (Dll1) is required to maintain quiescent NSCs in the adult mouse subventricular zone. Dll1 protein is induced in activated NSCs and segregates to one daughter cell during mitosis. Dll1-expressing cells reside in close proximity to quiescent NSCs, suggesting a feedback signal for NSC maintenance by their sister cells and progeny. Our data suggest a model in which NSCs produce their own niche cells for their maintenance through asymmetric Dll1 inheritance at mitosis.

  7. Determination of crack size around rivet hole through neural network using ultrasonic Lamb wave

    International Nuclear Information System (INIS)

    Choi, Sang Woo; Lee, Joon Hyun

    1998-01-01

    Rivets are typical structural features that are potential initiation sites for fatigue crack due to combination of local stress concentration around rivet hole and moisture trapping. For the viewpoint of structural assurance, it is crucial to evaluate the size of crack around rivets by appropriate nondestructive techniques. Guided waves, which direct wave energy along the plate, carry information about the material in their path and offer a potentially more efficient tool for nondestructive inspection of structural material. Neural network that is considered to be the most suitable for pattern recognition and has been used by researchers in NDE field to classify different types of flaws and flaw size. In this study, crack size determination around rivet through a neural network based on the back-propagation algorithm has been done by extracting some feature from time-domain waveforms of ultrasonic Lamb wave for Al 2024-T3 skin panel of aircraft. Special attention was paid to reduce the coupling effect between transducer and specimen by extracting some features related to only time component data in ultrasonic waveform. It was demonstrated clearly that features extraction based on time component data of the time-domain waveform of Lamb wave was very useful to determine crack size initiated from rivet hole through neural network.

  8. Automatic determination of pathological voice transformation coefficients for TDPDOLA using neural network

    International Nuclear Information System (INIS)

    Belgacem, H.; Cherif, A.

    2011-01-01

    One of the biggest challenges in vocal transformation with TD-PSOLA technique is the selection of modified parameters that will make a successful speech resynthesis. The best selection methods are by using human ratters. This study focuses on automatic determination of the pathological voice transformation coefficients using an Artificial Neural Network this way by comparing the results to the previous manual work. Four characterizied parameters (RATA-PLP, Jitter, Shimmer and RAP) were chosen. The system is developed with supervised training, consists of recognition (neural network) for synthesis (TD-PSOLA). The experimental results show that the parameter sets selected by the proposed system can be successfully used to resynthesize and demonstrating that our system can assist in vocal of pathological voice's transformation.

  9. Building the Future: Post-transcriptional Regulation of Cell Fate Decisions Prior to the Xenopus Midblastula Transition.

    Science.gov (United States)

    Sheets, Michael D

    2015-01-01

    In all animals, a critical period in early development is when embryonic cells switch from relying solely upon maternally deposited RNAs and proteins to relying upon molecules encoded by the zygotic genome. Xenopus embryos have served as a model for examining this switch, as well as the maternally controlled stages that prepare for it. In Xenopus, the robust activation of zygotic transcription occurs at the 12th cleavage division and is referred to as the midblastula transition (MBT). Prior to MBT, gene expression is regulated by post-transcriptional events including mRNA and protein localization, protein post-translational modification, and mRNA translation. After the MBT, appropriate transcriptional regulation of the zygotic genome becomes critical and predominates. However, it is important to realize that the first key cell fate decisions that have profound impacts on development occur prior to the MBT and these are governed by regulating the expression of maternally deposited regulatory mRNAs and proteins. In this chapter, I will discuss post-transcriptional mechanisms that function during the maternal stages of Xenopus development with an emphasis on mechanisms known to directly modulate cell fate decisions. Emerging approaches and technologies that will help better understand this phase of development will also be discussed. © 2015 Elsevier Inc. All rights reserved.

  10. Cell fate specification in the lingual epithelium is controlled by antagonistic activities of Sonic hedgehog and retinoic acid.

    Science.gov (United States)

    El Shahawy, Maha; Reibring, Claes-Göran; Neben, Cynthia L; Hallberg, Kristina; Marangoni, Pauline; Harfe, Brian D; Klein, Ophir D; Linde, Anders; Gritli-Linde, Amel

    2017-07-01

    The interaction between signaling pathways is a central question in the study of organogenesis. Using the developing murine tongue as a model, we uncovered unknown relationships between Sonic hedgehog (SHH) and retinoic acid (RA) signaling. Genetic loss of SHH signaling leads to enhanced RA activity subsequent to loss of SHH-dependent expression of Cyp26a1 and Cyp26c1. This causes a cell identity switch, prompting the epithelium of the tongue to form heterotopic minor salivary glands and to overproduce oversized taste buds. At developmental stages during which Wnt10b expression normally ceases and Shh becomes confined to taste bud cells, loss of SHH inputs causes the lingual epithelium to undergo an ectopic and anachronic expression of Shh and Wnt10b in the basal layer, specifying de novo taste placode induction. Surprisingly, in the absence of SHH signaling, lingual epithelial cells adopted a Merkel cell fate, but this was not caused by enhanced RA signaling. We show that RA promotes, whereas SHH, acting strictly within the lingual epithelium, inhibits taste placode and lingual gland formation by thwarting RA activity. These findings reveal key functions for SHH and RA in cell fate specification in the lingual epithelium and aid in deciphering the molecular mechanisms that assign cell identity.

  11. β-Catenin Signaling Biases Multipotent Lingual Epithelial Progenitors to Differentiate and Acquire Specific Taste Cell Fates.

    Directory of Open Access Journals (Sweden)

    Dany Gaillard

    2015-05-01

    Full Text Available Continuous taste bud cell renewal is essential to maintain taste function in adults; however, the molecular mechanisms that regulate taste cell turnover are unknown. Using inducible Cre-lox technology, we show that activation of β-catenin signaling in multipotent lingual epithelial progenitors outside of taste buds diverts daughter cells from a general epithelial to a taste bud fate. Moreover, while taste buds comprise 3 morphological types, β-catenin activation drives overproduction of primarily glial-like Type I taste cells in both anterior fungiform (FF and posterior circumvallate (CV taste buds, with a small increase in Type II receptor cells for sweet, bitter and umami, but does not alter Type III sour detector cells. Beta-catenin activation in post-mitotic taste bud precursors likewise regulates cell differentiation; forced activation of β-catenin in these Shh+ cells promotes Type I cell fate in both FF and CV taste buds, but likely does so non-cell autonomously. Our data are consistent with a model where β-catenin signaling levels within lingual epithelial progenitors dictate cell fate prior to or during entry of new cells into taste buds; high signaling induces Type I cells, intermediate levels drive Type II cell differentiation, while low levels may drive differentiation of Type III cells.

  12. β-Catenin Signaling Biases Multipotent Lingual Epithelial Progenitors to Differentiate and Acquire Specific Taste Cell Fates.

    Science.gov (United States)

    Gaillard, Dany; Xu, Mingang; Liu, Fei; Millar, Sarah E; Barlow, Linda A

    2015-05-01

    Continuous taste bud cell renewal is essential to maintain taste function in adults; however, the molecular mechanisms that regulate taste cell turnover are unknown. Using inducible Cre-lox technology, we show that activation of β-catenin signaling in multipotent lingual epithelial progenitors outside of taste buds diverts daughter cells from a general epithelial to a taste bud fate. Moreover, while taste buds comprise 3 morphological types, β-catenin activation drives overproduction of primarily glial-like Type I taste cells in both anterior fungiform (FF) and posterior circumvallate (CV) taste buds, with a small increase in Type II receptor cells for sweet, bitter and umami, but does not alter Type III sour detector cells. Beta-catenin activation in post-mitotic taste bud precursors likewise regulates cell differentiation; forced activation of β-catenin in these Shh+ cells promotes Type I cell fate in both FF and CV taste buds, but likely does so non-cell autonomously. Our data are consistent with a model where β-catenin signaling levels within lingual epithelial progenitors dictate cell fate prior to or during entry of new cells into taste buds; high signaling induces Type I cells, intermediate levels drive Type II cell differentiation, while low levels may drive differentiation of Type III cells.

  13. Cell fate specification in the lingual epithelium is controlled by antagonistic activities of Sonic hedgehog and retinoic acid.

    Directory of Open Access Journals (Sweden)

    Maha El Shahawy

    2017-07-01

    Full Text Available The interaction between signaling pathways is a central question in the study of organogenesis. Using the developing murine tongue as a model, we uncovered unknown relationships between Sonic hedgehog (SHH and retinoic acid (RA signaling. Genetic loss of SHH signaling leads to enhanced RA activity subsequent to loss of SHH-dependent expression of Cyp26a1 and Cyp26c1. This causes a cell identity switch, prompting the epithelium of the tongue to form heterotopic minor salivary glands and to overproduce oversized taste buds. At developmental stages during which Wnt10b expression normally ceases and Shh becomes confined to taste bud cells, loss of SHH inputs causes the lingual epithelium to undergo an ectopic and anachronic expression of Shh and Wnt10b in the basal layer, specifying de novo taste placode induction. Surprisingly, in the absence of SHH signaling, lingual epithelial cells adopted a Merkel cell fate, but this was not caused by enhanced RA signaling. We show that RA promotes, whereas SHH, acting strictly within the lingual epithelium, inhibits taste placode and lingual gland formation by thwarting RA activity. These findings reveal key functions for SHH and RA in cell fate specification in the lingual epithelium and aid in deciphering the molecular mechanisms that assign cell identity.

  14. A neural network based approach for determination of optical scattering and absorption coefficients of biological tissue

    International Nuclear Information System (INIS)

    Warncke, D; Lewis, E; Leahy, M; Lochmann, S

    2009-01-01

    The propagation of light in biological tissue depends on the absorption and reduced scattering coefficient. The aim of this project is the determination of these two optical properties using spatially resolved reflectance measurements. The sensor system consists of five laser sources at different wavelengths, an optical fibre probe and five photodiodes. For these kinds of measurements it has been shown that an often used solution of the diffusion equation can not be applied. Therefore a neural network is being developed to extract the needed optical properties out of the reflectance data. Data sets for the training, validation and testing process are provided by Monte Carlo Simulations.

  15. Determination of supersymmetric parameters with neural networks at the large hadron collider

    International Nuclear Information System (INIS)

    Bornhauser, Nicki

    2013-12-01

    The LHC is running and in the near future potentially some signs of new physics are measured. In this thesis it is assumed that the underlying theory of such a signal would be identified and that it is some kind of minimal supersymmetric extension of the Standard Model. Generally, the mapping from the measurable observables onto the parameter values of the supersymmetric theory is unknown. Instead, only the opposite direction is known, i.e. for fixed parameters the measurable observables can be computed with some uncertainties. In this thesis, the ability of artifical neural networks to determine this unknown function is demonstrated. At the end of a training process, the created networks are capable to calculate the parameter values with errors for an existing measurement. To do so, at first a set of mostly counting observables is introduced. In the following, the usefulness of these observables for the determination of supersymmetric parameters is checked. This is done by applying them on 283 pairs of parameter sets of a MSSM with 15 parameters. These pairs were found to be indistinguishable at the LHC by another study, even without the consideration of SM background. It can be shown that 260 of these pairs can be discriminated using the introduced observables. Without systematic errors even all pairs can be distinguished. Also with the consideration of SM background still most pairs can be disentangled (282 without and 237 with systematic errors). This result indicates the usefulness of the observables for the direct parameter determination. The performance of neural networks is investigated for four different parameter regions of the CMSSM. With the right set of observables, the neural network approach generally could also be used for any other (non-supersymmetric) theory. In each region, a reference point with around 1,000 events after cuts should be determined in the context of a LHC with a center of mass energy of 14 TeV and an integrated luminosity of 10 fb

  16. Progressive Recruitment of Mesenchymal Progenitors Reveals a Time-Dependent Process of Cell Fate Acquisition in Mouse and Human Nephrogenesis.

    Science.gov (United States)

    Lindström, Nils O; De Sena Brandine, Guilherme; Tran, Tracy; Ransick, Andrew; Suh, Gio; Guo, Jinjin; Kim, Albert D; Parvez, Riana K; Ruffins, Seth W; Rutledge, Elisabeth A; Thornton, Matthew E; Grubbs, Brendan; McMahon, Jill A; Smith, Andrew D; McMahon, Andrew P

    2018-06-04

    Mammalian nephrons arise from a limited nephron progenitor pool through a reiterative inductive process extending over days (mouse) or weeks (human) of kidney development. Here, we present evidence that human nephron patterning reflects a time-dependent process of recruitment of mesenchymal progenitors into an epithelial nephron precursor. Progressive recruitment predicted from high-resolution image analysis and three-dimensional reconstruction of human nephrogenesis was confirmed through direct visualization and cell fate analysis of mouse kidney organ cultures. Single-cell RNA sequencing of the human nephrogenic niche provided molecular insights into these early patterning processes and predicted developmental trajectories adopted by nephron progenitor cells in forming segment-specific domains of the human nephron. The temporal-recruitment model for nephron polarity and patterning suggested by direct analysis of human kidney development provides a framework for integrating signaling pathways driving mammalian nephrogenesis. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Identification of determinants for globalization of SMEs using multi-layer perceptron neural networks

    International Nuclear Information System (INIS)

    Draz, U.; Jahanzaib, M.; Asghar, G.

    2016-01-01

    SMEs (Small and Medium Sized Enterprises) sector is facing problems relating to implementation of international quality standards. These SMEs need to identify factors affecting business success abroad for intelligent allocation of resources to the process of internationalization. In this paper, MLP NN (Multi-Layer Perceptron Neural Network) has been used for identifying relative importance of key variables related to firm basics, manufacturing, quality inspection labs and level of education in determining the exporting status of Pakistani SMEs. A survey has been conducted for scoring out the pertinent variables in SMEs and coded in MLP NNs. It is found that firm registered with OEM (Original Equipment Manufacturer) and size of firm are the most important in determining exporting status of SMEs followed by other variables. For internationalization, the results aid policy makers in formulating strategies. (author)

  18. Ex vivo determination of chewing patterns using FBG and artificial neural networks

    Science.gov (United States)

    Karam, L. Z.; Pegorini, V.; Pitta, C. S. R.; Assmann, T. S.; Cardoso, R.; Kalinowski, H. J.; Silva, J. C. C.

    2014-05-01

    This paper reports the experimental procedures performed in a bovine head for the determination of chewing patterns during the mastication process. Mandible movements during the chewing have been simulated either by using two plasticine materials with different textures or without material. Fibre Bragg grating sensors were fixed in the jaw to monitor the biomechanical forces involved in the chewing process. The acquired signals from the sensors fed the input of an artificial neural network aiming at the classification of the measured chewing patterns for each material used in the experiment. The results obtained from the simulation of the chewing process presented different patterns for the different textures of plasticine, resulting on the determination of three chewing patterns with a classification error of 5%.

  19. Strategy of arm movement control is determined by minimization of neural effort for joint coordination.

    Science.gov (United States)

    Dounskaia, Natalia; Shimansky, Yury

    2016-06-01

    Optimality criteria underlying organization of arm movements are often validated by testing their ability to adequately predict hand trajectories. However, kinematic redundancy of the arm allows production of the same hand trajectory through different joint coordination patterns. We therefore consider movement optimality at the level of joint coordination patterns. A review of studies of multi-joint movement control suggests that a 'trailing' pattern of joint control is consistently observed during which a single ('leading') joint is rotated actively and interaction torque produced by this joint is the primary contributor to the motion of the other ('trailing') joints. A tendency to use the trailing pattern whenever the kinematic redundancy is sufficient and increased utilization of this pattern during skillful movements suggests optimality of the trailing pattern. The goal of this study is to determine the cost function minimization of which predicts the trailing pattern. We show that extensive experimental testing of many known cost functions cannot successfully explain optimality of the trailing pattern. We therefore propose a novel cost function that represents neural effort for joint coordination. That effort is quantified as the cost of neural information processing required for joint coordination. We show that a tendency to reduce this 'neurocomputational' cost predicts the trailing pattern and that the theoretically developed predictions fully agree with the experimental findings on control of multi-joint movements. Implications for future research of the suggested interpretation of the trailing joint control pattern and the theory of joint coordination underlying it are discussed.

  20. Simultaneous determination of copper, lead and cadmium by cathodic adsorptive stripping voltammetry using artificial neural network

    International Nuclear Information System (INIS)

    Ensafi, Ali A.; Khayamian, T.; Benvidi, A.; Mirmomtaz, E.

    2006-01-01

    In this work, simultaneous determination of two groups of elements consisting of Pb(II)-Cd(II) and Cu(II)-Pb(II)-Cd(II) using adsorptive cathodic stripping voltammetry are described. The method is based on accumulation of these metal ions on mercury electrode using xylenol orange as a suitable complexing agent. The potential was scanned to the negative direction and the differential pulse stripping voltammograms were recorded. The instrumental and chemical factors were optimized using artificial neural network. The optimized conditions were obtained in pH of 5.5, xylenol orange concentration of 4.0 μM, accumulation potential of -0.50 V, accumulation time of 30 s, scan rate of 10 mV/s and pulse height of 70 mV. The relationship between the peak current versus concentration was linear over the range of 5.0-150.0 ng ml -1 for cadmium and 5.0-150.0 ng ml -1 for lead. The limits of detection were 0.98 and 1.18 ng ml -1 for lead and cadmium ions, respectively. In simultaneous determination of Cu(II), Pb(II) and Cd(II) there are inter-metallic interactions, which result a non-linear relationship between the peak current and the ionic concentration for each of the element. Therefore, an artificial neural network was used as the multivariate calibration method. The ANN was constructed with three neurons as the output layer for the simultaneous determination of the three elements. The constructed model was able to predict the concentration of the elements in the ranges of 1.0-50.0, 5.0-200.0 and 10.0-200.0 ng ml -1 , for Cu(II), Pb(II) and Cd(II), respectively

  1. Determination of Electron Optical Properties for Aperture Zoom Lenses Using an Artificial Neural Network Method.

    Science.gov (United States)

    Isik, Nimet

    2016-04-01

    Multi-element electrostatic aperture lens systems are widely used to control electron or charged particle beams in many scientific instruments. By means of applied voltages, these lens systems can be operated for different purposes. In this context, numerous methods have been performed to calculate focal properties of these lenses. In this study, an artificial neural network (ANN) classification method is utilized to determine the focused/unfocused charged particle beam in the image point as a function of lens voltages for multi-element electrostatic aperture lenses. A data set for training and testing of ANN is taken from the SIMION 8.1 simulation program, which is a well known and proven accuracy program in charged particle optics. Mean squared error results of this study indicate that the ANN classification method provides notable performance characteristics for electrostatic aperture zoom lenses.

  2. Neural networks applied to determine the thermophysical properties of amino acid based ionic liquids.

    Science.gov (United States)

    Cancilla, John C; Perez, Ana; Wierzchoś, Kacper; Torrecilla, José S

    2016-03-14

    A series of models based on artificial neural networks (ANNs) have been designed to estimate the thermophysical properties of different amino acid-based ionic liquids (AAILs). Three different databases of AAILs were modeled using these algorithms with the goal set to estimate the density, viscosity, refractive index, ionic conductivity, and thermal expansion coefficient, and requiring only data regarding temperature and electronic polarizability of the chemicals. Additionally, a global model was designed combining all of the databases to determine the robustness of the method. In general, the results were successful, reaching mean prediction errors below 1% in many cases, as well as a statistically reliable and accurate global model. Attaining these successful models is a relevant fact as AAILs are novel biodegradable and biocompatible compounds which may soon make their way into the health sector forming a part of useful biomedical applications. Therefore, understanding the behavior and being able to estimate their thermophysical properties becomes crucial.

  3. Diversity among POU transcription factors in chromatin recognition and cell fate reprogramming.

    Science.gov (United States)

    Malik, Vikas; Zimmer, Dennis; Jauch, Ralf

    2018-05-01

    The POU (Pit-Oct-Unc) protein family is an evolutionary ancient group of transcription factors (TFs) that bind specific DNA sequences to direct gene expression programs. The fundamental importance of POU TFs to orchestrate embryonic development and to direct cellular fate decisions is well established, but the molecular basis for this activity is insufficiently understood. POU TFs possess a bipartite 'two-in-one' DNA binding domain consisting of two independently folding structural units connected by a poorly conserved and flexible linker. Therefore, they represent a paradigmatic example to study the molecular basis for the functional versatility of TFs. Their modular architecture endows POU TFs with the capacity to accommodate alternative composite DNA sequences by adopting different quaternary structures. Moreover, associations with partner proteins crucially influence the selection of their DNA binding sites. The plentitude of DNA binding modes confers the ability to POU TFs to regulate distinct genes in the context of different cellular environments. Likewise, different binding modes of POU proteins to DNA could trigger alternative regulatory responses in the context of different genomic locations of the same cell. Prominent POU TFs such as Oct4, Brn2, Oct6 and Brn4 are not only essential regulators of development but have also been successfully employed to reprogram somatic cells to pluripotency and neural lineages. Here we review biochemical, structural, genomic and cellular reprogramming studies to examine how the ability of POU TFs to select regulatory DNA, alone or with partner factors, is tied to their capacity to epigenetically remodel chromatin and drive specific regulatory programs that give cells their identities.

  4. Hierarchical neural network model of the visual system determining figure/ground relation

    Science.gov (United States)

    Kikuchi, Masayuki

    2017-07-01

    One of the most important functions of the visual perception in the brain is figure/ground interpretation from input images. Figural region in 2D image corresponding to object in 3D space are distinguished from background region extended behind the object. Previously the author proposed a neural network model of figure/ground separation constructed on the standpoint that local geometric features such as curvatures and outer angles at corners are extracted and propagated along input contour in a single layer network (Kikuchi & Akashi, 2001). However, such a processing principle has the defect that signal propagation requires manyiterations despite the fact that actual visual system determines figure/ground relation within the short period (Zhou et al., 2000). In order to attain speed-up for determining figure/ground, this study incorporates hierarchical architecture into the previous model. This study confirmed the effect of the hierarchization as for the computation time by simulation. As the number of layers increased, the required computation time reduced. However, such speed-up effect was saturatedas the layers increased to some extent. This study attempted to explain this saturation effect by the notion of average distance between vertices in the area of complex network, and succeeded to mimic the saturation effect by computer simulation.

  5. A new approach using artificial neural networks for determination of the thermodynamic properties of fluid couples

    International Nuclear Information System (INIS)

    Sencan, Arzu; Kalogirou, Soteris A.

    2005-01-01

    This paper presents a new approach using artificial neural networks (ANN) to determine the thermodynamic properties of two alternative refrigerant/absorbent couples (LiCl-H 2 O and LiBr + LiNO 3 + LiI + LiCl-H 2 O). These pairs can be used in absorption heat pump systems, and their main advantage is that they do not cause ozone depletion. In order to train the network, limited experimental measurements were used as training and test data. Two feedforward ANNs were trained, one for each pair, using the Levenberg-Marquardt algorithm. The training and validation were performed with good accuracy. The correlation coefficient obtained when unknown data were applied to the networks was 0.9997 and 0.9987 for the two pairs, respectively, which is very satisfactory. The present methodology proved to be much better than linear multiple regression analysis. Using the weights obtained from the trained network, a new formulation is presented for determination of the vapor pressures of the two refrigerant/absorbent couples. The use of this new formulation, which can be employed with any programming language or spreadsheet program for estimation of the vapor pressures of fluid couples, as described in this paper, may make the use of dedicated ANN software unnecessary

  6. Characterization of a photoacoustic system through neural networks to determine multicomponent samples

    Science.gov (United States)

    Zajarevich, N. M.; Peuriot, A. L.; Slezak, V. B.

    2016-07-01

    Photoacoustic spectroscopy for trace gases detection, based on a CO2 laser, can be used in a wide range of applications. The tunability of this laser in the mid-infrared (9.4-10.6 μm) allows the quantitative determination of different substances in multicomponent samples. In general, at traces level, the total photoacoustic amplitude at a certain wavelength may be approximated by a linear superposition of the amplitudes given by each of the species absorbing at that wavelength. However, in some cases, the sum of the individual signals is no longer valid. In particular, it is known the presence of CO2 delays the acoustic signal in relation to the laser excitation due to the exchange of vibrational energy between CO2 and N2. This phenomenon generates a slow V-T energy relaxation from a metastable N2 vibrational level and the sum of individual contributions may no longer be valid. Moreover, the resolution of a linear equation system has limitations, so the possibility to determine concentrations in photoacoustics based on neural network is proposed in this work. This procedure is tried in a particular case of a volatile organic compound, such as C2H4, and CO2 in air. The results are compared with the ones obtained with a model based on rate equations.

  7. Fast neutron spectra determination by threshold activation detectors using neural networks

    International Nuclear Information System (INIS)

    Kardan, M.R.; Koohi-Fayegh, R.; Setayeshi, S.; Ghiassi-Nejad, M.

    2004-01-01

    Neural network method was used for fast neutron spectra unfolding in spectrometry by threshold activation detectors. The input layer of the neural networks consisted of 11 neurons for the specific activities of neutron-induced nuclear reaction products, while the output layers were fast neutron spectra which had been subdivided into 6, 8, 10, 12, 15 and 20 energy bins. Neural network training was performed by 437 fast neutron spectra and corresponding threshold activation detector readings. The trained neural network have been applied for unfolding 50 spectra, which were not in training sets and the results were compared with real spectra and unfolded spectra by SANDII. The best results belong to 10 energy bin spectra. The neural network was also trained by detector readings with 5% uncertainty and the response of the trained neural network to detector readings with 5%, 10%, 15%, 20%, 25% and 50% uncertainty was compared with real spectra. Neural network algorithm, in comparison with other unfolding methods, is very fast and needless to detector response matrix and any prior information about spectra and also the outputs have low sensitivity to uncertainty in the activity measurements. The results show that the neural network algorithm is useful when a fast response is required with reasonable accuracy

  8. Bar represses dPax2 and decapentaplegic to regulate cell fate and morphogenetic cell death in Drosophila eye.

    Directory of Open Access Journals (Sweden)

    Jongkyun Kang

    Full Text Available The coordinated regulation of cell fate and cell survival is crucial for normal pattern formation in developing organisms. In Drosophila compound eye development, crystalline arrays of hexagonal ommatidia are established by precise assembly of diverse cell types, including the photoreceptor cells, cone cells and interommatidial (IOM pigment cells. The molecular basis for controlling the number of cone and IOM pigment cells during ommatidial pattern formation is not well understood. Here we present evidence that BarH1 and BarH2 homeobox genes are essential for eye patterning by inhibiting excess cone cell differentiation and promoting programmed death of IOM cells. Specifically, we show that loss of Bar from the undifferentiated retinal precursor cells leads to ectopic expression of Prospero and dPax2, two transcription factors essential for cone cell specification, resulting in excess cone cell differentiation. We also show that loss of Bar causes ectopic expression of the TGFβ homolog Decapentaplegic (Dpp posterior to the morphogenetic furrow in the larval eye imaginal disc. The ectopic Dpp expression is not responsible for the formation of excess cone cells in Bar loss-of-function mutant eyes. Instead, it causes reduction in IOM cell death in the pupal stage by antagonizing the function of pro-apoptotic gene reaper. Taken together, this study suggests a novel regulatory mechanism in the control of developmental cell death in which the repression of Dpp by Bar in larval eye disc is essential for IOM cell death in pupal retina.

  9. Single-Cell Profiling of Epigenetic Modifiers Identifies PRDM14 as an Inducer of Cell Fate in the Mammalian Embryo

    Directory of Open Access Journals (Sweden)

    Adam Burton

    2013-11-01

    Full Text Available Cell plasticity or potency is necessary for the formation of multiple cell types. The mechanisms underlying this plasticity are largely unknown. Preimplantation mouse embryos undergo drastic changes in cellular potency, starting with the totipotent zygote through to the formation of the pluripotent inner cell mass (ICM and differentiated trophectoderm in the blastocyst. Here, we set out to identify and functionally characterize chromatin modifiers that define the transitions of potency and cell fate in the mouse embryo. Using a quantitative microfluidics approach in single cells, we show that developmental transitions are marked by distinctive combinatorial profiles of epigenetic modifiers. Pluripotent cells of the ICM are distinct from their differentiated trophectoderm counterparts. We show that PRDM14 is heterogeneously expressed in 4-cell-stage embryos. Forced expression of PRDM14 at the 2-cell stage leads to increased H3R26me2 and can induce a pluripotent ICM fate. Our results shed light on the epigenetic networks that govern cellular potency and identity in vivo.

  10. Hippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructure

    KAUST Repository

    Mosqueira, Diogo

    2014-03-25

    Stem cell responsiveness to extracellular matrix (ECM) composition and mechanical cues has been the subject of a number of investigations so far, yet the molecular mechanisms underlying stem cell mechano-biology still need full clarification. Here we demonstrate that the paralog proteins YAP and TAZ exert a crucial role in adult cardiac progenitor cell mechano-sensing and fate decision. Cardiac progenitors respond to dynamic modifications in substrate rigidity and nanopattern by promptly changing YAP/TAZ intracellular localization. We identify a novel activity of YAP and TAZ in the regulation of tubulogenesis in 3D environments and highlight a role for YAP/TAZ in cardiac progenitor proliferation and differentiation. Furthermore, we show that YAP/TAZ expression is triggered in the heart cells located at the infarct border zone. Our results suggest a fundamental role for the YAP/TAZ axis in the response of resident progenitor cells to the modifications in microenvironment nanostructure and mechanics, thereby contributing to the maintenance of myocardial homeostasis in the adult heart. These proteins are indicated as potential targets to control cardiac progenitor cell fate by materials design. © 2014 American Chemical Society.

  11. [Sporulation or competence development? A genetic regulatory network model of cell-fate determination in Bacillus subtilis].

    Science.gov (United States)

    Lu, Zhenghui; Zhou, Yuling; Zhang, Xiaozhou; Zhang, Guimin

    2015-11-01

    Bacillus subtilis is a generally recognized as safe (GRAS) strain that has been widely used in industries including fodder, food, and biological control. In addition, B. subtilis expression system also plays a significant role in the production of industrial enzymes. However, its application is limited by its low sporulation frequency and transformation efficiency. Immense studies have been done on interpreting the molecular mechanisms of sporulation and competence development, whereas only few of them were focused on improving sporulation frequency and transformation efficiency of B. subtilis by genetic modification. The main challenge is that sporulation and competence development, as the two major developmental events in the stationary phase of B. subtilis, are regulated by the complicated intracellular genetic regulatory systems. In addition, mutual regulatory mechanisms also exist in these two developmental events. With the development of genetic and metabolic engineering, constructing genetic regulatory networks is currently one of the most attractive research fields, together with the genetic information of cell growth, metabolism, and development, to guide the industrial application. In this review, the mechanisms of sporulation and competence development of B. subtilis, their interactions, and the genetic regulation of cell growth were interpreted. In addition, the roles of these regulatory networks in guiding basic and applied research of B. subtilis and its related species were discussed.

  12. Distinct and overlapping gene regulatory networks in BMP- and HDAC-controlled cell fate determination in the embryonic forebrain

    Directory of Open Access Journals (Sweden)

    Scholl Catharina

    2012-07-01

    Full Text Available Abstract Background Both bone morphogenetic proteins (BMPs and histone deacetylases (HDACs have previously been established to play a role in the development of the three major cell types of the central nervous system: neurons, astrocytes, and oligodendrocytes. We have previously established a connection between these two protein families, showing that HDACs suppress BMP-promoted astrogliogenesis in the embryonic striatum. Since HDACs act in the nucleus to effect changes in transcription, an unbiased analysis of their transcriptional targets could shed light on their downstream effects on BMP-signaling. Results Using neurospheres from the embryonic striatum as an in vitro system to analyze this phenomenon, we have performed microarray expression profiling on BMP2- and TSA-treated cultures, followed by validation of the findings with quantitative RT-PCR and protein analysis. In BMP-treated cultures we first observed an upregulation of genes involved in cell-cell communication and developmental processes such as members of BMP and canonical Wnt signaling pathways. In contrast, in TSA-treated cultures we first observed an upregulation of genes involved in chromatin modification and transcription. Interestingly, we could not record direct changes in the protein levels of canonical members of BMP2 signaling, but we did observe an upregulation of both the transcription factor STAT3 and its active isoform phospho-STAT3 at the protein level. Conclusions STAT3 and SMAD1/5/8 interact synergistically to promote astrogliogenesis, and thus we show for the first time that HDACs act to suppress BMP-promoted astrogliogenesis by suppression of the crucial partner STAT3.

  13. The Mediator subunit MED23 couples H2B mono-ubiquitination to transcriptional control and cell fate determination.

    Science.gov (United States)

    Yao, Xiao; Tang, Zhanyun; Fu, Xing; Yin, Jingwen; Liang, Yan; Li, Chonghui; Li, Huayun; Tian, Qing; Roeder, Robert G; Wang, Gang

    2015-12-02

    The Mediator complex orchestrates multiple transcription factors with the Pol II apparatus for precise transcriptional control. However, its interplay with the surrounding chromatin remains poorly understood. Here, we analyze differential histone modifications between WT and MED23(-/-) (KO) cells and identify H2B mono-ubiquitination at lysine 120 (H2Bub) as a MED23-dependent histone modification. Using tandem affinity purification and mass spectrometry, we find that MED23 associates with the RNF20/40 complex, the enzyme for H2Bub, and show that this association is critical for the recruitment of RNF20/40 to chromatin. In a cell-free system, Mediator directly and substantially increases H2Bub on recombinant chromatin through its cooperation with RNF20/40 and the PAF complex. Integrative genome-wide analyses show that MED23 depletion specifically reduces H2Bub on a subset of MED23-controlled genes. Importantly, MED23-coupled H2Bub levels are oppositely regulated during myogenesis and lung carcinogenesis. In sum, these results establish a mechanistic link between the Mediator complex and a critical chromatin modification in coordinating transcription with cell growth and differentiation. © 2015 The Authors.

  14. Non-invasive determination of the absorption coefficient of the brain from time-resolved reflectance using a neural network

    International Nuclear Information System (INIS)

    Jaeger, Marion; Kienle, Alwin

    2011-01-01

    We investigated the performance of a neural network for derivation of the absorption coefficient of the brain from simulated non-invasive time-resolved reflectance measurements on the head. A five-layered geometry was considered assuming that the optical properties (except the absorption coefficient of the brain) and the thickness of all layers were known with an uncertainty. A solution of the layered diffusion equation was used to train the neural network. We determined the absorption coefficient of the brain with an RMS error of <6% from reflectance data at a single distance calculated by diffusion theory. By applying the neural network to reflectance curves obtained from Monte Carlo simulations, similar errors were found. (note)

  15. Controlling gene networks and cell fate with precision-targeted DNA-binding proteins and small-molecule-based genome readers.

    Science.gov (United States)

    Eguchi, Asuka; Lee, Garrett O; Wan, Fang; Erwin, Graham S; Ansari, Aseem Z

    2014-09-15

    Transcription factors control the fate of a cell by regulating the expression of genes and regulatory networks. Recent successes in inducing pluripotency in terminally differentiated cells as well as directing differentiation with natural transcription factors has lent credence to the efforts that aim to direct cell fate with rationally designed transcription factors. Because DNA-binding factors are modular in design, they can be engineered to target specific genomic sequences and perform pre-programmed regulatory functions upon binding. Such precision-tailored factors can serve as molecular tools to reprogramme or differentiate cells in a targeted manner. Using different types of engineered DNA binders, both regulatory transcriptional controls of gene networks, as well as permanent alteration of genomic content, can be implemented to study cell fate decisions. In the present review, we describe the current state of the art in artificial transcription factor design and the exciting prospect of employing artificial DNA-binding factors to manipulate the transcriptional networks as well as epigenetic landscapes that govern cell fate.

  16. Opposing regulation of PROX1 by interleukin-3 receptor and NOTCH directs differential host cell fate reprogramming by Kaposi sarcoma herpes virus.

    Directory of Open Access Journals (Sweden)

    Jaehyuk Yoo

    Full Text Available Lymphatic endothelial cells (LECs are differentiated from blood vascular endothelial cells (BECs during embryogenesis and this physiological cell fate specification is controlled by PROX1, the master regulator for lymphatic development. When Kaposi sarcoma herpes virus (KSHV infects host cells, it activates the otherwise silenced embryonic endothelial differentiation program and reprograms their cell fates. Interestingly, previous studies demonstrated that KSHV drives BECs to acquire a partial lymphatic phenotype by upregulating PROX1 (forward reprogramming, but stimulates LECs to regain some BEC-signature genes by downregulating PROX1 (reverse reprogramming. Despite the significance of this KSHV-induced bidirectional cell fate reprogramming in KS pathogenesis, its underlying molecular mechanism remains undefined. Here, we report that IL3 receptor alpha (IL3Rα and NOTCH play integral roles in the host cell type-specific regulation of PROX1 by KSHV. In BECs, KSHV upregulates IL3Rα and phosphorylates STAT5, which binds and activates the PROX1 promoter. In LECs, however, PROX1 was rather downregulated by KSHV-induced NOTCH signal via HEY1, which binds and represses the PROX1 promoter. Moreover, PROX1 was found to be required to maintain HEY1 expression in LECs, establishing a reciprocal regulation between PROX1 and HEY1. Upon co-activation of IL3Rα and NOTCH, PROX1 was upregulated in BECs, but downregulated in LECs. Together, our study provides the molecular mechanism underlying the cell type-specific endothelial fate reprogramming by KSHV.

  17. Determination of fluence-to-dose conversion coefficients by means of artificial neural networks

    International Nuclear Information System (INIS)

    Soto B, T. G.; Rivera P, E.; De Leon M, H. A.; Hernandez D, V. M.; Vega C, H. R.; Gallego, E.; Lorente, A.

    2012-10-01

    In this paper is presented an Artificial Neural Network (Ann) that has been designed, trained and validated to determinate the effective dose e, ambient dose equivalent h(10) and personal dose equivalent hp(10,θ) fluence-to-dose conversion coefficients at different positions, having as only input data 7 count rates obtained with a Bonner Sphere Spectrometer (Bss) system. A set of 211 neutron spectra and the fluence-to-dose conversion coefficients published by the International Atomic Energy Agency were used to train and validate the Ann. This set was divided into 2 subsets, one of 181 elements to train the Ann and the remaining 30 to validate it. The Ann was trained using Bss count rates as input data and the fluence-to-dose conversion coefficients as output data. The network was validated and tested with the set of 30 elements that were not used during the training process. Good results were obtained proving that Ann are a good choice for calculating the fluence-to-dose conversion coefficients having as only data the count rates obtained with a Bss. (Author)

  18. Determination of fluence-to-dose conversion coefficients by means of artificial neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Soto B, T. G.; Rivera P, E.; De Leon M, H. A.; Hernandez D, V. M.; Vega C, H. R. [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas (Mexico); Gallego, E.; Lorente, A., E-mail: tzinnia.soto@gmail.com [Universidad Politecnica de Madrid, Departamento de Ingenieria Nuclear, Jose Gutierrez Abascal No. 2, 28006 Madrid (Spain)

    2012-10-15

    In this paper is presented an Artificial Neural Network (Ann) that has been designed, trained and validated to determinate the effective dose e, ambient dose equivalent h(10) and personal dose equivalent hp(10,{theta}) fluence-to-dose conversion coefficients at different positions, having as only input data 7 count rates obtained with a Bonner Sphere Spectrometer (Bss) system. A set of 211 neutron spectra and the fluence-to-dose conversion coefficients published by the International Atomic Energy Agency were used to train and validate the Ann. This set was divided into 2 subsets, one of 181 elements to train the Ann and the remaining 30 to validate it. The Ann was trained using Bss count rates as input data and the fluence-to-dose conversion coefficients as output data. The network was validated and tested with the set of 30 elements that were not used during the training process. Good results were obtained proving that Ann are a good choice for calculating the fluence-to-dose conversion coefficients having as only data the count rates obtained with a Bss. (Author)

  19. Determining the Relationship Between Co-creation and Innovation by Neural Networks

    DEFF Research Database (Denmark)

    di Tollo, Giacomo; Tanev, Stoyan; Slim, Kassis Mohamed

    2014-01-01

    The growing complexity of markets, business development and administration has fostered the application of more sophisticated quantitative methods aiming at the analysis of common features and differences amongst different businesses. Amongst those quantitative methods, Neural Networks are gainin...

  20. Dissecting engineered cell types and enhancing cell fate conversion via CellNet

    Science.gov (United States)

    Morris, Samantha A.; Cahan, Patrick; Li, Hu; Zhao, Anna M.; San Roman, Adrianna K.; Shivdasani, Ramesh A.; Collins, James J.; Daley, George Q.

    2014-01-01

    SUMMARY Engineering clinically relevant cells in vitro holds promise for regenerative medicine, but most protocols fail to faithfully recapitulate target cell properties. To address this, we developed CellNet, a network biology platform that determines whether engineered cells are equivalent to their target tissues, diagnoses aberrant gene regulatory networks, and prioritizes candidate transcriptional regulators to enhance engineered conversions. Using CellNet, we improved B cell to macrophage conversion, transcriptionally and functionally, by knocking down predicted B cell regulators. Analyzing conversion of fibroblasts to induced hepatocytes (iHeps), CellNet revealed an unexpected intestinal program regulated by the master regulator Cdx2. We observed long-term functional engraftment of mouse colon by iHeps, thereby establishing their broader potential as endoderm progenitors and demonstrating direct conversion of fibroblasts into intestinal epithelium. Our studies illustrate how CellNet can be employed to improve direct conversion and to uncover unappreciated properties of engineered cells. PMID:25126792

  1. Stat3 signaling regulates embryonic stem cell fate in a dose-dependent manner

    Directory of Open Access Journals (Sweden)

    Chih-I Tai

    2014-09-01

    Full Text Available Stat3 is essential for mouse embryonic stem cell (mESC self-renewal mediated by LIF/gp130 receptor signaling. Current understanding of Stat3-mediated ESC self-renewal mechanisms is very limited, and has heretofore been dominated by the view that Stat3 signaling functions in a binary “on/off” manner. Here, in contrast to this binary viewpoint, we demonstrate a contextual, rheostat-like mechanism for Stat3's function in mESCs. Activation and expression levels determine whether Stat3 functions in a self-renewal or a differentiation role in mESCs. We also show that Stat3 induces rapid differentiation of mESCs toward the trophectoderm (TE lineage when its activation level exceeds certain thresholds. Stat3 induces this differentiation phenotype via induction of Tfap2c and its downstream target Cdx2. Our findings provide a novel concept in the realm of Stat3, self-renewal signaling, and pluripotent stem cell biology. Ultimately, this finding may facilitate the development of conditions for the establishment of authentic non-rodent ESCs.

  2. Simulation-based model checking approach to cell fate specification during Caenorhabditis elegans vulval development by hybrid functional Petri net with extension

    Directory of Open Access Journals (Sweden)

    Ueno Kazuko

    2009-04-01

    Full Text Available Abstract Background Model checking approaches were applied to biological pathway validations around 2003. Recently, Fisher et al. have proved the importance of model checking approach by inferring new regulation of signaling crosstalk in C. elegans and confirming the regulation with biological experiments. They took a discrete and state-based approach to explore all possible states of the system underlying vulval precursor cell (VPC fate specification for desired properties. However, since both discrete and continuous features appear to be an indispensable part of biological processes, it is more appropriate to use quantitative models to capture the dynamics of biological systems. Our key motivation of this paper is to establish a quantitative methodology to model and analyze in silico models incorporating the use of model checking approach. Results A novel method of modeling and simulating biological systems with the use of model checking approach is proposed based on hybrid functional Petri net with extension (HFPNe as the framework dealing with both discrete and continuous events. Firstly, we construct a quantitative VPC fate model with 1761 components by using HFPNe. Secondly, we employ two major biological fate determination rules – Rule I and Rule II – to VPC fate model. We then conduct 10,000 simulations for each of 48 sets of different genotypes, investigate variations of cell fate patterns under each genotype, and validate the two rules by comparing three simulation targets consisting of fate patterns obtained from in silico and in vivo experiments. In particular, an evaluation was successfully done by using our VPC fate model to investigate one target derived from biological experiments involving hybrid lineage observations. However, the understandings of hybrid lineages are hard to make on a discrete model because the hybrid lineage occurs when the system comes close to certain thresholds as discussed by Sternberg and Horvitz in

  3. ECM-dependent HIF induction directs trophoblast stem cell fate via LIMK1-mediated cytoskeletal rearrangement.

    Directory of Open Access Journals (Sweden)

    Hwa J Choi

    Full Text Available The Hypoxia-inducible Factor (HIF family of transcriptional regulators coordinates the expression of dozens of genes in response to oxygen deprivation. Mammalian development occurs in a hypoxic environment and HIF-null mice therefore die in utero due to multiple embryonic and placental defects. Mouse embryonic stem cells do not differentiate into placental cells; therefore, trophoblast stem cells (TSCs are used to study mouse placental development. Consistent with a requirement for HIF activity during placental development in utero, TSCs derived from HIF-null mice exhibit severe differentiation defects and fail to form trophoblast giant cells (TGCs in vitro. Interestingly, differentiating TSCs induce HIF activity independent of oxygen tension via unclear mechanisms. Here, we show that altering the extracellular matrix (ECM composition upon which TSCs are cultured changes their differentiation potential from TGCs to multinucleated syncytiotropholasts (SynTs and blocks oxygen-independent HIF induction. We further find that modulation of Mitogen Activated Protein Kinase Kinase-1/2 (MAP2K1/2, MEK-1/2 signaling by ECM composition is responsible for this effect. In the absence of ECM-dependent cues, hypoxia-signaling pathways activate this MAPK cascade to drive HIF induction and redirect TSC fate along the TGC lineage. In addition, we show that integrity of the microtubule and actin cytoskeleton is critical for TGC fate determination. HIF-2α ensures TSC cytoskeletal integrity and promotes invasive TGC formation by interacting with c-MYC to induce non-canonical expression of Lim domain kinase 1-an enzyme that regulates microtubule and actin stability, as well as cell invasion. Thus, we find that HIF can integrate positional and metabolic cues from within the TSC niche to regulate placental development by modulating the cellular cytoskeleton via non-canonical gene expression.

  4. Using Artificial Neural Networks to Determine Significant Factors Affecting the Pricing of WPT Effluent for Industrial Uses in Isfahan

    Directory of Open Access Journals (Sweden)

    Masoud Mirmohamadsaseghi

    2017-03-01

    Full Text Available The evidence indicates increasing trend of use of municipal wastewater treatment effluent as an alternative source of water both in developed and developing countries. Proper pricing of this unconventional water is one of the most effective economic tools to encourage optimum use of fresh water resources. In this study, artificial neural network is employed to identify and assess the factors affecting effluent tariffs supplied to local industries in Isfahan region. Given the wide variety of factors involved in the ultimate value of wastewater traement plant effluent, an assortment of relevant factors  has been considered in this study; the factors include the population served by the treatment plant, volume of effluent produced, maintenance, repair and replacement. costs of operating plants, topography, different water uses in the region, industrial wastewater collection fees, unit cost of pipe and fittings, and the volumes of water supplied from springs and aqueducts  in the region. Neural network modeling is used as a tool to determine the significance of each factor for pricing effluent. Based on the available data and the neural network models, the effects of different model architectures with different intermediate layers and numbers of nodes in each layer on the price of wastewater were investigated to develop aand adopt a final neural network model. Results indicate that the proposed neural network model enjoys a high potential and has been well capable of determining the weights of the parameter affecting in pricing effluent. Based on the the results of this study, the factors with the greatest role in effluent pricing are unit cost of pipe and fittings, industrial use of water, and the costs of plant maintentance, repair and replacement.

  5. Determination of the Interaction Position of Gamma Photons in Monolithic Scintillators Using Neural Network Fitting

    Science.gov (United States)

    Conde, P.; Iborra, A.; González, A. J.; Hernández, L.; Bellido, P.; Moliner, L.; Rigla, J. P.; Rodríguez-Álvarez, M. J.; Sánchez, F.; Seimetz, M.; Soriano, A.; Vidal, L. F.; Benlloch, J. M.

    2016-02-01

    In Positron Emission Tomography (PET) detectors based on monolithic scintillators, the photon interaction position needs to be estimated from the light distribution (LD) on the photodetector pixels. Due to the finite size of the scintillator volume, the symmetry of the LD is truncated everywhere except for the crystal center. This effect produces a poor estimation of the interaction positions towards the edges, an especially critical situation when linear algorithms, such as Center of Gravity (CoG), are used. When all the crystal faces are painted black, except the one in contact with the photodetector, the LD can be assumed to behave as the inverse square law, providing a simple theoretical model. Using this LD model, the interaction coordinates can be determined by means of fitting each event to a theoretical distribution. In that sense, the use of neural networks (NNs) has been shown to be an effective alternative to more traditional fitting techniques as nonlinear least squares (LS). The multilayer perceptron is one type of NN which can model non-linear functions well and can be trained to accurately generalize when presented with new data. In this work we have shown the capability of NNs to approximate the LD and provide the interaction coordinates of γ-photons with two different photodetector setups. One experimental setup was based on analog Silicon Photomultipliers (SiPMs) and a charge division diode network, whereas the second setup was based on digital SiPMs (dSiPMs). In both experiments NNs minimized border effects. Average spatial resolutions of 1.9 ±0.2 mm and 1.7 ±0.2 mm for the entire crystal surface were obtained for the analog and dSiPMs approaches, respectively.

  6. Determination of Blood Glucose Concentration by Using Wavelet Transform and Neural Networks

    Directory of Open Access Journals (Sweden)

    Vajravelu Ashok

    2013-03-01

    Full Text Available Background: Early and non-invasive determination of blood glucose level is of great importance. We aimed to present a new technique to accurately infer the blood glucose concentration in peripheral blood flow using non-invasive optical monitoring system.Methods: The data for the research were obtained from 900 individuals. Of them, 750 people had diabetes mellitus (DM. The system was designed using a helium neon laser source of 632.8 nm wavelength with 5mW power, photo detectors and digital storage oscilloscope. The laser beam was directed through a single optical fiber to the index finger and the scattered beams were collected by the photo detectors placed circumferentially to the transmitting fiber. The received signals were filtered using band pass filter and finally sent to a digital storage oscilloscope. These signals were then decomposed into approximation and detail coefficients using modified Haar Wavelet Transform. Back propagation neural and radial basis functions were employed for the prediction of blood glucose concentration.Results: The data of 450 patients were randomly used for training, 225 for testing and the rest for validation. The data showed that outputs from radial basis function were nearer to the clinical value. Significant variations could be seen from signals obtained from patients with DM and those without DM.Conclusion: The proposed non-invasive optical glucose monitoring system is able to predict the glucose concentration by proving that there is a definite variation in hematological distribution between patients with DM and those without DM.

  7. Discrimination Analysis of Earthquakes and Man-Made Events Using ARMA Coefficients Determination by Artificial Neural Networks

    International Nuclear Information System (INIS)

    AllamehZadeh, Mostafa

    2011-01-01

    A Quadratic Neural Networks (QNNs) model has been developed for identifying seismic source classification problem at regional distances using ARMA coefficients determination by Artificial Neural Networks (ANNs). We have devised a supervised neural system to discriminate between earthquakes and chemical explosions with filter coefficients obtained by windowed P-wave phase spectra (15 s). First, we preprocess the recording's signals to cancel out instrumental and attenuation site effects and obtain a compact representation of seismic records. Second, we use a QNNs system to obtain ARMA coefficients for feature extraction in the discrimination problem. The derived coefficients are then applied to the neural system to train and classification. In this study, we explore the possibility of using single station three-component (3C) covariance matrix traces from a priori-known explosion sites (learning) for automatically recognizing subsequent explosions from the same site. The results have shown that this feature extraction gives the best classifier for seismic signals and performs significantly better than other classification methods. The events have been tested, which include 36 chemical explosions at the Semipalatinsk test site in Kazakhstan and 61 earthquakes (mb = 5.0–6.5) recorded by the Iranian National Seismic Network (INSN). The 100% correct decisions were obtained between site explosions and some of non-site events. The above approach to event discrimination is very flexible as we can combine several 3C stations.

  8. Discrimination Analysis of Earthquakes and Man-Made Events Using ARMA Coefficients Determination by Artificial Neural Networks

    Energy Technology Data Exchange (ETDEWEB)

    AllamehZadeh, Mostafa, E-mail: dibaparima@yahoo.com [International Institute of Earthquake Engineering and Seismology (Iran, Islamic Republic of)

    2011-12-15

    A Quadratic Neural Networks (QNNs) model has been developed for identifying seismic source classification problem at regional distances using ARMA coefficients determination by Artificial Neural Networks (ANNs). We have devised a supervised neural system to discriminate between earthquakes and chemical explosions with filter coefficients obtained by windowed P-wave phase spectra (15 s). First, we preprocess the recording's signals to cancel out instrumental and attenuation site effects and obtain a compact representation of seismic records. Second, we use a QNNs system to obtain ARMA coefficients for feature extraction in the discrimination problem. The derived coefficients are then applied to the neural system to train and classification. In this study, we explore the possibility of using single station three-component (3C) covariance matrix traces from a priori-known explosion sites (learning) for automatically recognizing subsequent explosions from the same site. The results have shown that this feature extraction gives the best classifier for seismic signals and performs significantly better than other classification methods. The events have been tested, which include 36 chemical explosions at the Semipalatinsk test site in Kazakhstan and 61 earthquakes (mb = 5.0-6.5) recorded by the Iranian National Seismic Network (INSN). The 100% correct decisions were obtained between site explosions and some of non-site events. The above approach to event discrimination is very flexible as we can combine several 3C stations.

  9. The application of artificial neural networks and support vector regression for simultaneous spectrophotometric determination of commercial eye drop contents

    Science.gov (United States)

    Valizadeh, Maryam; Sohrabi, Mahmoud Reza

    2018-03-01

    In the present study, artificial neural networks (ANNs) and support vector regression (SVR) as intelligent methods coupled with UV spectroscopy for simultaneous quantitative determination of Dorzolamide (DOR) and Timolol (TIM) in eye drop. Several synthetic mixtures were analyzed for validating the proposed methods. At first, neural network time series, which one type of network from the artificial neural network was employed and its efficiency was evaluated. Afterwards, the radial basis network was applied as another neural network. Results showed that the performance of this method is suitable for predicting. Finally, support vector regression was proposed to construct the Zilomole prediction model. Also, root mean square error (RMSE) and mean recovery (%) were calculated for SVR method. Moreover, the proposed methods were compared to the high-performance liquid chromatography (HPLC) as a reference method. One way analysis of variance (ANOVA) test at the 95% confidence level applied to the comparison results of suggested and reference methods that there were no significant differences between them. Also, the effect of interferences was investigated in spike solutions.

  10. Classification of Antarctic algae by applying Kohonen neural network with 14 elements determined by inductively coupled plasma optical emission spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Balbinot, L. [Departamento de Quimica Analitica-Instituto de Quimica-Unicamp, PO Box 6154, CEP: 13083-971, Campinas, SP (Brazil); Smichowski, P. [Comision Nacional de Energia Atomica, Unidad de Actividad Quimica, Centro Atomico Constituyentes, Av. Gral Paz 1499, B1650KNA, San Martin, Provincia de Buenos Aires (Argentina); Farias, S. [Comision Nacional de Energia Atomica, Unidad de Actividad Quimica, Centro Atomico Constituyentes, Av. Gral Paz 1499, B1650KNA, San Martin, Provincia de Buenos Aires (Argentina); Arruda, M.A.Z. [Departamento de Quimica Analitica-Instituto de Quimica-Unicamp, PO Box 6154, CEP: 13083-971, Campinas, SP (Brazil); Vodopivez, C. [Instituto Antartico Argentino, Cerrito 1010, C1248AAZ, Buenos Aires (Argentina); Poppi, R.J. [Departamento de Quimica Analitica-Instituto de Quimica-Unicamp, PO Box 6154, CEP: 13083-971, Campinas, SP (Brazil)]. E-mail: ronei@iqm.unicamp.br

    2005-06-30

    Optical emission spectrometers can generate results, which sometimes are not easy to interpret, mainly when the analyses involve classifications. To make simultaneous data interpretation possible, the Kohonen neural network is used to classify different Antarctic algae according to their taxonomic groups from the determination of 14 analytes. The Kohonen neural network architecture used was 5x5 neurons, thus reducing 14-dimension input data to two-dimensional space. The input data were 14 analytes (As, Co, Cu, Fe, Mn, Sr, Zn, Cd, Cr, Mo, Ni, Pb, Se, V) with their concentrations, determined by inductively coupled plasma optical emission spectrometry in 11 different species of algae. Three taxonomic groups (Rhodophyta, Phaeophyta and Cholorophyta) can be differentiated and classified through only their Cu content.

  11. Classification of Antarctic algae by applying Kohonen neural network with 14 elements determined by inductively coupled plasma optical emission spectrometry

    International Nuclear Information System (INIS)

    Balbinot, L.; Smichowski, P.; Farias, S.; Arruda, M.A.Z.; Vodopivez, C.; Poppi, R.J.

    2005-01-01

    Optical emission spectrometers can generate results, which sometimes are not easy to interpret, mainly when the analyses involve classifications. To make simultaneous data interpretation possible, the Kohonen neural network is used to classify different Antarctic algae according to their taxonomic groups from the determination of 14 analytes. The Kohonen neural network architecture used was 5x5 neurons, thus reducing 14-dimension input data to two-dimensional space. The input data were 14 analytes (As, Co, Cu, Fe, Mn, Sr, Zn, Cd, Cr, Mo, Ni, Pb, Se, V) with their concentrations, determined by inductively coupled plasma optical emission spectrometry in 11 different species of algae. Three taxonomic groups (Rhodophyta, Phaeophyta and Cholorophyta) can be differentiated and classified through only their Cu content

  12. Determination of groundwater abstractions by means of GRACE data and Artificial Neural Networks

    Science.gov (United States)

    Gemitzi, Alexandra; Tsagkarakis, Konstantinos; Lakshmi, Venkat

    2017-04-01

    The EU Water Framework Directive requires for each groundwater body the determination of annual average rates of abstraction from all points providing more than 10m3 per day as well as groundwater level monitoring, so as to ensure that the available groundwater resource is not exceeded by the long-term annual average rate of abstraction. In order to acquire such information in situ observation networks are necessary. However, there are cases, e.g. Greece where WFD monitoring programme has not yet become operational due to bureaucratic, socioeconomic and often political constraints. The present study aims at determining groundwater use at the aquifer scale by using Gravity Recovery and Climate Experiment (GRACE) satellite data coupled with readily available meteorological data. Traditionally, GRACE data have been used at the global and regional scale due to their coarse resolution and the difficulties in disaggregating the various Total Water Storage (TWS) components. Previous works have evaluated the subsurface anomalies (ΔGW), using supplementary data sets and hydrologic modeling results in order to disaggregate GRACE TWS anomalies into their various components. Recent works however, have shown that changes in groundwater storage are dominating the GRACE Total Water Storage (TWS) changes, therefore it was though reasonable to use changes in Grace derived TWS in order to quantify abstractions from a groundwater body. Statistical downscaling was performed using an Artificial Neural Network in the form a Multilayer Perceptron model, in conjunction with local meteorological data. An ensemble of 100 ANNs provided a means of quantifying uncertainty and improving generalization. The methodology was applied in Rhodope area (NE Greece) and proved to be an efficient way of downscaling GRACE data in order to estimate the monthly quantity of water extracted from a certain aquifer. Although our methodology does not aim at estimating abstractions at single points, it manages

  13. Neural stem cell heterogeneity through time and space in the ventricular-subventricular zone.

    Science.gov (United States)

    Rushing, Gabrielle; Ihrie, Rebecca A

    2016-08-01

    The origin and classification of neural stem cells (NSCs) has been a subject of intense investigation for the past two decades. Efforts to categorize NSCs based on their location, function and expression have established that these cells are a heterogeneous pool in both the embryonic and adult brain. The discovery and additional characterization of adult NSCs has introduced the possibility of using these cells as a source for neuronal and glial replacement following injury or disease. To understand how one could manipulate NSC developmental programs for therapeutic use, additional work is needed to elucidate how NSCs are programmed and how signals during development are interpreted to determine cell fate. This review describes the identification, classification and characterization of NSCs within the large neurogenic niche of the ventricular-subventricular zone (V-SVZ). A literature search was conducted using Pubmed including the keywords "ventricular-subventricular zone," "neural stem cell," "heterogeneity," "identity" and/or "single cell" to find relevant manuscripts to include within the review. A special focus was placed on more recent findings using single-cell level analyses on neural stem cells within their niche(s). This review discusses over 20 research articles detailing findings on V-SVZ NSC heterogeneity, over 25 articles describing fate determinants of NSCs, and focuses on 8 recent publications using distinct single-cell analyses of neural stem cells including flow cytometry and RNA-seq. Additionally, over 60 manuscripts highlighting the markers expressed on cells within the NSC lineage are included in a chart divided by cell type. Investigation of NSC heterogeneity and fate decisions is ongoing. Thus far, much research has been conducted in mice however, findings in human and other mammalian species are also discussed here. Implications of NSC heterogeneity established in the embryo for the properties of NSCs in the adult brain are explored, including

  14. Prior Knowledge about Objects Determines Neural Color Representation in Human Visual Cortex.

    Science.gov (United States)

    Vandenbroucke, A R E; Fahrenfort, J J; Meuwese, J D I; Scholte, H S; Lamme, V A F

    2016-04-01

    To create subjective experience, our brain must translate physical stimulus input by incorporating prior knowledge and expectations. For example, we perceive color and not wavelength information, and this in part depends on our past experience with colored objects ( Hansen et al. 2006; Mitterer and de Ruiter 2008). Here, we investigated the influence of object knowledge on the neural substrates underlying subjective color vision. In a functional magnetic resonance imaging experiment, human subjects viewed a color that lay midway between red and green (ambiguous with respect to its distance from red and green) presented on either typical red (e.g., tomato), typical green (e.g., clover), or semantically meaningless (nonsense) objects. Using decoding techniques, we could predict whether subjects viewed the ambiguous color on typical red or typical green objects based on the neural response of veridical red and green. This shift of neural response for the ambiguous color did not occur for nonsense objects. The modulation of neural responses was observed in visual areas (V3, V4, VO1, lateral occipital complex) involved in color and object processing, as well as frontal areas. This demonstrates that object memory influences wavelength information relatively early in the human visual system to produce subjective color vision. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Pax6- and Six3-mediated induction of lens cell fate in mouse and human ES cells.

    Directory of Open Access Journals (Sweden)

    Raymond M Anchan

    Full Text Available Embryonic stem (ES cells provide a potentially useful in vitro model for the study of in vivo tissue differentiation. We used mouse and human ES cells to investigate whether the lens regulatory genes Pax6 and Six3 could induce lens cell fate in vitro. To help assess the onset of lens differentiation, we derived a new mES cell line (Pax6-GFP mES that expresses a GFP reporter under the control of the Pax6 P0 promoter and lens ectoderm enhancer. Pax6 or Six3 expression vectors were introduced into mES or hES cells by transfection or lentiviral infection and the differentiating ES cells analyzed for lens marker expression. Transfection of mES cells with Pax6 or Six3 but not with other genes induced the expression of lens cell markers and up-regulated GFP reporter expression in Pax6-GFP mES cells by 3 days post-transfection. By 7 days post-transfection, mES cell cultures exhibited a>10-fold increase over controls in the number of colonies expressing γA-crystallin, a lens fiber cell differentiation marker. RT-PCR and immunostaining revealed induction of additional lens epithelial or fiber cell differentiation markers including Foxe3, Prox1, α- and β-crystallins, and Tdrd7. Moreover, γA-crystallin- or Prox1-expressing lentoid bodies formed by 30 days in culture. In hES cells, Pax6 or Six3 lentiviral vectors also induced lens marker expression. mES cells that express lens markers reside close to but are distinct from the Pax6 or Six3 transduced cells, suggesting that the latter induce nearby undifferentiated ES cells to adopt a lens fate by non-cell autonomous mechanisms. In sum, we describe a novel mES cell GFP reporter line that is useful for monitoring induction of lens fate, and demonstrate that Pax6 or Six3 is sufficient to induce ES cells to adopt a lens fate, potentially via non-cell autonomous mechanisms. These findings should facilitate investigations of lens development.

  16. Neural net based determination of generator-shedding requirements in electric power systems

    Energy Technology Data Exchange (ETDEWEB)

    Djukanovic, M [Electrical Engineering Inst. ' Nikola Tesla' , Belgrade (Yugoslavia); Sobajic, D J; Pao, Y -H [Case Western Reserve Univ., Cleveland, OH (United States). Dept. of Electrical Engineering and Applied Physics Case Western Reserve Univ., Cleveland, OH (United States). Dept. of Computer Engineering and Science AI WARE Inc., Cleveland, OH (United States)

    1992-09-01

    This paper presents an application of artificial neural networks (ANN) in support of a decision-making process by power system operators directed towards the fast stabilisation of multi-machine systems. The proposed approach considers generator shedding as the most effective discrete supplementary control for improving the dynamic performance of faulted power systems and preventing instabilities. The sensitivity of the transient energy function (TEF) with respect to changes in the amount of dropped generation is used during the training phase of ANNs to assess the critical amount of generator shedding required to prevent the loss of synchronism. The learning capabilities of neural nets are used to establish complex mappings between fault information and the amount of generation to be shed, suggesting it as the control signal to the power system operator. (author)

  17. Determining bank effects on economic growth: An artificial neural network analysis

    OpenAIRE

    Alex Senajon

    2016-01-01

    This study characterized the influence of the banking industry’s influence on the growth of the economy. A neural network using the Multilayer Perception was used to define functions of Universal Bank, Cooperative Bank, and Thrift Bank as predictors of Gross Domestic Product growth. Using data series from 2003- 2013, it was found that Universal banks have been growing tremendously taking huge shares of growth compared to the other two bank types. Meantime, the Gross Domestic Product was fo...

  18. Determining bank effects on economic growth: An artificial neural network analysis

    Directory of Open Access Journals (Sweden)

    Alex Senajon

    2016-01-01

    Full Text Available This study characterized the influence of the banking industry’s influence on the growth of the economy. A neural network using the Multilayer Perception was used to define functions of Universal Bank, Cooperative Bank, and Thrift Bank as predictors of Gross Domestic Product growth. Using data series from 2003- 2013, it was found that Universal banks have been growing tremendously taking huge shares of growth compared to the other two bank types. Meantime, the Gross Domestic Product was found to be steadily growing over the same period with a significant spike in 2004. In addition, neural network presents the contribution of the bank types on Gross Domestic Product, and found that the assets and capital of rural banks positively affect the Gross Domestic Product growth. As such, the sensitivity analysis of the Artificial Neural Network indicates Rural banks asset as the most important predictor of all the chosen variables followed by Universal bank capital. However, the capital of Thrift banks was found to show least contribution on the growth of the Gross Domestic Product.

  19. Improvement in the determination of elemental concentrations in PIXE analyses using artificial neural system

    International Nuclear Information System (INIS)

    Correa, R.; Dinator, M.I.; Morales, J.R.; Miranda, P.A.; Cancino, S.A.; Vila, I.; Requena, I.

    2008-01-01

    An Artificial Neural System, ANS, has been designed to operate in the analysis of spectra obtained from a PIXE (Proton Induced X-ray Emissions) application. The special designed ANS was used in the calculation of the concentrations of the major elements in the samples. Neural systems using several feed-forward ANN of similar topology working in parallel were trained with error back propagation algorithm using sets of spectra of known elemental concentrations. Following the training phase of the neural networks, other PIXE spectra were analyzed with this methodology providing unknown elemental concentrations. ANS results were compared with results obtained by traditional computer codes like AXIL and GUPIX, obtaining correlations factors close to one. The rather short time required to process each spectrum, of the order of microseconds, allows fast analysis of a large number of samples. Here we present applications of ANS in the PIXE analyses of samples of organic nature like liver, gills and muscle from fishes. ANS results were compared with elemental concentrations obtained in a previous application where a single ANN was used for each analyzed element. PIXE analyses were performed at the Nuclear Physics Laboratory of the University of Chile, using 2.2 MeV proton beams provided by a Van de Graaff accelerator. (author)

  20. Methods of Monitoring Cell Fate and Tissue Growth in Three-Dimensional Scaffold-Based Strategies for In Vitro Tissue Engineering.

    Science.gov (United States)

    Leferink, Anne M; van Blitterswijk, Clemens A; Moroni, Lorenzo

    2016-08-01

    In the field of tissue engineering, there is a need for methods that allow assessing the performance of tissue-engineered constructs noninvasively in vitro and in vivo. To date, histological analysis is the golden standard to retrieve information on tissue growth, cellular distribution, and cell fate on tissue-engineered constructs after in vitro cell culture or on explanted specimens after in vivo applications. Yet, many advances have been made to optimize imaging techniques for monitoring tissue-engineered constructs with a sub-mm or μm resolution. Many imaging modalities have first been developed for clinical applications, in which a high penetration depth has been often more important than lateral resolution. In this study, we have reviewed the current state of the art in several imaging approaches that have shown to be promising in monitoring cell fate and tissue growth upon in vitro culture. Depending on the aimed tissue type and scaffold properties, some imaging methods are more applicable than others. Optical methods are mostly suited for transparent materials such as hydrogels, whereas magnetic resonance-based methods are mostly applied to obtain contrast between hard and soft tissues regardless of their transparency. Overall, this review shows that the field of imaging in scaffold-based tissue engineering is developing at a fast pace and has the potential to overcome the limitations of destructive endpoint analysis.

  1. The C. elegans SoxC protein SEM-2 opposes differentiation factors to promote a proliferative blast cell fate in the postembryonic mesoderm

    Science.gov (United States)

    Tian, Chenxi; Shi, Herong; Colledge, Clark; Stern, Michael; Waterston, Robert; Liu, Jun

    2011-01-01

    The proper development of multicellular organisms requires precise regulation and coordination of cell fate specification, cell proliferation and differentiation. Abnormal regulation and coordination of these processes could lead to disease, including cancer. We have examined the function of the sole C. elegans SoxC protein, SEM-2, in the M lineage, which produces the postembryonic mesoderm. We found that SEM-2/SoxC is both necessary and sufficient to promote a proliferating blast cell fate, the sex myoblast fate, over a differentiated striated bodywall muscle fate. A number of factors control the specific expression of sem-2 in the sex myoblast precursors and their descendants. This includes direct control of sem-2 expression by a Hox-PBC complex. The crucial nature of the HOX/PBC factors in directly enhancing expression of this proliferative factor in the C. elegans M lineage suggests a possible more general link between Hox-PBC factors and SoxC proteins in regulating cell proliferation. PMID:21307099

  2. Mis-specified cells die by an active gene-directed process, and inhibition of this death results in cell fate transformation in Drosophila

    Science.gov (United States)

    Werz, Christian; Lee, Tom V.; Lee, Peter L.; Lackey, Melinda; Bolduc, Clare; Stein, David S.; Bergmann, Andreas

    2009-01-01

    Summary Incorrectly specified or mis-specified cells often undergo cell death or are transformed to adopt a different cell fate during development. The underlying cause for this distinction is largely unknown. In many developmental mutants in Drosophila, large numbers of mis-specified cells die synchronously, providing a convenient model for analysis of this phenomenon. The maternal mutant bicoid is particularly useful model with which to address this issue because its mutant phenotype is a combination of both transformation of tissue (acron to telson) and cell death in the presumptive head and thorax regions. We show that a subset of these mis-specified cells die through an active gene-directed process involving transcriptional upregulation of the cell death inducer hid. Upregulation of hid also occurs in oskar mutants and other segmentation mutants. In hid bicoid double mutants, mis-specified cells in the presumptive head and thorax survive and continue to develop, but they are transformed to adopt a different cell fate. We provide evidence that the terminal torso signaling pathway protects the mis-specified telson tissue in bicoid mutants from hid-induced cell death, whereas mis-specified cells in the head and thorax die, presumably because equivalent survival signals are lacking. These data support a model whereby mis-specification can be tolerated if a survival pathway is provided, resulting in cellular transformation. PMID:16280349

  3. hESC Differentiation toward an Autonomic Neuronal Cell Fate Depends on Distinct Cues from the Co-Patterning Vasculature

    Directory of Open Access Journals (Sweden)

    Lisette M. Acevedo

    2015-06-01

    Full Text Available To gain insight into the cellular and molecular cues that promote neurovascular co-patterning at the earliest stages of human embryogenesis, we developed a human embryonic stem cell model to mimic the developing epiblast. Contact of ectoderm-derived neural cells with mesoderm-derived vasculature is initiated via the neural crest (NC, not the neural tube (NT. Neurovascular co-patterning then ensues with specification of NC toward an autonomic fate requiring vascular endothelial cell (EC-secreted nitric oxide (NO and direct contact with vascular smooth muscle cells (VSMCs via T-cadherin-mediated homotypic interactions. Once a neurovascular template has been established, NT-derived central neurons then align themselves with the vasculature. Our findings reveal that, in early human development, the autonomic nervous system forms in response to distinct molecular cues from VSMCs and ECs, providing a model for how other developing lineages might coordinate their co-patterning.

  4. Determination of power peak factor using control rods, ex-core detectors and neural networks

    International Nuclear Information System (INIS)

    Souza, Rose Mary Gomes do Prado

    2005-01-01

    This work presents a methodology based on the artificial neural network technique to predict in real time the power peak factor in a form that can be implemented in reactor protection systems. The neural network inputs were those available in the reactor protection systems, namely, the axial and quadrant power differences obtained from measured ex-core detector signals, and the position of control rods. The response of ex core detector signals was measured in experiments especially performed in the IPEN/MB-01 zero-power reactor. Several reactor states with different power density distribution were obtained by positioning the control rods in different configurations. The power distribution and its peak factor were calculated for each of these reactor states using the Citation code. The obtained results show that the power peak factor correlates well with the control rod position and the quadrant power difference, and with a lesser degree with the axial power differences. The data presented an inherent organisation and could be classified into different classes of power peak factor behaviour as a function of position of control rods, axial power difference and quadrant power difference. The RBF networks were able to identify classes and interpolate the power peak factor values. The relative error for the power peak factor estimation ranged from 0.19 % to 0.67 %, less than the one that was obtained performing a power density distribution map with in-core detectors. It was observed that the positions of control rods bear the detailed and localised information about the power density distribution, and that the axial and the quadrant power difference describe its global variations in the axial and radial directions. The results showed that the RBF and MLP networks produced similar results, and that a neural network correlation can be implemented in power reactor protection systems. (author)

  5. The wandering mood: psychological and neural determinants of rest-related negative affect

    Directory of Open Access Journals (Sweden)

    Michal eGruberger

    2013-12-01

    Full Text Available Rest related negative affect (RRNA has gained scientific interest in the past decade. However, it is mostly studied within the context of mind-wandering (MW, and the relevance of other psychological and neural aspects of the resting state to its' occurrence has never been studied. Several indications associate RRNA with internally directed attention, yet the nature of this relation remains largely unknown. Moreover, the role of neural networks associated with rest related phenomenology - the default mode (DMN, executive (EXE and salience (SAL networks, has not been studied in this context. To this end, we explored two 5- (baseline and 15-minute resting-state simultaneous fMRI-EEG scans of 29 participants. As vigilance has been shown to affect attention, and thus its availability for inward allocation, EEG-based vigilance levels were computed for each participant. Questionnaires for affective assessment were administered before and after scans, and retrospective reports of MW were additionally collected. Results revealed increased negative affect following rest, but only among participants who retained high vigilance levels. Among low-vigilance participants, changes in negative affect were negligible, despite reports of MW occurrence in both groups. In addition, in the high-vigilance group only, a significant increase in functional connectivity (FC levels was found between the DMN-related ventral anterior cingulate cortex (ACC,associated with emotional processing, and the EXE-related dorsal ACC, associated with monitoring of self and other's behavior. These heightened FC levels further correlated with reported negative affect among this group. Taken together, these results demonstrate that, rather than an unavoidable outcome of the resting state, RRNA depends on internal allocation of attention at rest. Results are discussed in terms of two rest-related possible scenarios which defer in mental and neural processing, and subsequently, in the

  6. The wandering mood: psychological and neural determinants of rest-related negative affect.

    Science.gov (United States)

    Gruberger, Michal; Maron-Katz, Adi; Sharon, Haggai; Hendler, Talma; Ben-Simon, Eti

    2013-01-01

    Rest related negative affect (RRNA) has gained scientific interest in the past decade. However, it is mostly studied within the context of mind-wandering (MW), and the relevance of other psychological and neural aspects of the resting state to its' occurrence has never been studied. Several indications associate RRNA with internally directed attention, yet the nature of this relation remains largely unknown. Moreover, the role of neural networks associated with rest related phenomenology - the default mode (DMN), executive (EXE), and salience (SAL) networks, has not been studied in this context. To this end, we explored two 5 (baseline) and 15-minute resting-state simultaneous fMRI-EEG scans of 29 participants. As vigilance has been shown to affect attention, and thus its availability for inward allocation, EEG-based vigilance levels were computed for each participant. Questionnaires for affective assessment were administered before and after scans, and retrospective reports of MW were additionally collected. Results revealed increased negative affect following rest, but only among participants who retained high vigilance levels. Among low-vigilance participants, changes in negative affect were negligible, despite reports of MW occurrence in both groups. In addition, in the high-vigilance group only, a significant increase in functional connectivity (FC) levels was found between the DMN-related ventral anterior cingulate cortex (ACC), associated with emotional processing, and the EXE-related dorsal ACC, associated with monitoring of self and other's behavior. These heightened FC levels further correlated with reported negative affect among this group. Taken together, these results demonstrate that, rather than an unavoidable outcome of the resting state, RRNA depends on internal allocation of attention at rest. Results are discussed in terms of two rest-related possible scenarios which defer in mental and neural processing, and subsequently, in the occurrence of

  7. A neural method for determining electromagnetic shower positions in laterally segmented calorimeters

    International Nuclear Information System (INIS)

    Roy, A.; Ray, A.; Mitra, T.; Roy, A.

    1995-01-01

    A method based on a neural network technique is proposed to calculate the coordinates of an incident photon striking a laterally segmented calorimeter and depositing shower energies in different segments. The technique uses a multilayer perceptron trained by back-propagation implemented through standard gradient descent followed by conjugate gradient algorithms and has been demonstrated with GEANT simulations of a BAF2 detector array. The position resolution results obtained by using this method are found to be substantially better than the first moment method with logarithmic weighting. (orig.)

  8. Artificial neural network for the determination of Hubble Space Telescope aberration from stellar images

    Science.gov (United States)

    Barrett, Todd K.; Sandler, David G.

    1993-01-01

    An artificial-neural-network method, first developed for the measurement and control of atmospheric phase distortion, using stellar images, was used to estimate the optical aberration of the Hubble Space Telescope. A total of 26 estimates of distortion was obtained from 23 stellar images acquired at several secondary-mirror axial positions. The results were expressed as coefficients of eight orthogonal Zernike polynomials: focus through third-order spherical. For all modes other than spherical the measured aberration was small. The average spherical aberration of the estimates was -0.299 micron rms, which is in good agreement with predictions obtained when iterative phase-retrieval algorithms were used.

  9. Using artificial neural networks to determine the location of wind farms. Miedzna district case study

    Directory of Open Access Journals (Sweden)

    Pokonieczny Krzysztof

    2016-09-01

    Full Text Available The article concerns issues pertaining to of selecting suitable areas for wind farms. The basic assumption of the study was to take into account both criteria related to the profitability of this type of power plant, as well as public interest, which means the harmonious and not burdensome functioning of these installations for local communities. The problem of wind farm localization may be solved by the application of artificial neural networks (ANN, which are a computational intelligence element. In the conducted analysis, the possibility of wind farm localization was considered for the primary grid field with dimensions of 100 by 100 m. To prepare the training set, topographic vector data from the VMap L2 and SRTM (Shuttle Radar Topography Mission digital terrain model were used. For each 100-meter × 100-meter grid, the input data was prepared, consisting of the factors which are important from the point of view of wind farm localization (forests, rivers, built-up areas etc.. Studies show that a properly trained neural network (using a representative number of samples and for the appropriate architecture, allows to process automation area classification in terms of placement on the wind turbines.

  10. Neural Determinants of Task Performance during Feature-Based Attention in Human Cortex

    Science.gov (United States)

    Gong, Mengyuan

    2018-01-01

    Abstract Studies of feature-based attention have associated activity in a dorsal frontoparietal network with putative attentional priority signals. Yet, how this neural activity mediates attentional selection and whether it guides behavior are fundamental questions that require investigation. We reasoned that endogenous fluctuations in the quality of attentional priority should influence task performance. Human subjects detected a speed increment while viewing clockwise (CW) or counterclockwise (CCW) motion (baseline task) or while attending to either direction amid distracters (attention task). In an fMRI experiment, direction-specific neural pattern similarity between the baseline task and the attention task revealed a higher level of similarity for correct than incorrect trials in frontoparietal regions. Using transcranial magnetic stimulation (TMS), we disrupted posterior parietal cortex (PPC) and found a selective deficit in the attention task, but not in the baseline task, demonstrating the necessity of this cortical area during feature-based attention. These results reveal that frontoparietal areas maintain attentional priority that facilitates successful behavioral selection. PMID:29497703

  11. Neural Network for Determining Risk Rate of Post-Heart Stroke Patients

    Directory of Open Access Journals (Sweden)

    Oldřich Trenz

    2014-01-01

    Full Text Available The ischemic heart disease presents an important health problem that affects a great part of the population and is the cause of one third of all deaths in the Czech Republic. The availability of data describing the patients’ prognosis enables their further analysis, with the aim of lowering the patients’ risk, by proposing optimum treatment. The main reason for creating the neural network model is not only to automate the process of establishing the risk rate of patients suffering from ischemic heart disease, but also to adapt it for practical use in clinical conditions. Our aim is to identify especially the specific group of risk-rate patients whose well-timed preventive care can improve the quality and prolong the length of their lives.The aim of the paper is to propose a patient-parameter structure, using which we could create a suitable model based on a self-taught neural network. The emphasis is placed on identifying key descriptive parameters (in the form of a reduction of the available descriptive parameters that are crucial for identifying the required patients, and simultaneously to achieve a portability of the model among individual clinical workplaces (availability of parameters.

  12. Mitochondrial metabolism in early neural fate and its relevance for neuronal disease modeling.

    Science.gov (United States)

    Lorenz, Carmen; Prigione, Alessandro

    2017-12-01

    Modulation of energy metabolism is emerging as a key aspect associated with cell fate transition. The establishment of a correct metabolic program is particularly relevant for neural cells given their high bioenergetic requirements. Accordingly, diseases of the nervous system commonly involve mitochondrial impairment. Recent studies in animals and in neural derivatives of human pluripotent stem cells (PSCs) highlighted the importance of mitochondrial metabolism for neural fate decisions in health and disease. The mitochondria-based metabolic program of early neurogenesis suggests that PSC-derived neural stem cells (NSCs) may be used for modeling neurological disorders. Understanding how metabolic programming is orchestrated during neural commitment may provide important information for the development of therapies against conditions affecting neural functions, including aging and mitochondrial disorders. Copyright © 2017. Published by Elsevier Ltd.

  13. Determination of penetration depth at high velocity impact using finite element method and artificial neural network tools

    Directory of Open Access Journals (Sweden)

    Namık KılıÇ

    2015-06-01

    Full Text Available Determination of ballistic performance of an armor solution is a complicated task and evolved significantly with the application of finite element methods (FEM in this research field. The traditional armor design studies performed with FEM requires sophisticated procedures and intensive computational effort, therefore simpler and accurate numerical approaches are always worthwhile to decrease armor development time. This study aims to apply a hybrid method using FEM simulation and artificial neural network (ANN analysis to approximate ballistic limit thickness for armor steels. To achieve this objective, a predictive model based on the artificial neural networks is developed to determine ballistic resistance of high hardness armor steels against 7.62 mm armor piercing ammunition. In this methodology, the FEM simulations are used to create training cases for Multilayer Perceptron (MLP three layer networks. In order to validate FE simulation methodology, ballistic shot tests on 20 mm thickness target were performed according to standard Stanag 4569. Afterwards, the successfully trained ANN(s is used to predict the ballistic limit thickness of 500 HB high hardness steel armor. Results show that even with limited number of data, FEM-ANN approach can be used to predict ballistic penetration depth with adequate accuracy.

  14. In-vivo determination of chewing patterns using FBG and artificial neural networks

    Science.gov (United States)

    Pegorini, Vinicius; Zen Karam, Leandro; Rocha Pitta, Christiano S.; Ribeiro, Richardson; Simioni Assmann, Tangriani; Cardozo da Silva, Jean Carlos; Bertotti, Fábio L.; Kalinowski, Hypolito J.; Cardoso, Rafael

    2015-09-01

    This paper reports the process of pattern classification of the chewing process of ruminants. We propose a simplified signal processing scheme for optical fiber Bragg grating (FBG) sensors based on machine learning techniques. The FBG sensors measure the biomechanical forces during jaw movements and an artificial neural network is responsible for the classification of the associated chewing pattern. In this study, three patterns associated to dietary supplement, hay and ryegrass were considered. Additionally, two other important events for ingestive behavior studies were monitored, rumination and idle period. Experimental results show that the proposed approach for pattern classification has been capable of differentiating the materials involved in the chewing process with a small classification error.

  15. Potentiometric determination of ibuprofen, indomethacin and naproxen using an artificial neural network calibration

    Directory of Open Access Journals (Sweden)

    A. HAKAN AKTAŞ

    2008-01-01

    Full Text Available In this study, three anti-inflammatory agents, namely ibuprofen, indomethacin and naproxen, were titrated potentiometrically using tetrabutylammonium hydroxide in acetonitrile solvent under a nitrogen atmosphere at 25 °C. MATLAB 7.0 software was applied for data treatment as a multivariate calibration tool in the potentiometric titration procedure. An artificial neural network (ANN was used as a multivariate calibration tool in the potentiometric titration to model the complex non-linear relationship between ibuprofen, indomethacin and naproxen concentrations and the millivolt (mV of the solutions measured after the addition of different volumes of the titrant. The optimized network predicted the concentrations of agents in synthetic mixtures. The results showed that the employed ANN can precede the titration data with an average relative error of prediction of less than 2.30 %.

  16. Application of deep learning in determining IR precipitation occurrence: a Convolutional Neural Network model

    Science.gov (United States)

    Wang, C.; Hong, Y.

    2017-12-01

    Infrared (IR) information from Geostationary satellites can be used to retrieve precipitation at pretty high spatiotemporal resolutions. Traditional artificial intelligence (AI) methodologies, such as artificial neural networks (ANN), have been designed to build the relationship between near-surface precipitation and manually derived IR features in products including PERSIANN and PERSIANN-CCS. This study builds an automatic precipitation detection model based on IR data using Convolutional Neural Network (CNN) which is implemented by the newly developed deep learning framework, Caffe. The model judges whether there is rain or no rain at pixel level. Compared with traditional ANN methods, CNN can extract features inside the raw data automatically and thoroughly. In this study, IR data from GOES satellites and precipitation estimates from the next generation QPE (Q2) over the central United States are used as inputs and labels, respectively. The whole datasets during the study period (June to August in 2012) are randomly partitioned to three sub datasets (train, validation and test) to establish the model at the spatial resolution of 0.08°×0.08° and the temporal resolution of 1 hour. The experiments show great improvements of CNN in rain identification compared to the widely used IR-based precipitation product, i.e., PERSIANN-CCS. The overall gain in performance is about 30% for critical success index (CSI), 32% for probability of detection (POD) and 12% for false alarm ratio (FAR). Compared to other recent IR-based precipitation retrieval methods (e.g., PERSIANN-DL developed by University of California Irvine), our model is simpler with less parameters, but achieves equally or even better results. CNN has been applied in computer vision domain successfully, and our results prove the method is suitable for IR precipitation detection. Future studies can expand the application of CNN from precipitation occurrence decision to precipitation amount retrieval.

  17. Determining the Neural Substrate for Encoding a Memory of Human Pain and the Influence of Anxiety.

    Science.gov (United States)

    Tseng, Ming-Tsung; Kong, Yazhuo; Eippert, Falk; Tracey, Irene

    2017-12-06

    To convert a painful stimulus into a briefly maintainable construct when the painful stimulus is no longer accessible is essential to guide human behavior and avoid dangerous situations. Because of the aversive nature of pain, this encoding process might be influenced by emotional aspects and could thus vary across individuals, but we have yet to understand both the basic underlying neural mechanisms as well as potential interindividual differences. Using fMRI in combination with a delayed-discrimination task in healthy volunteers of both sexes, we discovered that brain regions involved in this working memory encoding process were dissociable according to whether the to-be-remembered stimulus was painful or not, with the medial thalamus and the rostral anterior cingulate cortex encoding painful and the primary somatosensory cortex encoding nonpainful stimuli. Encoding of painful stimuli furthermore significantly enhanced functional connectivity between the thalamus and medial prefrontal cortex (mPFC). With regards to emotional aspects influencing encoding processes, we observed that more anxious participants showed significant performance advantages when encoding painful stimuli. Importantly, only during the encoding of pain, the interindividual differences in anxiety were associated with the strength of coupling between medial thalamus and mPFC, which was furthermore related to activity in the amygdala. These results indicate not only that there is a distinct signature for the encoding of a painful experience in humans, but also that this encoding process involves a strong affective component. SIGNIFICANCE STATEMENT To convert the sensation of pain into a briefly maintainable construct is essential to guide human behavior and avoid dangerous situations. Although this working memory encoding process is implicitly contained in the majority of studies, the underlying neural mechanisms remain unclear. Using fMRI in a delayed-discrimination task, we found that the

  18. Caenorhabditis elegans histone deacetylase hda-1 is required for morphogenesis of the vulva and LIN-12/Notch-mediated specification of uterine cell fates.

    Science.gov (United States)

    Ranawade, Ayush Vasant; Cumbo, Philip; Gupta, Bhagwati P

    2013-08-07

    Chromatin modification genes play crucial roles in development and disease. In Caenorhabditis elegans, the class I histone deacetylase family member hda-1, a component of the nucleosome remodeling and deacetylation complex, has been shown to control cell proliferation. We recovered hda-1 in an RNA interference screen for genes involved in the morphogenesis of the egg-laying system. We found that hda-1 mutants have abnormal vulva morphology and vulval-uterine connections (i.e., no uterine-seam cell). We characterized the vulval defects by using cell fate-specific markers and found that hda-1 is necessary for the specification of all seven vulval cell types. The analysis of the vulval-uterine connection defect revealed that hda-1 is required for the differentiation of the gonadal anchor cell (AC), which in turn induces ventral uterine granddaughters to adopt π fates, leading to the formation of the uterine-seam cell. Consistent with these results, hda-1 is expressed in the vulva and AC. A search for hda-1 target genes revealed that fos-1 (fos proto-oncogene family) acts downstream of hda-1 in vulval cells, whereas egl-43 (evi1 proto-oncogene family) and nhr-67 (tailless homolog, NHR family) mediate hda-1 function in the AC. Furthermore, we showed that AC expression of hda-1 plays a crucial role in the regulation of the lin-12/Notch ligand lag-2 to specify π cell fates. These results demonstrate the pivotal role of hda-1 in the formation of the vulva and the vulval-uterine connection. Given that hda-1 homologs are conserved across the phyla, our findings are likely to provide a better understanding of HDAC1 function in development and disease.

  19. Hippocampal cell fate regulation by chronic cocaine during periods of adolescent vulnerability: Consequences of cocaine exposure during adolescence on behavioral despair in adulthood.

    Science.gov (United States)

    García-Cabrerizo, R; Keller, B; García-Fuster, M J

    2015-09-24

    Given that adolescence represents a critical moment for shaping adult behavior and may predispose to disease vulnerability later in life, the aim of this study was to find a vulnerable period during adolescence in which hippocampal cell fate regulation was altered by cocaine exposure, and to evaluate the long-term consequences of a cocaine experience during adolescence in affecting hippocampal plasticity and behavioral despair in adulthood. Study I: Male rats were treated with cocaine (15mg/kg, i.p.) or saline for 7 consecutive days during adolescence (early post-natal day (PND) 33-39, mid PND 40-46, late PND 47-53). Hippocampal plasticity (i.e., cell fate regulation, cell genesis) was evaluated 24h after the last treatment dose during the course of adolescence (PND 40, PND 47, PND 54). Study II: The consequences of cocaine exposure during adolescence (PND 33-39 or PND 33-46; 7 or 14days) were measured in adulthood at the behavioral (i.e., forced swim test, PND 62-63) and molecular (hippocampal cell markers, PND 64) levels. Chronic cocaine during early adolescence dysregulated FADD forms only in the hippocampus (HC), as compared to other brain regions, and during mid adolescence, impaired cell proliferation (Ki-67) and increased PARP-1 cleavage (a cell death maker) in the HC. Interestingly, chronic cocaine exposure during adolescence did not alter the time adult rats spent immobile in the forced swim test. These results suggest that this paradigm of chronic cocaine administration during adolescence did not contribute to the later manifestation of behavioral despair (i.e., one pro-depressive symptom) as measured by the forced swim test in adulthood. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. The Drosophila T-box transcription factor Midline functions within the Notch–Delta signaling pathway to specify sensory organ precursor cell fates and regulates cell survival within the eye imaginal disc

    Science.gov (United States)

    Das, Sudeshna; Chen, Q. Brent; Saucier, Joseph D.; Drescher, Brandon; Zong, Yan; Morgan, Sarah; Forstall, John; Meriwether, Andrew; Toranzo, Randy; Leal, Sandra M.

    2014-01-01

    We report that the T-box transcription factor Midline (Mid), an evolutionary conserved homolog of the vertebrate Tbx20 protein, functions within the Notch–Delta signaling pathway essential for specifying the fates of sensory organ precursor cells. This complements an established history of research showing that Mid regulates the cell-fate specification of diverse cell types within the developing heart, epidermis and central nervous system. Tbx20 has been detected in diverse neuronal and epithelial cells of embryonic eye tissues in both mice and humans. However, the mechanisms by which either Mid or Tbx20 function to regulate cell-fate specification or other critical aspects of eye development including cell survival have not yet been elucidated. We have also gathered preliminary evidence suggesting that Mid may play an indirect, but vital role in selecting SOP cells within the third-instar larval eye disc by regulating the expression of the proneural gene atonal. During subsequent pupal stages, Mid specifies SOP cell fates as a member of the Notch–Delta signaling hierarchy and is essential for maintaining cell viability within by inhibiting apoptotic pathways. We present several new hypotheses that seek to understand the role of Mid in regulating developmental processes downstream of the Notch receptor that are critical for specifying unique cell fates, patterning the adult eye and maintaining cellular homeostasis during eye disc morphogenesis. PMID:23962751

  1. The Drosophila T-box transcription factor Midline functions within the Notch-Delta signaling pathway to specify sensory organ precursor cell fates and regulates cell survival within the eye imaginal disc.

    Science.gov (United States)

    Das, Sudeshna; Chen, Q Brent; Saucier, Joseph D; Drescher, Brandon; Zong, Yan; Morgan, Sarah; Forstall, John; Meriwether, Andrew; Toranzo, Randy; Leal, Sandra M

    2013-01-01

    We report that the T-box transcription factor Midline (Mid), an evolutionary conserved homolog of the vertebrate Tbx20 protein, functions within the Notch-Delta signaling pathway essential for specifying the fates of sensory organ precursor (SOP) cells. These findings complement an established history of research showing that Mid regulates the cell-fate specification of diverse cell types within the developing heart, epidermis and central nervous system. Tbx20 has been detected in unique neuronal and epithelial cells of embryonic eye tissues in both mice and humans. However, the mechanisms by which either Mid or Tbx20 function to regulate cell-fate specification or other critical aspects of eye development including cell survival have not yet been elucidated. We have also gathered preliminary evidence suggesting that Mid may play an indirect, but vital role in selecting SOP cells within the third-instar larval eye disc by regulating the expression of the proneural gene atonal. During subsequent pupal stages, Mid specifies SOP cell fates as a member of the Notch-Delta signaling hierarchy and is essential for maintaining cell viability by inhibiting apoptotic pathways. We present several new hypotheses that seek to understand the role of Mid in regulating developmental processes downstream of the Notch receptor that are critical for specifying unique cell fates, patterning the adult eye and maintaining cellular homeostasis during eye disc morphogenesis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. Application of artificial neural networks for the determination of proteins with CPA-pI by rayleigh light scattering technique

    Energy Technology Data Exchange (ETDEWEB)

    Dong Lijun [Department of Chemistry, Lanzhou University, Lanzhou 730000 (China); Chen Xingguo [Department of Chemistry, Lanzhou University, Lanzhou 730000 (China)]. E-mail: chenxg@lzu.edu.cn; Hu Zhide [Department of Chemistry, Lanzhou University, Lanzhou 730000 (China)

    2007-05-15

    The determination of proteins with 2-(4-chloro-2-phosphonophenylazo)-7-(4-iodophenylazo) -1,8-dihydroxynaphthalene-3,6-disulfonic acid (CPA-pI) by Rayleigh light scattering (RLS) was studied in this paper. The weak RLS of CPA-pI and BSA can be enhanced greatly by the addition of Al{sup 3+} at the pH 5.6 and an enhanced RLS signal was produced at 365-385 nm. Based on the reaction of CPA-pI, Al{sup 3+} and proteins, a new quantitative determination method for proteins has been developed. The effect of three variables for the determination of proteins was optimized by means of artificial neural networks (ANNs) using extended delta-bar-delta (EDBD) algorithms with the optimal network structure of 3-5-1. This method is very sensitive (2.5-35.4 {mu}g/ml for bovine serum albumin (BSA)), rapid (<2 min), simple (one step) and tolerance of most interfering substances. Six samples of protein in human serum were determined and the maximum relative error is no more than 2% and the recovery is between 95% and 105%.

  3. [Application of wavelet transform-radial basis function neural network in NIRS for determination of rifampicin and isoniazide tablets].

    Science.gov (United States)

    Lu, Jia-hui; Zhang, Yi-bo; Zhang, Zhuo-yong; Meng, Qing-fan; Guo, Wei-liang; Teng, Li-rong

    2008-06-01

    A calibration model (WT-RBFNN) combination of wavelet transform (WT) and radial basis function neural network (RBFNN) was proposed for synchronous and rapid determination of rifampicin and isoniazide in Rifampicin and Isoniazide tablets by near infrared reflectance spectroscopy (NIRS). The approximation coefficients were used for input data in RBFNN. The network parameters including the number of hidden layer neurons and spread constant (SC) were investigated. WT-RBFNN model which compressed the original spectra data, removed the noise and the interference of background, and reduced the randomness, the capabilities of prediction were well optimized. The root mean square errors of prediction (RMSEP) for the determination of rifampicin and isoniazide obtained from the optimum WT-RBFNN model are 0.00639 and 0.00587, and the root mean square errors of cross-calibration (RMSECV) for them are 0.00604 and 0.00457, respectively which are superior to those obtained by the optimum RBFNN and PLS models. Regression coefficient (R) between NIRS predicted values and RP-HPLC values for rifampicin and isoniazide are 0.99522 and 0.99392, respectively and the relative error is lower than 2.300%. It was verified that WT-RBFNN model is a suitable approach to dealing with NIRS. The proposed WT-RBFNN model is convenient, and rapid and with no pollution for the determination of rifampicin and isoniazide tablets.

  4. Spectrophotometric determination of fluoxetine by molecularly imprinted polypyrrole and optimization by experimental design, artificial neural network and genetic algorithm

    Science.gov (United States)

    Nezhadali, Azizollah; Motlagh, Maryam Omidvar; Sadeghzadeh, Samira

    2018-02-01

    A selective method based on molecularly imprinted polymer (MIP) solid-phase extraction (SPE) using UV-Vis spectrophotometry as a detection technique was developed for the determination of fluoxetine (FLU) in pharmaceutical and human serum samples. The MIPs were synthesized using pyrrole as a functional monomer in the presence of FLU as a template molecule. The factors that affecting the preparation and extraction ability of MIP such as amount of sorbent, initiator concentration, the amount of monomer to template ratio, uptake shaking rate, uptake time, washing buffer pH, take shaking rate, Taking time and polymerization time were considered for optimization. First a Plackett-Burman design (PBD) consists of 12 randomized runs were applied to determine the influence of each factor. The other optimization processes were performed using central composite design (CCD), artificial neural network (ANN) and genetic algorithm (GA). At optimal condition the calibration curve showed linearity over a concentration range of 10- 7-10- 8 M with a correlation coefficient (R2) of 0.9970. The limit of detection (LOD) for FLU was obtained 6.56 × 10- 9 M. The repeatability of the method was obtained 1.61%. The synthesized MIP sorbent showed a good selectivity and sensitivity toward FLU. The MIP/SPE method was used for the determination of FLU in pharmaceutical, serum and plasma samples, successfully.

  5. Spectrophotometric determination of fluoxetine by molecularly imprinted polypyrrole and optimization by experimental design, artificial neural network and genetic algorithm.

    Science.gov (United States)

    Nezhadali, Azizollah; Motlagh, Maryam Omidvar; Sadeghzadeh, Samira

    2018-02-05

    A selective method based on molecularly imprinted polymer (MIP) solid-phase extraction (SPE) using UV-Vis spectrophotometry as a detection technique was developed for the determination of fluoxetine (FLU) in pharmaceutical and human serum samples. The MIPs were synthesized using pyrrole as a functional monomer in the presence of FLU as a template molecule. The factors that affecting the preparation and extraction ability of MIP such as amount of sorbent, initiator concentration, the amount of monomer to template ratio, uptake shaking rate, uptake time, washing buffer pH, take shaking rate, Taking time and polymerization time were considered for optimization. First a Plackett-Burman design (PBD) consists of 12 randomized runs were applied to determine the influence of each factor. The other optimization processes were performed using central composite design (CCD), artificial neural network (ANN) and genetic algorithm (GA). At optimal condition the calibration curve showed linearity over a concentration range of 10 -7 -10 -8 M with a correlation coefficient (R 2 ) of 0.9970. The limit of detection (LOD) for FLU was obtained 6.56×10 -9 M. The repeatability of the method was obtained 1.61%. The synthesized MIP sorbent showed a good selectivity and sensitivity toward FLU. The MIP/SPE method was used for the determination of FLU in pharmaceutical, serum and plasma samples, successfully. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Calpain Determines the Propensity of Adult Hippocampal Neural Stem Cells to Autophagic Cell Death Following Insulin Withdrawal.

    Science.gov (United States)

    Chung, Kyung Min; Park, Hyunhee; Jung, Seonghee; Ha, Shinwon; Yoo, Seung-Jun; Woo, Hanwoong; Lee, Hyang Ju; Kim, Seong Who; Kim, Eun-Kyoung; Moon, Cheil; Yu, Seong-Woon

    2015-10-01

    Programmed cell death (PCD) has significant effects on the function of neural stem cells (NSCs) during brain development and degeneration. We have previously reported that adult rat hippocampal neural stem (HCN) cells underwent autophagic cell death (ACD) rather than apoptosis following insulin withdrawal despite their intact apoptotic capabilities. Here, we report a switch in the mode of cell death in HCN cells with calpain as a critical determinant. In HCN cells, calpain 1 expression was barely detectable while calpain 2 was predominant. Inhibition of calpain in insulin-deprived HCN cells further augmented ACD. In contrast, expression of calpain 1 switched ACD to apoptosis. The proteasome inhibitor lactacystin blocked calpain 2 degradation and elevated the intracellular Ca(2+) concentration. In combination, these effects potentiated calpain activity and converted the mode of cell death to apoptosis. Our results indicate that low calpain activity, due to absence of calpain 1 and degradation of calpain 2, results in a preference for ACD over apoptosis in insulin-deprived HCN cells. On the other hand, conditions leading to high calpain activity completely switch the mode of cell death to apoptosis. This is the first report on the PCD mode switching mechanism in NSCs. The dynamic change in calpain activity through the proteasome-mediated modulation of the calpain and intracellular Ca(2+) levels may be the critical contributor to the demise of NSCs. Our findings provide a novel insight into the complex mechanisms interconnecting autophagy and apoptosis and their roles in the regulation of NSC death. © 2015 AlphaMed Press.

  7. AKT signaling displays multifaceted functions in neural crest development.

    Science.gov (United States)

    Sittewelle, Méghane; Monsoro-Burq, Anne H

    2018-05-31

    AKT signaling is an essential intracellular pathway controlling cell homeostasis, cell proliferation and survival, as well as cell migration and differentiation in adults. Alterations impacting the AKT pathway are involved in many pathological conditions in human disease. Similarly, during development, multiple transmembrane molecules, such as FGF receptors, PDGF receptors or integrins, activate AKT to control embryonic cell proliferation, migration, differentiation, and also cell fate decisions. While many studies in mouse embryos have clearly implicated AKT signaling in the differentiation of several neural crest derivatives, information on AKT functions during the earliest steps of neural crest development had remained relatively scarce until recently. However, recent studies on known and novel regulators of AKT signaling demonstrate that this pathway plays critical roles throughout the development of neural crest progenitors. Non-mammalian models such as fish and frog embryos have been instrumental to our understanding of AKT functions in neural crest development, both in neural crest progenitors and in the neighboring tissues. This review combines current knowledge acquired from all these different vertebrate animal models to describe the various roles of AKT signaling related to neural crest development in vivo. We first describe the importance of AKT signaling in patterning the tissues involved in neural crest induction, namely the dorsal mesoderm and the ectoderm. We then focus on AKT signaling functions in neural crest migration and differentiation. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

    Energy Technology Data Exchange (ETDEWEB)

    Manceur, Aziza P. [Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario (Canada); Donnelly Centre, University of Toronto, Toronto, Ontario (Canada); Tseng, Michael [Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, ON (Canada); Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Holowacz, Tamara [Donnelly Centre, University of Toronto, Toronto, Ontario (Canada); Witterick, Ian [Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Department of Otolaryngology, Head and Neck Surgery, University of Toronto, ON (Canada); Weksberg, Rosanna [Institute of Medical Science, University of Toronto, Toronto, ON (Canada); The Hospital for Sick Children, Research Institute, Program in Genetics and Genomic Biology, Toronto, Ontario Canada (Canada); McCurdy, Richard D. [The Hospital for Sick Children, Research Institute, Program in Genetics and Genomic Biology, Toronto, Ontario Canada (Canada); Warsh, Jerry J. [Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, ON (Canada); Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Audet, Julie, E-mail: julie.audet@utoronto.ca [Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario (Canada); Donnelly Centre, University of Toronto, Toronto, Ontario (Canada)

    2011-09-10

    The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

  9. Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

    International Nuclear Information System (INIS)

    Manceur, Aziza P.; Tseng, Michael; Holowacz, Tamara; Witterick, Ian; Weksberg, Rosanna; McCurdy, Richard D.; Warsh, Jerry J.; Audet, Julie

    2011-01-01

    The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

  10. Menadione-mediated WST1 reduction assay for the determination of metabolic activity of cultured neural cells.

    Science.gov (United States)

    Stapelfeldt, Karsten; Ehrke, Eric; Steinmeier, Johann; Rastedt, Wiebke; Dringen, Ralf

    2017-12-01

    Cellular reduction of tetrazolium salts to their respective formazans is frequently used to determine the metabolic activity of cultured cells as an indicator of cell viability. For membrane-impermeable tetrazolium salts such as WST1 the application of a membrane-permeable electron cycler is usually required to mediate the transfer of intracellular electrons for extracellular WST1 reduction. Here we demonstrate that in addition to the commonly used electron cycler M-PMS, menadione can also serve as an efficient electron cycler for extracellular WST1 reduction in cultured neural cells. The increase in formazan absorbance in glial cell cultures for the WST1 reduction by menadione involves enzymatic menadione reduction and was twice that recorded for the cytosolic enzyme-independent WST1 reduction in the presence of M-PMS. The optimized WST1 reduction assay allowed within 30 min of incubation a highly reliable detection of compromised cell metabolism caused by 3-bromopyruvate and impaired membrane integrity caused by Triton X-100, with a sensitivity as good as that of spectrophotometric assays which determine cellular MTT reduction or lactate dehydrogenase release. The short incubation period of 30 min and the observed good sensitivity make this optimized menadione-mediated WST1 reduction assay a quick and reliable alternative to other viability and toxicity assays. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Image quality assessment for determining efficacy and limitations of Super-Resolution Convolutional Neural Network (SRCNN)

    Science.gov (United States)

    Ward, Chris M.; Harguess, Joshua; Crabb, Brendan; Parameswaran, Shibin

    2017-09-01

    Traditional metrics for evaluating the efficacy of image processing techniques do not lend themselves to under- standing the capabilities and limitations of modern image processing methods - particularly those enabled by deep learning. When applying image processing in engineering solutions, a scientist or engineer has a need to justify their design decisions with clear metrics. By applying blind/referenceless image spatial quality (BRISQUE), Structural SIMilarity (SSIM) index scores, and Peak signal-to-noise ratio (PSNR) to images before and after im- age processing, we can quantify quality improvements in a meaningful way and determine the lowest recoverable image quality for a given method.

  12. New fast MMN paradigm for determining the neural prerequisites for musical ability

    DEFF Research Database (Denmark)

    Vuust, Peter; Brattico, Elvira; Glerean, Enrico

    2011-01-01

    of auditory skills and musical expertise. MMN paradigms, however, are typically very long in duration, and far from sounding musical. Therefore, we developed a novel multi-feature MMN paradigm with 6 different deviant types integrated in a complex musical context of no more than 20 min in duration. We found......Studies have consistently shown that the mismatch negativity (MMN) for different auditory features correlates with musical skills, and that this effect is more pronounced for stimuli integrated in complex musical contexts. Hence, the MMN can potentially be used for determining the development...... significant MMNs for all 6 deviant types. Hence, this short objective measure can putatively be used as an index for auditory and musical development....

  13. Artificial Neural Network model for the determination of GSM Rxlevel from atmospheric parameters

    Directory of Open Access Journals (Sweden)

    Julia Ofure Eichie

    2017-04-01

    Full Text Available Accurate received signal level (Rxlevel values are useful for mobile telecommunication network planning. Rxlevel is affected by the dynamics of the atmosphere through which it propagates. Adequate knowledge of the prevailing atmospheric conditions in an environment is essential for proper network planning. However most of the existing GSM received signal determination model are function of distance between point of signal reception and transmitting site thus necessitating the development of a model that involve the use of atmospheric parameters in the determination of received GSM signal level. In this paper, a three stage approach was used in the development of the model using some atmospheric parameters such as atmospheric temperature, relative humidity and dew point. The selected and easily measurable atmospheric parameters were used as input parameters in developing two new models for computing the Rxlevel of GSM signal using a three-step approach. Data acquisition and pre-processing serves as the first stage and formulation of ANN design and the development of parametric model for the Rxlevel using ANN synaptic weights form the second stage of the proposed approach. The third stage involves the use of ANN weight and bias values, and network architecture in the development of the model equation. In evaluating the performance of the proposed models, network parameters were varied and the results obtained using mean squared error (MSE as performance measure showed the developed model with 33 neurons in the hidden layer and tansig activation, function in both the hidden and output layers as the optimal model with least MSE value of 0.056. Thus showing that the developed model has an acceptable accuracy value as demonstrated from comparison of results with actual measured values.

  14. Using Elman recurrent neural networks with conjugate gradient algorithm in determining the anesthetic the amount of anesthetic medicine to be applied.

    Science.gov (United States)

    Güntürkün, Rüştü

    2010-08-01

    In this study, Elman recurrent neural networks have been defined by using conjugate gradient algorithm in order to determine the depth of anesthesia in the continuation stage of the anesthesia and to estimate the amount of medicine to be applied at that moment. The feed forward neural networks are also used for comparison. The conjugate gradient algorithm is compared with back propagation (BP) for training of the neural Networks. The applied artificial neural network is composed of three layers, namely the input layer, the hidden layer and the output layer. The nonlinear activation function sigmoid (sigmoid function) has been used in the hidden layer and the output layer. EEG data has been recorded with Nihon Kohden 9200 brand 22-channel EEG device. The international 8-channel bipolar 10-20 montage system (8 TB-b system) has been used in assembling the recording electrodes. EEG data have been recorded by being sampled once in every 2 milliseconds. The artificial neural network has been designed so as to have 60 neurons in the input layer, 30 neurons in the hidden layer and 1 neuron in the output layer. The values of the power spectral density (PSD) of 10-second EEG segments which correspond to the 1-50 Hz frequency range; the ratio of the total power of PSD values of the EEG segment at that moment in the same range to the total of PSD values of EEG segment taken prior to the anesthesia.

  15. Determination of the mechanical and physical properties of cartilage by coupling poroelastic-based finite element models of indentation with artificial neural networks.

    Science.gov (United States)

    Arbabi, Vahid; Pouran, Behdad; Campoli, Gianni; Weinans, Harrie; Zadpoor, Amir A

    2016-03-21

    One of the most widely used techniques to determine the mechanical properties of cartilage is based on indentation tests and interpretation of the obtained force-time or displacement-time data. In the current computational approaches, one needs to simulate the indentation test with finite element models and use an optimization algorithm to estimate the mechanical properties of cartilage. The modeling procedure is cumbersome, and the simulations need to be repeated for every new experiment. For the first time, we propose a method for fast and accurate estimation of the mechanical and physical properties of cartilage as a poroelastic material with the aid of artificial neural networks. In our study, we used finite element models to simulate the indentation for poroelastic materials with wide combinations of mechanical and physical properties. The obtained force-time curves are then divided into three parts: the first two parts of the data is used for training and validation of an artificial neural network, while the third part is used for testing the trained network. The trained neural network receives the force-time curves as the input and provides the properties of cartilage as the output. We observed that the trained network could accurately predict the properties of cartilage within the range of properties for which it was trained. The mechanical and physical properties of cartilage could therefore be estimated very fast, since no additional finite element modeling is required once the neural network is trained. The robustness of the trained artificial neural network in determining the properties of cartilage based on noisy force-time data was assessed by introducing noise to the simulated force-time data. We found that the training procedure could be optimized so as to maximize the robustness of the neural network against noisy force-time data. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. The Dynamics and Neural Correlates of Audio-Visual Integration Capacity as Determined by Temporal Unpredictability, Proactive Interference, and SOA.

    Directory of Open Access Journals (Sweden)

    Jonathan M P Wilbiks

    Full Text Available Over 5 experiments, we challenge the idea that the capacity of audio-visual integration need be fixed at 1 item. We observe that the conditions under which audio-visual integration is most likely to exceed 1 occur when stimulus change operates at a slow rather than fast rate of presentation and when the task is of intermediate difficulty such as when low levels of proactive interference (3 rather than 8 interfering visual presentations are combined with the temporal unpredictability of the critical frame (Experiment 2, or, high levels of proactive interference are combined with the temporal predictability of the critical frame (Experiment 4. Neural data suggest that capacity might also be determined by the quality of perceptual information entering working memory. Experiment 5 supported the proposition that audio-visual integration was at play during the previous experiments. The data are consistent with the dynamic nature usually associated with cross-modal binding, and while audio-visual integration capacity likely cannot exceed uni-modal capacity estimates, performance may be better than being able to associate only one visual stimulus with one auditory stimulus.

  17. The Dynamics and Neural Correlates of Audio-Visual Integration Capacity as Determined by Temporal Unpredictability, Proactive Interference, and SOA.

    Science.gov (United States)

    Wilbiks, Jonathan M P; Dyson, Benjamin J

    2016-01-01

    Over 5 experiments, we challenge the idea that the capacity of audio-visual integration need be fixed at 1 item. We observe that the conditions under which audio-visual integration is most likely to exceed 1 occur when stimulus change operates at a slow rather than fast rate of presentation and when the task is of intermediate difficulty such as when low levels of proactive interference (3 rather than 8 interfering visual presentations) are combined with the temporal unpredictability of the critical frame (Experiment 2), or, high levels of proactive interference are combined with the temporal predictability of the critical frame (Experiment 4). Neural data suggest that capacity might also be determined by the quality of perceptual information entering working memory. Experiment 5 supported the proposition that audio-visual integration was at play during the previous experiments. The data are consistent with the dynamic nature usually associated with cross-modal binding, and while audio-visual integration capacity likely cannot exceed uni-modal capacity estimates, performance may be better than being able to associate only one visual stimulus with one auditory stimulus.

  18. Artificial neural network for the determination of neutron spectra in the bunker of a Linac of 18 MV

    International Nuclear Information System (INIS)

    Banuelos F, A.; Borja H, C. G.; Valero L, C.; Guzman G, K. A.; Hernandez D, V. M.; Vega C, H. R.

    2011-11-01

    The neutron spectrum and equivalent of environmental dose H(10) were calculated for a radiotherapy room in 16 punctual detectors, 15 inside of and 1 outside of the same one. The calculations were carried out with the Monte Carlo method and with the code MCNP5 for a generic room model with a Linac of 18 MV, obtaining this way 16 spectra with 47 intervals of energy class, starting from these spectra the values of H(10) were calculated. On the other hand, an artificial neural network was designed and trained to determine the spectra by neutrons in 15 different locations inside the radiotherapy room starting from the value of H(10) in the detector 16 located in the exterior of the room, using as training data the spectra and calculated dose by neutrons, of which a medium quadratic error was obtained (m se) in the adjustment between the objective data and the exit data of m se=1E(-8). The results demonstrate that the use of the artificial intelligence as technique is an useful tool in the spectrometry and dosimetry of neutrons, since it simplifies the characterization process of neutron fields in radiotherapy rooms without the use of spectrometry systems, and that once the energy distribution of the neutrons produced by the Linac is known and the corresponding doses be calculated H(10), they can take the appropriate cautions for the security patient in treatment as well as for the personnel in the room. (Author)

  19. Melt ponds on Arctic sea ice determined from MODIS satellite data using an artificial neural network

    Directory of Open Access Journals (Sweden)

    A. Rösel

    2012-04-01

    Full Text Available Melt ponds on sea ice strongly reduce the surface albedo and accelerate the decay of Arctic sea ice. Due to different spectral properties of snow, ice, and water, the fractional coverage of these distinct surface types can be derived from multispectral sensors like the Moderate Resolution Image Spectroradiometer (MODIS using a spectral unmixing algorithm. The unmixing was implemented using a multilayer perceptron to reduce computational costs.

    Arctic-wide melt pond fractions and sea ice concentrations are derived from the level 3 MODIS surface reflectance product. The validation of the MODIS melt pond data set was conducted with aerial photos from the MELTEX campaign 2008 in the Beaufort Sea, data sets from the National Snow and Ice Data Center (NSIDC for 2000 and 2001 from four sites spread over the entire Arctic, and with ship observations from the trans-Arctic HOTRAX cruise in 2005. The root-mean-square errors range from 3.8 % for the comparison with HOTRAX data, over 10.7 % for the comparison with NSIDC data, to 10.3 % and 11.4 % for the comparison with MELTEX data, with coefficient of determination ranging from R2=0.28 to R2=0.45. The mean annual cycle of the melt pond fraction per grid cell for the entire Arctic shows a strong increase in June, reaching a maximum of 15 % by the end of June. The zonal mean of melt pond fractions indicates a dependence of the temporal development of melt ponds on the geographical latitude, and has its maximum in mid-July at latitudes between 80° and 88° N.

    Furthermore, the MODIS results are used to estimate the influence of melt ponds on retrievals of sea ice concentrations from passive microwave data. Results from a case study comparing sea ice concentrations from ARTIST Sea Ice-, NASA Team 2-, and Bootstrap-algorithms with MODIS sea ice concentrations indicate an underestimation of around 40 % for sea ice concentrations retrieved with microwave

  20. A Positive Regulatory Loop between a Wnt-Regulated Non-coding RNA and ASCL2 Controls Intestinal Stem Cell Fate.

    Science.gov (United States)

    Giakountis, Antonis; Moulos, Panagiotis; Zarkou, Vasiliki; Oikonomou, Christina; Harokopos, Vaggelis; Hatzigeorgiou, Artemis G; Reczko, Martin; Hatzis, Pantelis

    2016-06-21

    The canonical Wnt pathway plays a central role in stem cell maintenance, differentiation, and proliferation in the intestinal epithelium. Constitutive, aberrant activity of the TCF4/β-catenin transcriptional complex is the primary transforming factor in colorectal cancer. We identify a nuclear long non-coding RNA, termed WiNTRLINC1, as a direct target of TCF4/β-catenin in colorectal cancer cells. WiNTRLINC1 positively regulates the expression of its genomic neighbor ASCL2, a transcription factor that controls intestinal stem cell fate. WiNTRLINC1 interacts with TCF4/β-catenin to mediate the juxtaposition of its promoter with the regulatory regions of ASCL2. ASCL2, in turn, regulates WiNTRLINC1 transcriptionally, closing a feedforward regulatory loop that controls stem cell-related gene expression. This regulatory circuitry is highly amplified in colorectal cancer and correlates with increased metastatic potential and decreased patient survival. Our results uncover the interplay between non-coding RNA-mediated regulation and Wnt signaling and point to the diagnostic and therapeutic potential of WiNTRLINC1. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  1. Cell-type-specific responses of RT4 neural cell lines to dibutyryl-cAMP: branch determination versus maturation

    International Nuclear Information System (INIS)

    Droms, K.; Sueoka, N.

    1987-01-01

    This report describes the induction of cell-type-specific maturation, by dibutyryl-cAMP and testololactone, of neuronal and glial properties in a family of cell lines derived from a rat peripheral neurotumor, RT4. This maturation allows further understanding of the process of determination because of the close lineage relationship between the cell types of the RT4 family. The RT4 family is characterized by the spontaneous conversion of one of the cell types, RT4-AC (stem-cell type), to any of three derivative cell types, RT4-B, RT4-D, or RT4-E, with a frequency of about 10(-5). The RT4-AC cells express some properties characteristic of both neuronal and glial cells. Of these neural properties expressed by RT4-AC cells, only the neuronal properties are expressed by the RT4-B and RT4-E cells, and only the glial properties are expressed by the RT4-D cells. This in vitro cell-type conversion of RT4-AC to three derivative cell types is a branch point for the coordinate regulation of several properties and seems to resemble determination in vivo. In our standard culture conditions, several other neuronal and glial properties are not expressed by these cell types. However, addition of dibutyryl-cAMP induces expression of additional properties, in a cell-type-specific manner: formation of long cellular processes in the RT4-B8 and RT4-E5 cell lines and expression of high-affinity uptake of gamma-aminobutyric acid, by a glial-cell-specific mechanism, in the RT4-D6-2 cell line. These new properties are maximally expressed 2-3 days after addition of dibutyryl-cAMP

  2. The Role of Retinal Determination Gene Network (RDGN) in Hormone Signaling Transduction and Prostate Tumorigenes

    Science.gov (United States)

    2015-12-01

    S, Zhang W, Zhou J, Wang J, Ertel A, Li Z, Rui H, Quong A, Lisanti MP, Tozeren A, Tanes C, Addya S, Gormley M, Wang C, McMahon SB, Pestell RG...MP, Wang C, Pestell RG. Acetylation of the cell-fate factor dachshund determines p53 binding and signaling modules in breast cancer. Oncotarget...MP, Quong A, Ertel A, Pestell RG. Cell fate factor DACH1 represses YB-1-mediated oncogenic transcription and translation. Cancer Res. 2014;74(3):829

  3. The level of the transcription factor Pax6 is essential for controlling the balance between neural stem cell self-renewal and neurogenesis.

    Directory of Open Access Journals (Sweden)

    Stephen N Sansom

    2009-06-01

    Full Text Available Neural stem cell self-renewal, neurogenesis, and cell fate determination are processes that control the generation of specific classes of neurons at the correct place and time. The transcription factor Pax6 is essential for neural stem cell proliferation, multipotency, and neurogenesis in many regions of the central nervous system, including the cerebral cortex. We used Pax6 as an entry point to define the cellular networks controlling neural stem cell self-renewal and neurogenesis in stem cells of the developing mouse cerebral cortex. We identified the genomic binding locations of Pax6 in neocortical stem cells during normal development and ascertained the functional significance of genes that we found to be regulated by Pax6, finding that Pax6 positively and directly regulates cohorts of genes that promote neural stem cell self-renewal, basal progenitor cell genesis, and neurogenesis. Notably, we defined a core network regulating neocortical stem cell decision-making in which Pax6 interacts with three other regulators of neurogenesis, Neurog2, Ascl1, and Hes1. Analyses of the biological function of Pax6 in neural stem cells through phenotypic analyses of Pax6 gain- and loss-of-function mutant cortices demonstrated that the Pax6-regulated networks operating in neural stem cells are highly dosage sensitive. Increasing Pax6 levels drives the system towards neurogenesis and basal progenitor cell genesis by increasing expression of a cohort of basal progenitor cell determinants, including the key transcription factor Eomes/Tbr2, and thus towards neurogenesis at the expense of self-renewal. Removing Pax6 reduces cortical stem cell self-renewal by decreasing expression of key cell cycle regulators, resulting in excess early neurogenesis. We find that the relative levels of Pax6, Hes1, and Neurog2 are key determinants of a dynamic network that controls whether neural stem cells self-renew, generate cortical neurons, or generate basal progenitor cells

  4. Amplification of R-spondin1 signaling induces granulosa cell fate defects and cancers in mouse adult ovary

    NARCIS (Netherlands)

    De Cian, M-C; Pauper, E.; Bandiera, R.; Vidal, V. P. I.; Sacco, S.; Gregoire, E. P.; Chassot, A-A; Panzolini, C.; WILHELM, D; Pailhoux, E.; Youssef, Sameh A.; de Bruin, A.; Teerds, K.; Schedl, A.; Gillot, I.; Chaboissier, M-C

    2017-01-01

    R-spondin1 is a secreted regulator of WNT signaling, involved in both embryonic development and homeostasis of adult organs. It can have a dual role, acting either as a mitogen or as a tumor suppressor. During ovarian development, Rspo1 is a key factor required for sex determination and

  5. The neural determinants of age-related changes in fluid intelligence: a pre-registered, longitudinal analysis in UK Biobank.

    Science.gov (United States)

    Kievit, Rogier A; Fuhrmann, Delia; Borgeest, Gesa Sophia; Simpson-Kent, Ivan L; Henson, Richard N A

    2018-01-01

    Background:  Fluid intelligence declines with advancing age, starting in early adulthood. Within-subject declines in fluid intelligence are highly correlated with contemporaneous declines in the ability to live and function independently. To support healthy aging, the mechanisms underlying these declines need to be better understood. Methods:  In this pre-registered analysis, we applied latent growth curve modelling to investigate the neural determinants of longitudinal changes in fluid intelligence across three time points in 185,317 individuals (N=9,719 two waves, N=870 three waves) from the UK Biobank (age range: 39-73 years). Results:  We found a weak but significant effect of cross-sectional age on the mean fluid intelligence score, such that older individuals scored slightly lower. However, the mean longitudinal slope was positive, rather than negative, suggesting improvement across testing occasions. Despite the considerable sample size, the slope variance was non-significant, suggesting no reliable individual differences in change over time. This null-result is likely due to the nature of the cognitive test used. In a subset of individuals, we found that white matter microstructure (N=8839, as indexed by fractional anisotropy) and grey-matter volume (N=9931) in pre-defined regions-of-interest accounted for complementary and unique variance in mean fluid intelligence scores. The strongest effects were such that higher grey matter volume in the frontal pole and greater white matter microstructure in the posterior thalamic radiations were associated with higher fluid intelligence scores. Conclusions:  In a large preregistered analysis, we demonstrate a weak but significant negative association between age and fluid intelligence. However, we did not observe plausible longitudinal patterns, instead observing a weak increase across testing occasions, and no significant individual differences in rates of change, likely due to the suboptimal task design

  6. Neural networks for aircraft control

    Science.gov (United States)

    Linse, Dennis

    1990-01-01

    Current research in Artificial Neural Networks indicates that networks offer some potential advantages in adaptation and fault tolerance. This research is directed at determining the possible applicability of neural networks to aircraft control. The first application will be to aircraft trim. Neural network node characteristics, network topology and operation, neural network learning and example histories using neighboring optimal control with a neural net are discussed.

  7. Neural crest stem cell multipotency requires Foxd3 to maintain neural potential and repress mesenchymal fates.

    Science.gov (United States)

    Mundell, Nathan A; Labosky, Patricia A

    2011-02-01

    Neural crest (NC) progenitors generate a wide array of cell types, yet molecules controlling NC multipotency and self-renewal and factors mediating cell-intrinsic distinctions between multipotent versus fate-restricted progenitors are poorly understood. Our earlier work demonstrated that Foxd3 is required for maintenance of NC progenitors in the embryo. Here, we show that Foxd3 mediates a fate restriction choice for multipotent NC progenitors with loss of Foxd3 biasing NC toward a mesenchymal fate. Neural derivatives of NC were lost in Foxd3 mutant mouse embryos, whereas abnormally fated NC-derived vascular smooth muscle cells were ectopically located in the aorta. Cranial NC defects were associated with precocious differentiation towards osteoblast and chondrocyte cell fates, and individual mutant NC from different anteroposterior regions underwent fate changes, losing neural and increasing myofibroblast potential. Our results demonstrate that neural potential can be separated from NC multipotency by the action of a single gene, and establish novel parallels between NC and other progenitor populations that depend on this functionally conserved stem cell protein to regulate self-renewal and multipotency.

  8. A methodology for distinguishing divergent cell fates within a common progenitor population: adenoma- and neuroendocrine-like cells are confounders of rat ileal epithelial cell (IEC-18 culture

    Directory of Open Access Journals (Sweden)

    Paxton Jessica B

    2005-01-01

    Full Text Available Abstract Background IEC-18 cells are a non-transformed, immortal cell line derived from juvenile rat ileal crypt cells. They may have experimental advantages over tumor-derived gastrointestinal lineages, including preservation of phenotype, normal endocrine responses and retention of differentiation potential. However, their proclivity for spontaneous differentiation / transformation may be stereotypical and could represent a more profound experimental confounder than previously realized. We hypothesized that IEC-18 cells spontaneously diverge towards a uniform mixture of epigenetic fates, with corresponding phenotypes, rather than persist as a single progenitor lineage. Results IEC-18 cells were cultured for 72 hours in serum free media (SFM, with and without various insulin-like growth factor agonists to differentially boost the basal rate of proliferation. A strategy was employed to identify constitutive genes as markers of divergent fates through gene array analysis by cross-referencing fold-change trends for individual genes against crypt cell abundance in each treatment. We then confirmed the cell-specific phenotype by immunolocalization of proteins corresponding to those genes. The majority of IEC-18 cells in SFM alone had a loss in expression of the adenomatous polyposis coli (APC gene at the mRNA and protein levels, consistent with adenoma-like transformation. In addition, a small subset of cells expressed the serotonin receptor 2A gene and had neuroendocrine-like morphology. Conclusions IEC-18 cells commonly undergo a change in cell fate prior to reaching confluence. The most common fate switch that we were able to detect correlates with a down regulation of the APC gene and transformation into an adenoma-like phenotype.

  9. Genetic and biochemical evidence that haploinsufficiency of the Nf1 tumor suppressor gene modulates melanocyte and mast cell fates in vivo.

    Science.gov (United States)

    Ingram, D A; Yang, F C; Travers, J B; Wenning, M J; Hiatt, K; New, S; Hood, A; Shannon, K; Williams, D A; Clapp, D W

    2000-01-03

    Neurofibromatosis type 1 (NF1) is a common autosomal-dominant disorder characterized by cutaneous neurofibromas infiltrated with large numbers of mast cells, melanocyte hyperplasia, and a predisposition to develop malignant neoplasms. NF1 encodes a GTPase activating protein (GAP) for Ras. Consistent with Knudson's "two hit" model of tumor suppressor genes, leukemias and malignant solid tumors in NF1 patients frequently demonstrate somatic loss of the normal NF1 allele. However, the phenotypic and biochemical consequences of heterozygous inactivation of Nf1 are largely unknown. Recently neurofibromin, the protein encoded by NF1, was shown to negatively regulate Ras activity in Nf1-/- murine myeloid hematopoietic cells in vitro through the c-kit receptor tyrosine kinase (dominant white spotting, W). Since the W and Nf1 locus appear to function along a common developmental pathway, we generated mice with mutations at both loci to examine potential interactions in vivo. Here, we show that haploinsufficiency at Nf1 perturbs cell fates in mast cells in vivo, and partially rescues coat color and mast cell defects in W(41) mice. Haploinsufficiency at Nf1 also increased mast cell proliferation, survival, and colony formation in response to Steel factor, the ligand for c-kit. Furthermore, haploinsufficiency was associated with enhanced Ras-mitogen-activated protein kinase activity, a major downstream effector of Ras, via wild-type and mutant (W(41)) c-kit receptors. These observations identify a novel interaction between c-kit and neurofibromin in vivo, and offer experimental evidence that haploinsufficiency of Nf1 alters both cellular and biochemical phenotypes in two cell lineages that are affected in individuals with NF1. Collectively, these data support the emerging concept that heterozygous inactivation of tumor suppressor genes may have profound biological effects in multiple cell types.

  10. The neural determinants of age-related changes in fluid intelligence: a pre-registered, longitudinal analysis in UK Biobank

    Science.gov (United States)

    Kievit, Rogier A.; Fuhrmann, Delia; Henson, Richard N. A.

    2018-01-01

    Background: Fluid intelligence declines with advancing age, starting in early adulthood. Within-subject declines in fluid intelligence are highly correlated with contemporaneous declines in the ability to live and function independently. To support healthy aging, the mechanisms underlying these declines need to be better understood. Methods: In this pre-registered analysis, we applied latent growth curve modelling to investigate the neural determinants of longitudinal changes in fluid intelligence across three time points in 185,317 individuals (N=9,719 two waves, N=870 three waves) from the UK Biobank (age range: 39-73 years). Results: We found a weak but significant effect of cross-sectional age on the mean fluid intelligence score, such that older individuals scored slightly lower. However, the mean longitudinal slope was positive, rather than negative, suggesting improvement across testing occasions. Despite the considerable sample size, the slope variance was non-significant, suggesting no reliable individual differences in change over time. This null-result is likely due to the nature of the cognitive test used. In a subset of individuals, we found that white matter microstructure (N=8839, as indexed by fractional anisotropy) and grey-matter volume (N=9931) in pre-defined regions-of-interest accounted for complementary and unique variance in mean fluid intelligence scores. The strongest effects were such that higher grey matter volume in the frontal pole and greater white matter microstructure in the posterior thalamic radiations were associated with higher fluid intelligence scores. Conclusions: In a large preregistered analysis, we demonstrate a weak but significant negative association between age and fluid intelligence. However, we did not observe plausible longitudinal patterns, instead observing a weak increase across testing occasions, and no significant individual differences in rates of change, likely due to the suboptimal task design. Finally

  11. Chemically Induced Reprogramming of Somatic Cells to Pluripotent Stem Cells and Neural Cells.

    Science.gov (United States)

    Biswas, Dhruba; Jiang, Peng

    2016-02-06

    The ability to generate transplantable neural cells in a large quantity in the laboratory is a critical step in the field of developing stem cell regenerative medicine for neural repair. During the last few years, groundbreaking studies have shown that cell fate of adult somatic cells can be reprogrammed through lineage specific expression of transcription factors (TFs)-and defined culture conditions. This key concept has been used to identify a number of potent small molecules that could enhance the efficiency of reprogramming with TFs. Recently, a growing number of studies have shown that small molecules targeting specific epigenetic and signaling pathways can replace all of the reprogramming TFs. Here, we provide a detailed review of the studies reporting the generation of chemically induced pluripotent stem cells (ciPSCs), neural stem cells (ciNSCs), and neurons (ciN). We also discuss the main mechanisms of actions and the pathways that the small molecules regulate during chemical reprogramming.

  12. Determination of Elastic and Dissipative Properties of Material Using Combination of FEM and Complex Artificial Neural Networks

    Science.gov (United States)

    Soloviev, A. N.; Giang, N. D. T.; Chang, S.-H.

    This paper describes the application of complex artificial neural networks (CANN) in the inverse identification problem of the elastic and dissipative properties of solids. Additional information for the inverse problem serves the components of the displacement vector measured on the body boundary, which performs harmonic oscillations at the first resonant frequency. The process of displacement measurement in this paper is simulated using calculation of finite element (FE) software ANSYS. In the shown numerical example, we focus on the accurate identification of elastic modulus and quality of material depending on the number of measurement points and their locations as well as on the architecture of neural network and time of the training process, which is conducted by using algorithms RProp, QuickProp.

  13. Application of neural network technique to determine a corrector surface for global geopotential model using GPS/levelling measurements in Egypt

    Science.gov (United States)

    Elshambaky, Hossam Talaat

    2018-01-01

    Owing to the appearance of many global geopotential models, it is necessary to determine the most appropriate model for use in Egyptian territory. In this study, we aim to investigate three global models, namely EGM2008, EIGEN-6c4, and GECO. We use five mathematical transformation techniques, i.e., polynomial expression, exponential regression, least-squares collocation, multilayer feed forward neural network, and radial basis neural networks to make the conversion from regional geometrical geoid to global geoid models and vice versa. From a statistical comparison study based on quality indexes between previous transformation techniques, we confirm that the multilayer feed forward neural network with two neurons is the most accurate of the examined transformation technique, and based on the mean tide condition, EGM2008 represents the most suitable global geopotential model for use in Egyptian territory to date. The final product gained from this study was the corrector surface that was used to facilitate the transformation process between regional geometrical geoid model and the global geoid model.

  14. Application of artificial neural networks to determine the authentication of fattening diets of Iberian pigs according to their triacylglycerol profiles

    Directory of Open Access Journals (Sweden)

    León-Camacho, M.

    2013-04-01

    Full Text Available The triacylglycerols in the subcutaneous fat from Iberian pigs reared on four different feeding types, Montanera, Recebo, extensive Cebo and intensive Cebo, have been determined by gas chromatography with a flame ionization detector. Analyses were performed in a column coated with a bonded stationary phase (50% phenyl-50% methylpolysiloxane with hydrogen as the carrier gas. Lipids were extracted by melting the subcutaneous fat in a microwave oven and then filtering and dissolving it in hexane. A total amount of 2783 samples from several campaigns were considered. Using the triacylglycerols as chemical descriptors, a study on the discriminating power to differentiate samples according to the pig feeding type and system was performed. With this aim, pattern recognition techniques, such as linear discriminant analysis (LDA and multilayer perceptron artificial neural networks (MLPANN, have been used. ANN performed better than LDA, with a mean prediction ability of approximately 97% in the differentiation of fattening diets such as Montanera, extensive Cebo and intensive Cebo. In the case of including the recebo fattening diet, the model presents a mean performance of 82%. The differentiation of fattening systems has also been achieved by means of ANN, with a mean performance of 96%.Se ha determinado mediante cromatografía de gases con detector de ionización de llama los triglicéridos de la grasa subcutánea de cerdos ibéricos, cebados con cuatro tipos de alimentación: montanera, recebo, cebo extensivo y cebo intensivo. Los análisis se realizaron en una columna con una fase estacionaria ligada químicamente (50% fenil-50% metilpolisiloxano usando hidrógeno como gas portador. La grasa subcutánea se extrajo por fusión en horno de microondas, posteriormente se filtró y se disolvió en hexano. Un total de 2.783 muestras de varias campañas fueron analizadas. Usando los triglicéridos como descriptores químicos se ha llevado a cabo un estudio

  15. Strabismus-mediated primary archenteron invagination is uncoupled from Wnt/β-catenin-dependent endoderm cell fate specification in Nematostella vectensis (Anthozoa, Cnidaria: Implications for the evolution of gastrulation

    Directory of Open Access Journals (Sweden)

    Kumburegama Shalika

    2011-01-01

    Full Text Available Abstract Background Gastrulation is a uniquely metazoan character, and its genesis was arguably the key step that enabled the remarkable diversification within this clade. The process of gastrulation involves two tightly coupled events during embryogenesis of most metazoans. Morphogenesis produces a distinct internal epithelial layer in the embryo, and this epithelium becomes segregated as an endoderm/endomesodermal germ layer through the activation of a specific gene regulatory program. The developmental mechanisms that induced archenteron formation and led to the segregation of germ layers during metazoan evolution are unknown. But an increased understanding of development in early diverging taxa at the base of the metazoan tree may provide insights into the origins of these developmental mechanisms. Results In the anthozoan cnidarian Nematostella vectensis, initial archenteron formation begins with bottle cell-induced buckling of the blastula epithelium at the animal pole. Here, we show that bottle cell formation and initial gut invagination in Nematostella requires NvStrabismus (NvStbm, a maternally-expressed core component of the Wnt/Planar Cell Polarity (PCP pathway. The NvStbm protein is localized to the animal pole of the zygote, remains asymmetrically expressed through the cleavage stages, and becomes restricted to the apical side of invaginating bottle cells at the blastopore. Antisense morpholino-mediated NvStbm-knockdown blocks bottle cell formation and initial archenteron invagination, but it has no effect on Wnt/ß-catenin signaling-mediated endoderm cell fate specification. Conversely, selectively blocking Wnt/ß-catenin signaling inhibits endoderm cell fate specification but does not affect bottle cell formation and initial archenteron invagination. Conclusions Our results demonstrate that Wnt/PCP-mediated initial archenteron invagination can be uncoupled from Wnt/ß-catenin-mediated endoderm cell fate specification in

  16. Residual Convolutional Neural Network for the Determination of IDH Status in Low- and High-Grade Gliomas from MR Imaging.

    Science.gov (United States)

    Chang, Ken; Bai, Harrison X; Zhou, Hao; Su, Chang; Bi, Wenya Linda; Agbodza, Ena; Kavouridis, Vasileios K; Senders, Joeky T; Boaro, Alessandro; Beers, Andrew; Zhang, Biqi; Capellini, Alexandra; Liao, Weihua; Shen, Qin; Li, Xuejun; Xiao, Bo; Cryan, Jane; Ramkissoon, Shakti; Ramkissoon, Lori; Ligon, Keith; Wen, Patrick Y; Bindra, Ranjit S; Woo, John; Arnaout, Omar; Gerstner, Elizabeth R; Zhang, Paul J; Rosen, Bruce R; Yang, Li; Huang, Raymond Y; Kalpathy-Cramer, Jayashree

    2018-03-01

    Purpose: Isocitrate dehydrogenase ( IDH ) mutations in glioma patients confer longer survival and may guide treatment decision making. We aimed to predict the IDH status of gliomas from MR imaging by applying a residual convolutional neural network to preoperative radiographic data. Experimental Design: Preoperative imaging was acquired for 201 patients from the Hospital of University of Pennsylvania (HUP), 157 patients from Brigham and Women's Hospital (BWH), and 138 patients from The Cancer Imaging Archive (TCIA) and divided into training, validation, and testing sets. We trained a residual convolutional neural network for each MR sequence (FLAIR, T2, T1 precontrast, and T1 postcontrast) and built a predictive model from the outputs. To increase the size of the training set and prevent overfitting, we augmented the training set images by introducing random rotations, translations, flips, shearing, and zooming. Results: With our neural network model, we achieved IDH prediction accuracies of 82.8% (AUC = 0.90), 83.0% (AUC = 0.93), and 85.7% (AUC = 0.94) within training, validation, and testing sets, respectively. When age at diagnosis was incorporated into the model, the training, validation, and testing accuracies increased to 87.3% (AUC = 0.93), 87.6% (AUC = 0.95), and 89.1% (AUC = 0.95), respectively. Conclusions: We developed a deep learning technique to noninvasively predict IDH genotype in grade II-IV glioma using conventional MR imaging using a multi-institutional data set. Clin Cancer Res; 24(5); 1073-81. ©2017 AACR . ©2017 American Association for Cancer Research.

  17. Determination of size distribution of bubbles in a bubbly column two phase flows by ultrasound and neural networks

    International Nuclear Information System (INIS)

    Baroni, Douglas B.; Lamy, Carlos A.; Bittencourt, Marcelo S.Q.; Pereira, Claudio M.N.A.; Cunha Filho, Jurandyr S.; Motta, Mauricio S.

    2011-01-01

    The development of advanced nuclear reactor conceptions depends largely on the amount of available data to the designer. Non invasive ultrasonic techniques can contribute to the evaluation of gas-liquid two-phase regimes in the nuclear thermo-hydraulic circuits. A key-point for success of those techniques is the interpretation of the ultrasonic signal. In this work, a methodology based in artificial neural networks (ANN) is proposed to predict size distribution of bubbles in a bubbly flow. To accomplish that, an air feed system control was used to obtain specific bubbly flows in an experimental system utilizing a Plexiglas vertical bubbly column. Four different size distribution of bubbles were generated. The bubbles were photographed and measured. To evaluate the different size distribution of bubbles it was used the ultrasonic reflected echo on the opposite wall of the column. Then, an ANN has been developed for predicting size distribution of bubbles by using the frequency spectra of the ultrasonic signal as input. A trained artificial neural network using ultrasonic signal in the frequency domain can evaluate with a good precision the size distribution of bubbles generated in this system. (author)

  18. Determination of size distribution of bubbles in a bubbly column two phase flows by ultrasound and neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Baroni, Douglas B.; Lamy, Carlos A.; Bittencourt, Marcelo S.Q.; Pereira, Claudio M.N.A., E-mail: douglasbaroni@ien.gov.b, E-mail: lamy@ien.gov.b, E-mail: bittenc@ien.gov.b, E-mail: cmnap@ien.gov.b [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Cunha Filho, Jurandyr S. [Escola Tecnica Estadual Visconde de Maua (ETEVM/RJ), Rio de Janeiro, RJ (Brazil); Motta, Mauricio S., E-mail: mmotta@cefet-rj.b [Centro Federal de Educacao Tecnologica Celso Suckow da Fonseca (CEFET/RJ), Rio de Janeiro, RJ (Brazil)

    2011-07-01

    The development of advanced nuclear reactor conceptions depends largely on the amount of available data to the designer. Non invasive ultrasonic techniques can contribute to the evaluation of gas-liquid two-phase regimes in the nuclear thermo-hydraulic circuits. A key-point for success of those techniques is the interpretation of the ultrasonic signal. In this work, a methodology based in artificial neural networks (ANN) is proposed to predict size distribution of bubbles in a bubbly flow. To accomplish that, an air feed system control was used to obtain specific bubbly flows in an experimental system utilizing a Plexiglas vertical bubbly column. Four different size distribution of bubbles were generated. The bubbles were photographed and measured. To evaluate the different size distribution of bubbles it was used the ultrasonic reflected echo on the opposite wall of the column. Then, an ANN has been developed for predicting size distribution of bubbles by using the frequency spectra of the ultrasonic signal as input. A trained artificial neural network using ultrasonic signal in the frequency domain can evaluate with a good precision the size distribution of bubbles generated in this system. (author)

  19. Use of recurrent neural networks for determination of 7-epiclusianone acidity constants in ethanol-water mixtures; Uso de redes neurais recorrentes na determinacao das constantes de acidez para a 7-epiclusianona em misturas etanol-agua

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Ederson D' Martin; Lemes, Nelson Henrique Teixeira, E-mail: nelson.lemes@unifal-mg.edu.br [Instituto de Ciencias Exatas, Universidade Federal de Alfenas, Alfenas, MG (Brazil); Santos, Marcelo Henrique dos [Instituto de Ciencias Farmaceuticas, Universidade Federal de Alfenas, Alfenas, MG (Brazil); Braga, Joao Pedro [Departamento de Quimica, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)

    2012-07-01

    This work propose a recursive neural network to solve inverse equilibrium problem. The acidity constants of 7-epiclusianone in ethanol-water binary mixtures were determined from multiwavelength spectrophotometric data. A linear relationship between acidity constants and the % w/v of ethanol in the solvent mixture was observed. The proposed method efficiency is compared with the Simplex method, commonly used in nonlinear optimization techniques. The neural network method is simple, numerically stable and has a broad range of applicability. (author)

  20. Combined wavelet transform-artificial neural network use in tablet active content determination by near-infrared spectroscopy.

    Science.gov (United States)

    Chalus, Pascal; Walter, Serge; Ulmschneider, Michel

    2007-05-22

    The pharmaceutical industry faces increasing regulatory pressure to optimize quality control. Content uniformity is a basic release test for solid dosage forms. To accelerate test throughput and comply with the Food and Drug Administration's process analytical technology initiative, attention is increasingly turning to nondestructive spectroscopic techniques, notably near-infrared (NIR) spectroscopy (NIRS). However, validation of NIRS using requisite linearity and standard error of prediction (SEP) criteria remains a challenge. This study applied wavelet transformation of the NIR spectra of a commercial tablet to build a model using conventional partial least squares (PLS) regression and an artificial neural network (ANN). Wavelet coefficients in the PLS and ANN models reduced SEP by up to 60% compared to PLS models using mathematical spectra pretreatment. ANN modeling yielded high-linearity calibration and a correlation coefficient exceeding 0.996.

  1. Determination of relevant neuron-neuron connections for neural prosthetics using time-delayed mutual information: tutorial and preliminary results.

    Science.gov (United States)

    Taghva, Alexander; Song, Dong; Hampson, Robert E; Deadwyler, Sam A; Berger, Theodore W

    2012-12-01

    Identification of functional dependence among neurons is a necessary component in both the rational design of neural prostheses as well as in the characterization of network physiology. The objective of this article is to provide a tutorial for neurosurgeons regarding information theory, specifically time-delayed mutual information, and to compare time-delayed mutual information, an information theoretic quantity based on statistical dependence, with cross-correlation, a commonly used metric for this task in a preliminary analysis of rat hippocampal neurons. Spike trains were recorded from rats performing delayed nonmatch-to-sample task using an array of electrodes surgically implanted into the hippocampus of each hemisphere of the brain. In addition, spike train simulations of positively correlated neurons, negatively correlated neurons, and neurons correlated by nonlinear functions were generated. These were evaluated by time-delayed mutual information (MI) and cross-correlation. Application of time-delayed MI to experimental data indicated the optimal bin size for information capture in the CA3-CA1 system was 40 ms, which may provide some insight into the spatiotemporal nature of encoding in the rat hippocampus. On simulated data, time-delayed MI showed peak values at appropriate time lags in positively correlated, negatively correlated, and complexly correlated data. Cross-correlation showed peak and troughs with positively correlated and negatively correlated data, but failed to capture some higher order correlations. Comparison of time-delayed MI to cross-correlation in identification of functionally dependent neurons indicates that the methods are not equivalent. Time-delayed MI appeared to capture some interactions between CA3-CA1 neurons at physiologically plausible time delays missed by cross-correlation. It should be considered as a method for identification of functional dependence between neurons and may be useful in the development of neural

  2. Chemo-mechanical control of neural stem cell differentiation

    Science.gov (United States)

    Geishecker, Emily R.

    , immunocytochemistry (ICC), and neurite measurements. Data indicates that chemo-mechanical signaling is highly combinatorial in directing differentiation of C17.2s along a neuronal lineage in vitro. Chapter 4 discusses the design, synthesis, and characterization of a novel nanomaterial platform to investigate ligand-receptor binding. PEGylated nanoparticles were successfully synthesized and found to be relatively homogenous in size and morphology, as observed by transmission electron microscopy. However, successful binding of RGD peptide to the nanoparticle was not confirmed. Finally, a method for proteomic analysis of the C17.2 secretome is discussed in Chapter 5. Secreted proteins are of great importance as they can both influence cell behaviors as well as act as biomarkers of differentiation. Methods have been selected and optimized for protein extraction and two dimensional gel electrophoresis to be followed by mass spectrometry and protein identification. A temporal analysis of unique proteins expressed by C17.2s will result in a differentiation timeline. Deducing the dynamics of neuronal cell secretions will greatly contribute to the characterization of the C17.2 cell line and improve its relevance as a neural stem cell model. Overall, results illustrate the importance of chemical and mechanical cues in manipulating neural stem cell fate. These material platforms in combination with the further characterization of the C17.2 neural stem cells could have a great impact in the fields of neuronal biology, translational therapeutics, and pharmaceutical research.

  3. Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans

    Directory of Open Access Journals (Sweden)

    Jinah Han

    2015-02-01

    Full Text Available Neural stem cells (NSCs continuously produce new neurons within the adult mammalian hippocampus. NSCs are typically quiescent but activated to self-renew or differentiate into neural progenitor cells. The molecular mechanisms of NSC activation remain poorly understood. Here, we show that adult hippocampal NSCs express vascular endothelial growth factor receptor (VEGFR 3 and its ligand VEGF-C, which activates quiescent NSCs to enter the cell cycle and generate progenitor cells. Hippocampal NSC activation and neurogenesis are impaired by conditional deletion of Vegfr3 in NSCs. Functionally, this is associated with compromised NSC activation in response to VEGF-C and physical activity. In NSCs derived from human embryonic stem cells (hESCs, VEGF-C/VEGFR3 mediates intracellular activation of AKT and ERK pathways that control cell fate and proliferation. These findings identify VEGF-C/VEGFR3 signaling as a specific regulator of NSC activation and neurogenesis in mammals.

  4. Spectrophotometric determination of iron species using a combination of artificial neural networks and dispersive liquid–liquid microextraction based on solidification of floating organic drop

    International Nuclear Information System (INIS)

    Moghadam, Masoud Rohani; Shabani, Ali Mohammad Haji; Dadfarnia, Shayessteh

    2011-01-01

    Highlights: ► Combination of DLLME-SFO/fiber optic-linear array detection/chemometric methods. ► Simultaneous determination of complexes with overlapping spectra. ► A novel DLLME-SFO method is proposed for extraction of iron species. ► The extracted iron species are simultaneous determined using PC-ANNs. ► The enhancement factor of 162 and 125 are achieved for Fe 3+ and Fe 2+ , respectively. - Abstract: A dispersive liquid–liquid microextraction based on solidification of floating organic drop (DLLME-SFO) and artificial neural networks method was developed for the simultaneous separation/preconcentration and speciation of iron in water samples. In this method, an appropriate mixture of ethanol (as the disperser solvent) and 1-undecanol (as the extracting solvent) containing appropriate amount of 2-thenoyltrifluoroacetone (TTA) (as the complexing agent) was injected rapidly into the water sample containing iron (II) and iron (III) species. At this step, the iron species interacted with the TTA and extracted into the 1-undecanol. After the phase separation, the absorbance of the extracted irons was measured in the wavelength region of 450–600 nm. The artificial neural networks were then applied for simultaneous determination of individual iron species. Under optimum conditions, the calibration graphs were linear in the range of 95–1070 μg L −1 and 31–350 μg L −1 with detection limits of 25 and 8 μg L −1 for iron (II) and iron (III), respectively. The relative standard deviations (R.S.D., n = 6) were lower than 4.2%. The enhancement factor of 162 and 125 were obtained for Fe 3+ and Fe 2+ ions, respectively. The procedure was applied to power plant drum water and several potable water samples; and accuracy was assessed through the recovery experiments and independent analysis by graphite furnace atomic absorption spectrometry.

  5. Classification and source determination of medium petroleum distillates by chemometric and artificial neural networks: a self organizing feature approach.

    Science.gov (United States)

    Mat-Desa, Wan N S; Ismail, Dzulkiflee; NicDaeid, Niamh

    2011-10-15

    Three different medium petroleum distillate (MPD) products (white spirit, paint brush cleaner, and lamp oil) were purchased from commercial stores in Glasgow, Scotland. Samples of 10, 25, 50, 75, 90, and 95% evaporated product were prepared, resulting in 56 samples in total which were analyzed using gas chromatography-mass spectrometry. Data sets from the chromatographic patterns were examined and preprocessed for unsupervised multivariate analyses using principal component analysis (PCA), hierarchical cluster analysis (HCA), and a self organizing feature map (SOFM) artificial neural network. It was revealed that data sets comprised of higher boiling point hydrocarbon compounds provided a good means for the classification of the samples and successfully linked highly weathered samples back to their unevaporated counterpart in every case. The classification abilities of SOFM were further tested and validated for their predictive abilities where one set of weather data in each case was withdrawn from the sample set and used as a test set of the retrained network. This revealed SOFM to be an outstanding mechanism for sample discrimination and linkage over the more conventional PCA and HCA methods often suggested for such data analysis. SOFM also has the advantage of providing additional information through the evaluation of component planes facilitating the investigation of underlying variables that account for the classification. © 2011 American Chemical Society

  6. Multi-criteria decision making development of ion chromatographic method for determination of inorganic anions in oilfield waters based on artificial neural networks retention model.

    Science.gov (United States)

    Stefanović, Stefica Cerjan; Bolanča, Tomislav; Luša, Melita; Ukić, Sime; Rogošić, Marko

    2012-02-24

    This paper describes the development of ad hoc methodology for determination of inorganic anions in oilfield water, since their composition often significantly differs from the average (concentration of components and/or matrix). Therefore, fast and reliable method development has to be performed in order to ensure the monitoring of desired properties under new conditions. The method development was based on computer assisted multi-criteria decision making strategy. The used criteria were: maximal value of objective functions used, maximal robustness of the separation method, minimal analysis time, and maximal retention distance between two nearest components. Artificial neural networks were used for modeling of anion retention. The reliability of developed method was extensively tested by the validation of performance characteristics. Based on validation results, the developed method shows satisfactory performance characteristics, proving the successful application of computer assisted methodology in the described case study. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Self-consistent determination of the spike-train power spectrum in a neural network with sparse connectivity

    Directory of Open Access Journals (Sweden)

    Benjamin eDummer

    2014-09-01

    Full Text Available A major source of random variability in cortical networks is the quasi-random arrival of presynaptic action potentials from many other cells. In network studies as well as in the study of the response properties of single cells embedded in a network, synaptic background input is often approximated by Poissonian spike trains. However, the output statistics of the cells is in most cases far from being Poisson. This is inconsistent with the assumption of similar spike-train statistics for pre- and postsynaptic cells in a recurrent network. Here we tackle this problem for the popular class of integrate-and-fire neurons and study a self-consistent statistics of input and output spectra of neural spike trains. Instead of actually using a large network, we use an iterative scheme, in which we simulate a single neuron over several generations. In each of these generations, the neuron is stimulated with surrogate stochastic input that has a similar statistics as the output of the previous generation. For the surrogate input, we employ two distinct approximations: (i a superposition of renewal spike trains with the same interspike interval density as observed in the previous generation and (ii a Gaussian current with a power spectrum proportional to that observed in the previous generation. For input parameters that correspond to balanced input in the network, both the renewal and the Gaussian iteration procedure converge quickly and yield comparable results for the self-consistent spike-train power spectrum. We compare our results to large-scale simulations of a random sparsely connected network of leaky integrate-and-fire neurons (Brunel, J. Comp. Neurosci. 2000 and show that in the asynchronous regime close to a state of balanced synaptic input from the network, our iterative schemes provide excellent approximations to the autocorrelation of spike trains in the recurrent network.

  8. Novel perspectives of neural stem cell differentiation: from neurotransmitters to therapeutics.

    Science.gov (United States)

    Trujillo, Cleber A; Schwindt, Telma T; Martins, Antonio H; Alves, Janaína M; Mello, Luiz Eugênio; Ulrich, Henning

    2009-01-01

    In the past years, many reports have described the existence of neural progenitor and stem cells in the adult central nervous system capable of generating new neurons, astrocytes, and oligodendrocytes. This discovery has overturned the central assumption in the neuroscience field, of no new neurons being originated in the brain after birth and provided the fundaments to understand the molecular basis of neural differentiation and to develop new therapies for neural tissue repair. Although the mechanisms underlying cell fate during neural development are not yet understood, the importance of intrinsic and extrinsic factors and of an appropriate microenvironment is well known. In this context, emerging evidence strongly suggests that glial cells play a key role in controlling multiple steps of neurogenesis. Those cells, of particular radial glia, are important for migration, cell specification, and integration of neurons into a functional neural network. This review aims to present an update in the neurogenesis area and highlight the modulation of neural stem cell differentiation by neurotransmitters, growth factors, and their receptors, with possible applications for cell therapy strategies of neurological disorders.

  9. Neural networks

    International Nuclear Information System (INIS)

    Denby, Bruce; Lindsey, Clark; Lyons, Louis

    1992-01-01

    The 1980s saw a tremendous renewal of interest in 'neural' information processing systems, or 'artificial neural networks', among computer scientists and computational biologists studying cognition. Since then, the growth of interest in neural networks in high energy physics, fueled by the need for new information processing technologies for the next generation of high energy proton colliders, can only be described as explosive

  10. Biophysical characteristics reveal neural stem cell differentiation potential.

    Directory of Open Access Journals (Sweden)

    Fatima H Labeed

    Full Text Available Distinguishing human neural stem/progenitor cell (huNSPC populations that will predominantly generate neurons from those that produce glia is currently hampered by a lack of sufficient cell type-specific surface markers predictive of fate potential. This limits investigation of lineage-biased progenitors and their potential use as therapeutic agents. A live-cell biophysical and label-free measure of fate potential would solve this problem by obviating the need for specific cell surface markers.We used dielectrophoresis (DEP to analyze the biophysical, specifically electrophysiological, properties of cortical human and mouse NSPCs that vary in differentiation potential. Our data demonstrate that the electrophysiological property membrane capacitance inversely correlates with the neurogenic potential of NSPCs. Furthermore, as huNSPCs are continually passaged they decrease neuron generation and increase membrane capacitance, confirming that this parameter dynamically predicts and negatively correlates with neurogenic potential. In contrast, differences in membrane conductance between NSPCs do not consistently correlate with the ability of the cells to generate neurons. DEP crossover frequency, which is a quantitative measure of cell behavior in DEP, directly correlates with neuron generation of NSPCs, indicating a potential mechanism to separate stem cells biased to particular differentiated cell fates.We show here that whole cell membrane capacitance, but not membrane conductance, reflects and predicts the neurogenic potential of human and mouse NSPCs. Stem cell biophysical characteristics therefore provide a completely novel and quantitative measure of stem cell fate potential and a label-free means to identify neuron- or glial-biased progenitors.

  11. Determining degree of roasting in cocoa beans by artificial neural network (ANN)-based electronic nose system and gas chromatography/mass spectrometry (GC/MS).

    Science.gov (United States)

    Tan, Juzhong; Kerr, William L

    2018-08-01

    Roasting is a critical step in chocolate processing, where moisture content is decreased and unique flavors and texture are developed. The determination of the degree of roasting in cocoa beans is important to ensure the quality of chocolate. Determining the degree of roasting relies on human specialists or sophisticated chemical analyses that are inaccessible to small manufacturers and farmers. In this study, an electronic nose system was constructed consisting of an array of gas sensors and used to detect volatiles emanating from cocoa beans roasted for 0, 20, 30 and 40 min. The several signals were used to train a three-layer artificial neural network (ANN). Headspace samples were also analyzed by gas chromatography/mass spectrometry (GC/MS), with 23 select volatiles used to train a separate ANN. Both ANNs were used to predict the degree of roasting of cocoa beans. The electronic nose had a prediction accuracy of 94.4% using signals from sensors TGS 813, 826, 822, 830, 830, 2620, 2602 and 2610. In comparison, the GC/MS predicted the degree of roasting with an accuracy of 95.8%. The electronic nose system is able to predict the extent of roasting, as well as a more sophisticated approach using GC/MS. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

  12. Trace determination of safranin O dye using ultrasound assisted dispersive solid-phase micro extraction: Artificial neural network-genetic algorithm and response surface methodology.

    Science.gov (United States)

    Dil, Ebrahim Alipanahpour; Ghaedi, Mehrorang; Asfaram, Arash; Mehrabi, Fatemeh; Bazrafshan, Ali Akbar; Ghaedi, Abdol Mohammad

    2016-11-01

    In this study, ultrasound assisted dispersive solid-phase micro extraction combined with spectrophotometry (USA-DSPME-UV) method based on activated carbon modified with Fe2O3 nanoparticles (Fe2O3-NPs-AC) was developed for pre-concentration and determination of safranin O (SO). It is known that the efficiency of USA-DSPME-UV method may be affected by pH, amount of adsorbent, ultrasound time and eluent volume and the extent and magnitude of their contribution on response (in term of main and interaction part) was studied by using central composite design (CCD) and artificial neural network-genetic algorithms (ANN-GA). Accordingly by adjustment of experimental conditions suggested by ANN-GA at pH 6.5, 1.1mg of adsorbent, 10min ultrasound and 150μL of eluent volume led to achievement of best operation performance like low LOD (6.3ngmL(-1)) and LOQ (17.5ngmL(-1)) in the range of 25-3500ngmL(-1). In following stage, the SO content in real water and wastewater samples with recoveries between 93.27-99.41% with RSD lower than 3% was successfully determined. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Determination of Optimal Initial Weights of an Artificial Neural Network by Using the Harmony Search Algorithm: Application to Breakwater Armor Stones

    Directory of Open Access Journals (Sweden)

    Anzy Lee

    2016-05-01

    Full Text Available In this study, an artificial neural network (ANN model is developed to predict the stability number of breakwater armor stones based on the experimental data reported by Van der Meer in 1988. The harmony search (HS algorithm is used to determine the near-global optimal initial weights in the training of the model. The stratified sampling is used to sample the training data. A total of 25 HS-ANN hybrid models are tested with different combinations of HS algorithm parameters. The HS-ANN models are compared with the conventional ANN model, which uses a Monte Carlo simulation to determine the initial weights. Each model is run 50 times and the statistical analyses are conducted for the model results. The present models using stratified sampling are shown to be more accurate than those of previous studies. The statistical analyses for the model results show that the HS-ANN model with proper values of HS algorithm parameters can give much better and more stable prediction than the conventional ANN model.

  14. Altered epidermal growth factor-like sequences provide evidence for a role of Notch as a receptor in cell fate decisions.

    Science.gov (United States)

    Heitzler, P; Simpson, P

    1993-03-01

    In Drosophila each neural precursor is chosen from a group of cells through cell interactions mediated by Notch and Delta which may function as receptor and ligand (signal), respectively, in a lateral signalling pathway. The cells of a group are equipotential and express both Notch and Delta. Hyperactive mutant Notch molecules, (Abruptex), probably have an enhanced affinity for the ligand. When adjacent to wild-type cells, cells bearing the Abruptex proteins are unable to produce the signal. It is suggested that in addition to the binding of Notch molecules on one cell to the Delta molecules of opposing cells, the Notch and Delta proteins on the surface of the same cell may interact. Binding between a cell's own Notch and Delta molecules would alter the availability of these proteins to interact with their counterparts on adjacent cells.

  15. Neural fate decisions mediated by combinatorial regulation of Hes1 and miR-9.

    Science.gov (United States)

    Li, Shanshan; Liu, Yanwei; Liu, Zengrong; Wang, Ruiqi

    2016-01-01

    In the nervous system, Hes1 shows an oscillatory manner in neural progenitors but a persistent one in neurons. Many models involving Hes1 have been provided for the study of neural differentiation but few of them take the role of microRNA into account. It is known that a microRNA, miR-9, plays crucial roles in modulating Hes1 oscillations. However, the roles of miR-9 in controlling Hes1 oscillations and inducing transition between different cell fates still need to be further explored. Here we provide a mathematical model to show the interaction between miR-9 and Hes1, with the aim of understanding how the Hes1 oscillations are produced, how they are controlled, and further, how they are terminated. Based on the experimental findings, the model demonstrates the essential roles of Hes1 and miR-9 in regulating the dynamics of the system. In particular, the model suggests that the balance between miR-9 and Hes1 plays important roles in the choice between progenitor maintenance and neural differentiation. In addition, the synergistic (or antagonistic) effects of several important regulations are investigated so as to elucidate the effects of combinatorial regulation in neural decision-making. Our model provides a qualitative mechanism for understanding the process in neural fate decisions regulated by Hes1 and miR-9.

  16. Separation and Determination of Honokiol and Magnolol in Chinese Traditional Medicines by Capillary Electrophoresis with the Application of Response Surface Methodology and Radial Basis Function Neural Network

    Science.gov (United States)

    Han, Ping; Luan, Feng; Yan, Xizu; Gao, Yuan; Liu, Huitao

    2012-01-01

    A method for the separation and determination of honokiol and magnolol in Magnolia officinalis and its medicinal preparation is developed by capillary zone electrophoresis and response surface methodology. The concentration of borate, content of organic modifier, and applied voltage are selected as variables. The optimized conditions (i.e., 16 mmol/L sodium tetraborate at pH 10.0, 11% methanol, applied voltage of 25 kV and UV detection at 210 nm) are obtained and successfully applied to the analysis of honokiol and magnolol in Magnolia officinalis and Huoxiang Zhengqi Liquid. Good separation is achieved within 6 min. The limits of detection are 1.67 µg/mL for honokiol and 0.83 µg/mL for magnolol, respectively. In addition, an artificial neural network with “3-7-1” structure based on the ratio of peak resolution to the migration time of the later component (Rs/t) given by Box-Behnken design is also reported, and the predicted results are in good agreement with the values given by the mathematic software and the experimental results. PMID:22291059

  17. An interplay between extracellular signalling and the dynamics of the exit from pluripotency drives cell fate decisions in mouse ES cells

    Directory of Open Access Journals (Sweden)

    David A. Turner

    2014-06-01

    Full Text Available Embryonic Stem cells derived from the epiblast tissue of the mammalian blastocyst retain the capability to differentiate into any adult cell type and are able to self-renew indefinitely under appropriate culture conditions. Despite the large amount of knowledge that we have accumulated to date about the regulation and control of self-renewal, efficient directed differentiation into specific tissues remains elusive. In this work, we have analysed in a systematic manner the interaction between the dynamics of loss of pluripotency and Activin/Nodal, BMP4 and Wnt signalling in fate assignment during the early stages of differentiation of mouse ES cells in culture. During the initial period of differentiation, cells exit from pluripotency and enter an Epi-like state. Following this transient stage, and under the influence of Activin/Nodal and BMP signalling, cells face a fate choice between differentiating into neuroectoderm and contributing to Primitive Streak fates. We find that Wnt signalling does not suppress neural development as previously thought and that it aids both fates in a context dependent manner. Our results suggest that as cells exit pluripotency they are endowed with a primary neuroectodermal fate and that the potency to become endomesodermal rises with time. We suggest that this situation translates into a “race for fates” in which the neuroectodermal fate has an advantage.

  18. Artificial neural networks study of the catalytic reduction of resazurin: stopped-flow injection kinetic-spectrophotometric determination of Cu(II) and Ni(II)

    International Nuclear Information System (INIS)

    Magni, Diana M.; Olivieri, Alejandro C.; Bonivardi, Adrian L.

    2005-01-01

    An artificial neural network (ANN) procedure was used in the development of a catalytic spectrophotometric method for the determination of Cu(II) and Ni(II) employing a stopped-flow injection system. The method is based on the catalytic action of these ions on the reduction of resazurin by sulfide. ANNs trained by back-propagation of errors allowed us to model the systems in a concentration range of 0.5-6 and 1-15 mg l -1 for Cu(II) and Ni(II), respectively, with a low relative error of prediction (REP) for each cation: REP Cu(II) = 0.85% and REP Ni(II) = 0.79%. The standard deviations of the repeatability (s r ) and of the within-laboratory reproducibility (s w ) were measured using standard solutions of Cu(II) and Ni(II) equal to 2.75 and 3.5 mg l -1 , respectively: s r [Cu(II)] = 0.039 mg l -1 , s r [Ni(II)] = 0.044 mg l -1 , s w [Ni(II)] = 0.045 mg l -1 and s w [Ni(II)] = 0.050 mg l -1 . The ANNs-kinetic method has been applied to the determination of Cu(II) and Ni(II) in electroplating solutions and provided satisfactory results as compared with flame atomic absorption spectrophotometry method. The effect of resazurin, NaOH and Na 2 S concentrations and the reaction temperature on the analytical sensitivity is discussed

  19. Multiplicity of Buc copies in Atlantic salmon contrasts with loss of the germ cell determinant in primates, rodents and axolotl

    OpenAIRE

    Skugor, Adrijana; Tveiten, Helge; Johnsen, Hanne; Andersen, Øivind

    2016-01-01

    Background The primordial germ cells (PGCs) giving rise to gametes are determined by two different mechanisms in vertebrates. While the germ cell fate in mammals and salamanders is induced by zygotic signals, maternally delivered germ cell determinants specify the PGCs in birds, frogs and teleost fish. Assembly of the germ plasm in the oocyte is organized by the single Buc in zebrafish, named Velo1 in Xenopus, and by Oskar in Drosophila. Secondary loss of oskar in several insect lineages coin...

  20. Neural Networks

    International Nuclear Information System (INIS)

    Smith, Patrick I.

    2003-01-01

    Physicists use large detectors to measure particles created in high-energy collisions at particle accelerators. These detectors typically produce signals indicating either where ionization occurs along the path of the particle, or where energy is deposited by the particle. The data produced by these signals is fed into pattern recognition programs to try to identify what particles were produced, and to measure the energy and direction of these particles. Ideally, there are many techniques used in this pattern recognition software. One technique, neural networks, is particularly suitable for identifying what type of particle caused by a set of energy deposits. Neural networks can derive meaning from complicated or imprecise data, extract patterns, and detect trends that are too complex to be noticed by either humans or other computer related processes. To assist in the advancement of this technology, Physicists use a tool kit to experiment with several neural network techniques. The goal of this research is interface a neural network tool kit into Java Analysis Studio (JAS3), an application that allows data to be analyzed from any experiment. As the final result, a physicist will have the ability to train, test, and implement a neural network with the desired output while using JAS3 to analyze the results or output. Before an implementation of a neural network can take place, a firm understanding of what a neural network is and how it works is beneficial. A neural network is an artificial representation of the human brain that tries to simulate the learning process [5]. It is also important to think of the word artificial in that definition as computer programs that use calculations during the learning process. In short, a neural network learns by representative examples. Perhaps the easiest way to describe the way neural networks learn is to explain how the human brain functions. The human brain contains billions of neural cells that are responsible for processing

  1. Evolvable synthetic neural system

    Science.gov (United States)

    Curtis, Steven A. (Inventor)

    2009-01-01

    An evolvable synthetic neural system includes an evolvable neural interface operably coupled to at least one neural basis function. Each neural basis function includes an evolvable neural interface operably coupled to a heuristic neural system to perform high-level functions and an autonomic neural system to perform low-level functions. In some embodiments, the evolvable synthetic neural system is operably coupled to one or more evolvable synthetic neural systems in a hierarchy.

  2. Encapsulated oligodendrocyte precursor cell fate is dependent on PDGF-AA release kinetics in a 3D microparticle-hydrogel drug delivery system.

    Science.gov (United States)

    Pinezich, Meghan R; Russell, Lauren N; Murphy, Nicholas P; Lampe, Kyle J

    2018-04-16

    Biomaterial drug delivery systems (DDS) can be used to regulate growth factor release and combat the limited intrinsic regeneration capabilities of central nervous system (CNS) tissue following injury and disease. Of particular interest are systems that aid in oligodendrocyte regeneration, as oligodendrocytes generate myelin which surrounds neuronal axons and helps transmit signals throughout the CNS. Oligodendrocyte precursor cells (OPCs) are found in small numbers in the adult CNS, but are unable to effectively differentiate following CNS injury. Delivery of signaling molecules can initiate a favorable OPC response, such as proliferation or differentiation. Here, we investigate the delivery of one such molecule, platelet derived growth factor-AA (PDGF-AA), from poly(lactic-co-glycolic) acid microparticles to OPCs in a 3D polyethylene glycol-based hydrogel. The goal of this DDS was to better understand the relationship between PDGF-AA release kinetics and OPC fate. The system approximates native brain tissue stiffness, while incorporating PDGF-AA under seven different delivery scenarios. Within this DDS, supply of PDGF-AA followed by PDGF-AA withdrawal caused OPCs to upregulate gene expression of myelin basic protein (MBP) by factors of 1.6-9.2, whereas continuous supply of PDGF-AA caused OPCs to remain proliferative. At the protein expression level, we observed an upregulation in O1, a marker for mature oligodendrocytes. Together, these results show that burst release followed by withdrawal of PDGF-AA from a hydrogel DDS stimulates survival, proliferation, and differentiation of OPCs in vitro. Our results could inform the development of improved neural regeneration strategies that incorporate delivery of PDGF-AA to the injured CNS. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2018. © 2018 Wiley Periodicals, Inc.

  3. Neural network to diagnose lining condition

    Science.gov (United States)

    Yemelyanov, V. A.; Yemelyanova, N. Y.; Nedelkin, A. A.; Zarudnaya, M. V.

    2018-03-01

    The paper presents data on the problem of diagnosing the lining condition at the iron and steel works. The authors describe the neural network structure and software that are designed and developed to determine the lining burnout zones. The simulation results of the proposed neural networks are presented. The authors note the low learning and classification errors of the proposed neural networks. To realize the proposed neural network, the specialized software has been developed.

  4. dp53 Restrains ectopic neural stem cell formation in the Drosophila brain in a non-apoptotic mechanism involving Archipelago and cyclin E.

    Directory of Open Access Journals (Sweden)

    Yingshi Ouyang

    Full Text Available Accumulating evidence suggests that tumor-initiating stem cells or cancer stem cells (CSCs possibly originating from normal stem cells may be the root cause of certain malignancies. How stem cell homeostasis is impaired in tumor tissues is not well understood, although certain tumor suppressors have been implicated. In this study, we use the Drosophila neural stem cells (NSCs called neuroblasts as a model to study this process. Loss-of-function of Numb, a key cell fate determinant with well-conserved mammalian counterparts, leads to the formation of ectopic neuroblasts and a tumor phenotype in the larval brain. Overexpression of the Drosophila tumor suppressor p53 (dp53 was able to suppress ectopic neuroblast formation caused by numb loss-of-function. This occurred in a non-apoptotic manner and was independent of Dacapo, the fly counterpart of the well-characterized mammalian p53 target p21 involved in cellular senescence. The observation that dp53 affected Edu incorporation into neuroblasts led us to test the hypothesis that dp53 acts through regulation of factors involved in cell cycle progression. Our results show that the inhibitory effect of dp53 on ectopic neuroblast formation was mediated largely through its regulation of Cyclin E (Cyc E. Overexpression of Cyc E was able to abrogate dp53's ability to rescue numb loss-of-function phenotypes. Increasing Cyc E levels by attenuating Archipelago (Ago, a recently identified transcriptional target of dp53 and a negative regulator of Cyc E, had similar effects. Conversely, reducing Cyc E activity by overexpressing Ago blocked ectopic neuroblast formation in numb mutant. Our results reveal an intimate connection between cell cycle progression and NSC self-renewal vs. differentiation control, and indicate that p53-mediated regulation of ectopic NSC self-renewal through the Ago/Cyc E axis becomes particularly important when NSC homeostasis is perturbed as in numb loss-of-function condition. This has

  5. The C. elegans Spalt-like protein SEM-4 functions through the SoxC transcription factor SEM-2 to promote a proliferative blast cell fate in the postembryonic mesoderm.

    Science.gov (United States)

    Shen, Qinfang; Shi, Herong; Tian, Chenxi; Ghai, Vikas; Liu, Jun

    2017-09-01

    Proper development of a multicellular organism relies on well-coordinated regulation of cell fate specification, cell proliferation and cell differentiation. The C. elegans postembryonic mesoderm provides a useful system for uncovering factors involved in these processes and for further dissecting their regulatory relationships. The single Spalt-like zinc finger containing protein SEM-4/SALL is known to be involved in specifying the proliferative sex myoblast (SM) fate. We have found that SEM-4/SALL is sufficient to promote the SM fate and that it does so in a cell autonomous manner. We further showed that SEM-4/SALL acts through the SoxC transcription factor SEM-2 to promote the SM fate. SEM-2 is known to promote the SM fate by inhibiting the expression of two BWM-specifying transcription factors. In light of recent findings in mammals showing that Sall4, one of the mammalian homologs of SEM-4, contributes to pluripotency regulation by inhibiting differentiation, our work suggests that the function of SEM-4/SALL proteins in regulating pluripotency versus differentiation appears to be evolutionarily conserved. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Level of Notch activation determines the effect on growth and stem cell-like features in glioblastoma multiforme neurosphere cultures

    DEFF Research Database (Denmark)

    Kristoffersen, Karina; Villingshøj, Mette; Poulsen, Hans Skovgaard

    2013-01-01

    Brain cancer stem-like cells (bCSC) are cancer cells with neural stem cell (NSC)-like properties found in glioblastoma multiforme (GBM) and they are assigned a central role in tumor initiation, progression and relapse. The Notch pathway is important for maintenance and cell fate decisions...... in the normal NSC population. Notch signaling is often deregulated in GBM and recent results suggest that this pathway plays a significant role in bCSC as well. We therefore wished to further elucidate the role of Notch activation in GBM-derived bCSC....

  7. Determination of the load state of lead-acid batteries using neural networks; Determinacion del estado de carga de baterias plomo-acido utilizando redes neuronales

    Energy Technology Data Exchange (ETDEWEB)

    Cristin V, Miguel A; Ortega S, Cesar A [Instituto de Investigaciones Electricas, Cuernavaca, Morelos (Mexico)

    2005-07-01

    The charge of lead-acid batteries (LAB), as in any other type of batteries, consists of replacing the energy consumed during the discharge. Nevertheless, as no physical or chemical process is good enough to totality recharge a battery, it is necessary to supply to it more than the 100% of the energy demanded during its discharge. A critical factor to make a suitable load control of the batteries is to determine its own state of load. That is to say, to have an efficient load control, it is necessary to count on means that allow to accurately determining the residual capacity of the battery to deliver load. This one is the one of the aspects of greater interest in the research centers around world. For this reason, in this work it was pretended to develop a calculation algorithm of the state of load of batteries based on a fuzzy-neural network that could calculate the state of load without using the battery current as an input. This is because one of the main problems for the designers of battery load controllers is the correct supervision of the current that circulates around the system in all the rank of operation of the same one because the sensors do not have a linear behavior. [Spanish] La recarga de baterias plomo-acido (BPA), como cualquier otro tipo de baterias, consiste en reponer la energia consumida durante la descarga. Sin embargo, como ningun proceso fisico o quimico es lo bastante eficiente para recargar a totalidad una bateria, es necesario suministrarle mas del 100% de la energia demandada durante su descarga. Un factor critico para realizar un adecuado control de carga de las baterias, es determinar su propio estado de carga. Es decir, para tener un control de carga eficiente, es necesario contar con un medio que permita determinar con precision la capacidad remanente de la bateria para entregar carga. Este es uno de los aspectos de mayor interes en los centros de investigacion alrededor el mundo. Por tal razon, en este trabajo se propuso

  8. Lessons for Inductive Germline Determination

    Science.gov (United States)

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

    2015-01-01

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

  9. Constitutively active Notch1 converts cranial neural crest-derived frontonasal mesenchyme to perivascular cells in vivo

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    Sophie R. Miller

    2017-03-01

    Full Text Available Perivascular/mural cells originate from either the mesoderm or the cranial neural crest. Regardless of their origin, Notch signalling is necessary for their formation. Furthermore, in both chicken and mouse, constitutive Notch1 activation (via expression of the Notch1 intracellular domain is sufficient in vivo to convert trunk mesoderm-derived somite cells to perivascular cells, at the expense of skeletal muscle. In experiments originally designed to investigate the effect of premature Notch1 activation on the development of neural crest-derived olfactory ensheathing glial cells (OECs, we used in ovo electroporation to insert a tetracycline-inducible NotchΔE construct (encoding a constitutively active mutant of mouse Notch1 into the genome of chicken cranial neural crest cell precursors, and activated NotchΔE expression by doxycycline injection at embryonic day 4. NotchΔE-targeted cells formed perivascular cells within the frontonasal mesenchyme, and expressed a perivascular marker on the olfactory nerve. Hence, constitutively activating Notch1 is sufficient in vivo to drive not only somite cells, but also neural crest-derived frontonasal mesenchyme and perhaps developing OECs, to a perivascular cell fate. These results also highlight the plasticity of neural crest-derived mesenchyme and glia.

  10. Overexpression of miR-183/-96/-182 triggers neuronal cell fate in Human Retinal Pigment Epithelial (hRPE) cells in culture.

    Science.gov (United States)

    Davari, Maliheh; Soheili, Zahra-Soheila; Samiei, Shahram; Sharifi, Zohreh; Pirmardan, Ehsan Ranaei

    2017-01-29

    miR-183 cluster, composed of miR-183/-96/-182 genes, is highly expressed in the adult retina, particularly in photoreceptors. It involves in development, maturation and normal function of neuroretina. Ectopic overexpression of miR-183/-96/-182 genes was performed to assess reprogramming of hRPE cells. They were amplified from genomic DNA and cloned independently or in tandem configuration into pAAV.MCS vector. hRPE cells were then transfected with the recombinant constructs. Real-Time PCR was performed to measure the expression levels of miR-183/-96/-182 and that of several retina-specific neuronal genes such as OTX2, NRL, PDC and DCT. The transfected cells also were immunocytochemically examined for retina-specific neuronal markers, including Rhodopsin, red opsin, CRX, Thy1, CD73, recoverin and PKCα, to determine the cellular fate of the transfected hRPE cells. Data showed that upon miR-183/-96/-182 overexpression in hRPE cultures, the expression of neuronal genes including OTX2, NRL, PDC and DCT was also upregulated. Moreover, miR-183 cluster-treated hRPE cells were immunoreactive for neuronal markers such as Rhodopsin, red opsin, CRX and Thy1. Both transcriptional and translational upregulation of neuronal genes in miR-183 cluster-treated hRPE cells suggests that in vitro overexpression of miR-183 cluster could trigger reprogramming of hRPE cells to retinal neuron fate. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Neural Networks

    Directory of Open Access Journals (Sweden)

    Schwindling Jerome

    2010-04-01

    Full Text Available This course presents an overview of the concepts of the neural networks and their aplication in the framework of High energy physics analyses. After a brief introduction on the concept of neural networks, the concept is explained in the frame of neuro-biology, introducing the concept of multi-layer perceptron, learning and their use as data classifer. The concept is then presented in a second part using in more details the mathematical approach focussing on typical use cases faced in particle physics. Finally, the last part presents the best way to use such statistical tools in view of event classifers, putting the emphasis on the setup of the multi-layer perceptron. The full article (15 p. corresponding to this lecture is written in french and is provided in the proceedings of the book SOS 2008.

  12. The transcription factor Nerfin-1 prevents reversion of neurons into neural stem cells.

    Science.gov (United States)

    Froldi, Francesca; Szuperak, Milan; Weng, Chen-Fang; Shi, Wei; Papenfuss, Anthony T; Cheng, Louise Y

    2015-01-15

    Cellular dedifferentiation is the regression of a cell from a specialized state to a more multipotent state and is implicated in cancer. However, the transcriptional network that prevents differentiated cells from reacquiring stem cell fate is so far unclear. Neuroblasts (NBs), the Drosophila neural stem cells, are a model for the regulation of stem cell self-renewal and differentiation. Here we show that the Drosophila zinc finger transcription factor Nervous fingers 1 (Nerfin-1) locks neurons into differentiation, preventing their reversion into NBs. Following Prospero-dependent neuronal specification in the ganglion mother cell (GMC), a Nerfin-1-specific transcriptional program maintains differentiation in the post-mitotic neurons. The loss of Nerfin-1 causes reversion to multipotency and results in tumors in several neural lineages. Both the onset and rate of neuronal dedifferentiation in nerfin-1 mutant lineages are dependent on Myc- and target of rapamycin (Tor)-mediated cellular growth. In addition, Nerfin-1 is required for NB differentiation at the end of neurogenesis. RNA sequencing (RNA-seq) and chromatin immunoprecipitation (ChIP) analysis show that Nerfin-1 administers its function by repression of self-renewing-specific and activation of differentiation-specific genes. Our findings support the model of bidirectional interconvertibility between neural stem cells and their post-mitotic progeny and highlight the importance of the Nerfin-1-regulated transcriptional program in neuronal maintenance. © 2015 Froldi et al.; Published by Cold Spring Harbor Laboratory Press.

  13. Neural Conversion and Patterning of Human Pluripotent Stem Cells: A Developmental Perspective.

    Science.gov (United States)

    Zirra, Alexandra; Wiethoff, Sarah; Patani, Rickie

    2016-01-01

    Since the reprogramming of adult human terminally differentiated somatic cells into induced pluripotent stem cells (hiPSCs) became a reality in 2007, only eight years have passed. Yet over this relatively short period, myriad experiments have revolutionized previous stem cell dogmata. The tremendous promise of hiPSC technology for regenerative medicine has fuelled rising expectations from both the public and scientific communities alike. In order to effectively harness hiPSCs to uncover fundamental mechanisms of disease, it is imperative to first understand the developmental neurobiology underpinning their lineage restriction choices in order to predictably manipulate cell fate to desired derivatives. Significant progress in developmental biology provides an invaluable resource for rationalising directed differentiation of hiPSCs to cellular derivatives of the nervous system. In this paper we begin by reviewing core developmental concepts underlying neural induction in order to provide context for how such insights have guided reductionist in vitro models of neural conversion from hiPSCs. We then discuss early factors relevant in neural patterning, again drawing upon crucial knowledge gained from developmental neurobiological studies. We conclude by discussing open questions relating to these concepts and how their resolution might serve to strengthen the promise of pluripotent stem cells in regenerative medicine.

  14. Neural Conversion and Patterning of Human Pluripotent Stem Cells: A Developmental Perspective

    Directory of Open Access Journals (Sweden)

    Alexandra Zirra

    2016-01-01

    Full Text Available Since the reprogramming of adult human terminally differentiated somatic cells into induced pluripotent stem cells (hiPSCs became a reality in 2007, only eight years have passed. Yet over this relatively short period, myriad experiments have revolutionized previous stem cell dogmata. The tremendous promise of hiPSC technology for regenerative medicine has fuelled rising expectations from both the public and scientific communities alike. In order to effectively harness hiPSCs to uncover fundamental mechanisms of disease, it is imperative to first understand the developmental neurobiology underpinning their lineage restriction choices in order to predictably manipulate cell fate to desired derivatives. Significant progress in developmental biology provides an invaluable resource for rationalising directed differentiation of hiPSCs to cellular derivatives of the nervous system. In this paper we begin by reviewing core developmental concepts underlying neural induction in order to provide context for how such insights have guided reductionist in vitro models of neural conversion from hiPSCs. We then discuss early factors relevant in neural patterning, again drawing upon crucial knowledge gained from developmental neurobiological studies. We conclude by discussing open questions relating to these concepts and how their resolution might serve to strengthen the promise of pluripotent stem cells in regenerative medicine.

  15. Hematopoietic stem cell fate through metabolic control.

    Science.gov (United States)

    Ito, Kyoko; Ito, Keisuke

    2018-05-25

    Hematopoietic stem cells (HSCs) maintain a quiescent state in the bone marrow to preserve their self-renewal capacity, but also undergo cell divisions as required. Organelles such as the mitochondria sustain cumulative damage during these cell divisions, and this damage may eventually compromise the cells' self-renewal capacity. HSC divisions result in either self-renewal or differentiation, with the balance between the two directly impacting hematopoietic homeostasis; but the heterogeneity of available HSC-enriched fractions, together with the technical challenges of observing HSC behavior, has long hindered the analysis of individual HSCs, and prevented the elucidation of this process. However, recent advances in genetic models, metabolomics analyses and single-cell approaches have revealed the contributions made to HSC self-renewal by metabolic cues, mitochondrial biogenesis, and autophagy/mitophagy, which have highlighted mitochondrial quality as a key control factor in the equilibrium of HSCs. A deeper understanding of precisely how specific modes of metabolism control HSC fate at the single cell level is therefore not only of great biological interest, but will have clear clinical implications for the development of therapies for hematological disease. Copyright © 2018. Published by Elsevier Inc.

  16. Epigenetic control of embryonic stem cell fate

    DEFF Research Database (Denmark)

    Christophersen, Nicolaj Strøyer; Helin, Kristian

    2010-01-01

    Embryonic stem (ES) cells are derived from the inner cell mass of the preimplantation embryo and are pluripotent, as they are able to differentiate into all cell types of the adult organism. Once established, the pluripotent ES cells can be maintained under defined culture conditions, but can also...... be induced rapidly to differentiate. Maintaining this balance of stability versus plasticity is a challenge, and extensive studies in recent years have focused on understanding the contributions of transcription factors and epigenetic enzymes to the "stemness" properties of these cells. Identifying...... the molecular switches that regulate ES cell self-renewal versus differentiation can provide insights into the nature of the pluripotent state and enhance the potential use of these cells in therapeutic applications. Here, we review the latest models for how changes in chromatin methylation can modulate ES cell...

  17. Progenitor Cell Fate Decisions in Mammary Tumorigenesis

    Science.gov (United States)

    2013-03-01

    effects of co-transplantation of these populations. Understanding the relationships between normal and transformed mammary epithelial cells has... effect of E2 against double-strand break damage was dependent on ER expression. NBS1 mediated the E2 protective effects against ionizing radiation...transfected with 2 Jeg of pGL3 lucif - erase reporter vector containing S’ flanking constructs of the NBSl promoter, ellon 1 and intron 1 (-360/+1076

  18. Redox Regulation of Endothelial Cell Fate

    Science.gov (United States)

    Song, Ping; Zou, Ming-Hui

    2014-01-01

    Endothelial cells (ECs) are present throughout blood vessels and have variable roles in both physiological and pathological settings. EC fate is altered and regulated by several key factors in physiological or pathological conditions. Reactive nitrogen species and reactive oxygen species derived from NAD(P)H oxidases, mitochondria, or nitric oxide-producing enzymes are not only cytotoxic but also compose a signaling network in the redox system. The formation, actions, key molecular interactions, and physiological and pathological relevance of redox signals in ECs remain unclear. We review the identities, sources, and biological actions of oxidants and reductants produced during EC function or dysfunction. Further, we discuss how ECs shape key redox sensors and examine the biological functions, transcriptional responses, and post-translational modifications evoked by the redox system in ECs. We summarize recent findings regarding the mechanisms by which redox signals regulate the fate of ECs and address the outcome of altered EC fate in health and disease. Future studies will examine if the redox biology of ECs can be targeted in pathophysiological conditions. PMID:24633153

  19. Memristor-based neural networks

    International Nuclear Information System (INIS)

    Thomas, Andy

    2013-01-01

    The synapse is a crucial element in biological neural networks, but a simple electronic equivalent has been absent. This complicates the development of hardware that imitates biological architectures in the nervous system. Now, the recent progress in the experimental realization of memristive devices has renewed interest in artificial neural networks. The resistance of a memristive system depends on its past states and exactly this functionality can be used to mimic the synaptic connections in a (human) brain. After a short introduction to memristors, we present and explain the relevant mechanisms in a biological neural network, such as long-term potentiation and spike time-dependent plasticity, and determine the minimal requirements for an artificial neural network. We review the implementations of these processes using basic electric circuits and more complex mechanisms that either imitate biological systems or could act as a model system for them. (topical review)

  20. Application of an artificial neural network model for diagnosing type 2 diabetes mellitus and determining the relative importance of risk factors.

    Science.gov (United States)

    Borzouei, Shiva; Soltanian, Ali Reza

    2018-01-01

    To identify the most important demographic risk factors for a diagnosis of type 2 diabetes mellitus (T2DM) using a neural network model. This study was conducted on a sample of 234 individuals, in whom T2DM was diagnosed using hemoglobin A1c levels. A multilayer perceptron artificial neural network was used to identify demographic risk factors for T2DM and their importance. The DeLong method was used to compare the models by fitting in sequential steps. Variables found to be significant at a level of pneural network modeling, only waist circumference (100.0%), age (78.5%), BMI (78.2%), hypertension (69.4%), stress (54.2%), smoking (49.3%), and a family history of T2DM (37.2%) were identified as predictors of the diagnosis of T2DM. In this study, waist circumference and age were the most important predictors of T2DM. Due to the sensitivity, specificity, and accuracy of the final model, it is suggested that these variables should be used for T2DM risk assessment in screening tests.

  1. Using Animal Models to Determine the Role of Gustatory Neural Input in the Control of Ingestive Behavior and the Maintenance of Body Weight.

    Science.gov (United States)

    Ciullo, Dana L; Dotson, Cedrick D

    2015-08-01

    Decades of research have suggested that nutritional intake contributes to the development of human disease, mainly by influencing the development of obesity and obesity-related conditions. A relatively large body of research indicates that functional variation in human taste perception can influence nutritional intake as well as body mass accumulation. However, there are a considerable number of studies that suggest that no link between these variables actually exists. These discrepancies in the literature likely result from the confounding influence of a variety of other, uncontrolled, factors that can influence ingestive behavior. In this review, the use of controlled animal experimentation to alleviate at least some of these issues related to the lack of control of experimental variables is discussed. Specific examples of the use of some of these techniques are examined. The review will close with some specific suggestions aimed at strengthening the link between gustatory neural input and its putative influence on ingestive behaviors and the maintenance of body weight.

  2. Determining

    Directory of Open Access Journals (Sweden)

    Bahram Andarzian

    2015-06-01

    Full Text Available Wheat production in the south of Khuzestan, Iran is constrained by heat stress for late sowing dates. For optimization of yield, sowing at the appropriate time to fit the cultivar maturity length and growing season is critical. Crop models could be used to determine optimum sowing window for a locality. The objectives of this study were to evaluate the Cropping System Model (CSM-CERES-Wheat for its ability to simulate growth, development, grain yield of wheat in the tropical regions of Iran, and to study the impact of different sowing dates on wheat performance. The genetic coefficients of cultivar Chamran were calibrated for the CSM-CERES-Wheat model and crop model performance was evaluated with experimental data. Wheat cultivar Chamran was sown on different dates, ranging from 5 November to 9 January during 5 years of field experiments that were conducted in the Khuzestan province, Iran, under full and deficit irrigation conditions. The model was run for 8 sowing dates starting on 25 October and repeated every 10 days until 5 January using long-term historical weather data from the Ahvaz, Behbehan, Dezful and Izeh locations. The seasonal analysis program of DSSAT was used to determine the optimum sowing window for different locations as well. Evaluation with the experimental data showed that performance of the model was reasonable as indicated by fairly accurate simulation of crop phenology, biomass accumulation and grain yield against measured data. The normalized RMSE were 3%, 2%, 11.8%, and 3.4% for anthesis date, maturity date, grain yield and biomass, respectively. Optimum sowing window was different among locations. It was opened and closed on 5 November and 5 December for Ahvaz; 5 November and 15 December for Behbehan and Dezful;and 1 November and 15 December for Izeh, respectively. CERES-Wheat model could be used as a tool to evaluate the effect of sowing date on wheat performance in Khuzestan conditions. Further model evaluations

  3. Restriction of neural precursor ability to respond to Nurr1 by early regional specification.

    Directory of Open Access Journals (Sweden)

    Chiara Soldati

    Full Text Available During neural development, spatially regulated expression of specific transcription factors is crucial for central nervous system (CNS regionalization, generation of neural precursors (NPs and subsequent differentiation of specific cell types within defined regions. A critical role in dopaminergic differentiation in the midbrain (MB has been assigned to the transcription factor Nurr1. Nurr1 controls the expression of key genes involved in dopamine (DA neurotransmission, e.g. tyrosine hydroxylase (TH and the DA transporter (DAT, and promotes the dopaminergic phenotype in embryonic stem cells. We investigated whether cells derived from different areas of the mouse CNS could be directed to differentiate into dopaminergic neurons in vitro by forced expression of the transcription factor Nurr1. We show that Nurr1 overexpression can promote dopaminergic cell fate specification only in NPs obtained from E13.5 ganglionic eminence (GE and MB, but not in NPs isolated from E13.5 cortex (CTX and spinal cord (SC or from the adult subventricular zone (SVZ. Confirming previous studies, we also show that Nurr1 overexpression can increase the generation of TH-positive neurons in mouse embryonic stem cells. These data show that Nurr1 ability to induce a dopaminergic phenotype becomes restricted during CNS development and is critically dependent on the region of NPs derivation. Our results suggest that the plasticity of NPs and their ability to activate a dopaminergic differentiation program in response to Nurr1 is regulated during early stages of neurogenesis, possibly through mechanisms controlling CNS regionalization.

  4. Comparative Analysis Between Flaviviruses Reveals Specific Neural Stem Cell Tropism for Zika Virus in the Mouse Developing Neocortex

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Brault

    2016-08-01

    Full Text Available The recent Zika outbreak in South America and French Polynesia was associated with an epidemic of microcephaly, a disease characterized by a reduced size of the cerebral cortex. Other members of the Flavivirus genus, including West Nile virus (WNV, can cause encephalitis but were not demonstrated to cause microcephaly. It remains unclear whether Zika virus (ZIKV and other flaviviruses may infect different cell populations in the developing neocortex and lead to distinct developmental defects. Here, we describe an assay to infect mouse E15 embryonic brain slices with ZIKV, WNV and dengue virus serotype 4 (DENV-4. We show that this tissue is able to support viral replication of ZIKV and WNV, but not DENV-4. Cell fate analysis reveals a remarkable tropism of ZIKV infection for neural stem cells. Closely related WNV displays a very different tropism of infection, with a bias towards neurons. We further show that ZIKV infection, but not WNV infection, impairs cell cycle progression of neural stem cells. Both viruses inhibited apoptosis at early stages of infection. This work establishes a powerful comparative approach to identify ZIKV-specific alterations in the developing neocortex and reveals specific preferential infection of neural stem cells by ZIKV.

  5. Generation of Regionally Specified Neural Progenitors and Functional Neurons from Human Embryonic Stem Cells under Defined Conditions

    Directory of Open Access Journals (Sweden)

    Agnete Kirkeby

    2012-06-01

    Full Text Available To model human neural-cell-fate specification and to provide cells for regenerative therapies, we have developed a method to generate human neural progenitors and neurons from human embryonic stem cells, which recapitulates human fetal brain development. Through the addition of a small molecule that activates canonical WNT signaling, we induced rapid and efficient dose-dependent specification of regionally defined neural progenitors ranging from telencephalic forebrain to posterior hindbrain fates. Ten days after initiation of differentiation, the progenitors could be transplanted to the adult rat striatum, where they formed neuron-rich and tumor-free grafts with maintained regional specification. Cells patterned toward a ventral midbrain (VM identity generated a high proportion of authentic dopaminergic neurons after transplantation. The dopamine neurons showed morphology, projection pattern, and protein expression identical to that of human fetal VM cells grafted in parallel. VM-patterned but not forebrain-patterned neurons released dopamine and reversed motor deficits in an animal model of Parkinson's disease.

  6. The neural cell adhesion molecule

    DEFF Research Database (Denmark)

    Berezin, V; Bock, E; Poulsen, F M

    2000-01-01

    During the past year, the understanding of the structure and function of neural cell adhesion has advanced considerably. The three-dimensional structures of several of the individual modules of the neural cell adhesion molecule (NCAM) have been determined, as well as the structure of the complex...... between two identical fragments of the NCAM. Also during the past year, a link between homophilic cell adhesion and several signal transduction pathways has been proposed, connecting the event of cell surface adhesion to cellular responses such as neurite outgrowth. Finally, the stimulation of neurite...

  7. Placental determinants of fetal growth: identification of key factors in the insulin-like growth factor and cytokine systems using artificial neural networks

    Directory of Open Access Journals (Sweden)

    Faleschini Elena

    2008-06-01

    Full Text Available Abstract Background Changes and relationships of components of the cytokine and IGF systems have been shown in placenta and cord serum of fetal growth restricted (FGR compared with normal newborns (AGA. This study aimed to analyse a data set of clinical and biochemical data in FGR and AGA newborns to assess if a mathematical model existed and was capable of identifying these two different conditions in order to identify the variables which had a mathematically consistent biological relevance to fetal growth. Methods Whole villous tissue was collected at birth from FGR (N = 20 and AGA neonates (N = 28. Total RNA was extracted, reverse transcribed and then real-time quantitative (TaqMan RT-PCR was performed to quantify cDNA for IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IL-6. The corresponding proteins with TNF-α in addition were assayed in placental lysates using specific kits. The data were analysed using Artificial Neural Networks (supervised networks, and principal component analysis and connectivity map. Results The IGF system and IL-6 allowed to predict FGR in approximately 92% of the cases and AGA in 85% of the cases with a low number of errors. IGF-II, IGFBP-2, and IL-6 content in the placental lysates were the most important factors connected with FGR. The condition of being FGR was connected mainly with the IGF-II placental content, and the latter with IL-6 and IGFBP-2 concentrations in placental lysates. Conclusion These results suggest that further research in humans should focus on these biochemical data. Furthermore, this study offered a critical revision of previous studies. The understanding of this system biology is relevant to the development of future therapeutical interventions possibly aiming at reducing IL-6 and IGFBP-2 concentrations preserving IGF bioactivity in both placenta and fetus.

  8. Determination of volume fraction in biphasic flows oil-gas and water-gas using artificial neural network and gamma densitometry

    International Nuclear Information System (INIS)

    Peixoto, Philippe Netto Belache

    2016-01-01

    This study presents a methodology based on the principles of gamma ray attenuation to identify volume fractions in biphasic systems composed of oil-gas-water and gas which are found in the offshore oil industry. This methodology is based on the acknowledgment counts per second on the photopeak energy using a detection system composed of a NaI (Tl) detector, a source of 137 Cs without collimation positioned at 180 ° relative to the detector on a smooth stratified flow regime. The mathematical modeling for computational simulation using the code MCNP-X was performed using the experimental measurements of the detector characteristics (energy resolution and efficiency), characteristics of the material water and oil (density and coefficient attenuation) and measurement of the volume fractions. To predict these fractions were used artificial neural networks (ANNs), and to obtain an adequate training the ANNs for the prediction of volume fractions were simulated a larger number of volume fractions in MCNP-X. The experimental data were used in the set data necessary for validation of ANNs and the data generated using the computer code MCNP-X were used in training and test sets of the ANNs. Were used ANNs of type feed-forward Multilayer Perceptron (MLP) and analyzed two functions of training, Levenberg-Marquardt (LM) and gradient descent with momentum (GDM), both using the Backpropagation training algorithm. The ANNs identified correctly the volume fractions of the multiphase system with mean relative errors lower than 1.21 %, enabling the application of this methodology for this purpose. (author)

  9. The Effect of Agmatine on Expression of IL-1β and TLX Which Promotes Neuronal Differentiation in Lipopolysaccharide-Treated Neural Progenitors.

    Science.gov (United States)

    Song, Juhyun; Kumar, Bokara Kiran; Kang, Somang; Park, Kyung Ah; Lee, Won Taek; Lee, Jong Eun

    2013-12-01

    Differentiation of neural progenitor cells (NPCs) is important for protecting neural cells and brain tissue during inflammation. Interleukin-1 beta (IL-1β) is the most common pro- inflammatory cytokine in brain inflammation, and increased IL-1β levels can decrease the proliferation of NPCs. We aimed to investigate whether agmatine (Agm), a primary polyamine that protects neural cells, could trigger differentiation of NPCs by activating IL-1β in vitro. The cortex of ICR mouse embryos (E14) was dissociated to culture NPCs. NPCs were stimulated by lipopolysaccharide (LPS). After 6 days, protein expression of stem cell markers and differentiation signal factors was confirmed by using western blot analysis. Also, immunocytochemistry was used to confirm the cell fate. Agm treatment activated NPC differentiation significantly more than in the control group, which was evident by the increased expression of a neuronal marker, MAP2, in the LPS-induced, Agm-treated group. Differentiation of LPS-induced, Agm-treated NPCs was regulated by the MAPK pathway and is thought to be related to IL-1β activation and decreased expression of TLX, a transcription factor that regulates NPC differentiation. Our results reveal that Agm can promote NPC differentiation to neural stem cells by modulating IL-1β expression under inflammatory condition, and they suggest that Agm may be a novel therapeutic strategy for neuroinflammatory diseases.

  10. Morphological neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Ritter, G.X.; Sussner, P. [Univ. of Florida, Gainesville, FL (United States)

    1996-12-31

    The theory of artificial neural networks has been successfully applied to a wide variety of pattern recognition problems. In this theory, the first step in computing the next state of a neuron or in performing the next layer neural network computation involves the linear operation of multiplying neural values by their synaptic strengths and adding the results. Thresholding usually follows the linear operation in order to provide for nonlinearity of the network. In this paper we introduce a novel class of neural networks, called morphological neural networks, in which the operations of multiplication and addition are replaced by addition and maximum (or minimum), respectively. By taking the maximum (or minimum) of sums instead of the sum of products, morphological network computation is nonlinear before thresholding. As a consequence, the properties of morphological neural networks are drastically different than those of traditional neural network models. In this paper we consider some of these differences and provide some particular examples of morphological neural network.

  11. Neural Tube Defects

    Science.gov (United States)

    Neural tube defects are birth defects of the brain, spine, or spinal cord. They happen in the ... that she is pregnant. The two most common neural tube defects are spina bifida and anencephaly. In ...

  12. Neural tissue-spheres

    DEFF Research Database (Denmark)

    Andersen, Rikke K; Johansen, Mathias; Blaabjerg, Morten

    2007-01-01

    By combining new and established protocols we have developed a procedure for isolation and propagation of neural precursor cells from the forebrain subventricular zone (SVZ) of newborn rats. Small tissue blocks of the SVZ were dissected and propagated en bloc as free-floating neural tissue...... content, thus allowing experimental studies of neural precursor cells and their niche...

  13. MiR-34a targeting of Notch ligand delta-like 1 impairs CD15+/CD133+ tumor-propagating cells and supports neural differentiation in medulloblastoma.

    Directory of Open Access Journals (Sweden)

    Pasqualino de Antonellis

    Full Text Available Through negative regulation of gene expression, microRNAs (miRNAs can function as oncosuppressors in cancers, and can themselves show altered expression in various tumor types. Here, we have investigated medulloblastoma tumors (MBs, which arise from an early impairment of developmental processes in the cerebellum, where Notch signaling is involved in many of the cell-fate-determining stages. Notch regulates a subset of MB cells that have stem-cell-like properties and can promote tumor growth. On the basis of this evidence, we hypothesized that miRNAs targeting the Notch pathway can regulate these phenomena, and can be used in anti-cancer therapies.In a screening of potential targets within Notch signaling, miR-34a was seen to be a regulator of the Notch pathway through its targeting of Notch ligand Delta-like 1 (Dll1. Down-regulation of Dll1 expression by miR-34a negatively regulates cell proliferation, and induces apoptosis and neural differentiation in MB cells. Using an inducible tetracycline on-off model of miR-34a expression, we show that in Daoy MB cells, Dll1 is the first target that is regulated in MB, as compared to the other targets analyzed here: Cyclin D1, cMyc and CDK4. MiR-34a expression negatively affects CD133(+/CD15(+ tumor-propagating cells, then we assay through reverse-phase proteomic arrays, Akt and Stat3 signaling hypo-phosphorylation. Adenoviruses carrying the precursor miR-34a induce neurogenesis of tumor spheres derived from a genetic animal model of MB (Patch1(+/- p53(-/-, thus providing further evidence that the miR-34a/Dll1 axis controls both autonomous and non autonomous signaling of Notch. In vivo, miR-34a overexpression carried by adenoviruses reduces tumor burden in cerebellum xenografts of athymic mice, thus demonstrating an anti-tumorigenic role of miR-34a in vivo.Despite advances in our understanding of the pathogenesis of MB, one-third of patients with MB remain incurable. Here, we show that stable nucleic

  14. Neural Synchronization and Cryptography

    Science.gov (United States)

    Ruttor, Andreas

    2007-11-01

    Neural networks can synchronize by learning from each other. In the case of discrete weights full synchronization is achieved in a finite number of steps. Additional networks can be trained by using the inputs and outputs generated during this process as examples. Several learning rules for both tasks are presented and analyzed. In the case of Tree Parity Machines synchronization is much faster than learning. Scaling laws for the number of steps needed for full synchronization and successful learning are derived using analytical models. They indicate that the difference between both processes can be controlled by changing the synaptic depth. In the case of bidirectional interaction the synchronization time increases proportional to the square of this parameter, but it grows exponentially, if information is transmitted in one direction only. Because of this effect neural synchronization can be used to construct a cryptographic key-exchange protocol. Here the partners benefit from mutual interaction, so that a passive attacker is usually unable to learn the generated key in time. The success probabilities of different attack methods are determined by numerical simulations and scaling laws are derived from the data. They show that the partners can reach any desired level of security by just increasing the synaptic depth. Then the complexity of a successful attack grows exponentially, but there is only a polynomial increase of the effort needed to generate a key. Further improvements of security are possible by replacing the random inputs with queries generated by the partners.

  15. Determination of the mechanical and physical properties of cartilage by coupling poroelastic-based finite element models of indentation with artificial neural networks

    NARCIS (Netherlands)

    Arbabi, Vahid; Pouran, B; Campoli, Gianni; Weinans, Harrie; Zadpoor, Amir A

    2016-01-01

    One of the most widely used techniques to determine the mechanical properties of cartilage is based on indentation tests and interpretation of the obtained force-time or displacement-time data. In the current computational approaches, one needs to simulate the indentation test with finite element

  16. Pathologic Stimulus Determines Lineage Commitment of Cardiac C-kit+ Cells.

    Science.gov (United States)

    Chen, Zhongming; Zhu, Wuqiang; Bender, Ingrid; Gong, Wuming; Kwak, Il-Youp; Yellamilli, Amritha; Hodges, Thomas J; Nemoto, Natsumi; Zhang, Jianyi; Garry, Daniel J; van Berlo, Jop H

    2017-12-12

    Although cardiac c-kit + cells are being tested in clinical trials, the circumstances that determine lineage differentiation of c-kit + cells in vivo are unknown. Recent findings suggest that endogenous cardiac c-kit + cells rarely contribute cardiomyocytes to the adult heart. We assessed whether various pathological stimuli differentially affect the eventual cell fates of c-kit + cells. We used single-cell sequencing and genetic lineage tracing of c-kit + cells to determine whether various pathological stimuli would result in different fates of c-kit + cells. Single-cell sequencing of cardiac CD45 - c-kit + cells showed innate heterogeneity, indicative of the existence of vascular and mesenchymal c-kit + cells in normal hearts. Cardiac pressure overload resulted in a modest increase in c-kit-derived cardiomyocytes, with significant increases in the numbers of endothelial cells and fibroblasts. Doxorubicin-induced acute cardiotoxicity did not increase c-kit-derived endothelial cell fates but instead induced cardiomyocyte differentiation. Mechanistically, doxorubicin-induced DNA damage in c-kit + cells resulted in expression of p53. Inhibition of p53 blocked cardiomyocyte differentiation in response to doxorubicin, whereas stabilization of p53 was sufficient to increase c-kit-derived cardiomyocyte differentiation. These results demonstrate that different pathological stimuli induce different cell fates of c-kit + cells in vivo. Although the overall rate of cardiomyocyte formation from c-kit + cells is still below clinically relevant levels, we show that p53 is central to the ability of c-kit + cells to adopt cardiomyocyte fates, which could lead to the development of strategies to preferentially generate cardiomyocytes from c-kit + cells. © 2017 American Heart Association, Inc.

  17. Neural electrical activity and neural network growth.

    Science.gov (United States)

    Gafarov, F M

    2018-05-01

    The development of central and peripheral neural system depends in part on the emergence of the correct functional connectivity in its input and output pathways. Now it is generally accepted that molecular factors guide neurons to establish a primary scaffold that undergoes activity-dependent refinement for building a fully functional circuit. However, a number of experimental results obtained recently shows that the neuronal electrical activity plays an important role in the establishing of initial interneuronal connections. Nevertheless, these processes are rather difficult to study experimentally, due to the absence of theoretical description and quantitative parameters for estimation of the neuronal activity influence on growth in neural networks. In this work we propose a general framework for a theoretical description of the activity-dependent neural network growth. The theoretical description incorporates a closed-loop growth model in which the neural activity can affect neurite outgrowth, which in turn can affect neural activity. We carried out the detailed quantitative analysis of spatiotemporal activity patterns and studied the relationship between individual cells and the network as a whole to explore the relationship between developing connectivity and activity patterns. The model, developed in this work will allow us to develop new experimental techniques for studying and quantifying the influence of the neuronal activity on growth processes in neural networks and may lead to a novel techniques for constructing large-scale neural networks by self-organization. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Nonequilibrium landscape theory of neural networks.

    Science.gov (United States)

    Yan, Han; Zhao, Lei; Hu, Liang; Wang, Xidi; Wang, Erkang; Wang, Jin

    2013-11-05

    The brain map project aims to map out the neuron connections of the human brain. Even with all of the wirings mapped out, the global and physical understandings of the function and behavior are still challenging. Hopfield quantified the learning and memory process of symmetrically connected neural networks globally through equilibrium energy. The energy basins of attractions represent memories, and the memory retrieval dynamics is determined by the energy gradient. However, the realistic neural networks are asymmetrically connected, and oscillations cannot emerge from symmetric neural networks. Here, we developed a nonequilibrium landscape-flux theory for realistic asymmetrically connected neural networks. We uncovered the underlying potential landscape and the associated Lyapunov function for quantifying the global stability and function. We found the dynamics and oscillations in human brains responsible for cognitive processes and physiological rhythm regulations are determined not only by the landscape gradient but also by the flux. We found that the flux is closely related to the degrees of the asymmetric connections in neural networks and is the origin of the neural oscillations. The neural oscillation landscape shows a closed-ring attractor topology. The landscape gradient attracts the network down to the ring. The flux is responsible for coherent oscillations on the ring. We suggest the flux may provide the driving force for associations among memories. We applied our theory to rapid-eye movement sleep cycle. We identified the key regulation factors for function through global sensitivity analysis of landscape topography against wirings, which are in good agreements with experiments.

  19. Nonequilibrium landscape theory of neural networks

    Science.gov (United States)

    Yan, Han; Zhao, Lei; Hu, Liang; Wang, Xidi; Wang, Erkang; Wang, Jin

    2013-01-01

    The brain map project aims to map out the neuron connections of the human brain. Even with all of the wirings mapped out, the global and physical understandings of the function and behavior are still challenging. Hopfield quantified the learning and memory process of symmetrically connected neural networks globally through equilibrium energy. The energy basins of attractions represent memories, and the memory retrieval dynamics is determined by the energy gradient. However, the realistic neural networks are asymmetrically connected, and oscillations cannot emerge from symmetric neural networks. Here, we developed a nonequilibrium landscape–flux theory for realistic asymmetrically connected neural networks. We uncovered the underlying potential landscape and the associated Lyapunov function for quantifying the global stability and function. We found the dynamics and oscillations in human brains responsible for cognitive processes and physiological rhythm regulations are determined not only by the landscape gradient but also by the flux. We found that the flux is closely related to the degrees of the asymmetric connections in neural networks and is the origin of the neural oscillations. The neural oscillation landscape shows a closed-ring attractor topology. The landscape gradient attracts the network down to the ring. The flux is responsible for coherent oscillations on the ring. We suggest the flux may provide the driving force for associations among memories. We applied our theory to rapid-eye movement sleep cycle. We identified the key regulation factors for function through global sensitivity analysis of landscape topography against wirings, which are in good agreements with experiments. PMID:24145451

  20. Tip Deflection Determination of a Barrel for the Effect of an Accelerating Projectile Before Firing Using Finite Element and Artificial Neural Network Combined Algorithm

    Directory of Open Access Journals (Sweden)

    Mehmet Akif Koç

    Full Text Available Abstract For realistic applications, design and control engineers have limited modelling options in dealing with some vibration problems that hold many nonlinearity such as non-uniform geometry, variable velocity loadings, indefinite damping cases, etc. For these reasons numerous time consuming experimental studies at high costs must be done for determining the actual behaviour such nonlinear systems. However, using advantages of multiple computational methods like Finite Element Method (FEM together with an Artificial Intelligence (ANN, many complicated engineering problems can be handled and solved to some extent. This study, proposes a new collective method to deal with the nonlinear vibrations of the barrels in order to fulfil accurate shooting expectancy. Using known analytical methods, in practical, to determine dynamic behaviour of the barrel beam is not possible for all conditions of firing that include numerous varieties of ammunition for different purposes, and each projectile of different ammunition has different mass and exit velocity. In order to cover all cases this study proposes a new method that combines a precise FEM with ANN, and can be used for determining the exact dynamic behaviour of a barrel for some cases and then for precisely predicting the behaviour for all other possible cases of firing. In this study, the whole nonlinear behaviour of an antiaircraft barrel were obtained with 3.5% accuracy errors by ANN trained by FEM using calculated analysis results of ammunitions for a particular range. The proposed FEM-ANN combined method can be very useful for design and control engineers in design and control of barrels in order to compensate the effect of nonlinear vibrations of a barrel for achieving a higher shooting accuracy; and can reduce high-cost experimental works.

  1. The Prdm13 histone methyltransferase encoding gene is a Ptf1a-Rbpj downstream target that suppresses glutamatergic and promotes GABAergic neuronal fate in the dorsal neural tube

    DEFF Research Database (Denmark)

    Hanotel, Julie; Bessodes, Nathalie; Thélie, Aurore

    2014-01-01

    The basic helix-loop-helix (bHLH) transcriptional activator Ptf1a determines inhibitory GABAergic over excitatory glutamatergic neuronal cell fate in progenitors of the vertebrate dorsal spinal cord, cerebellum and retina. In an in situ hybridization expression survey of PR domain containing genes...... encoding putative chromatin-remodeling zinc finger transcription factors in Xenopus embryos, we identified Prdm13 as a histone methyltransferase belonging to the Ptf1a synexpression group. Gain and loss of Ptf1a function analyses in both frog and mice indicates that Prdm13 is positively regulated by Ptf1a...

  2. Neural network design with combined backpropagation and creeping random search learning algorithms applied to the determination of retained austenite in TRIP steels; Diseno de redes neuronales con aprendizaje combinado de retropropagacion y busqueda aleatoria progresiva aplicado a la determinacion de austenita retenida en aceros TRIP

    Energy Technology Data Exchange (ETDEWEB)

    Toda-Caraballo, I.; Garcia-Mateo, C.; Capdevila, C.

    2010-07-01

    At the beginning of the decade of the nineties, the industrial interest for TRIP steels leads to a significant increase of the investigation and application in this field. In this work, the flexibility of neural networks for the modelling of complex properties is used to tackle the problem of determining the retained austenite content in TRIP-steel. Applying a combination of two learning algorithms (backpropagation and creeping-random-search) for the neural network, a model has been created that enables the prediction of retained austenite in low-Si / low-Al multiphase steels as a function of processing parameters. (Author). 34 refs.

  3. Chaotic diagonal recurrent neural network

    International Nuclear Information System (INIS)

    Wang Xing-Yuan; Zhang Yi

    2012-01-01

    We propose a novel neural network based on a diagonal recurrent neural network and chaos, and its structure and learning algorithm are designed. The multilayer feedforward neural network, diagonal recurrent neural network, and chaotic diagonal recurrent neural network are used to approach the cubic symmetry map. The simulation results show that the approximation capability of the chaotic diagonal recurrent neural network is better than the other two neural networks. (interdisciplinary physics and related areas of science and technology)

  4. Preliminary Study on Application of Artificial Neural Networks (ANN) for Determining the Peroxide Value of Three Commercial Palm Oil Based FTIR Spectrum)

    International Nuclear Information System (INIS)

    Azwan Mat Lazim; Musa Ahmad; Zuriati Zakaria; Mohd Suzeren Jamil; Suria Ramli; Faiz Zainuddin; Mohd Nasir Taib; Mat Nasir Mat Arip

    2013-01-01

    Peroxide value is one of the measurements that being used to determine the peroxide in oil samples produce from the peroxide compound and hydroperoxide group at the primary level of lipid oxidation. In this study, 3 commercial palm cooking oils were selected and labeled as A, B and C. Two different conditions were applied to the samples. First, the oil sample was exposed to the air for three months (labeled as A) while samples B and C were used for frying for many times. Two inputs from FTIR spectra (3444 cm -1 and 3450 cm -1 ) were chosen for the ANN training. The suitable architecture for this training is 2:20:1. The prediction made by ANN was very accurate and compatible to the result which obtained from the standard method. A low average error (0.48) was obtained when the hidden neuron (20) and the epochs (300) were used. (author)

  5. A key role for poly(ADP-ribose polymerase 3 in ectodermal specification and neural crest development.

    Directory of Open Access Journals (Sweden)

    Michèle Rouleau

    2011-01-01

    Full Text Available The PARP family member poly(ADP-ribose polymerase 3 (PARP3 is structurally related to the well characterized PARP1 that orchestrates cellular responses to DNA strand breaks and cell death by the synthesis of poly(ADP-ribose. In contrast to PARP1 and PARP2, the functions of PARP3 are undefined. Here, we reveal critical functions for PARP3 during vertebrate development.We have used several in vitro and in vivo approaches to examine the possible functions of PARP3 as a transcriptional regulator, a function suggested from its previously reported association with several Polycomb group (PcG proteins. We demonstrate that PARP3 gene occupancy in the human neuroblastoma cell line SK-N-SH occurs preferentially with developmental genes regulating cell fate specification, tissue patterning, craniofacial development and neurogenesis. Addressing the significance of this association during zebrafish development, we show that morpholino oligonucleotide-directed inhibition of parp3 expression in zebrafish impairs the expression of the neural crest cell specifier sox9a and of dlx3b/dlx4b, the formation of cranial sensory placodes, inner ears and pectoral fins. It delays pigmentation and severely impedes the development of the median fin fold and tail bud.Our findings demonstrate that Parp3 is crucial in the early stages of zebrafish development, possibly by exerting its transcriptional regulatory functions as early as during the specification of the neural plate border.

  6. Evolvable Neural Software System

    Science.gov (United States)

    Curtis, Steven A.

    2009-01-01

    The Evolvable Neural Software System (ENSS) is composed of sets of Neural Basis Functions (NBFs), which can be totally autonomously created and removed according to the changing needs and requirements of the software system. The resulting structure is both hierarchical and self-similar in that a given set of NBFs may have a ruler NBF, which in turn communicates with other sets of NBFs. These sets of NBFs may function as nodes to a ruler node, which are also NBF constructs. In this manner, the synthetic neural system can exhibit the complexity, three-dimensional connectivity, and adaptability of biological neural systems. An added advantage of ENSS over a natural neural system is its ability to modify its core genetic code in response to environmental changes as reflected in needs and requirements. The neural system is fully adaptive and evolvable and is trainable before release. It continues to rewire itself while on the job. The NBF is a unique, bilevel intelligence neural system composed of a higher-level heuristic neural system (HNS) and a lower-level, autonomic neural system (ANS). Taken together, the HNS and the ANS give each NBF the complete capabilities of a biological neural system to match sensory inputs to actions. Another feature of the NBF is the Evolvable Neural Interface (ENI), which links the HNS and ANS. The ENI solves the interface problem between these two systems by actively adapting and evolving from a primitive initial state (a Neural Thread) to a complicated, operational ENI and successfully adapting to a training sequence of sensory input. This simulates the adaptation of a biological neural system in a developmental phase. Within the greater multi-NBF and multi-node ENSS, self-similar ENI s provide the basis for inter-NBF and inter-node connectivity.

  7. Determination of the influence of the variation of reducing and non-reducing sugars on coffee quality with use of artificial neural network Determinação da influência da variação de açúcar redutor e não redutor na qualidade da bebida do café com utilização de rede neural artificial

    Directory of Open Access Journals (Sweden)

    José A. T. Messias

    2012-04-01

    Full Text Available The present study aimed at evaluating the use of Artificial Neural Network to correlate the values resulting from chemical analyses of samples of coffee with the values of their sensory analyses. The coffee samples used were from the Coffea arabica L., cultivars Acaiá do Cerrado, Topázio, Acaiá 474-19 and Bourbon, collected in the southern region of the state of Minas Gerais. The chemical analyses were carried out for reducing and non-reducing sugars. The quality of the beverage was evaluated by sensory analysis. The Artificial Neural Network method used values from chemical analyses as input variables and values from sensory analysis as output values. The multiple linear regression of sensory analysis values, according to the values from chemical analyses, presented a determination coefficient of 0.3106, while the Artificial Neural Network achieved a level of 80.00% of success in the classification of values from the sensory analysis.Este trabalho teve como objetivo avaliar a utilização de Rede Neural Artificial para correlacionar os valores resultantes de análises químicas de amostras de café com os valores de sua análise sensorial. As amostras de café utilizadas foram referentes ao café Coffea arabica L., cultivar Acaiá do Cerrado, Topázio, Acaiá 474-19 e Bourbon, coletados na região sul de Minas Gerais. As análises químicas foram de açúcar não redutor e açúcar redutor, sendo a qualidade da bebida avaliada pela análise sensorial. O método de Rede Neural Artificial utilizou os valores das análises químicas como variáveis de entrada e os valores da análise sensorial como valores de saída. A regressão linear múltipla dos valores de análise sensorial, em função dos valores das análises químicas, teve coeficiente de determinação de 0,3106, enquanto o método de Rede Neural Artificial empregado obteve um nível de acerto na classificação dos valores da análise sensorial de 80,00%.

  8. Adaptive competitive learning neural networks

    Directory of Open Access Journals (Sweden)

    Ahmed R. Abas

    2013-11-01

    Full Text Available In this paper, the adaptive competitive learning (ACL neural network algorithm is proposed. This neural network not only groups similar input feature vectors together but also determines the appropriate number of groups of these vectors. This algorithm uses a new proposed criterion referred to as the ACL criterion. This criterion evaluates different clustering structures produced by the ACL neural network for an input data set. Then, it selects the best clustering structure and the corresponding network architecture for this data set. The selected structure is composed of the minimum number of clusters that are compact and balanced in their sizes. The selected network architecture is efficient, in terms of its complexity, as it contains the minimum number of neurons. Synaptic weight vectors of these neurons represent well-separated, compact and balanced clusters in the input data set. The performance of the ACL algorithm is evaluated and compared with the performance of a recently proposed algorithm in the literature in clustering an input data set and determining its number of clusters. Results show that the ACL algorithm is more accurate and robust in both determining the number of clusters and allocating input feature vectors into these clusters than the other algorithm especially with data sets that are sparsely distributed.

  9. Fibronectin promotes differentiation of neural crest progenitors endowed with smooth muscle cell potential

    International Nuclear Information System (INIS)

    Costa-Silva, Bruno; Coelho da Costa, Meline; Melo, Fernanda Rosene; Neves, Cynara Mendes; Alvarez-Silva, Marcio; Calloni, Giordano Wosgrau; Trentin, Andrea Goncalves

    2009-01-01

    The neural crest (NC) is a model system used to investigate multipotency during vertebrate development. Environmental factors control NC cell fate decisions. Despite the well-known influence of extracellular matrix molecules in NC cell migration, the issue of whether they also influence NC cell differentiation has not been addressed at the single cell level. By analyzing mass and clonal cultures of mouse cephalic and quail trunk NC cells, we show for the first time that fibronectin (FN) promotes differentiation into the smooth muscle cell phenotype without affecting differentiation into glia, neurons, and melanocytes. Time course analysis indicated that the FN-induced effect was not related to massive cell death or proliferation of smooth muscle cells. Finally, by comparing clonal cultures of quail trunk NC cells grown on FN and collagen type IV (CLIV), we found that FN strongly increased both NC cell survival and the proportion of unipotent and oligopotent NC progenitors endowed with smooth muscle potential. In contrast, melanocytic progenitors were prominent in clonogenic NC cells grown on CLIV. Taken together, these results show that FN promotes NC cell differentiation along the smooth muscle lineage, and therefore plays an important role in fate decisions of NC progenitor cells

  10. Determination of fat, moisture, and protein in meat and meat products by using the FOSS FoodScan Near-Infrared Spectrophotometer with FOSS Artificial Neural Network Calibration Model and Associated Database: collaborative study.

    Science.gov (United States)

    Anderson, Shirley

    2007-01-01

    A collaborative study was conducted to evaluate the repeatability and reproducibility of the FOSS FoodScan near-infrared spectrophotometer with artificial neural network calibration model and database for the determination of fat, moisture, and protein in meat and meat products. Representative samples were homogenized by grinding according to AOAC Official Method 983.18. Approximately 180 g ground sample was placed in a 140 mm round sample dish, and the dish was placed in the FoodScan. The operator ID was entered, the meat product profile within the software was selected, and the scanning process was initiated by pressing the "start" button. Results were displayed for percent (g/100 g) fat, moisture, and protein. Ten blind duplicate samples were sent to 15 collaborators in the United States. The within-laboratory (repeatability) relative standard deviation (RSD(r)) ranged from 0.22 to 2.67% for fat, 0.23 to 0.92% for moisture, and 0.35 to 2.13% for protein. The between-laboratories (reproducibility) relative standard deviation (RSD(R)) ranged from 0.52 to 6.89% for fat, 0.39 to 1.55% for moisture, and 0.54 to 5.23% for protein. The method is recommended for Official First Action.

  11. A neural flow estimator

    DEFF Research Database (Denmark)

    Jørgensen, Ivan Harald Holger; Bogason, Gudmundur; Bruun, Erik

    1995-01-01

    This paper proposes a new way to estimate the flow in a micromechanical flow channel. A neural network is used to estimate the delay of random temperature fluctuations induced in a fluid. The design and implementation of a hardware efficient neural flow estimator is described. The system...... is implemented using switched-current technique and is capable of estimating flow in the μl/s range. The neural estimator is built around a multiplierless neural network, containing 96 synaptic weights which are updated using the LMS1-algorithm. An experimental chip has been designed that operates at 5 V...

  12. Neural Systems Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — As part of the Electrical and Computer Engineering Department and The Institute for System Research, the Neural Systems Laboratory studies the functionality of the...

  13. Cracking the Neural Code for Sensory Perception by Combining Statistics, Intervention, and Behavior.

    Science.gov (United States)

    Panzeri, Stefano; Harvey, Christopher D; Piasini, Eugenio; Latham, Peter E; Fellin, Tommaso

    2017-02-08

    The two basic processes underlying perceptual decisions-how neural responses encode stimuli, and how they inform behavioral choices-have mainly been studied separately. Thus, although many spatiotemporal features of neural population activity, or "neural codes," have been shown to carry sensory information, it is often unknown whether the brain uses these features for perception. To address this issue, we propose a new framework centered on redefining the neural code as the neural features that carry sensory information used by the animal to drive appropriate behavior; that is, the features that have an intersection between sensory and choice information. We show how this framework leads to a new statistical analysis of neural activity recorded during behavior that can identify such neural codes, and we discuss how to combine intersection-based analysis of neural recordings with intervention on neural activity to determine definitively whether specific neural activity features are involved in a task. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Neural Networks in Mobile Robot Motion

    Directory of Open Access Journals (Sweden)

    Danica Janglová

    2004-03-01

    Full Text Available This paper deals with a path planning and intelligent control of an autonomous robot which should move safely in partially structured environment. This environment may involve any number of obstacles of arbitrary shape and size; some of them are allowed to move. We describe our approach to solving the motion-planning problem in mobile robot control using neural networks-based technique. Our method of the construction of a collision-free path for moving robot among obstacles is based on two neural networks. The first neural network is used to determine the “free” space using ultrasound range finder data. The second neural network “finds” a safe direction for the next robot section of the path in the workspace while avoiding the nearest obstacles. Simulation examples of generated path with proposed techniques will be presented.

  15. NEURAL NETWORKS FOR STOCK MARKET OPTION PRICING

    Directory of Open Access Journals (Sweden)

    Sergey A. Sannikov

    2017-03-01

    Full Text Available Introduction: The use of neural networks for non-linear models helps to understand where linear model drawbacks, coused by their specification, reveal themselves. This paper attempts to find this out. The objective of research is to determine the meaning of “option prices calculation using neural networks”. Materials and Methods: We use two kinds of variables: endogenous (variables included in the model of neural network and variables affecting on the model (permanent disturbance. Results: All data are divided into 3 sets: learning, affirming and testing. All selected variables are normalised from 0 to 1. Extreme values of income were shortcut. Discussion and Conclusions: Using the 33-14-1 neural network with direct links we obtained two sets of forecasts. Optimal criteria of strategies in stock markets’ option pricing were developed.

  16. Neural Networks: Implementations and Applications

    OpenAIRE

    Vonk, E.; Veelenturf, L.P.J.; Jain, L.C.

    1996-01-01

    Artificial neural networks, also called neural networks, have been used successfully in many fields including engineering, science and business. This paper presents the implementation of several neural network simulators and their applications in character recognition and other engineering areas

  17. Optimum Neural Network Architecture for Precipitation Prediction of Myanmar

    OpenAIRE

    Khaing Win Mar; Thinn Thu Naing

    2008-01-01

    Nowadays, precipitation prediction is required for proper planning and management of water resources. Prediction with neural network models has received increasing interest in various research and application domains. However, it is difficult to determine the best neural network architecture for prediction since it is not immediately obvious how many input or hidden nodes are used in the model. In this paper, neural network model is used as a forecasting tool. The major aim is to evaluate a s...

  18. Critical Branching Neural Networks

    Science.gov (United States)

    Kello, Christopher T.

    2013-01-01

    It is now well-established that intrinsic variations in human neural and behavioral activity tend to exhibit scaling laws in their fluctuations and distributions. The meaning of these scaling laws is an ongoing matter of debate between isolable causes versus pervasive causes. A spiking neural network model is presented that self-tunes to critical…

  19. Consciousness and neural plasticity

    DEFF Research Database (Denmark)

    changes or to abandon the strong identity thesis altogether. Were one to pursue a theory according to which consciousness is not an epiphenomenon to brain processes, consciousness may in fact affect its own neural basis. The neural correlate of consciousness is often seen as a stable structure, that is...

  20. Determination of size distribution using neural networks

    NARCIS (Netherlands)

    Stevens, JH; Nijhuis, JAG; Spaanenburg, L; Mohammadian, M

    1999-01-01

    In this paper we present a novel approach to the estimation of size distributions of grains in water from images. External conditions such as the concentrations of grains in water cannot be controlled. This poses problems for local image analysis which tries to identify and measure single grains.

  1. Analysis of epigenetic factors in mouse embryonic neural stem cells exposed to hyperglycemia.

    Directory of Open Access Journals (Sweden)

    Sukanya Shyamasundar

    Full Text Available BACKGROUND: Maternal diabetes alters gene expression leading to neural tube defects (NTDs in the developing brain. The mechanistic pathways that deregulate the gene expression remain unknown. It is hypothesized that exposure of neural stem cells (NSCs to high glucose/hyperglycemia results in activation of epigenetic mechanisms which alter gene expression and cell fate during brain development. METHODS AND FINDINGS: NSCs were isolated from normal pregnancy and streptozotocin induced-diabetic pregnancy and cultured in physiological glucose. In order to examine hyperglycemia induced epigenetic changes in NSCs, chromatin reorganization, global histone status at lysine 9 residue of histone H3 (acetylation and trimethylation and global DNA methylation were examined and found to be altered by hyperglycemia. In NSCs, hyperglycemia increased the expression of Dcx (Doublecortin and Pafah1b1 (Platelet activating factor acetyl hydrolase, isoform 1b, subunit 1 proteins concomitant with decreased expression of four microRNAs (mmu-miR-200a, mmu-miR-200b, mmu-miR-466a-3p and mmu-miR-466 d-3p predicted to target these genes. Knockdown of specific microRNAs in NSCs resulted in increased expression of Dcx and Pafah1b1 proteins confirming target prediction and altered NSC fate by increasing the expression of neuronal and glial lineage markers. CONCLUSION/INTERPRETATION: This study revealed that hyperglycemia alters the epigenetic mechanisms in NSCs, resulting in altered expression of some development control genes which may form the basis for the NTDs. Since epigenetic changes are reversible, they may be valuable therapeutic targets in order to improve fetal outcomes in diabetic pregnancy.

  2. Brain-specific noncoding RNAs are likely to originate in repeats and may play a role in up-regulating genes in cis

    DEFF Research Database (Denmark)

    Francescatto, Margherita; Vitezic, Morana; Heutink, Peter

    2014-01-01

    The mouse and human brain express a large number of noncoding RNAs (ncRNAs). Some of these are known to participate in neural progenitor cell fate determination, cell differentiation, neuronal and synaptic plasticity and transposable elements derived ncRNAs contribute to somatic variation...

  3. Nestin-positive mesenchymal stem cells favour the astroglial lineage in neural progenitors and stem cells by releasing active BMP4

    Directory of Open Access Journals (Sweden)

    Leprince Pierre

    2004-09-01

    Full Text Available Abstract Background Spontaneous repair is limited after CNS injury or degeneration because neurogenesis and axonal regrowth rarely occur in the adult brain. As a result, cell transplantation has raised much interest as potential treatment for patients with CNS lesions. Several types of cells have been considered as candidates for such cell transplantation and replacement therapies. Foetal brain tissue has already been shown to have significant effects in patients with Parkinson's disease. Clinical use of the foetal brain tissue is, however, limited by ethical and technical problems as it requires high numbers of grafted foetal cells and immunosuppression. Alternatively, several reports suggested that mesenchymal stem cells, isolated from adult bone marrow, are multipotent cells and could be used in autograft approach for replacement therapies. Results In this study, we addressed the question of the possible influence of mesenchymal stem cells on neural stem cell fate. We have previously reported that adult rat mesenchymal stem cells are able to express nestin in defined culture conditions (in the absence of serum and after 25 cell population doublings and we report here that nestin-positive (but not nestin-negative mesenchymal stem cells are able to favour the astroglial lineage in neural progenitors and stem cells cultivated from embryonic striatum. The increase of the number of GFAP-positive cells is associated with a significant decrease of the number of Tuj1- and O4-positive cells. Using quantitative RT-PCR, we demonstrate that mesenchymal stem cells express LIF, CNTF, BMP2 and BMP4 mRNAs, four cytokines known to play a role in astroglial fate decision. In this model, BMP4 is responsible for the astroglial stimulation and oligodendroglial inhibition, as 1 this cytokine is present in a biologically-active form only in nestin-positive mesenchymal stem cells conditioned medium and 2 anti-BMP4 antibodies inhibit the nestin-positive mesenchymal

  4. Diabetic retinopathy screening using deep neural network.

    Science.gov (United States)

    Ramachandran, Nishanthan; Hong, Sheng Chiong; Sime, Mary J; Wilson, Graham A

    2017-09-07

    There is a burgeoning interest in the use of deep neural network in diabetic retinal screening. To determine whether a deep neural network could satisfactorily detect diabetic retinopathy that requires referral to an ophthalmologist from a local diabetic retinal screening programme and an international database. Retrospective audit. Diabetic retinal photos from Otago database photographed during October 2016 (485 photos), and 1200 photos from Messidor international database. Receiver operating characteristic curve to illustrate the ability of a deep neural network to identify referable diabetic retinopathy (moderate or worse diabetic retinopathy or exudates within one disc diameter of the fovea). Area under the receiver operating characteristic curve, sensitivity and specificity. For detecting referable diabetic retinopathy, the deep neural network had an area under receiver operating characteristic curve of 0.901 (95% confidence interval 0.807-0.995), with 84.6% sensitivity and 79.7% specificity for Otago and 0.980 (95% confidence interval 0.973-0.986), with 96.0% sensitivity and 90.0% specificity for Messidor. This study has shown that a deep neural network can detect referable diabetic retinopathy with sensitivities and specificities close to or better than 80% from both an international and a domestic (New Zealand) database. We believe that deep neural networks can be integrated into community screening once they can successfully detect both diabetic retinopathy and diabetic macular oedema. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

  5. Dynamics of neural cryptography.

    Science.gov (United States)

    Ruttor, Andreas; Kinzel, Wolfgang; Kanter, Ido

    2007-05-01

    Synchronization of neural networks has been used for public channel protocols in cryptography. In the case of tree parity machines the dynamics of both bidirectional synchronization and unidirectional learning is driven by attractive and repulsive stochastic forces. Thus it can be described well by a random walk model for the overlap between participating neural networks. For that purpose transition probabilities and scaling laws for the step sizes are derived analytically. Both these calculations as well as numerical simulations show that bidirectional interaction leads to full synchronization on average. In contrast, successful learning is only possible by means of fluctuations. Consequently, synchronization is much faster than learning, which is essential for the security of the neural key-exchange protocol. However, this qualitative difference between bidirectional and unidirectional interaction vanishes if tree parity machines with more than three hidden units are used, so that those neural networks are not suitable for neural cryptography. In addition, the effective number of keys which can be generated by the neural key-exchange protocol is calculated using the entropy of the weight distribution. As this quantity increases exponentially with the system size, brute-force attacks on neural cryptography can easily be made unfeasible.

  6. Dynamics of neural cryptography

    International Nuclear Information System (INIS)

    Ruttor, Andreas; Kinzel, Wolfgang; Kanter, Ido

    2007-01-01

    Synchronization of neural networks has been used for public channel protocols in cryptography. In the case of tree parity machines the dynamics of both bidirectional synchronization and unidirectional learning is driven by attractive and repulsive stochastic forces. Thus it can be described well by a random walk model for the overlap between participating neural networks. For that purpose transition probabilities and scaling laws for the step sizes are derived analytically. Both these calculations as well as numerical simulations show that bidirectional interaction leads to full synchronization on average. In contrast, successful learning is only possible by means of fluctuations. Consequently, synchronization is much faster than learning, which is essential for the security of the neural key-exchange protocol. However, this qualitative difference between bidirectional and unidirectional interaction vanishes if tree parity machines with more than three hidden units are used, so that those neural networks are not suitable for neural cryptography. In addition, the effective number of keys which can be generated by the neural key-exchange protocol is calculated using the entropy of the weight distribution. As this quantity increases exponentially with the system size, brute-force attacks on neural cryptography can easily be made unfeasible

  7. Dynamics of neural cryptography

    Science.gov (United States)

    Ruttor, Andreas; Kinzel, Wolfgang; Kanter, Ido

    2007-05-01

    Synchronization of neural networks has been used for public channel protocols in cryptography. In the case of tree parity machines the dynamics of both bidirectional synchronization and unidirectional learning is driven by attractive and repulsive stochastic forces. Thus it can be described well by a random walk model for the overlap between participating neural networks. For that purpose transition probabilities and scaling laws for the step sizes are derived analytically. Both these calculations as well as numerical simulations show that bidirectional interaction leads to full synchronization on average. In contrast, successful learning is only possible by means of fluctuations. Consequently, synchronization is much faster than learning, which is essential for the security of the neural key-exchange protocol. However, this qualitative difference between bidirectional and unidirectional interaction vanishes if tree parity machines with more than three hidden units are used, so that those neural networks are not suitable for neural cryptography. In addition, the effective number of keys which can be generated by the neural key-exchange protocol is calculated using the entropy of the weight distribution. As this quantity increases exponentially with the system size, brute-force attacks on neural cryptography can easily be made unfeasible.

  8. Photon spectrometry utilizing neural networks

    International Nuclear Information System (INIS)

    Silveira, R.; Benevides, C.; Lima, F.; Vilela, E.

    2015-01-01

    Having in mind the time spent on the uneventful work of characterization of the radiation beams used in a ionizing radiation metrology laboratory, the Metrology Service of the Centro Regional de Ciencias Nucleares do Nordeste - CRCN-NE verified the applicability of artificial intelligence (artificial neural networks) to perform the spectrometry in photon fields. For this, was developed a multilayer neural network, as an application for the classification of patterns in energy, associated with a thermoluminescent dosimetric system (TLD-700 and TLD-600). A set of dosimeters was initially exposed to various well known medium energies, between 40 keV and 1.2 MeV, coinciding with the beams determined by ISO 4037 standard, for the dose of 10 mSv in the quantity Hp(10), on a chest phantom (ISO slab phantom) with the purpose of generating a set of training data for the neural network. Subsequently, a new set of dosimeters irradiated in unknown energies was presented to the network with the purpose to test the method. The methodology used in this work was suitable for application in the classification of energy beams, having obtained 100% of the classification performed. (authors)

  9. Evolutionary Algorithms For Neural Networks Binary And Real Data Classification

    Directory of Open Access Journals (Sweden)

    Dr. Hanan A.R. Akkar

    2015-08-01

    Full Text Available Artificial neural networks are complex networks emulating the way human rational neurons process data. They have been widely used generally in prediction clustering classification and association. The training algorithms that used to determine the network weights are almost the most important factor that influence the neural networks performance. Recently many meta-heuristic and Evolutionary algorithms are employed to optimize neural networks weights to achieve better neural performance. This paper aims to use recently proposed algorithms for optimizing neural networks weights comparing these algorithms performance with other classical meta-heuristic algorithms used for the same purpose. However to evaluate the performance of such algorithms for training neural networks we examine such algorithms to classify four opposite binary XOR clusters and classification of continuous real data sets such as Iris and Ecoli.

  10. ANT Advanced Neural Tool

    Energy Technology Data Exchange (ETDEWEB)

    Labrador, I.; Carrasco, R.; Martinez, L.

    1996-07-01

    This paper describes a practical introduction to the use of Artificial Neural Networks. Artificial Neural Nets are often used as an alternative to the traditional symbolic manipulation and first order logic used in Artificial Intelligence, due the high degree of difficulty to solve problems that can not be handled by programmers using algorithmic strategies. As a particular case of Neural Net a Multilayer Perception developed by programming in C language on OS9 real time operating system is presented. A detailed description about the program structure and practical use are included. Finally, several application examples that have been treated with the tool are presented, and some suggestions about hardware implementations. (Author) 15 refs.

  11. ANT Advanced Neural Tool

    International Nuclear Information System (INIS)

    Labrador, I.; Carrasco, R.; Martinez, L.

    1996-01-01

    This paper describes a practical introduction to the use of Artificial Neural Networks. Artificial Neural Nets are often used as an alternative to the traditional symbolic manipulation and first order logic used in Artificial Intelligence, due the high degree of difficulty to solve problems that can not be handled by programmers using algorithmic strategies. As a particular case of Neural Net a Multilayer Perception developed by programming in C language on OS9 real time operating system is presented. A detailed description about the program structure and practical use are included. Finally, several application examples that have been treated with the tool are presented, and some suggestions about hardware implementations. (Author) 15 refs

  12. Suprahyoid Muscle Complex: A Reliable Neural Assessment Tool For Dysphagia?

    DEFF Research Database (Denmark)

    Kothari, Mohit; Stubbs, Peter William; Pedersen, Asger Roer

    be a non-invasive reliable neural assessment tool for patients with dysphagia. Objective: To investigate the possibility of using the suprahyoid muscle complex (SMC) using surface electromyography (sEMG) to assess changes to neural pathways by determining the reliability of measurements in healthy...

  13. Novel paths towards neural cellular products for neurological disorders.

    Science.gov (United States)

    Daadi, Marcel M

    2011-11-01

    The prospect of using neural cells derived from stem cells or from reprogrammed adult somatic cells provides a unique opportunity in cell therapy and drug discovery for developing novel strategies for brain repair. Cell-based therapeutic approaches for treating CNS afflictions caused by disease or injury aim to promote structural repair of the injured or diseased neural tissue, an outcome currently not achieved by drug therapy. Preclinical research in animal models of various diseases or injuries report that grafts of neural cells enhance endogenous repair, provide neurotrophic support to neurons undergoing degeneration and replace lost neural cells. In recent years, the sources of neural cells for treating neurological disorders have been rapidly expanding and in addition to offering therapeutic potential, neural cell products hold promise for disease modeling and drug discovery use. Specific neural cell types have been derived from adult or fetal brain, from human embryonic stem cells, from induced pluripotent stem cells and directly transdifferentiated from adult somatic cells, such as skin cells. It is yet to be determined if the latter approach will evolve into a paradigm shift in the fields of stem cell research and regenerative medicine. These multiple sources of neural cells cover a wide spectrum of safety that needs to be balanced with efficacy to determine the viability of the cellular product. In this article, we will review novel sources of neural cells and discuss current obstacles to developing them into viable cellular products for treating neurological disorders.

  14. Eddy Current Flaw Characterization Using Neural Networks

    International Nuclear Information System (INIS)

    Song, S. J.; Park, H. J.; Shin, Y. K.

    1998-01-01

    Determination of location, shape and size of a flaw from its eddy current testing signal is one of the fundamental issues in eddy current nondestructive evaluation of steam generator tubes. Here, we propose an approach to this problem; an inversion of eddy current flaw signal using neural networks trained by finite element model-based synthetic signatures. Total 216 eddy current signals from four different types of axisymmetric flaws in tubes are generated by finite element models of which the accuracy is experimentally validated. From each simulated signature, total 24 eddy current features are extracted and among them 13 features are finally selected for flaw characterization. Based on these features, probabilistic neural networks discriminate flaws into four different types according to the location and the shape, and successively back propagation neural networks determine the size parameters of the discriminated flaw

  15. Global Robust Stability of Switched Interval Neural Networks with Discrete and Distributed Time-Varying Delays of Neural Type

    Directory of Open Access Journals (Sweden)

    Huaiqin Wu

    2012-01-01

    Full Text Available By combing the theories of the switched systems and the interval neural networks, the mathematics model of the switched interval neural networks with discrete and distributed time-varying delays of neural type is presented. A set of the interval parameter uncertainty neural networks with discrete and distributed time-varying delays of neural type are used as the individual subsystem, and an arbitrary switching rule is assumed to coordinate the switching between these networks. By applying the augmented Lyapunov-Krasovskii functional approach and linear matrix inequality (LMI techniques, a delay-dependent criterion is achieved to ensure to such switched interval neural networks to be globally asymptotically robustly stable in terms of LMIs. The unknown gain matrix is determined by solving this delay-dependent LMIs. Finally, an illustrative example is given to demonstrate the validity of the theoretical results.

  16. Hidden neural networks

    DEFF Research Database (Denmark)

    Krogh, Anders Stærmose; Riis, Søren Kamaric

    1999-01-01

    A general framework for hybrids of hidden Markov models (HMMs) and neural networks (NNs) called hidden neural networks (HNNs) is described. The article begins by reviewing standard HMMs and estimation by conditional maximum likelihood, which is used by the HNN. In the HNN, the usual HMM probability...... parameters are replaced by the outputs of state-specific neural networks. As opposed to many other hybrids, the HNN is normalized globally and therefore has a valid probabilistic interpretation. All parameters in the HNN are estimated simultaneously according to the discriminative conditional maximum...... likelihood criterion. The HNN can be viewed as an undirected probabilistic independence network (a graphical model), where the neural networks provide a compact representation of the clique functions. An evaluation of the HNN on the task of recognizing broad phoneme classes in the TIMIT database shows clear...

  17. NMDA Receptor Signaling Is Important for Neural Tube Formation and for Preventing Antiepileptic Drug-Induced Neural Tube Defects.

    Science.gov (United States)

    Sequerra, Eduardo B; Goyal, Raman; Castro, Patricio A; Levin, Jacqueline B; Borodinsky, Laura N

    2018-05-16

    Failure of neural tube closure leads to neural tube defects (NTDs), which can have serious neurological consequences or be lethal. Use of antiepileptic drugs (AEDs) during pregnancy increases the incidence of NTDs in offspring by unknown mechanisms. Here we show that during Xenopus laevis neural tube formation, neural plate cells exhibit spontaneous calcium dynamics that are partially mediated by glutamate signaling. We demonstrate that NMDA receptors are important for the formation of the neural tube and that the loss of their function induces an increase in neural plate cell proliferation and impairs neural cell migration, which result in NTDs. We present evidence that the AED valproic acid perturbs glutamate signaling, leading to NTDs that are rescued with varied efficacy by preventing DNA synthesis, activating NMDA receptors, or recruiting the NMDA receptor target ERK1/2. These findings may prompt mechanistic identification of AEDs that do not interfere with neural tube formation. SIGNIFICANCE STATEMENT Neural tube defects are one of the most common birth defects. Clinical investigations have determined that the use of antiepileptic drugs during pregnancy increases the incidence of these defects in the offspring by unknown mechanisms. This study discovers that glutamate signaling regulates neural plate cell proliferation and oriented migration and is necessary for neural tube formation. We demonstrate that the widely used antiepileptic drug valproic acid interferes with glutamate signaling and consequently induces neural tube defects, challenging the current hypotheses arguing that they are side effects of this antiepileptic drug that cause the increased incidence of these defects. Understanding the mechanisms of neurotransmitter signaling during neural tube formation may contribute to the identification and development of antiepileptic drugs that are safer during pregnancy. Copyright © 2018 the authors 0270-6474/18/384762-12$15.00/0.

  18. Blastema cells derived from New Zealand white rabbit's pinna carry stemness properties as shown by differentiation into insulin producing, neural, and osteogenic lineages representing three embryonic germ layers.

    Science.gov (United States)

    Saeinasab, Morvarid; Matin, Maryam M; Rassouli, Fatemeh B; Bahrami, Ahmad Reza

    2016-05-01

    Stem cells (SCs) are known as undifferentiated cells with self-renewal and differentiation capacities. Regeneration is a phenomenon that occurs in a limited number of animals after injury, during which blastema tissue is formed. It has been hypothesized that upon injury, the dedifferentiation of surrounding tissues leads into the appearance of cells with SC characteristics. In present study, stem-like cells (SLCs) were obtained from regenerating tissue of New Zealand white rabbit's pinna and their stemness properties were examined by their capacity to differentiate toward insulin producing cells (IPCs), as well as neural and osteogenic lineages. Differentiation was induced by culture of SLCs in defined medium, and cell fates were monitored by specific staining, RT-PCR and flow cytometry assays. Our results revealed that dithizone positive cells, which represent IPCs, and islet-like structures appeared 1 week after induction of SLCs, and this observation was confirmed by the elevated expression of Ins, Pax6 and Glut4 at mRNA level. Furthermore, SLCs were able to express neural markers as early as 1 week after retinoic acid treatment. Finally, SLCs were able to differentiate into osteogenic lineage, as confirmed by Alizarin Red S staining and RT-PCR studies. In conclusion, SLCs, which could successfully differentiate into cells derived from all three germ layers, can be considered as a valuable model to study developmental biology and regenerative medicine.

  19. MicroRNA Cluster miR-17-92 Regulates Neural Stem Cell Expansion and Transition to Intermediate Progenitors in the Developing Mouse Neocortex

    Directory of Open Access Journals (Sweden)

    Shan Bian

    2013-05-01

    Full Text Available During development of the embryonic neocortex, tightly regulated expansion of neural stem cells (NSCs and their transition to intermediate progenitors (IPs are critical for normal cortical formation and function. Molecular mechanisms that regulate NSC expansion and transition remain unclear. Here, we demonstrate that the microRNA (miRNA miR-17-92 cluster is required for maintaining proper populations of cortical radial glial cells (RGCs and IPs through repression of Pten and Tbr2 protein. Knockout of miR-17-92 and its paralogs specifically in the developing neocortex restricts NSC proliferation, suppresses RGC expansion, and promotes transition of RGCs to IPs. Moreover, Pten and Tbr2 protectors specifically block silencing activities of endogenous miR-17-92 and control proper numbers of RGCs and IPs in vivo. Our results demonstrate a critical role for miRNAs in promoting NSC proliferation and modulating the cell-fate decision of generating distinct neural progenitors in the developing neocortex.

  20. Estimation of neural energy in microelectrode signals

    Science.gov (United States)

    Gaumond, R. P.; Clement, R.; Silva, R.; Sander, D.

    2004-09-01

    We considered the problem of determining the neural contribution to the signal recorded by an intracortical electrode. We developed a linear least-squares approach to determine the energy fraction of a signal attributable to an arbitrary number of autocorrelation-defined signals buried in noise. Application of the method requires estimation of autocorrelation functions Rap(tgr) characterizing the action potential (AP) waveforms and Rn(tgr) characterizing background noise. This method was applied to the analysis of chronically implanted microelectrode signals from motor cortex of rat. We found that neural (AP) energy consisted of a large-signal component which grows linearly with the number of threshold-detected neural events and a small-signal component unrelated to the count of threshold-detected AP signals. The addition of pseudorandom noise to electrode signals demonstrated the algorithm's effectiveness for a wide range of noise-to-signal energy ratios (0.08 to 39). We suggest, therefore, that the method could be of use in providing a measure of neural response in situations where clearly identified spike waveforms cannot be isolated, or in providing an additional 'background' measure of microelectrode neural activity to supplement the traditional AP spike count.

  1. Active Neural Localization

    OpenAIRE

    Chaplot, Devendra Singh; Parisotto, Emilio; Salakhutdinov, Ruslan

    2018-01-01

    Localization is the problem of estimating the location of an autonomous agent from an observation and a map of the environment. Traditional methods of localization, which filter the belief based on the observations, are sub-optimal in the number of steps required, as they do not decide the actions taken by the agent. We propose "Active Neural Localizer", a fully differentiable neural network that learns to localize accurately and efficiently. The proposed model incorporates ideas of tradition...

  2. Neural cryptography with feedback.

    Science.gov (United States)

    Ruttor, Andreas; Kinzel, Wolfgang; Shacham, Lanir; Kanter, Ido

    2004-04-01

    Neural cryptography is based on a competition between attractive and repulsive stochastic forces. A feedback mechanism is added to neural cryptography which increases the repulsive forces. Using numerical simulations and an analytic approach, the probability of a successful attack is calculated for different model parameters. Scaling laws are derived which show that feedback improves the security of the system. In addition, a network with feedback generates a pseudorandom bit sequence which can be used to encrypt and decrypt a secret message.

  3. Tumour necrosis factor-alpha impairs neuronal differentiation but not proliferation of hippocampal neural precursor cells: Role of Hes1.

    Science.gov (United States)

    Keohane, Aoife; Ryan, Sinead; Maloney, Eimer; Sullivan, Aideen M; Nolan, Yvonne M

    2010-01-01

    Tumour necrosis factor-alpha (TNFalpha) is a pro-inflammatory cytokine, which influences neuronal survival and function yet there is limited information available on its effects on hippocampal neural precursor cells (NPCs). We show that TNFalpha treatment during proliferation had no effect on the percentage of proliferating cells prepared from embryonic rat hippocampal neurosphere cultures, nor did it affect cell fate towards either an astrocytic or neuronal lineage when cells were then allowed to differentiate. However, when cells were differentiated in the presence of TNFalpha, significantly reduced percentages of newly born and post-mitotic neurons, significantly increased percentages of astrocytes and increased expression of TNFalpha receptors, TNF-R1 and TNF-R2, as well as expression of the anti-neurogenic Hes1 gene, were observed. These data indicate that exposure of hippocampal NPCs to TNFalpha when they are undergoing differentiation but not proliferation has a detrimental effect on their neuronal lineage fate, which may be mediated through increased expression of Hes1. Copyright 2009 Elsevier Inc. All rights reserved.

  4. p600 regulates spindle orientation in apical neural progenitors and contributes to neurogenesis in the developing neocortex

    Directory of Open Access Journals (Sweden)

    Camille Belzil

    2014-05-01

    Full Text Available Apical neural progenitors (aNPs drive neurogenesis by means of a program consisting of self-proliferative and neurogenic divisions. The balance between these two manners of division sustains the pool of apical progenitors into late neurogenesis, thereby ensuring their availability to populate the brain with terminal cell types. Using knockout and in utero electroporation mouse models, we report a key role for the microtubule-associated protein 600 (p600 in the regulation of spindle orientation in aNPs, a cellular event that has been associated with cell fate and neurogenesis. We find that p600 interacts directly with the neurogenic protein Ndel1 and that aNPs knockout for p600, depleted of p600 by shRNA or expressing a Ndel1-binding p600 fragment all display randomized spindle orientation. Depletion of p600 by shRNA or expression of the Ndel1-binding p600 fragment also results in a decreased number of Pax6-positive aNPs and an increased number of Tbr2-positive basal progenitors destined to become neurons. These Pax6-positive aNPs display a tilted mitotic spindle. In mice wherein p600 is ablated in progenitors, the production of neurons is significantly impaired and this defect is associated with microcephaly. We propose a working model in which p600 controls spindle orientation in aNPs and discuss its implication for neurogenesis.

  5. Pax7 lineage contributions to the mammalian neural crest.

    Directory of Open Access Journals (Sweden)

    Barbara Murdoch

    Full Text Available Neural crest cells are vertebrate-specific multipotent cells that contribute to a variety of tissues including the peripheral nervous system, melanocytes, and craniofacial bones and cartilage. Abnormal development of the neural crest is associated with several human maladies including cleft/lip palate, aggressive cancers such as melanoma and neuroblastoma, and rare syndromes, like Waardenburg syndrome, a complex disorder involving hearing loss and pigment defects. We previously identified the transcription factor Pax7 as an early marker, and required component for neural crest development in chick embryos. In mammals, Pax7 is also thought to play a role in neural crest development, yet the precise contribution of Pax7 progenitors to the neural crest lineage has not been determined.Here we use Cre/loxP technology in double transgenic mice to fate map the Pax7 lineage in neural crest derivates. We find that Pax7 descendants contribute to multiple tissues including the cranial, cardiac and trunk neural crest, which in the cranial cartilage form a distinct regional pattern. The Pax7 lineage, like the Pax3 lineage, is additionally detected in some non-neural crest tissues, including a subset of the epithelial cells in specific organs.These results demonstrate a previously unappreciated widespread distribution of Pax7 descendants within and beyond the neural crest. They shed light regarding the regionally distinct phenotypes observed in Pax3 and Pax7 mutants, and provide a unique perspective into the potential roles of Pax7 during disease and development.

  6. Requirement of mouse BCCIP for neural development and progenitor proliferation.

    Directory of Open Access Journals (Sweden)

    Yi-Yuan Huang

    Full Text Available Multiple DNA repair pathways are involved in the orderly development of neural systems at distinct stages. The homologous recombination (HR pathway is required to resolve stalled replication forks and critical for the proliferation of progenitor cells during neural development. BCCIP is a BRCA2 and CDKN1A interacting protein implicated in HR and inhibition of DNA replication stress. In this study, we determined the role of BCCIP in neural development using a conditional BCCIP knock-down mouse model. BCCIP deficiency impaired embryonic and postnatal neural development, causing severe ataxia, cerebral and cerebellar defects, and microcephaly. These development defects are associated with spontaneous DNA damage and subsequent cell death in the proliferative cell populations of the neural system during embryogenesis. With in vitro neural spheroid cultures, BCCIP deficiency impaired neural progenitor's self-renewal capability, and spontaneously activated p53. These data suggest that BCCIP and its anti-replication stress functions are essential for normal neural development by maintaining an orderly proliferation of neural progenitors.

  7. Neural correlates underlying musical semantic memory.

    Science.gov (United States)

    Groussard, M; Viader, F; Landeau, B; Desgranges, B; Eustache, F; Platel, H

    2009-07-01

    Numerous functional imaging studies have examined the neural basis of semantic memory mainly using verbal and visuospatial materials. Musical material also allows an original way to explore semantic memory processes. We used PET imaging to determine the neural substrates that underlie musical semantic memory using different tasks and stimuli. The results of three PET studies revealed a greater involvement of the anterior part of the temporal lobe. Concerning clinical observations and our neuroimaging data, the musical lexicon (and most widely musical semantic memory) appears to be sustained by a temporo-prefrontal cerebral network involving right and left cerebral regions.

  8. Comprehensive Identification of Long Non-coding RNAs in Purified Cell Types from the Brain Reveals Functional LncRNA in OPC Fate Determination.

    Directory of Open Access Journals (Sweden)

    Xiaomin Dong

    2015-12-01

    Full Text Available Long non-coding RNAs (lncRNAs (> 200 bp play crucial roles in transcriptional regulation during numerous biological processes. However, it is challenging to comprehensively identify lncRNAs, because they are often expressed at low levels and with more cell-type specificity than are protein-coding genes. In the present study, we performed ab initio transcriptome reconstruction using eight purified cell populations from mouse cortex and detected more than 5000 lncRNAs. Predicting the functions of lncRNAs using cell-type specific data revealed their potential functional roles in Central Nervous System (CNS development. We performed motif searches in ENCODE DNase I digital footprint data and Mouse ENCODE promoters to infer transcription factor (TF occupancy. By integrating TF binding and cell-type specific transcriptomic data, we constructed a novel framework that is useful for systematically identifying lncRNAs that are potentially essential for brain cell fate determination. Based on this integrative analysis, we identified lncRNAs that are regulated during Oligodendrocyte Precursor Cell (OPC differentiation from Neural Stem Cells (NSCs and that are likely to be involved in oligodendrogenesis. The top candidate, lnc-OPC, shows highly specific expression in OPCs and remarkable sequence conservation among placental mammals. Interestingly, lnc-OPC is significantly up-regulated in glial progenitors from experimental autoimmune encephalomyelitis (EAE mouse models compared to wild-type mice. OLIG2-binding sites in the upstream regulatory region of lnc-OPC were identified by ChIP (chromatin immunoprecipitation-Sequencing and validated by luciferase assays. Loss-of-function experiments confirmed that lnc-OPC plays a functional role in OPC genesis. Overall, our results substantiated the role of lncRNA in OPC fate determination and provided an unprecedented data source for future functional investigations in CNS cell types. We present our datasets and

  9. Open quantum generalisation of Hopfield neural networks

    Science.gov (United States)

    Rotondo, P.; Marcuzzi, M.; Garrahan, J. P.; Lesanovsky, I.; Müller, M.

    2018-03-01

    We propose a new framework to understand how quantum effects may impact on the dynamics of neural networks. We implement the dynamics of neural networks in terms of Markovian open quantum systems, which allows us to treat thermal and quantum coherent effects on the same footing. In particular, we propose an open quantum generalisation of the Hopfield neural network, the simplest toy model of associative memory. We determine its phase diagram and show that quantum fluctuations give rise to a qualitatively new non-equilibrium phase. This novel phase is characterised by limit cycles corresponding to high-dimensional stationary manifolds that may be regarded as a generalisation of storage patterns to the quantum domain.

  10. Parallel consensual neural networks.

    Science.gov (United States)

    Benediktsson, J A; Sveinsson, J R; Ersoy, O K; Swain, P H

    1997-01-01

    A new type of a neural-network architecture, the parallel consensual neural network (PCNN), is introduced and applied in classification/data fusion of multisource remote sensing and geographic data. The PCNN architecture is based on statistical consensus theory and involves using stage neural networks with transformed input data. The input data are transformed several times and the different transformed data are used as if they were independent inputs. The independent inputs are first classified using the stage neural networks. The output responses from the stage networks are then weighted and combined to make a consensual decision. In this paper, optimization methods are used in order to weight the outputs from the stage networks. Two approaches are proposed to compute the data transforms for the PCNN, one for binary data and another for analog data. The analog approach uses wavelet packets. The experimental results obtained with the proposed approach show that the PCNN outperforms both a conjugate-gradient backpropagation neural network and conventional statistical methods in terms of overall classification accuracy of test data.

  11. Artificial neural network intelligent method for prediction

    Science.gov (United States)

    Trifonov, Roumen; Yoshinov, Radoslav; Pavlova, Galya; Tsochev, Georgi

    2017-09-01

    Accounting and financial classification and prediction problems are high challenge and researchers use different methods to solve them. Methods and instruments for short time prediction of financial operations using artificial neural network are considered. The methods, used for prediction of financial data as well as the developed forecasting system with neural network are described in the paper. The architecture of a neural network used four different technical indicators, which are based on the raw data and the current day of the week is presented. The network developed is used for forecasting movement of stock prices one day ahead and consists of an input layer, one hidden layer and an output layer. The training method is algorithm with back propagation of the error. The main advantage of the developed system is self-determination of the optimal topology of neural network, due to which it becomes flexible and more precise The proposed system with neural network is universal and can be applied to various financial instruments using only basic technical indicators as input data.

  12. Efficient Cancer Detection Using Multiple Neural Networks.

    Science.gov (United States)

    Shell, John; Gregory, William D

    2017-01-01

    The inspection of live excised tissue specimens to ascertain malignancy is a challenging task in dermatopathology and generally in histopathology. We introduce a portable desktop prototype device that provides highly accurate neural network classification of malignant and benign tissue. The handheld device collects 47 impedance data samples from 1 Hz to 32 MHz via tetrapolar blackened platinum electrodes. The data analysis was implemented with six different backpropagation neural networks (BNN). A data set consisting of 180 malignant and 180 benign breast tissue data files in an approved IRB study at the Aurora Medical Center, Milwaukee, WI, USA, were utilized as a neural network input. The BNN structure consisted of a multi-tiered consensus approach autonomously selecting four of six neural networks to determine a malignant or benign classification. The BNN analysis was then compared with the histology results with consistent sensitivity of 100% and a specificity of 100%. This implementation successfully relied solely on statistical variation between the benign and malignant impedance data and intricate neural network configuration. This device and BNN implementation provides a novel approach that could be a valuable tool to augment current medical practice assessment of the health of breast, squamous, and basal cell carcinoma and other excised tissue without requisite tissue specimen expertise. It has the potential to provide clinical management personnel with a fast non-invasive accurate assessment of biopsied or sectioned excised tissue in various clinical settings.

  13. Characterization of Radar Signals Using Neural Networks

    Science.gov (United States)

    1990-12-01

    e***e*e*eeeeeeeeeeeesseeeeeese*eee*e*e************s /* Function Name: load.input.ptterns Number: 4.1 /* Description: This function determines wether ...XSE.last.layer Number: 8.5 */ /* Description: The function determines wether to backpropate the *f /* parameter by the sigmoidal or linear update...Sigmoidal Function," Mathematics of Control, Signals and Systems, 2:303-314 (March 1989). 6. Dayhoff, Judith E. Neural Network Architectures. New York: Van

  14. Neural Architectures for Control

    Science.gov (United States)

    Peterson, James K.

    1991-01-01

    The cerebellar model articulated controller (CMAC) neural architectures are shown to be viable for the purposes of real-time learning and control. Software tools for the exploration of CMAC performance are developed for three hardware platforms, the MacIntosh, the IBM PC, and the SUN workstation. All algorithm development was done using the C programming language. These software tools were then used to implement an adaptive critic neuro-control design that learns in real-time how to back up a trailer truck. The truck backer-upper experiment is a standard performance measure in the neural network literature, but previously the training of the controllers was done off-line. With the CMAC neural architectures, it was possible to train the neuro-controllers on-line in real-time on a MS-DOS PC 386. CMAC neural architectures are also used in conjunction with a hierarchical planning approach to find collision-free paths over 2-D analog valued obstacle fields. The method constructs a coarse resolution version of the original problem and then finds the corresponding coarse optimal path using multipass dynamic programming. CMAC artificial neural architectures are used to estimate the analog transition costs that dynamic programming requires. The CMAC architectures are trained in real-time for each obstacle field presented. The coarse optimal path is then used as a baseline for the construction of a fine scale optimal path through the original obstacle array. These results are a very good indication of the potential power of the neural architectures in control design. In order to reach as wide an audience as possible, we have run a seminar on neuro-control that has met once per week since 20 May 1991. This seminar has thoroughly discussed the CMAC architecture, relevant portions of classical control, back propagation through time, and adaptive critic designs.

  15. Sacred or Neural?

    DEFF Research Database (Denmark)

    Runehov, Anne Leona Cesarine

    Are religious spiritual experiences merely the product of the human nervous system? Anne L.C. Runehov investigates the potential of contemporary neuroscience to explain religious experiences. Following the footsteps of Michael Persinger, Andrew Newberg and Eugene d'Aquili she defines...... the terminological bounderies of "religious experiences" and explores the relevant criteria for the proper evaluation of scientific research, with a particular focus on the validity of reductionist models. Runehov's theis is that the perspectives looked at do not necessarily exclude each other but can be merged....... The question "sacred or neural?" becomes a statement "sacred and neural". The synergies thus produced provide manifold opportunities for interdisciplinary dialogue and research....

  16. Deconvolution using a neural network

    Energy Technology Data Exchange (ETDEWEB)

    Lehman, S.K.

    1990-11-15

    Viewing one dimensional deconvolution as a matrix inversion problem, we compare a neural network backpropagation matrix inverse with LMS, and pseudo-inverse. This is a largely an exercise in understanding how our neural network code works. 1 ref.

  17. Introduction to Artificial Neural Networks

    DEFF Research Database (Denmark)

    Larsen, Jan

    1999-01-01

    The note addresses introduction to signal analysis and classification based on artificial feed-forward neural networks.......The note addresses introduction to signal analysis and classification based on artificial feed-forward neural networks....

  18. Identifying Emotions on the Basis of Neural Activation.

    Science.gov (United States)

    Kassam, Karim S; Markey, Amanda R; Cherkassky, Vladimir L; Loewenstein, George; Just, Marcel Adam

    2013-01-01

    We attempt to determine the discriminability and organization of neural activation corresponding to the experience of specific emotions. Method actors were asked to self-induce nine emotional states (anger, disgust, envy, fear, happiness, lust, pride, sadness, and shame) while in an fMRI scanner. Using a Gaussian Naïve Bayes pooled variance classifier, we demonstrate the ability to identify specific emotions experienced by an individual at well over chance accuracy on the basis of: 1) neural activation of the same individual in other trials, 2) neural activation of other individuals who experienced similar trials, and 3) neural activation of the same individual to a qualitatively different type of emotion induction. Factor analysis identified valence, arousal, sociality, and lust as dimensions underlying the activation patterns. These results suggest a structure for neural representations of emotion and inform theories of emotional processing.

  19. Identifying Emotions on the Basis of Neural Activation.

    Directory of Open Access Journals (Sweden)

    Karim S Kassam

    Full Text Available We attempt to determine the discriminability and organization of neural activation corresponding to the experience of specific emotions. Method actors were asked to self-induce nine emotional states (anger, disgust, envy, fear, happiness, lust, pride, sadness, and shame while in an fMRI scanner. Using a Gaussian Naïve Bayes pooled variance classifier, we demonstrate the ability to identify specific emotions experienced by an individual at well over chance accuracy on the basis of: 1 neural activation of the same individual in other trials, 2 neural activation of other individuals who experienced similar trials, and 3 neural activation of the same individual to a qualitatively different type of emotion induction. Factor analysis identified valence, arousal, sociality, and lust as dimensions underlying the activation patterns. These results suggest a structure for neural representations of emotion and inform theories of emotional processing.

  20. Designing neural networks that process mean values of random variables

    International Nuclear Information System (INIS)

    Barber, Michael J.; Clark, John W.

    2014-01-01

    We develop a class of neural networks derived from probabilistic models posed in the form of Bayesian networks. Making biologically and technically plausible assumptions about the nature of the probabilistic models to be represented in the networks, we derive neural networks exhibiting standard dynamics that require no training to determine the synaptic weights, that perform accurate calculation of the mean values of the relevant random variables, that can pool multiple sources of evidence, and that deal appropriately with ambivalent, inconsistent, or contradictory evidence. - Highlights: • High-level neural computations are specified by Bayesian belief networks of random variables. • Probability densities of random variables are encoded in activities of populations of neurons. • Top-down algorithm generates specific neural network implementation of given computation. • Resulting “neural belief networks” process mean values of random variables. • Such networks pool multiple sources of evidence and deal properly with inconsistent evidence

  1. Designing neural networks that process mean values of random variables

    Energy Technology Data Exchange (ETDEWEB)

    Barber, Michael J. [AIT Austrian Institute of Technology, Innovation Systems Department, 1220 Vienna (Austria); Clark, John W. [Department of Physics and McDonnell Center for the Space Sciences, Washington University, St. Louis, MO 63130 (United States); Centro de Ciências Matemáticas, Universidade de Madeira, 9000-390 Funchal (Portugal)

    2014-06-13

    We develop a class of neural networks derived from probabilistic models posed in the form of Bayesian networks. Making biologically and technically plausible assumptions about the nature of the probabilistic models to be represented in the networks, we derive neural networks exhibiting standard dynamics that require no training to determine the synaptic weights, that perform accurate calculation of the mean values of the relevant random variables, that can pool multiple sources of evidence, and that deal appropriately with ambivalent, inconsistent, or contradictory evidence. - Highlights: • High-level neural computations are specified by Bayesian belief networks of random variables. • Probability densities of random variables are encoded in activities of populations of neurons. • Top-down algorithm generates specific neural network implementation of given computation. • Resulting “neural belief networks” process mean values of random variables. • Such networks pool multiple sources of evidence and deal properly with inconsistent evidence.

  2. Neural Network Ensembles

    DEFF Research Database (Denmark)

    Hansen, Lars Kai; Salamon, Peter

    1990-01-01

    We propose several means for improving the performance an training of neural networks for classification. We use crossvalidation as a tool for optimizing network parameters and architecture. We show further that the remaining generalization error can be reduced by invoking ensembles of similar...... networks....

  3. Neural correlates of consciousness

    African Journals Online (AJOL)

    neural cells.1 Under this approach, consciousness is believed to be a product of the ... possible only when the 40 Hz electrical hum is sustained among the brain circuits, ... expect the brain stem ascending reticular activating system. (ARAS) and the ... related synchrony of cortical neurons.11 Indeed, stimulation of brainstem ...

  4. Neural Networks and Micromechanics

    Science.gov (United States)

    Kussul, Ernst; Baidyk, Tatiana; Wunsch, Donald C.

    The title of the book, "Neural Networks and Micromechanics," seems artificial. However, the scientific and technological developments in recent decades demonstrate a very close connection between the two different areas of neural networks and micromechanics. The purpose of this book is to demonstrate this connection. Some artificial intelligence (AI) methods, including neural networks, could be used to improve automation system performance in manufacturing processes. However, the implementation of these AI methods within industry is rather slow because of the high cost of conducting experiments using conventional manufacturing and AI systems. To lower the cost, we have developed special micromechanical equipment that is similar to conventional mechanical equipment but of much smaller size and therefore of lower cost. This equipment could be used to evaluate different AI methods in an easy and inexpensive way. The proved methods could be transferred to industry through appropriate scaling. In this book, we describe the prototypes of low cost microequipment for manufacturing processes and the implementation of some AI methods to increase precision, such as computer vision systems based on neural networks for microdevice assembly and genetic algorithms for microequipment characterization and the increase of microequipment precision.

  5. Introduction to neural networks

    International Nuclear Information System (INIS)

    Pavlopoulos, P.

    1996-01-01

    This lecture is a presentation of today's research in neural computation. Neural computation is inspired by knowledge from neuro-science. It draws its methods in large degree from statistical physics and its potential applications lie mainly in computer science and engineering. Neural networks models are algorithms for cognitive tasks, such as learning and optimization, which are based on concepts derived from research into the nature of the brain. The lecture first gives an historical presentation of neural networks development and interest in performing complex tasks. Then, an exhaustive overview of data management and networks computation methods is given: the supervised learning and the associative memory problem, the capacity of networks, the Perceptron networks, the functional link networks, the Madaline (Multiple Adalines) networks, the back-propagation networks, the reduced coulomb energy (RCE) networks, the unsupervised learning and the competitive learning and vector quantization. An example of application in high energy physics is given with the trigger systems and track recognition system (track parametrization, event selection and particle identification) developed for the CPLEAR experiment detectors from the LEAR at CERN. (J.S.). 56 refs., 20 figs., 1 tab., 1 appendix

  6. Learning from neural control.

    Science.gov (United States)

    Wang, Cong; Hill, David J

    2006-01-01

    One of the amazing successes of biological systems is their ability to "learn by doing" and so adapt to their environment. In this paper, first, a deterministic learning mechanism is presented, by which an appropriately designed adaptive neural controller is capable of learning closed-loop system dynamics during tracking control to a periodic reference orbit. Among various neural network (NN) architectures, the localized radial basis function (RBF) network is employed. A property of persistence of excitation (PE) for RBF networks is established, and a partial PE condition of closed-loop signals, i.e., the PE condition of a regression subvector constructed out of the RBFs along a periodic state trajectory, is proven to be satisfied. Accurate NN approximation for closed-loop system dynamics is achieved in a local region along the periodic state trajectory, and a learning ability is implemented during a closed-loop feedback control process. Second, based on the deterministic learning mechanism, a neural learning control scheme is proposed which can effectively recall and reuse the learned knowledge to achieve closed-loop stability and improved control performance. The significance of this paper is that the presented deterministic learning mechanism and the neural learning control scheme provide elementary components toward the development of a biologically-plausible learning and control methodology. Simulation studies are included to demonstrate the effectiveness of the approach.

  7. Neural systems for control

    National Research Council Canada - National Science Library

    Omidvar, Omid; Elliott, David L

    1997-01-01

    ... is reprinted with permission from A. Barto, "Reinforcement Learning," Handbook of Brain Theory and Neural Networks, M.A. Arbib, ed.. The MIT Press, Cambridge, MA, pp. 804-809, 1995. Chapter 4, Figures 4-5 and 7-9 and Tables 2-5, are reprinted with permission, from S. Cho, "Map Formation in Proprioceptive Cortex," International Jour...

  8. Neural underpinnings of music

    DEFF Research Database (Denmark)

    Vuust, Peter; Gebauer, Line K; Witek, Maria A G

    2014-01-01

    . According to this theory, perception and learning is manifested through the brain’s Bayesian minimization of the error between the input to the brain and the brain’s prior expectations. Fourth, empirical studies of neural and behavioral effects of syncopation, polyrhythm and groove will be reported, and we...

  9. Ordered self-assembled monolayers terminated with different chemical functional groups direct neural stem cell linage behaviours

    International Nuclear Information System (INIS)

    Yao, Shenglian; Liu, Xi; He, Jin; Wang, Xiumei; Wang, Ying; Cui, Fu-Zhai

    2016-01-01

    Neural stem cells (NSCs) have been a promising candidate for stem cell-based nerve tissue regeneration. Therefore, the design of idea biomaterials that deliver precise regulatory signals to control stem cell fate is currently a crucial issue that depends on a profound understanding of the interactions between NSCs with the surrounding micro-environment. In this work, self-assembled monolayers of alkanethiols on gold with different chemical groups, including hydroxyl (−OH), amino (−NH 2 ), carboxyl (−COOH) and methyl (−CH 3 ), were used as a simple model to study the effects of surface chemistry on NSC fate decisions. Contact angle measurement and x-ray photoelectron spectroscopy (XPS) examination implied that all types of alkanethiols self-assembled on gold into a close-packed phase structure with similar molecular densities. In this study, we evaluated NSC adhesion, migration and differentiation in response to different chemical functional groups cultured under serum-free conditions. Our studies showed that NSCs exhibited certain phenotypes with extreme sensitivity to surface chemical groups. Compared with other functional groups, the SAMs with hydroxyl end-groups provided the best micro-environment in promoting NSC migration and maintaining an undifferentiated or neuronal differentiation state.  −NH 2 surfaces directed neural stem cells into astrocytic lineages, while NSCs on  −COOH and  −CH 3 surfaces had a similar potency to differentiate into three nerve lineages. To further investigate the possible signaling pathway, the gene expression of integrin β1 and β4 were examined. The results indicated that a high expression of β1 integrin would probably have a tight correlation with the expression of nestin, which implied the stemness of NSCs, while β4 integrin seemed to correspond to the differentiated NSCs. The results presented here give useful information for the future design of biomaterials to regulate the preservation

  10. Conserved gene regulatory module specifies lateral neural borders across bilaterians.

    Science.gov (United States)

    Li, Yongbin; Zhao, Di; Horie, Takeo; Chen, Geng; Bao, Hongcun; Chen, Siyu; Liu, Weihong; Horie, Ryoko; Liang, Tao; Dong, Biyu; Feng, Qianqian; Tao, Qinghua; Liu, Xiao

    2017-08-01

    The lateral neural plate border (NPB), the neural part of the vertebrate neural border, is composed of central nervous system (CNS) progenitors and peripheral nervous system (PNS) progenitors. In invertebrates, PNS progenitors are also juxtaposed to the lateral boundary of the CNS. Whether there are conserved molecular mechanisms determining vertebrate and invertebrate lateral neural borders remains unclear. Using single-cell-resolution gene-expression profiling and genetic analysis, we present evidence that orthologs of the NPB specification module specify the invertebrate lateral neural border, which is composed of CNS and PNS progenitors. First, like in vertebrates, the conserved neuroectoderm lateral border specifier Msx/vab-15 specifies lateral neuroblasts in Caenorhabditis elegans Second, orthologs of the vertebrate NPB specification module ( Msx/vab-15 , Pax3/7/pax-3 , and Zic/ref-2 ) are significantly enriched in worm lateral neuroblasts. In addition, like in other bilaterians, the expression domain of Msx/vab-15 is more lateral than those of Pax3/7/pax-3 and Zic/ref- 2 in C. elegans Third, we show that Msx/vab-15 regulates the development of mechanosensory neurons derived from lateral neural progenitors in multiple invertebrate species, including C. elegans , Drosophila melanogaster , and Ciona intestinalis We also identify a novel lateral neural border specifier, ZNF703/tlp-1 , which functions synergistically with Msx/vab- 15 in both C. elegans and Xenopus laevis These data suggest a common origin of the molecular mechanism specifying lateral neural borders across bilaterians.

  11. Neural redundancy applied to the parity space for signal validation

    International Nuclear Information System (INIS)

    Mol, Antonio Carlos de Abreu; Pereira, Claudio Marcio Nascimento Abreu; Martinez, Aquilino Senra

    2005-01-01

    The objective of signal validation is to provide more reliable information from the plant sensor data The method presented in this work introduces the concept of neural redundancy and applies it to the space parity method [1] to overcome an inherent deficiency of this method - the determination of the best estimative of the redundant measures when they are inconsistent. The concept of neural redundancy consists on the calculation of a redundancy through neural networks based on the time series of the own state variable. Therefore, neural networks, dynamically trained with the time series, will estimate the current value of the own measure, which will be used as referee of the redundant measures in the parity space. For this purpose the neural network should have the capacity to supply the neural redundancy in real time and with maximum error corresponding to the group deviation. The historical series should be enough to allow the estimate of the next value, during transients and at the same time, it should be optimized to facilitate the retraining of the neural network to each acquisition. In order to have the capacity to reproduce the tendency of the time series even under accident condition, the dynamic training of the neural network privileges the recent points of the time series. The tests accomplished with simulated data of a nuclear plant, demonstrated that this method applied on the parity space method improves the signal validation process. (author)

  12. Neural redundancy applied to the parity space for signal validation

    Energy Technology Data Exchange (ETDEWEB)

    Mol, Antonio Carlos de Abreu; Pereira, Claudio Marcio Nascimento Abreu [Instituto de Engenharia Nuclear (IEN), Rio de Janeiro, RJ (Brazil)]. E-mail: cmnap@ien.gov.br; Martinez, Aquilino Senra [Universidade Federal, Rio de Janeiro, RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia]. E-mail: aquilino@lmp.br

    2005-07-01

    The objective of signal validation is to provide more reliable information from the plant sensor data The method presented in this work introduces the concept of neural redundancy and applies it to the space parity method [1] to overcome an inherent deficiency of this method - the determination of the best estimative of the redundant measures when they are inconsistent. The concept of neural redundancy consists on the calculation of a redundancy through neural networks based on the time series of the own state variable. Therefore, neural networks, dynamically trained with the time series, will estimate the current value of the own measure, which will be used as referee of the redundant measures in the parity space. For this purpose the neural network should have the capacity to supply the neural redundancy in real time and with maximum error corresponding to the group deviation. The historical series should be enough to allow the estimate of the next value, during transients and at the same time, it should be optimized to facilitate the retraining of the neural network to each acquisition. In order to have the capacity to reproduce the tendency of the time series even under accident condition, the dynamic training of the neural network privileges the recent points of the time series. The tests accomplished with simulated data of a nuclear plant, demonstrated that this method applied on the parity space method improves the signal validation process. (author)

  13. Neural complexity: A graph theoretic interpretation

    Science.gov (United States)

    Barnett, L.; Buckley, C. L.; Bullock, S.

    2011-04-01

    One of the central challenges facing modern neuroscience is to explain the ability of the nervous system to coherently integrate information across distinct functional modules in the absence of a central executive. To this end, Tononi [Proc. Natl. Acad. Sci. USA.PNASA60027-842410.1073/pnas.91.11.5033 91, 5033 (1994)] proposed a measure of neural complexity that purports to capture this property based on mutual information between complementary subsets of a system. Neural complexity, so defined, is one of a family of information theoretic metrics developed to measure the balance between the segregation and integration of a system’s dynamics. One key question arising for such measures involves understanding how they are influenced by network topology. Sporns [Cereb. Cortex53OPAV1047-321110.1093/cercor/10.2.127 10, 127 (2000)] employed numerical models in order to determine the dependence of neural complexity on the topological features of a network. However, a complete picture has yet to be established. While De Lucia [Phys. Rev. EPLEEE81539-375510.1103/PhysRevE.71.016114 71, 016114 (2005)] made the first attempts at an analytical account of this relationship, their work utilized a formulation of neural complexity that, we argue, did not reflect the intuitions of the original work. In this paper we start by describing weighted connection matrices formed by applying a random continuous weight distribution to binary adjacency matrices. This allows us to derive an approximation for neural complexity in terms of the moments of the weight distribution and elementary graph motifs. In particular, we explicitly establish a dependency of neural complexity on cyclic graph motifs.

  14. Cotton genotypes selection through artificial neural networks.

    Science.gov (United States)

    Júnior, E G Silva; Cardoso, D B O; Reis, M C; Nascimento, A F O; Bortolin, D I; Martins, M R; Sousa, L B

    2017-09-27

    Breeding programs currently use statistical analysis to assist in the identification of superior genotypes at various stages of a cultivar's development. Differently from these analyses, the computational intelligence approach has been little explored in genetic improvement of cotton. Thus, this study was carried out with the objective of presenting the use of artificial neural networks as auxiliary tools in the improvement of the cotton to improve fiber quality. To demonstrate the applicability of this approach, this research was carried out using the evaluation data of 40 genotypes. In order to classify the genotypes for fiber quality, the artificial neural networks were trained with replicate data of 20 genotypes of cotton evaluated in the harvests of 2013/14 and 2014/15, regarding fiber length, uniformity of length, fiber strength, micronaire index, elongation, short fiber index, maturity index, reflectance degree, and fiber quality index. This quality index was estimated by means of a weighted average on the determined score (1 to 5) of each characteristic of the HVI evaluated, according to its industry standards. The artificial neural networks presented a high capacity of correct classification of the 20 selected genotypes based on the fiber quality index, so that when using fiber length associated with the short fiber index, fiber maturation, and micronaire index, the artificial neural networks presented better results than using only fiber length and previous associations. It was also observed that to submit data of means of new genotypes to the neural networks trained with data of repetition, provides better results of classification of the genotypes. When observing the results obtained in the present study, it was verified that the artificial neural networks present great potential to be used in the different stages of a genetic improvement program of the cotton, aiming at the improvement of the fiber quality of the future cultivars.

  15. Microbiota promote secretory cell determination in the intestinal epithelium by modulating host Notch signaling.

    Science.gov (United States)

    Troll, Joshua V; Hamilton, M Kristina; Abel, Melissa L; Ganz, Julia; Bates, Jennifer M; Stephens, W Zac; Melancon, Ellie; van der Vaart, Michiel; Meijer, Annemarie H; Distel, Martin; Eisen, Judith S; Guillemin, Karen

    2018-02-23

    Resident microbes promote many aspects of host development, although the mechanisms by which microbiota influence host tissues remain unclear. We showed previously that the microbiota is required for allocation of appropriate numbers of secretory cells in the zebrafish intestinal epithelium. Because Notch signaling is crucial for secretory fate determination, we conducted epistasis experiments to establish whether the microbiota modulates host Notch signaling. We also investigated whether innate immune signaling transduces microbiota cues via the Myd88 adaptor protein. We provide the first evidence that microbiota-induced, Myd88-dependent signaling inhibits host Notch signaling in the intestinal epithelium, thereby promoting secretory cell fate determination. These results connect microbiota activity via innate immune signaling to the Notch pathway, which also plays crucial roles in intestinal homeostasis throughout life and when impaired can result in chronic inflammation and cancer. © 2018. Published by The Company of Biologists Ltd.

  16. Cellular responses to a prolonged delay in mitosis are determined by a DNA damage response controlled by Bcl-2 family proteins.

    Science.gov (United States)

    Colin, Didier J; Hain, Karolina O; Allan, Lindsey A; Clarke, Paul R

    2015-03-01

    Anti-cancer drugs that disrupt mitosis inhibit cell proliferation and induce apoptosis, although the mechanisms of these responses are poorly understood. Here, we characterize a mitotic stress response that determines cell fate in response to microtubule poisons. We show that mitotic arrest induced by these drugs produces a temporally controlled DNA damage response (DDR) characterized by the caspase-dependent formation of γH2AX foci in non-apoptotic cells. Following exit from a delayed mitosis, this initial response results in activation of DDR protein kinases, phosphorylation of the tumour suppressor p53 and a delay in subsequent cell cycle progression. We show that this response is controlled by Mcl-1, a regulator of caspase activation that becomes degraded during mitotic arrest. Chemical inhibition of Mcl-1 and the related proteins Bcl-2 and Bcl-xL by a BH3 mimetic enhances the mitotic DDR, promotes p53 activation and inhibits subsequent cell cycle progression. We also show that inhibitors of DDR protein kinases as well as BH3 mimetics promote apoptosis synergistically with taxol (paclitaxel) in a variety of cancer cell lines. Our work demonstrates the role of mitotic DNA damage responses in determining cell fate in response to microtubule poisons and BH3 mimetics, providing a rationale for anti-cancer combination chemotherapies.

  17. Bioprinting for Neural Tissue Engineering.

    Science.gov (United States)

    Knowlton, Stephanie; Anand, Shivesh; Shah, Twisha; Tasoglu, Savas

    2018-01-01

    Bioprinting is a method by which a cell-encapsulating bioink is patterned to create complex tissue architectures. Given the potential impact of this technology on neural research, we review the current state-of-the-art approaches for bioprinting neural tissues. While 2D neural cultures are ubiquitous for studying neural cells, 3D cultures can more accurately replicate the microenvironment of neural tissues. By bioprinting neuronal constructs, one can precisely control the microenvironment by specifically formulating the bioink for neural tissues, and by spatially patterning cell types and scaffold properties in three dimensions. We review a range of bioprinted neural tissue models and discuss how they can be used to observe how neurons behave, understand disease processes, develop new therapies and, ultimately, design replacement tissues. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Neural growth into a microchannel network: towards a regenerative neural interface

    NARCIS (Netherlands)

    Wieringa, P.A.; Wiertz, Remy; le Feber, Jakob; Rutten, Wim

    2009-01-01

    We propose and validated a design for a highly selective 'endcap' regenerative neural interface towards a neuroprosthesis. In vitro studies using rat cortical neurons determine if a branching microchannel structure can counter fasciculated growth and cause neurites to separte from one another,

  19. DNA methyltransferase 3b is dispensable for mouse neural crest development.

    Directory of Open Access Journals (Sweden)

    Bridget T Jacques-Fricke

    Full Text Available The neural crest is a population of multipotent cells that migrates extensively throughout vertebrate embryos to form diverse structures. Mice mutant for the de novo DNA methyltransferase DNMT3b exhibit defects in two neural crest derivatives, the craniofacial skeleton and cardiac ventricular septum, suggesting that DNMT3b activity is necessary for neural crest development. Nevertheless, the requirement for DNMT3b specifically in neural crest cells, as opposed to interacting cell types, has not been determined. Using a conditional DNMT3b allele crossed to the neural crest cre drivers Wnt1-cre and Sox10-cre, neural crest DNMT3b mutants were generated. In both neural crest-specific and fully DNMT3b-mutant embryos, cranial neural crest cells exhibited only subtle migration defects, with increased numbers of dispersed cells trailing organized streams in the head. In spite of this, the resulting cranial ganglia, craniofacial skeleton, and heart developed normally when neural crest cells lacked DNMT3b. This indicates that DNTM3b is not necessary in cranial neural crest cells for their development. We conclude that defects in neural crest derivatives in DNMT3b mutant mice reflect a requirement for DNMT3b in lineages such as the branchial arch mesendoderm or the cardiac mesoderm that interact with neural crest cells during formation of these structures.

  20. Neural Tube Defects and Pregnancy

    Directory of Open Access Journals (Sweden)

    Emine Çoşar

    2009-09-01

    Full Text Available OBJECTIVE: Neural tube defects are congenital malformations those mostly causing life-long morbidities. They are prevented by the periconseptional folic acid usage and prenatal diagnostic methods. MATERIALS-METHODS: Pregnants from Afyonkarahisar and neighbourhood cities applied to our hospital and determined NTD, were investigated. RESULTS: In our obstetrics clinic 1403 delivery were made and 43 of them had fetus with NTD. Among these fetuses 41.3% had meningomyelocel, 17.4% had meningocel, 21.7% had encephalocel, 8.7% had unencephali and 4.3% had iniencephali. CONCLUSION: Incidence of NTD is high in our region and geographic region, nutrition and other socioeconomic factors may be related to the high incidence. Education of the mother and periconceptional folic acid usage may reduce teh incidence of NTD.

  1. Forex Market Prediction Using NARX Neural Network with Bagging

    Directory of Open Access Journals (Sweden)

    Shahbazi Nima

    2016-01-01

    Full Text Available We propose a new methodfor predicting movements in Forex market based on NARX neural network withtime shifting bagging techniqueand financial indicators, such as relative strength index and stochastic indicators. Neural networks have prominent learning ability but they often exhibit bad and unpredictable performance for noisy data. When compared with the static neural networks, our method significantly reducesthe error rate of the responseandimproves the performance of the prediction. We tested three different types ofarchitecture for predicting the response and determined the best network approach. We applied our method to prediction the hourly foreign exchange rates and found remarkable predictability in comprehensive experiments with 2 different foreign exchange rates (GBPUSD and EURUSD.

  2. Analysis of neural data

    CERN Document Server

    Kass, Robert E; Brown, Emery N

    2014-01-01

    Continual improvements in data collection and processing have had a huge impact on brain research, producing data sets that are often large and complicated. By emphasizing a few fundamental principles, and a handful of ubiquitous techniques, Analysis of Neural Data provides a unified treatment of analytical methods that have become essential for contemporary researchers. Throughout the book ideas are illustrated with more than 100 examples drawn from the literature, ranging from electrophysiology, to neuroimaging, to behavior. By demonstrating the commonality among various statistical approaches the authors provide the crucial tools for gaining knowledge from diverse types of data. Aimed at experimentalists with only high-school level mathematics, as well as computationally-oriented neuroscientists who have limited familiarity with statistics, Analysis of Neural Data serves as both a self-contained introduction and a reference work.

  3. Deep Neural Yodelling

    OpenAIRE

    Pfäffli, Daniel (Autor/in)

    2018-01-01

    Yodel music differs from most other genres by exercising the transition from chest voice to falsetto with an audible glottal stop which is recognised even by laymen. Yodel often consists of a yodeller with a choir accompaniment. In Switzerland, it is differentiated between the natural yodel and yodel songs. Today's approaches to music generation with machine learning algorithms are based on neural networks, which are best described by stacked layers of neurons which are connected with neurons...

  4. Neural networks for triggering

    International Nuclear Information System (INIS)

    Denby, B.; Campbell, M.; Bedeschi, F.; Chriss, N.; Bowers, C.; Nesti, F.

    1990-01-01

    Two types of neural network beauty trigger architectures, based on identification of electrons in jets and recognition of secondary vertices, have been simulated in the environment of the Fermilab CDF experiment. The efficiencies for B's and rejection of background obtained are encouraging. If hardware tests are successful, the electron identification architecture will be tested in the 1991 run of CDF. 10 refs., 5 figs., 1 tab

  5. Artificial neural network modelling

    CERN Document Server

    Samarasinghe, Sandhya

    2016-01-01

    This book covers theoretical aspects as well as recent innovative applications of Artificial Neural networks (ANNs) in natural, environmental, biological, social, industrial and automated systems. It presents recent results of ANNs in modelling small, large and complex systems under three categories, namely, 1) Networks, Structure Optimisation, Robustness and Stochasticity 2) Advances in Modelling Biological and Environmental Systems and 3) Advances in Modelling Social and Economic Systems. The book aims at serving undergraduates, postgraduates and researchers in ANN computational modelling. .

  6. Rotation Invariance Neural Network

    OpenAIRE

    Li, Shiyuan

    2017-01-01

    Rotation invariance and translation invariance have great values in image recognition tasks. In this paper, we bring a new architecture in convolutional neural network (CNN) named cyclic convolutional layer to achieve rotation invariance in 2-D symbol recognition. We can also get the position and orientation of the 2-D symbol by the network to achieve detection purpose for multiple non-overlap target. Last but not least, this architecture can achieve one-shot learning in some cases using thos...

  7. Neural Mechanisms of Foraging

    OpenAIRE

    Kolling, Nils; Behrens, Timothy EJ; Mars, Rogier B; Rushworth, Matthew FS

    2012-01-01

    Behavioural economic studies, involving limited numbers of choices, have provided key insights into neural decision-making mechanisms. By contrast, animals’ foraging choices arise in the context of sequences of encounters with prey/food. On each encounter the animal chooses to engage or whether the environment is sufficiently rich that searching elsewhere is merited. The cost of foraging is also critical. We demonstrate humans can alternate between two modes of choice, comparative decision-ma...

  8. Foot Plantar Pressure Estimation Using Artificial Neural Networks

    OpenAIRE

    Xidias , Elias; Koutkalaki , Zoi; Papagiannis , Panagiotis; Papanikos , Paraskevas; Azariadis , Philip

    2015-01-01

    Part 1: Smart Products; International audience; In this paper, we present a novel approach to estimate the maximum pressure over the foot plantar surface exerted by a two-layer shoe sole for three distinct phases of the gait cycle. The proposed method is based on Artificial Neural Networks and can be utilized for the determination of the comfort that is related to the sole construction. Input parameters to the proposed neural network are the material properties and the thicknesses of the sole...

  9. Precision Scaling of Neural Networks for Efficient Audio Processing

    OpenAIRE

    Ko, Jong Hwan; Fromm, Josh; Philipose, Matthai; Tashev, Ivan; Zarar, Shuayb

    2017-01-01

    While deep neural networks have shown powerful performance in many audio applications, their large computation and memory demand has been a challenge for real-time processing. In this paper, we study the impact of scaling the precision of neural networks on the performance of two common audio processing tasks, namely, voice-activity detection and single-channel speech enhancement. We determine the optimal pair of weight/neuron bit precision by exploring its impact on both the performance and ...

  10. IRE1: ER stress sensor and cell fate executor.

    Science.gov (United States)

    Chen, Yani; Brandizzi, Federica

    2013-11-01

    Cells operate a signaling network termed the unfolded protein response (UPR) to monitor protein-folding capacity in the endoplasmic reticulum (ER). Inositol-requiring enzyme 1 (IRE1) is an ER transmembrane sensor that activates the UPR to maintain the ER and cellular function. Although mammalian IRE1 promotes cell survival, it can initiate apoptosis via decay of antiapoptotic miRNAs. Convergent and divergent IRE1 characteristics between plants and animals underscore its significance in cellular homeostasis. This review provides an updated scenario of the IRE1 signaling model, discusses emerging IRE1 sensing mechanisms, compares IRE1 features among species, and outlines exciting future directions in UPR research. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. IL-21: an executor of B cell fate.

    Science.gov (United States)

    Konforte, Danijela; Simard, Nathalie; Paige, Christopher J

    2009-02-15

    IL-21 is a type I cytokine that shares the common receptor gamma-chain with IL-2, IL-4, IL-7, IL-9, and IL-15. B cells are one of the lymphoid cell types whose development and function are regulated by IL-21. Depending on the interplay with costimulatory signals and on the developmental stage of a B cell, IL-21 can induce proliferation, differentiation into Ig-producing plasma cells, or apoptosis in both mice and humans. Alone and in combination with Th cell-derived cytokines IL-21 can regulate class switch recombination to IgG, IgA, or IgE isotypes, indicating its important role in shaping the effector function of B cells. This review highlights the role of IL-21 in B cell development, function, and disease and provides some perspectives on the future studies in this area.

  12. Self-organising sensor web using cell-fate optimisation

    CSIR Research Space (South Africa)

    Van Zyl, TL

    2009-07-01

    Full Text Available The Sensor Web as an open complex adaptive system exhibits many characteristics that are common to self organising systems. One of the characteristics of the Sensor Web is that of self-adaptivity in a changing environment. The changing environment...

  13. Control of Cell Fate in the Circulatory and Ventilatory Systems

    CERN Document Server

    Thiriet, Marc

    2012-01-01

    The volumes in this authoritative series present a multidisciplinary approach to modeling and simulation of flows in the cardiovascular and ventilatory systems, especially multiscale modeling and coupled simulations. The cardiovascular and respiratory systems are tightly coupled, as their primary function is to supply oxygen to and remove carbon dioxide from the body's cells. Because physiological conduits have deformable and reactive walls, macroscopic flow behavior and prediction must be coupled to nano- and microscopic events in a corrector scheme of regulated mechanisms. Therefore, investigation of flows of blood and air in physiological conduits requires an understanding of the biology, chemistry, and physics of these systems together with the mathematical tools to describe their functioning. Volumes 1 and 2 are devoted to cell organization and fate, as well as activities that are autoregulated and/or controlled by the cell environment. Volume 1 examined cellular features that allow adaptation to env...

  14. Discovery of a stem-like multipotent cell fate.

    Science.gov (United States)

    Paffhausen, Emily S; Alowais, Yasir; Chao, Cara W; Callihan, Evan C; Creswell, Karen; Bracht, John R

    2018-01-01

    Adipose derived stem cells (ASCs) can be obtained from lipoaspirates and induced in vitro to differentiate into bone, cartilage, and fat. Using this powerful model system we show that after in vitro adipose differentiation a population of cells retain stem-like qualities including multipotency. They are lipid (-), retain the ability to propagate, express two known stem cell markers, and maintain the capacity for trilineage differentiation into chondrocytes, adipocytes, and osteoblasts. However, these cells are not traditional stem cells because gene expression analysis showed an overall expression profile similar to that of adipocytes. In addition to broadening our understanding of cellular multipotency, our work may be particularly relevant to obesity-associated metabolic disorders. The adipose expandability hypothesis proposes that inability to differentiate new adipocytes is a primary cause of metabolic syndrome in obesity, including diabetes and cardiovascular disease. Here we have defined a differentiation-resistant stem-like multipotent cell population that may be involved in regulation of adipose expandability in vivo and may therefore play key roles in the comorbidities of obesity.

  15. Polylox barcoding reveals haematopoietic stem cell fates realized in vivo.

    Science.gov (United States)

    Pei, Weike; Feyerabend, Thorsten B; Rössler, Jens; Wang, Xi; Postrach, Daniel; Busch, Katrin; Rode, Immanuel; Klapproth, Kay; Dietlein, Nikolaus; Quedenau, Claudia; Chen, Wei; Sauer, Sascha; Wolf, Stephan; Höfer, Thomas; Rodewald, Hans-Reimer

    2017-08-24

    Developmental deconvolution of complex organs and tissues at the level of individual cells remains challenging. Non-invasive genetic fate mapping has been widely used, but the low number of distinct fluorescent marker proteins limits its resolution. Much higher numbers of cell markers have been generated using viral integration sites, viral barcodes, and strategies based on transposons and CRISPR-Cas9 genome editing; however, temporal and tissue-specific induction of barcodes in situ has not been achieved. Here we report the development of an artificial DNA recombination locus (termed Polylox) that enables broadly applicable endogenous barcoding based on the Cre-loxP recombination system. Polylox recombination in situ reaches a practical diversity of several hundred thousand barcodes, allowing tagging of single cells. We have used this experimental system, combined with fate mapping, to assess haematopoietic stem cell (HSC) fates in vivo. Classical models of haematopoietic lineage specification assume a tree with few major branches. More recently, driven in part by the development of more efficient single-cell assays and improved transplantation efficiencies, different models have been proposed, in which unilineage priming may occur in mice and humans at the level of HSCs. We have introduced barcodes into HSC progenitors in embryonic mice, and found that the adult HSC compartment is a mosaic of embryo-derived HSC clones, some of which are unexpectedly large. Most HSC clones gave rise to multilineage or oligolineage fates, arguing against unilineage priming, and suggesting coherent usage of the potential of cells in a clone. The spreading of barcodes, both after induction in embryos and in adult mice, revealed a basic split between common myeloid-erythroid development and common lymphocyte development, supporting the long-held but contested view of a tree-like haematopoietic structure.

  16. Biomaterial property-controlled stem cell fates for cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Yanyi Xu

    2016-09-01

    Full Text Available Myocardial infarction (MI affects more than 8 million people in the United States alone. Due to the insufficient regeneration capacity of the native myocardium, one widely studied approach is cardiac tissue engineering, in which cells are delivered with or without biomaterials and/or regulatory factors to fully regenerate the cardiac functions. Specifically, in vitro cardiac tissue engineering focuses on using biomaterials as a reservoir for cells to attach, as well as a carrier of various regulatory factors such as growth factors and peptides, providing high cell retention and a proper microenvironment for cells to migrate, grow and differentiate within the scaffolds before implantation. Many studies have shown that the full establishment of a functional cardiac tissue in vitro requires synergistic actions between the seeded cells, the tissue culture condition, and the biochemical and biophysical environment provided by the biomaterials-based scaffolds. Proper electrical stimulation and mechanical stretch during the in vitro culture can induce the ordered orientation and differentiation of the seeded cells. On the other hand, the various scaffolds biochemical and biophysical properties such as polymer composition, ligand concentration, biodegradability, scaffold topography and mechanical properties can also have a significant effect on the cellular processes.

  17. Harnessing cell-material interaction to control cell fate: design ...

    Indian Academy of Sciences (India)

    Rajat K Das

    2017-10-26

    Oct 26, 2017 ... cytoplasmic domain is believed to be the crucial step for the activation of integrins and .... These gels can be degraded both via hydrolysis as well as enzymolysis. Thus, the ... tions.25,26 In one of the early examples of synthetic, proteolytically ... poly(ethylene glycol) (PEG) based gels with MMP degradable ...

  18. Cdc20 control of cell fate during prolonged mitotic arrest

    DEFF Research Database (Denmark)

    Nilsson, Jakob

    2011-01-01

    The fate of cells arrested in mitosis by antimitotic compounds is complex but is influenced by competition between pathways promoting cell death and pathways promoting mitotic exit. As components of both of these pathways are regulated by Cdc20-dependent degradation, I hypothesize that variations...

  19. Polylox barcoding reveals haematopoietic stem cell fates realized in vivo

    Science.gov (United States)

    Rössler, Jens; Wang, Xi; Postrach, Daniel; Busch, Katrin; Rode, Immanuel; Klapproth, Kay; Dietlein, Nikolaus; Quedenau, Claudia; Chen, Wei; Sauer, Sascha; Wolf, Stephan; Höfer, Thomas; Rodewald, Hans-Reimer

    2017-01-01

    Developmental deconvolution of complex organs and tissues at the level of individual cells remains challenging. Non-invasive genetic fate mapping1 has been widely used, but the low number of distinct fluorescent marker proteins limits its resolution. Much higher numbers of cell markers have been generated using viral integration sites2, viral barcodes3, and strategies based on transposons4 and CRISPR/Cas9 genome editing5; however, temporal and tissue-specific induction of barcodes in situ has not been achieved. Here we report the development of an artificial DNA recombination locus (termed Polylox) that enables broadly applicable endogenous barcoding based on the Cre-loxP recombination system6,7. Polylox recombination in situ reaches a practical diversity of several hundred thousand barcodes, allowing tagging of single cells. We have used this experimental system, combined with fate mapping, to assess haematopoietic stem cell (HSC) fates in vivo. Classical models of haematopoietic lineage specification assume a tree with few major branches. More recently, driven in part by the development of more efficient single-cell assays and improved transplantation efficiencies, different models have been proposed, in which unilineage priming may occur in mice and humans at the level of HSCs8–10. We have introduced barcodes into HSC progenitors in embryonic mice, and found that the adult HSC compartment is a mosaic of embryo-derived HSC clones, some of which are unexpectedly large. Most HSC clones gave rise to multilineage or oligolineage fates, arguing against unilineage priming, and suggesting coherent usage of the potential of cells in a clone. The spreading of barcodes, both after induction in embryos and in adult mice, revealed a basic split between common myeloid-erythroid development and common lymphocyte development, supporting the long-held but contested view of a tree-like haematopoietic structure. PMID:28813413

  20. Intracellular Events and Cell Fate in Filovirus Infection

    Directory of Open Access Journals (Sweden)

    Elena Ryabchikova

    2011-08-01

    Full Text Available Marburg and Ebola viruses cause a severe hemorrhagic disease in humans with high fatality rates. Early target cells of filoviruses are monocytes, macrophages, and dendritic cells. The infection spreads to the liver, spleen and later other organs by blood and lymph flow. A hallmark of filovirus infection is the depletion of non-infected lymphocytes; however, the molecular mechanisms leading to the observed bystander lymphocyte apoptosis are poorly understood. Also, there is limited knowledge about the fate of infected cells in filovirus disease. In this review we will explore what is known about the intracellular events leading to virus amplification and cell damage in filovirus infection. Furthermore, we will discuss how cellular dysfunction and cell death may correlate with disease pathogenesis.

  1. Stochastic Cell Fate Progression in Embryonic Stem Cells

    Science.gov (United States)

    Zou, Ling-Nan; Doyle, Adele; Jang, Sumin; Ramanathan, Sharad

    2013-03-01

    Studies on the directed differentiation of embryonic stem (ES) cells suggest that some early developmental decisions may be stochastic in nature. To identify the sources of this stochasticity, we analyzed the heterogeneous expression of key transcription factors in single ES cells as they adopt distinct germ layer fates. We find that under sufficiently stringent signaling conditions, the choice of lineage is unambiguous. ES cells flow into differentiated fates via diverging paths, defined by sequences of transitional states that exhibit characteristic co-expression of multiple transcription factors. These transitional states have distinct responses to morphogenic stimuli; by sequential exposure to multiple signaling conditions, ES cells are steered towards specific fates. However, the rate at which cells travel down a developmental path is stochastic: cells exposed to the same signaling condition for the same amount of time can populate different states along the same path. The heterogeneity of cell states seen in our experiments therefore does not reflect the stochastic selection of germ layer fates, but the stochastic rate of progression along a chosen developmental path. Supported in part by the Jane Coffin Childs Fund

  2. Soluble Factors on Stage to Direct Mesenchymal Stem Cells Fate

    Directory of Open Access Journals (Sweden)

    Cristina Sobacchi

    2017-05-01

    Full Text Available Mesenchymal stem cells (MSCs are multipotent stromal cells that are identified by in vitro plastic adherence, colony-forming capacity, expression of a panel of surface molecules, and ability to differentiate at least toward osteogenic, adipogenic, and chondrogenic lineages. They also produce trophic factors with immunomodulatory, proangiogenic, and antiapoptotic functions influencing the behavior of neighboring cells. On the other hand, a reciprocal regulation takes place; in fact, MSCs can be isolated from several tissues, and depending on the original microenvironment and the range of stimuli received from there, they can display differences in their essential characteristics. Here, we focus mainly on the bone tissue and how soluble factors, such as growth factors, cytokines, and hormones, present in this microenvironment can orchestrate bone marrow-derived MSCs fate. We also briefly describe the alteration of MSCs behavior in pathological settings such as hematological cancer, bone metastasis, and bone marrow failure syndromes. Overall, the possibility to modulate MSCs plasticity makes them an attractive tool for diverse applications of tissue regeneration in cell therapy. Therefore, the comprehensive understanding of the microenvironment characteristics and components better suited to obtain a specific MSCs response can be extremely useful for clinical use.

  3. Functionalized scaffolds to control dental pulp stem cell fate

    Science.gov (United States)

    Piva, Evandro; Silva, Adriana F.; Nör, Jacques E.

    2014-01-01

    Emerging understanding about interactions between stem cells, scaffolds and morphogenic factors has accelerated translational research in the field of dental pulp tissue engineering. Dental pulp stem cells constitute a sub-population of cells endowed with self-renewal and multipotency. Dental pulp stem cells seeded in biodegradable scaffolds and exposed to dentin-derived morphogenic signals give rise to a pulp-like tissue capable of generating new dentin. Notably, dentin-derived proteins are sufficient to induce dental pulp stem cell differentiation into odontoblasts. Ongoing work is focused on developing ways of mobilizing dentin-derived proteins and disinfecting the root canal of necrotic teeth without compromising the morphogenic potential of these signaling molecules. On the other hand, dentin by itself does not appear to be capable of inducing endothelial differentiation of dental pulp stem cells, despite the well known presence of angiogenic factors in dentin. This is particularly relevant in the context of dental pulp tissue engineering in full root canals, where access to blood supply is limited to the apical foramina. To address this challenge, scientists are looking at ways to use the scaffold as a controlled release device for angiogenic factors. The aim of this manuscript is to present and discuss current strategies to functionalize injectable scaffolds and customize them for dental pulp tissue engineering. The long-term goal of this work is to develop stem cell-based therapies that enable the engineering of functional dental pulps capable of generating new tubular dentin in humans. PMID:24698691

  4. Polarized DIS Structure Functions from Neural Networks

    International Nuclear Information System (INIS)

    Del Debbio, L.; Guffanti, A.; Piccione, A.

    2007-01-01

    We present a parametrization of polarized Deep-Inelastic-Scattering (DIS) structure functions based on Neural Networks. The parametrization provides a bias-free determination of the probability measure in the space of structure functions, which retains information on experimental errors and correlations. As an example we discuss the application of this method to the study of the structure function g 1 p (x,Q 2 )

  5. Neural Based Orthogonal Data Fitting The EXIN Neural Networks

    CERN Document Server

    Cirrincione, Giansalvo

    2008-01-01

    Written by three leaders in the field of neural based algorithms, Neural Based Orthogonal Data Fitting proposes several neural networks, all endowed with a complete theory which not only explains their behavior, but also compares them with the existing neural and traditional algorithms. The algorithms are studied from different points of view, including: as a differential geometry problem, as a dynamic problem, as a stochastic problem, and as a numerical problem. All algorithms have also been analyzed on real time problems (large dimensional data matrices) and have shown accurate solutions. Wh

  6. Sejarah, Penerapan, dan Analisis Resiko dari Neural Network: Sebuah Tinjauan Pustaka

    Directory of Open Access Journals (Sweden)

    Cristina Cristina

    2018-05-01

    Full Text Available A neural network is a form of artificial intelligence that has the ability to learn, grow, and adapt in a dynamic environment. Neural network began since 1890 because a great American psychologist named William James created the book "Principles of Psycology". James was the first one publish a number of facts related to the structure and function of the brain. The history of neural network development is divided into 4 epochs, the Camelot era, the Depression, the Renaissance, and the Neoconnectiosm era. Neural networks used today are not 100 percent accurate. However, neural networks are still used because of better performance than alternative computing models. The use of neural network consists of pattern recognition, signal analysis, robotics, and expert systems. For risk analysis of the neural network, it is first performed using hazards and operability studies (HAZOPS. Determining the neural network requirements in a good way will help in determining its contribution to system hazards and validating the control or mitigation of any hazards. After completion of the first stage at HAZOPS and the second stage determines the requirements, the next stage is designing. Neural network underwent repeated design-train-test development. At the design stage, the hazard analysis should consider the design aspects of the development, which include neural network architecture, size, intended use, and so on. It will be continued at the implementation stage, test phase, installation and inspection phase, operation phase, and ends at the maintenance stage.

  7. What the success of brain imaging implies about the neural code.

    Science.gov (United States)

    Guest, Olivia; Love, Bradley C

    2017-01-19

    The success of fMRI places constraints on the nature of the neural code. The fact that researchers can infer similarities between neural representations, despite fMRI's limitations, implies that certain neural coding schemes are more likely than others. For fMRI to succeed given its low temporal and spatial resolution, the neural code must be smooth at the voxel and functional level such that similar stimuli engender similar internal representations. Through proof and simulation, we determine which coding schemes are plausible given both fMRI's successes and its limitations in measuring neural activity. Deep neural network approaches, which have been forwarded as computational accounts of the ventral stream, are consistent with the success of fMRI, though functional smoothness breaks down in the later network layers. These results have implications for the nature of the neural code and ventral stream, as well as what can be successfully investigated with fMRI.

  8. Identification-based chaos control via backstepping design using self-organizing fuzzy neural networks

    International Nuclear Information System (INIS)

    Peng Yafu; Hsu, C.-F.

    2009-01-01

    This paper proposes an identification-based adaptive backstepping control (IABC) for the chaotic systems. The IABC system is comprised of a neural backstepping controller and a robust compensation controller. The neural backstepping controller containing a self-organizing fuzzy neural network (SOFNN) identifier is the principal controller, and the robust compensation controller is designed to dispel the effect of minimum approximation error introduced by the SOFNN identifier. The SOFNN identifier is used to online estimate the chaotic dynamic function with structure and parameter learning phases of fuzzy neural network. The structure learning phase consists of the growing and pruning of fuzzy rules; thus the SOFNN identifier can avoid the time-consuming trial-and-error tuning procedure for determining the neural structure of fuzzy neural network. The parameter learning phase adjusts the interconnection weights of neural network to achieve favorable approximation performance. Finally, simulation results verify that the proposed IABC can achieve favorable tracking performance.

  9. Two-way regulation between cells and aligned collagen fibrils: local 3D matrix formation and accelerated neural differentiation of human decidua parietalis placental stem cells.

    Science.gov (United States)

    Li, Wen; Zhu, Bofan; Strakova, Zuzana; Wang, Rong

    2014-08-08

    It has been well established that an aligned matrix provides structural and signaling cues to guide cell polarization and cell fate decision. However, the modulation role of cells in matrix remodeling and the feedforward effect on stem cell differentiation have not been studied extensively. In this study, we report on the concerted changes of human decidua parietalis placental stem cells (hdpPSCs) and the highly ordered collagen fibril matrix in response to cell-matrix interaction. With high-resolution imaging, we found the hdpPSCs interacted with the matrix by deforming the cell shape, harvesting the nearby collagen fibrils, and reorganizing the fibrils around the cell body to transform a 2D matrix to a localized 3D matrix. Such a unique 3D matrix prompted high expression of β-1 integrin around the cell body that mediates and facilitates the stem cell differentiation toward neural cells. The study offers insights into the coordinated, dynamic changes at the cell-matrix interface and elucidates cell modulation of its matrix to establish structural and biochemical cues for effective cell growth and differentiation. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Robo signaling regulates the production of cranial neural crest cells.

    Science.gov (United States)

    Li, Yan; Zhang, Xiao-Tan; Wang, Xiao-Yu; Wang, Guang; Chuai, Manli; Münsterberg, Andrea; Yang, Xuesong

    2017-12-01

    Slit/Robo signaling plays an important role in the guidance of developing neurons in developing embryos. However, it remains obscure whether and how Slit/Robo signaling is involved in the production of cranial neural crest cells. In this study, we examined Robo1 deficient mice to reveal developmental defects of mouse cranial frontal and parietal bones, which are derivatives of cranial neural crest cells. Therefore, we determined the production of HNK1 + cranial neural crest cells in early chick embryo development after knock-down (KD) of Robo1 expression. Detection of markers for pre-migratory and migratory neural crest cells, PAX7 and AP-2α, showed that production of both was affected by Robo1 KD. In addition, we found that the transcription factor slug is responsible for the aberrant delamination/EMT of cranial neural crest cells induced by Robo1 KD, which also led to elevated expression of E- and N-Cadherin. N-Cadherin expression was enhanced when blocking FGF signaling with dominant-negative FGFR1 in half of the neural tube. Taken together, we show that Slit/Robo signaling influences the delamination/EMT of cranial neural crest cells, which is required for cranial bone development. Copyright © 2017. Published by Elsevier Inc.

  11. Trimaran Resistance Artificial Neural Network

    Science.gov (United States)

    2011-01-01

    11th International Conference on Fast Sea Transportation FAST 2011, Honolulu, Hawaii, USA, September 2011 Trimaran Resistance Artificial Neural Network Richard...Trimaran Resistance Artificial Neural Network 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e... Artificial Neural Network and is restricted to the center and side-hull configurations tested. The value in the parametric model is that it is able to

  12. Effects of Substrate and Co-Culture on Neural Progenitor Cell Differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Erin Boote [Iowa State Univ., Ames, IA (United States)

    2008-01-01

    In recent years the study of stem and progenitor cells has moved to the forefront of research. Since the isolation of human hematopoietic stem cells in 1988 and the subsequent discovery of a self renewing population of multipotent cells in many tissues, many researchers have envisioned a better understanding of development and potential clinical usage in intractable diseases. Both these goals, however, depend on a solid understanding of the intracellular and extracellular forces that cause stem cells to differentiate to a specific cell fate. Many diseases of large scale cell loss have been suggested as candidates for stem cell based treatments. It is proposed that replacing the function of the damaged or defective cells by specific differentiation of stem or progenitor cells could treat the disease. Before cells can be directed to specific lineages, the mechanisms of differentiation must be better understood. Differentiation in vivo is an intensively complex system that is difficult to study. The goal of this research is to develop further understanding of the effects of soluble and extracellular matrix (ECM) cues on the differentiation of neural progenitor cells with the use of a simplified in vitro culture system. Specific research objectives are to study the differentiation of neural progenitor cells in response to astrocyte conditioned medium and protein substrate composition and concentration. In an effort to reveal the mechanism of the conditioned medium interaction, a test for the presence of a feedback loop between progenitor cells and astrocytes is presented along with an examination of conditioned medium storage temperature, which can reveal enzymatic dependencies. An examination of protein substrate composition and concentration will help to reveal the role of any ECM interactions on differentiation. This thesis is organized into a literature review covering recent advances in use of external modulators of differentiation such as surface coatings, co

  13. Optics in neural computation

    Science.gov (United States)

    Levene, Michael John

    In all attempts to emulate the considerable powers of the brain, one is struck by both its immense size, parallelism, and complexity. While the fields of neural networks, artificial intelligence, and neuromorphic engineering have all attempted oversimplifications on the considerable complexity, all three can benefit from the inherent scalability and parallelism of optics. This thesis looks at specific aspects of three modes in which optics, and particularly volume holography, can play a part in neural computation. First, holography serves as the basis of highly-parallel correlators, which are the foundation of optical neural networks. The huge input capability of optical neural networks make them most useful for image processing and image recognition and tracking. These tasks benefit from the shift invariance of optical correlators. In this thesis, I analyze the capacity of correlators, and then present several techniques for controlling the amount of shift invariance. Of particular interest is the Fresnel correlator, in which the hologram is displaced from the Fourier plane. In this case, the amount of shift invariance is limited not just by the thickness of the hologram, but by the distance of the hologram from the Fourier plane. Second, volume holography can provide the huge storage capacity and high speed, parallel read-out necessary to support large artificial intelligence systems. However, previous methods for storing data in volume holograms have relied on awkward beam-steering or on as-yet non- existent cheap, wide-bandwidth, tunable laser sources. This thesis presents a new technique, shift multiplexing, which is capable of very high densities, but which has the advantage of a very simple implementation. In shift multiplexing, the reference wave consists of a focused spot a few millimeters in front of the hologram. Multiplexing is achieved by simply translating the hologram a few tens of microns or less. This thesis describes the theory for how shift

  14. Neural network-based nonlinear model predictive control vs. linear quadratic gaussian control

    Science.gov (United States)

    Cho, C.; Vance, R.; Mardi, N.; Qian, Z.; Prisbrey, K.

    1997-01-01

    One problem with the application of neural networks to the multivariable control of mineral and extractive processes is determining whether and how to use them. The objective of this investigation was to compare neural network control to more conventional strategies and to determine if there are any advantages in using neural network control in terms of set-point tracking, rise time, settling time, disturbance rejection and other criteria. The procedure involved developing neural network controllers using both historical plant data and simulation models. Various control patterns were tried, including both inverse and direct neural network plant models. These were compared to state space controllers that are, by nature, linear. For grinding and leaching circuits, a nonlinear neural network-based model predictive control strategy was superior to a state space-based linear quadratic gaussian controller. The investigation pointed out the importance of incorporating state space into neural networks by making them recurrent, i.e., feeding certain output state variables into input nodes in the neural network. It was concluded that neural network controllers can have better disturbance rejection, set-point tracking, rise time, settling time and lower set-point overshoot, and it was also concluded that neural network controllers can be more reliable and easy to implement in complex, multivariable plants.

  15. Pacemaker Therapy in Patients With Neurally Mediated Syncope and Documented Asystole Third International Study on Syncope of Uncertain Etiology (ISSUE-3) A Randomized Trial

    NARCIS (Netherlands)

    Brignole, Michele; Menozzi, Carlo; Moya, Angel; Andresen, Dietrich; Blanc, Jean Jacques; Krahn, Andrew D.; Wieling, Wouter; Beiras, Xulio; Deharo, Jean Claude; Russo, Vitantonio; Tomaino, Marco; Sutton, Richard; Tomaino, M.; Pescoller, F.; Donateo, P.; Oddone, D.; Russo, V.; Pierri, F.; Matino, M. G.; Vitale, E.; Massa, R.; Piccinni, G.; Melissano, D.; Menozzi, C.; Lolli, G.; Gulizia, M.; Francese, M.; Iorfida, M.; Golzio, P.; Gaggioli, G.; Laffi, M.; Rabjoli, F.; Cecchinato, C.; Ungar, A.; Rafanelli, M.; Chisciotti, V.; Morrione, A.; del Rosso, A.; Guernaccia, V.; Palella, M.; D'Agostino, C.; Campana, A.; Brigante, M.; Miracapillo, G.; Addonisio, L.; Proclemer, A.; Facchin, D.; Vado, A.; Knops, R. E.; Dekker, L. R. C.

    2012-01-01

    Background-The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with neurally mediated syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic neurally mediated syncope. Methods and

  16. Project of neural network for steel grade selection with the assumed CCT diagram

    OpenAIRE

    S. Malara; L.A. Dobrzański; J. Trzaska

    2008-01-01

    Purpose: The aim of this paper was developing a project of neural network for selection of steel grade with the specified CCT diagram – structure and of harness after heat treatment.Design/methodology/approach: The goal has been achieved in the following stages: at the first stage characteristic points of CCT diagram have been determined. At the second stage neural network has been developed and optimized.Findings: The neural network was developed in this paper, that allowed selection of stee...

  17. Analysis of neural networks

    CERN Document Server

    Heiden, Uwe

    1980-01-01

    The purpose of this work is a unified and general treatment of activity in neural networks from a mathematical pOint of view. Possible applications of the theory presented are indica­ ted throughout the text. However, they are not explored in de­ tail for two reasons : first, the universal character of n- ral activity in nearly all animals requires some type of a general approach~ secondly, the mathematical perspicuity would suffer if too many experimental details and empirical peculiarities were interspersed among the mathematical investigation. A guide to many applications is supplied by the references concerning a variety of specific issues. Of course the theory does not aim at covering all individual problems. Moreover there are other approaches to neural network theory (see e.g. Poggio-Torre, 1978) based on the different lev­ els at which the nervous system may be viewed. The theory is a deterministic one reflecting the average be­ havior of neurons or neuron pools. In this respect the essay is writt...

  18. Neural Networks for Optimal Control

    DEFF Research Database (Denmark)

    Sørensen, O.

    1995-01-01

    Two neural networks are trained to act as an observer and a controller, respectively, to control a non-linear, multi-variable process.......Two neural networks are trained to act as an observer and a controller, respectively, to control a non-linear, multi-variable process....

  19. Neural networks at the Tevatron

    International Nuclear Information System (INIS)

    Badgett, W.; Burkett, K.; Campbell, M.K.; Wu, D.Y.; Bianchin, S.; DeNardi, M.; Pauletta, G.; Santi, L.; Caner, A.; Denby, B.; Haggerty, H.; Lindsey, C.S.; Wainer, N.; Dall'Agata, M.; Johns, K.; Dickson, M.; Stanco, L.; Wyss, J.L.

    1992-10-01

    This paper summarizes neural network applications at the Fermilab Tevatron, including the first online hardware application in high energy physics (muon tracking): the CDF and DO neural network triggers; offline quark/gluon discrimination at CDF; ND a new tool for top to multijets recognition at CDF

  20. Neural Networks for the Beginner.

    Science.gov (United States)

    Snyder, Robin M.

    Motivated by the brain, neural networks are a right-brained approach to artificial intelligence that is used to recognize patterns based on previous training. In practice, one would not program an expert system to recognize a pattern and one would not train a neural network to make decisions from rules; but one could combine the best features of…

  1. Neural fields theory and applications

    CERN Document Server

    Graben, Peter; Potthast, Roland; Wright, James

    2014-01-01

    With this book, the editors present the first comprehensive collection in neural field studies, authored by leading scientists in the field - among them are two of the founding-fathers of neural field theory. Up to now, research results in the field have been disseminated across a number of distinct journals from mathematics, computational neuroscience, biophysics, cognitive science and others. Starting with a tutorial for novices in neural field studies, the book comprises chapters on emergent patterns, their phase transitions and evolution, on stochastic approaches, cortical development, cognition, robotics and computation, large-scale numerical simulations, the coupling of neural fields to the electroencephalogram and phase transitions in anesthesia. The intended readership are students and scientists in applied mathematics, theoretical physics, theoretical biology, and computational neuroscience. Neural field theory and its applications have a long-standing tradition in the mathematical and computational ...

  2. Artificial neural networks in NDT

    International Nuclear Information System (INIS)

    Abdul Aziz Mohamed

    2001-01-01

    Artificial neural networks, simply known as neural networks, have attracted considerable interest in recent years largely because of a growing recognition of the potential of these computational paradigms as powerful alternative models to conventional pattern recognition or function approximation techniques. The neural networks approach is having a profound effect on almost all fields, and has been utilised in fields Where experimental inter-disciplinary work is being carried out. Being a multidisciplinary subject with a broad knowledge base, Nondestructive Testing (NDT) or Nondestructive Evaluation (NDE) is no exception. This paper explains typical applications of neural networks in NDT/NDE. Three promising types of neural networks are highlighted, namely, back-propagation, binary Hopfield and Kohonen's self-organising maps. (Author)

  3. Rationale and Methodology of Reprogramming for Generation of Induced Pluripotent Stem Cells and Induced Neural Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Zuojun Tian

    2016-04-01

    Full Text Available Great progress has been made regarding the capabilities to modify somatic cell fate ever since the technology for generation of induced pluripotent stem cells (iPSCs was discovered in 2006. Later, induced neural progenitor cells (iNPCs were generated from mouse and human cells, bypassing some of the concerns and risks of using iPSCs in neuroscience applications. To overcome the limitation of viral vector induced reprogramming, bioactive small molecules (SM have been explored to enhance the efficiency of reprogramming or even replace transcription factors (TFs, making the reprogrammed cells more amenable to clinical application. The chemical induced reprogramming process is a simple process from a technical perspective, but the choice of SM at each step is vital during the procedure. The mechanisms underlying cell transdifferentiation are still poorly understood, although, several experimental data and insights have indicated the rationale of cell reprogramming. The process begins with the forced expression of specific TFs or activation/inhibition of cell signaling pathways by bioactive chemicals in defined culture condition, which initiates the further reactivation of endogenous gene program and an optimal stoichiometric expression of the endogenous pluri- or multi-potency genes, and finally leads to the birth of reprogrammed cells such as iPSCs and iNPCs. In this review, we first outline the rationale and discuss the methodology of iPSCs and iNPCs in a stepwise manner; and then we also discuss the chemical-based reprogramming of iPSCs and iNPCs.

  4. Interacting neural networks

    Science.gov (United States)

    Metzler, R.; Kinzel, W.; Kanter, I.

    2000-08-01

    Several scenarios of interacting neural networks which are trained either in an identical or in a competitive way are solved analytically. In the case of identical training each perceptron receives the output of its neighbor. The symmetry of the stationary state as well as the sensitivity to the used training algorithm are investigated. Two competitive perceptrons trained on mutually exclusive learning aims and a perceptron which is trained on the opposite of its own output are examined analytically. An ensemble of competitive perceptrons is used as decision-making algorithms in a model of a closed market (El Farol Bar problem or the Minority Game. In this game, a set of agents who have to make a binary decision is considered.); each network is trained on the history of minority decisions. This ensemble of perceptrons relaxes to a stationary state whose performance can be better than random.

  5. Neural circuitry and immunity

    Science.gov (United States)

    Pavlov, Valentin A.; Tracey, Kevin J.

    2015-01-01

    Research during the last decade has significantly advanced our understanding of the molecular mechanisms at the interface between the nervous system and the immune system. Insight into bidirectional neuroimmune communication has characterized the nervous system as an important partner of the immune system in the regulation of inflammation. Neuronal pathways, including the vagus nerve-based inflammatory reflex are physiological regulators of immune function and inflammation. In parallel, neuronal function is altered in conditions characterized by immune dysregulation and inflammation. Here, we review these regulatory mechanisms and describe the neural circuitry modulating immunity. Understanding these mechanisms reveals possibilities to use targeted neuromodulation as a therapeutic approach for inflammatory and autoimmune disorders. These findings and current clinical exploration of neuromodulation in the treatment of inflammatory diseases defines the emerging field of Bioelectronic Medicine. PMID:26512000

  6. Neural Darwinism and consciousness.

    Science.gov (United States)

    Seth, Anil K; Baars, Bernard J

    2005-03-01

    Neural Darwinism (ND) is a large scale selectionist theory of brain development and function that has been hypothesized to relate to consciousness. According to ND, consciousness is entailed by reentrant interactions among neuronal populations in the thalamocortical system (the 'dynamic core'). These interactions, which permit high-order discriminations among possible core states, confer selective advantages on organisms possessing them by linking current perceptual events to a past history of value-dependent learning. Here, we assess the consistency of ND with 16 widely recognized properties of consciousness, both physiological (for example, consciousness is associated with widespread, relatively fast, low amplitude interactions in the thalamocortical system), and phenomenal (for example, consciousness involves the existence of a private flow of events available only to the experiencing subject). While no theory accounts fully for all of these properties at present, we find that ND and its recent extensions fare well.

  7. Neural network-based model reference adaptive control system.

    Science.gov (United States)

    Patino, H D; Liu, D

    2000-01-01

    In this paper, an approach to model reference adaptive control based on neural networks is proposed and analyzed for a class of first-order continuous-time nonlinear dynamical systems. The controller structure can employ either a radial basis function network or a feedforward neural network to compensate adaptively the nonlinearities in the plant. A stable controller-parameter adjustment mechanism, which is determined using the Lyapunov theory, is constructed using a sigma-modification-type updating law. The evaluation of control error in terms of the neural network learning error is performed. That is, the control error converges asymptotically to a neighborhood of zero, whose size is evaluated and depends on the approximation error of the neural network. In the design and analysis of neural network-based control systems, it is important to take into account the neural network learning error and its influence on the control error of the plant. Simulation results showing the feasibility and performance of the proposed approach are given.

  8. Neural Network Machine Learning and Dimension Reduction for Data Visualization

    Science.gov (United States)

    Liles, Charles A.

    2014-01-01

    Neural network machine learning in computer science is a continuously developing field of study. Although neural network models have been developed which can accurately predict a numeric value or nominal classification, a general purpose method for constructing neural network architecture has yet to be developed. Computer scientists are often forced to rely on a trial-and-error process of developing and improving accurate neural network models. In many cases, models are constructed from a large number of input parameters. Understanding which input parameters have the greatest impact on the prediction of the model is often difficult to surmise, especially when the number of input variables is very high. This challenge is often labeled the "curse of dimensionality" in scientific fields. However, techniques exist for reducing the dimensionality of problems to just two dimensions. Once a problem's dimensions have been mapped to two dimensions, it can be easily plotted and understood by humans. The ability to visualize a multi-dimensional dataset can provide a means of identifying which input variables have the highest effect on determining a nominal or numeric output. Identifying these variables can provide a better means of training neural network models; models can be more easily and quickly trained using only input variables which appear to affect the outcome variable. The purpose of this project is to explore varying means of training neural networks and to utilize dimensional reduction for visualizing and understanding complex datasets.

  9. Identifying Broadband Rotational Spectra with Neural Networks

    Science.gov (United States)

    Zaleski, Daniel P.; Prozument, Kirill

    2017-06-01

    A typical broadband rotational spectrum may contain several thousand observable transitions, spanning many species. Identifying the individual spectra, particularly when the dynamic range reaches 1,000:1 or even 10,000:1, can be challenging. One approach is to apply automated fitting routines. In this approach, combinations of 3 transitions can be created to form a "triple", which allows fitting of the A, B, and C rotational constants in a Watson-type Hamiltonian. On a standard desktop computer, with a target molecule of interest, a typical AUTOFIT routine takes 2-12 hours depending on the spectral density. A new approach is to utilize machine learning to train a computer to recognize the patterns (frequency spacing and relative intensities) inherit in rotational spectra and to identify the individual spectra in a raw broadband rotational spectrum. Here, recurrent neural networks have been trained to identify different types of rotational spectra and classify them accordingly. Furthermore, early results in applying convolutional neural networks for spectral object recognition in broadband rotational spectra appear promising. Perez et al. "Broadband Fourier transform rotational spectroscopy for structure determination: The water heptamer." Chem. Phys. Lett., 2013, 571, 1-15. Seifert et al. "AUTOFIT, an Automated Fitting Tool for Broadband Rotational Spectra, and Applications to 1-Hexanal." J. Mol. Spectrosc., 2015, 312, 13-21. Bishop. "Neural networks for pattern recognition." Oxford university press, 1995.

  10. Program Helps Simulate Neural Networks

    Science.gov (United States)

    Villarreal, James; Mcintire, Gary

    1993-01-01

    Neural Network Environment on Transputer System (NNETS) computer program provides users high degree of flexibility in creating and manipulating wide variety of neural-network topologies at processing speeds not found in conventional computing environments. Supports back-propagation and back-propagation-related algorithms. Back-propagation algorithm used is implementation of Rumelhart's generalized delta rule. NNETS developed on INMOS Transputer(R). Predefines back-propagation network, Jordan network, and reinforcement network to assist users in learning and defining own networks. Also enables users to configure other neural-network paradigms from NNETS basic architecture. Small portion of software written in OCCAM(R) language.

  11. Artificial Neural Network Analysis System

    Science.gov (United States)

    2001-02-27

    Contract No. DASG60-00-M-0201 Purchase request no.: Foot in the Door-01 Title Name: Artificial Neural Network Analysis System Company: Atlantic... Artificial Neural Network Analysis System 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Powell, Bruce C 5d. PROJECT NUMBER 5e. TASK NUMBER...34) 27-02-2001 Report Type N/A Dates Covered (from... to) ("DD MON YYYY") 28-10-2000 27-02-2001 Title and Subtitle Artificial Neural Network Analysis

  12. Cooperating attackers in neural cryptography.

    Science.gov (United States)

    Shacham, Lanir N; Klein, Einat; Mislovaty, Rachel; Kanter, Ido; Kinzel, Wolfgang

    2004-06-01

    A successful attack strategy in neural cryptography is presented. The neural cryptosystem, based on synchronization of neural networks by mutual learning, has been recently shown to be secure under different attack strategies. The success of the advanced attacker presented here, called the "majority-flipping attacker," does not decay with the parameters of the model. This attacker's outstanding success is due to its using a group of attackers which cooperate throughout the synchronization process, unlike any other attack strategy known. An analytical description of this attack is also presented, and fits the results of simulations.

  13. Histological evaluation of acute covering of an experimental neural tube defect with biomatrices in fetal sheep.

    NARCIS (Netherlands)

    Eggink, A.J.; Roelofs, L.A.J.; Lammens, M.M.Y.; Feitz, W.F.J.; Wijnen, R.M.H.; Mullaart, R.A.; Moerkerk, H.T.B. van; Kuppevelt, A.H.M.S.M. van; Crevels, A.J.; Hanssen, A.; Lotgering, F.K.; Berg, P.P. van den

    2006-01-01

    OBJECTIVE: The aim of the study was to determine the histological effect on the neural tissue of in utero covering of an experimental neural tube defect in fetal lambs, with the use of two different biomatrices. MATERIALS AND METHODS: In 23 fetal sheep, surgery was performed at 79 days' gestation.

  14. Creative-Dynamics Approach To Neural Intelligence

    Science.gov (United States)

    Zak, Michail A.

    1992-01-01

    Paper discusses approach to mathematical modeling of artificial neural networks exhibiting complicated behaviors reminiscent of creativity and intelligence of biological neural networks. Neural network treated as non-Lipschitzian dynamical system - as described in "Non-Lipschitzian Dynamics For Modeling Neural Networks" (NPO-17814). System serves as tool for modeling of temporal-pattern memories and recognition of complicated spatial patterns.

  15. Diagnosis method utilizing neural networks

    International Nuclear Information System (INIS)

    Watanabe, K.; Tamayama, K.

    1990-01-01

    Studies have been made on the technique of neural networks, which will be used to identify a cause of a small anomalous state in the reactor coolant system of the ATR (Advance Thermal Reactor). Three phases of analyses were carried out in this study. First, simulation for 100 seconds was made to determine how the plant parameters respond after the occurence of a transient decrease in reactivity, flow rate and temperature of feed water and increase in the steam flow rate and steam pressure, which would produce a decrease of water level in a steam drum of the ATR. Next, the simulation data was analysed utilizing an autoregressive model. From this analysis, a total of 36 coherency functions up to 0.5 Hz in each transient were computed among nine important and detectable plant parameters: neutron flux, flow rate of coolant, steam or feed water, water level in the steam drum, pressure and opening area of control valve in a steam pipe, feed water temperature and electrical power. Last, learning of neural networks composed of 96 input, 4-9 hidden and 5 output layer units was done by use of the generalized delta rule, namely a back-propagation algorithm. These convergent computations were continued as far as the difference between the desired outputs, 1 for direct cause or 0 for four other ones and actual outputs reached less than 10%. (1) Coherency functions were not governed by decreasing rate of reactivity in the range of 0.41x10 -2 dollar/s to 1.62x10 -2 dollar /s or by decreasing depth of the feed water temperature in the range of 3 deg C to 10 deg C or by a change of 10% or less in the three other causes. Change in coherency functions only depended on the type of cause. (2) The direct cause from the other four ones could be discriminated with 0.94+-0.01 of output level. A maximum of 0.06 output height was found among the other four causes. (3) Calculation load which is represented as products of learning times and numbers of the hidden units did not depend on the

  16. Parameter extraction with neural networks

    Science.gov (United States)

    Cazzanti, Luca; Khan, Mumit; Cerrina, Franco

    1998-06-01

    In semiconductor processing, the modeling of the process is becoming more and more important. While the ultimate goal is that of developing a set of tools for designing a complete process (Technology CAD), it is also necessary to have modules to simulate the various technologies and, in particular, to optimize specific steps. This need is particularly acute in lithography, where the continuous decrease in CD forces the technologies to operate near their limits. In the development of a 'model' for a physical process, we face several levels of challenges. First, it is necessary to develop a 'physical model,' i.e. a rational description of the process itself on the basis of know physical laws. Second, we need an 'algorithmic model' to represent in a virtual environment the behavior of the 'physical model.' After a 'complete' model has been developed and verified, it becomes possible to do performance analysis. In many cases the input parameters are poorly known or not accessible directly to experiment. It would be extremely useful to obtain the values of these 'hidden' parameters from experimental results by comparing model to data. This is particularly severe, because the complexity and costs associated with semiconductor processing make a simple 'trial-and-error' approach infeasible and cost- inefficient. Even when computer models of the process already exists, obtaining data through simulations may be time consuming. Neural networks (NN) are powerful computational tools to predict the behavior of a system from an existing data set. They are able to adaptively 'learn' input/output mappings and to act as universal function approximators. In this paper we use artificial neural networks to build a mapping from the input parameters of the process to output parameters which are indicative of the performance of the process. Once the NN has been 'trained,' it is also possible to observe the process 'in reverse,' and to extract the values of the inputs which yield outputs

  17. Neural Differentiation Is Inhibited through HIF1 alpha/ beta-Catenin Signaling in Embryoid Bodies

    Czech Academy of Sciences Publication Activity Database

    Veceřa, J.; Kudová, Jana; Kučera, J.; Kubala, Lukáš; Pachernik, J.

    2017-01-01

    Roč. 2017, č. 2017 (2017), č. článku 8715798. ISSN 1687-966X Institutional support: RVO:68081707 Keywords : stem- cell fate * hypoxia * oxygen Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Genetics and heredity (medical genetics to be 3) Impact factor: 3.540, year: 2016

  18. Neural components of altruistic punishment

    Directory of Open Access Journals (Sweden)

    Emily eDu

    2015-02-01

    Full Text Available Altruistic punishment, which occurs when an individual incurs a cost to punish in response to unfairness or a norm violation, may play a role in perpetuating cooperation. The neural correlates underlying costly punishment have only recently begun to be explored. Here we review the current state of research on the neural basis of altruism from the perspectives of costly punishment, emphasizing the importance of characterizing elementary neural processes underlying a decision to punish. In particular, we emphasize three cognitive processes that contribute to the decision to altruistically punish in most scenarios: inequity aversion, cost-benefit calculation, and social reference frame to distinguish self from others. Overall, we argue for the importance of understanding the neural correlates of altruistic punishment with respect to the core computations necessary to achieve a decision to punish.

  19. Neural complexity, dissociation, and schizophrenia

    Czech Academy of Sciences Publication Activity Database

    Bob, P.; Šusta, M.; Chládek, Jan; Glaslová, K.; Fedor-Ferybergh, P.

    2007-01-01

    Roč. 13, č. 10 (2007), HY1-5 ISSN 1234-1010 Institutional research plan: CEZ:AV0Z20650511 Keywords : neural complexity * dissociation * schizophrenia Subject RIV: FH - Neurology Impact factor: 1.607, year: 2007

  20. Neural Networks in Control Applications

    DEFF Research Database (Denmark)

    Sørensen, O.

    The intention of this report is to make a systematic examination of the possibilities of applying neural networks in those technical areas, which are familiar to a control engineer. In other words, the potential of neural networks in control applications is given higher priority than a detailed...... study of the networks themselves. With this end in view the following restrictions have been made: - Amongst numerous neural network structures, only the Multi Layer Perceptron (a feed-forward network) is applied. - Amongst numerous training algorithms, only four algorithms are examined, all...... in a recursive form (sample updating). The simplest is the Back Probagation Error Algorithm, and the most complex is the recursive Prediction Error Method using a Gauss-Newton search direction. - Over-fitting is often considered to be a serious problem when training neural networks. This problem is specifically...

  1. Complex-Valued Neural Networks

    CERN Document Server

    Hirose, Akira

    2012-01-01

    This book is the second enlarged and revised edition of the first successful monograph on complex-valued neural networks (CVNNs) published in 2006, which lends itself to graduate and undergraduate courses in electrical engineering, informatics, control engineering, mechanics, robotics, bioengineering, and other relevant fields. In the second edition the recent trends in CVNNs research are included, resulting in e.g. almost a doubled number of references. The parametron invented in 1954 is also referred to with discussion on analogy and disparity. Also various additional arguments on the advantages of the complex-valued neural networks enhancing the difference to real-valued neural networks are given in various sections. The book is useful for those beginning their studies, for instance, in adaptive signal processing for highly functional sensing and imaging, control in unknown and changing environment, robotics inspired by human neural systems, and brain-like information processing, as well as interdisciplina...

  2. Artificial intelligence: Deep neural reasoning

    Science.gov (United States)

    Jaeger, Herbert

    2016-10-01

    The human brain can solve highly abstract reasoning problems using a neural network that is entirely physical. The underlying mechanisms are only partially understood, but an artificial network provides valuable insight. See Article p.471

  3. Optical Neural Network Classifier Architectures

    National Research Council Canada - National Science Library

    Getbehead, Mark

    1998-01-01

    We present an adaptive opto-electronic neural network hardware architecture capable of exploiting parallel optics to realize real-time processing and classification of high-dimensional data for Air...

  4. Sequential neural models with stochastic layers

    DEFF Research Database (Denmark)

    Fraccaro, Marco; Sønderby, Søren Kaae; Paquet, Ulrich

    2016-01-01

    How can we efficiently propagate uncertainty in a latent state representation with recurrent neural networks? This paper introduces stochastic recurrent neural networks which glue a deterministic recurrent neural network and a state space model together to form a stochastic and sequential neural...... generative model. The clear separation of deterministic and stochastic layers allows a structured variational inference network to track the factorization of the model's posterior distribution. By retaining both the nonlinear recursive structure of a recurrent neural network and averaging over...

  5. Analysis of Recurrent Analog Neural Networks

    Directory of Open Access Journals (Sweden)

    Z. Raida

    1998-06-01

    Full Text Available In this paper, an original rigorous analysis of recurrent analog neural networks, which are built from opamp neurons, is presented. The analysis, which comes from the approximate model of the operational amplifier, reveals causes of possible non-stable states and enables to determine convergence properties of the network. Results of the analysis are discussed in order to enable development of original robust and fast analog networks. In the analysis, the special attention is turned to the examination of the influence of real circuit elements and of the statistical parameters of processed signals to the parameters of the network.

  6. SEVERITY CLASSIFICATION OF MICROANEURYSMS USING NEURAL NETWORK

    Directory of Open Access Journals (Sweden)

    Shree Divya R

    2014-01-01

    Full Text Available Diabetic Retinopathy is one of the most common causes of blindness that leads to the loss of vision to the human eye. Several methods have been proposed to detect several defects of the human eye like hemorrhages, exudates etc. which are to be considered as the major symptoms. Among them, Microaneurysms should be considered as one of the severe condition for the early blindness. Several techniques have been proposed based on this, but they have certain drawbacks. A new technique called neural network taken for presentation, helps to detect and determine the severity of Microaneurysms which would be able to give a better performance than the existing techniques.

  7. Implantable Neural Interfaces for Sharks

    Science.gov (United States)

    2007-05-01

    technology for recording and stimulating from the auditory and olfactory sensory nervous systems of the awake, swimming nurse shark , G. cirratum (Figures...overlay of the central nervous system of the nurse shark on a horizontal MR image. Implantable Neural Interfaces for Sharks ...Neural Interfaces for Characterizing Population Responses to Odorants and Electrical Stimuli in the Nurse Shark , Ginglymostoma cirratum.” AChemS Abs

  8. What are artificial neural networks?

    DEFF Research Database (Denmark)

    Krogh, Anders

    2008-01-01

    Artificial neural networks have been applied to problems ranging from speech recognition to prediction of protein secondary structure, classification of cancers and gene prediction. How do they work and what might they be good for? Udgivelsesdato: 2008-Feb......Artificial neural networks have been applied to problems ranging from speech recognition to prediction of protein secondary structure, classification of cancers and gene prediction. How do they work and what might they be good for? Udgivelsesdato: 2008-Feb...

  9. Neural correlates of hate.

    Directory of Open Access Journals (Sweden)

    Semir Zeki

    Full Text Available In this work, we address an important but unexplored topic, namely the neural correlates of hate. In a block-design fMRI study, we scanned 17 normal human subjects while they viewed the face of a person they hated and also faces of acquaintances for whom they had neutral feelings. A hate score was obtained for the object of hate for each subject and this was used as a covariate in a between-subject random effects analysis. Viewing a hated face resulted in increased activity in the medial frontal gyrus, right putamen, bilaterally in premotor cortex, in the frontal pole and bilaterally in the medial insula. We also found three areas where activation correlated linearly with the declared level of hatred, the right insula, right premotor cortex and the right fronto-medial gyrus. One area of deactivation was found in the right superior frontal gyrus. The study thus shows that there is a unique pattern of activity in the brain in the context of hate. Though distinct from the pattern of activity that correlates with romantic love, this pattern nevertheless shares two areas with the latter, namely the putamen and the insula.

  10. neural control system

    International Nuclear Information System (INIS)

    Elshazly, A.A.E.

    2002-01-01

    Automatic power stabilization control is the desired objective for any reactor operation , especially, nuclear power plants. A major problem in this area is inevitable gap between a real plant ant the theory of conventional analysis and the synthesis of linear time invariant systems. in particular, the trajectory tracking control of a nonlinear plant is a class of problems in which the classical linear transfer function methods break down because no transfer function can represent the system over the entire operating region . there is a considerable amount of research on the model-inverse approach using feedback linearization technique. however, this method requires a prices plant model to implement the exact linearizing feedback, for nuclear reactor systems, this approach is not an easy task because of the uncertainty in the plant parameters and un-measurable state variables . therefore, artificial neural network (ANN) is used either in self-tuning control or in improving the conventional rule-based exper system.the main objective of this thesis is to suggest an ANN, based self-learning controller structure . this method is capable of on-line reinforcement learning and control for a nuclear reactor with a totally unknown dynamics model. previously, researches are based on back- propagation algorithm . back -propagation (BP), fast back -propagation (FBP), and levenberg-marquardt (LM), algorithms are discussed and compared for reinforcement learning. it is found that, LM algorithm is quite superior

  11. Influence of neural adaptation on dynamics and equilibrium state of neural activities in a ring neural network

    Science.gov (United States)

    Takiyama, Ken

    2017-12-01

    How neural adaptation affects neural information processing (i.e. the dynamics and equilibrium state of neural activities) is a central question in computational neuroscience. In my previous works, I analytically clarified the dynamics and equilibrium state of neural activities in a ring-type neural network model that is widely used to model the visual cortex, motor cortex, and several other brain regions. The neural dynamics and the equilibrium state in the neural network model corresponded to a Bayesian computation and statistically optimal multiple information integration, respectively, under a biologically inspired condition. These results were revealed in an analytically tractable manner; however, adaptation effects were not considered. Here, I analytically reveal how the dynamics and equilibrium state of neural activities in a ring neural network are influenced by spike-frequency adaptation (SFA). SFA is an adaptation that causes gradual inhibition of neural activity when a sustained stimulus is applied, and the strength of this inhibition depends on neural activities. I reveal that SFA plays three roles: (1) SFA amplifies the influence of external input in neural dynamics; (2) SFA allows the history of the external input to affect neural dynamics; and (3) the equilibrium state corresponds to the statistically optimal multiple information integration independent of the existence of SFA. In addition, the equilibrium state in a ring neural network model corresponds to the statistically optimal integration of multiple information sources under biologically inspired conditions, independent of the existence of SFA.

  12. Prospero-related homeobox 1 (Prox1 at the crossroads of diverse pathways during adult neural fate specification

    Directory of Open Access Journals (Sweden)

    Athanasios eStergiopoulos

    2015-01-01

    Full Text Available Over the last decades, adult neurogenesis in the central nervous system (CNS has emerged as a fundamental process underlying physiology and disease. Recent evidence indicates that the homeobox transcription factor Prox1 is a critical intrinsic regulator of neurogenesis in the embryonic CNS and adult dentate gyrus (DG of the hippocampus, acting in multiple ways and instructed by extrinsic cues and intrinsic factors. In the embryonic CNS, Prox1 is mechanistically involved in the regulation of proliferation versus differentiation decisions of NSCs, promoting cell cycle exit and neuronal differentiation, while inhibits astrogliogenesis. During the complex differentiation events in adult hippocampal neurogenesis, Prox1 is required for maintenance of intermediate progenitors (IPs, differentiation and maturation of glutamatergic interneurons, as well as specification of DG cell identity over CA3 pyramidal fate. The mechanism by which Prox1 exerts multiple functions involves distinct signaling pathways currently not fully highlighted. In this mini-review, we thoroughly discuss the Prox1-dependent phenotypes and molecular pathways in adult neurogenesis in relation to different upstream signaling cues and cell fate determinants. In addition, we discuss the possibility that Prox1 may act as a cross-talk point between diverse signaling cascades to achieve specific outcomes during adult neurogenesis.

  13. Ship Benchmark Shaft and Engine Gain FDI Using Neural Network

    DEFF Research Database (Denmark)

    Bendtsen, Jan Dimon; Izadi-Zamanabadi, Roozbeh

    2002-01-01

    threshold value. In the paper a method for determining this threshold based on the neural network model is proposed, which can be used for a design strategy to handle residual sensitivity to input variations. The proposed method is used for successful FDI of a diesel engine gain fault in a ship propulsion...

  14. Fractional Hopfield Neural Networks: Fractional Dynamic Associative Recurrent Neural Networks.

    Science.gov (United States)

    Pu, Yi-Fei; Yi, Zhang; Zhou, Ji-Liu

    2017-10-01

    This paper mainly discusses a novel conceptual framework: fractional Hopfield neural networks (FHNN). As is commonly known, fractional calculus has been incorporated into artificial neural networks, mainly because of its long-term memory and nonlocality. Some researchers have made interesting attempts at fractional neural networks and gained competitive advantages over integer-order neural networks. Therefore, it is naturally makes one ponder how to generalize the first-order Hopfield neural networks to the fractional-order ones, and how to implement FHNN by means of fractional calculus. We propose to introduce a novel mathematical method: fractional calculus to implement FHNN. First, we implement fractor in the form of an analog circuit. Second, we implement FHNN by utilizing fractor and the fractional steepest descent approach, construct its Lyapunov function, and further analyze its attractors. Third, we perform experiments to analyze the stability and convergence of FHNN, and further discuss its applications to the defense against chip cloning attacks for anticounterfeiting. The main contribution of our work is to propose FHNN in the form of an analog circuit by utilizing a fractor and the fractional steepest descent approach, construct its Lyapunov function, prove its Lyapunov stability, analyze its attractors, and apply FHNN to the defense against chip cloning attacks for anticounterfeiting. A significant advantage of FHNN is that its attractors essentially relate to the neuron's fractional order. FHNN possesses the fractional-order-stability and fractional-order-sensitivity characteristics.

  15. Resolution of Singularities Introduced by Hierarchical Structure in Deep Neural Networks.

    Science.gov (United States)

    Nitta, Tohru

    2017-10-01

    We present a theoretical analysis of singular points of artificial deep neural networks, resulting in providing deep neural network models having no critical points introduced by a hierarchical structure. It is considered that such deep neural network models have good nature for gradient-based optimization. First, we show that there exist a large number of critical points introduced by a hierarchical structure in deep neural networks as straight lines, depending on the number of hidden layers and the number of hidden neurons. Second, we derive a sufficient condition for deep neural networks having no critical points introduced by a hierarchical structure, which can be applied to general deep neural networks. It is also shown that the existence of critical points introduced by a hierarchical structure is determined by the rank and the regularity of weight matrices for a specific class of deep neural networks. Finally, two kinds of implementation methods of the sufficient conditions to have no critical points are provided. One is a learning algorithm that can avoid critical points introduced by the hierarchical structure during learning (called avoidant learning algorithm). The other is a neural network that does not have some critical points introduced by the hierarchical structure as an inherent property (called avoidant neural network).

  16. A novel neural-wavelet approach for process diagnostics and complex system modeling

    Science.gov (United States)

    Gao, Rong

    Neural networks have been effective in several engineering applications because of their learning abilities and robustness. However certain shortcomings, such as slow convergence and local minima, are always associated with neural networks, especially neural networks applied to highly nonlinear and non-stationary problems. These problems can be effectively alleviated by integrating a new powerful tool, wavelets, into conventional neural networks. The multi-resolution analysis and feature localization capabilities of the wavelet transform offer neural networks new possibilities for learning. A neural wavelet network approach developed in this thesis enjoys fast convergence rate with little possibility to be caught at a local minimum. It combines the localization properties of wavelets with the learning abilities of neural networks. Two different testbeds are used for testing the efficiency of the new approach. The first is magnetic flowmeter-based process diagnostics: here we extend previous work, which has demonstrated that wavelet groups contain process information, to more general process diagnostics. A loop at Applied Intelligent Systems Lab (AISL) is used for collecting and analyzing data through the neural-wavelet approach. The research is important for thermal-hydraulic processes in nuclear and other engineering fields. The neural-wavelet approach developed is also tested with data from the electric power grid. More specifically, the neural-wavelet approach is used for performing short-term and mid-term prediction of power load demand. In addition, the feasibility of determining the type of load using the proposed neural wavelet approach is also examined. The notion of cross scale product has been developed as an expedient yet reliable discriminator of loads. Theoretical issues involved in the integration of wavelets and neural networks are discussed and future work outlined.

  17. Prediction of proteasome cleavage motifs by neural networks

    DEFF Research Database (Denmark)

    Kesimir, C.; Nussbaum, A.K.; Schild, H.

    2002-01-01

    physiological conditions. Our algorithm has been trained not only on in vitro data, but also on MHC Class I ligand data, which reflect a combination of immunoproteasome and constitutive proteasome specificity. This feature, together with the use of neural networks, a non-linear classification technique, make...... the prediction of MHC Class I ligand boundaries more accurate: 65% of the cleavage sites and 85% of the non-cleavage sites are correctly determined. Moreover, we show that the neural networks trained on the constitutive proteasome data learns a specificity that differs from that of the networks trained on MHC...

  18. Neural basis of social status hierarchy across species.

    Science.gov (United States)

    Chiao, Joan Y

    2010-12-01

    Social status hierarchy is a ubiquitous principle of social organization across the animal kingdom. Recent findings in social neuroscience reveal distinct neural networks associated with the recognition and experience of social hierarchy in humans, as well as modulation of these networks by personality and culture. Additionally, allelic variation in the serotonin transporter gene is associated with prevalence of social hierarchy across species and cultures, suggesting the importance of the study of genetic factors underlying social hierarchy. Future studies are needed to determine how genetic and environmental factors shape neural systems involved in the production and maintenance of social hierarchy across ontogeny and phylogeny. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Neural network for prediction of superheater fireside corrosion

    Energy Technology Data Exchange (ETDEWEB)

    Makkonen, P. [Foster Wheeler Energia Oy, Karhula R and D Center, Karhula (Finland)

    1998-12-31

    Superheater corrosion causes vast annual losses to the power companies. If the corrosion could be reliably predicted, new power plants could be designed accordingly, and knowledge of fuel selection and determination of process conditions could be utilized to minimize superheater corrosion. If relations between inputs and the output are poorly known, conventional models depending on corrosion theories will fail. A prediction model based on a neural network is capable of learning from errors and improving its performance as the amount of data increases. The neural network developed during this study predicts superheater corrosion with 80 % accuracy at early stage of the project. (orig.) 10 refs.

  20. Neural network for prediction of superheater fireside corrosion

    Energy Technology Data Exchange (ETDEWEB)

    Makkonen, P [Foster Wheeler Energia Oy, Karhula R and D Center, Karhula (Finland)

    1999-12-31

    Superheater corrosion causes vast annual losses to the power companies. If the corrosion could be reliably predicted, new power plants could be designed accordingly, and knowledge of fuel selection and determination of process conditions could be utilized to minimize superheater corrosion. If relations between inputs and the output are poorly known, conventional models depending on corrosion theories will fail. A prediction model based on a neural network is capable of learning from errors and improving its performance as the amount of data increases. The neural network developed during this study predicts superheater corrosion with 80 % accuracy at early stage of the project. (orig.) 10 refs.