Science.gov

Sample records for cell states spans

  1. SNEV overexpression extends the life span of human endothelial cells

    SciTech Connect

    Voglauer, Regina; Chang, Martina Wei-Fen; Dampier, Brigitta; Wieser, Matthias; Baumann, Kristin; Sterovsky, Thomas; Schreiber, Martin; Katinger, Hermann; Grillari, Johannes . E-mail: j.grillari@iam.boku.ac.at

    2006-04-01

    In a recent screening for genes downregulated in replicatively senescent human umbilical vein endothelial cells (HUVECs), we have isolated the novel protein SNEV. Since then SNEV has proven as a multifaceted protein playing a role in pre-mRNA splicing, DNA repair, and the ubiquitin/proteosome system. Here, we report that SNEV mRNA decreases in various cell types during replicative senescence, and that it is increased in various immortalized cell lines, as well as in breast tumors, where SNEV transcript levels also correlate with the survival of breast cancer patients. Since these mRNA profiles suggested a role of SNEV in the regulation of cell proliferation, the effect of its overexpression was tested. Thereby, a significant extension of the cellular life span was observed, which was not caused by altered telomerase activity or telomere dynamics but rather by enhanced stress resistance. When SNEV overexpressing cells were treated with bleomycin or bleomycin combined with BSO, inducing DNA damage as well as reactive oxygen species, a significantly lower fraction of apoptotic cells was found in comparison to vector control cells. These data suggest that high levels of SNEV might extend the cellular life span by increasing the resistance to stress or by improving the DNA repair capacity of the cells.

  2. Oxygen analyzers: failure rates and life spans of galvanic cells.

    PubMed

    Meyer, R M

    1990-07-01

    Competing technologies exist for measuring oxygen concentrations in breathing circuits. Over a 4-year period, two types of oxygen analyzers were studied prospectively in routine clinical use to determine the incidence and nature of malfunctions. Newer AC-powered galvanic analyzers (North American Dräger O2med) were compared with older, battery-powered polarographic analyzers (Ohmeda 201) by recording all failures and necessary repairs. The AC-powered galvanic analyzer had a significantly lower incidence of failures (0.12 +/- 0.04 failures per machine-month) than the battery-powered polarographic analyzer (4.0 +/- 0.3 failures per machine-month). Disposable capsules containing the active galvanic cells lasted 12 +/- 7 months. Although the galvanic analyzers tended to remain out of service longer, awaiting the arrival of costly parts, the polarographic analyzers were more expensive to keep operating when calculations included the cost of time spent on repairs. Stocking galvanic capsules would have decreased the amount of time the galvanic analyzers were out of service, while increasing costs. In conclusion, galvanic oxygen analyzers appear capable of delivering more reliable service at a lower overall cost. By keeping the galvanic capsules exposed to room air during periods of storage, it should be possible to prolong their life span, further decreasing the cost of using them. In addition, recognizing the aberrations in their performance that warn of the exhaustion of the galvanic cells should permit timely recording and minimize downtime.

  3. Epigenetic rejuvenation of mesenchymal stromal cells derived from induced pluripotent stem cell>s.

    PubMed

    Frobel, Joana; Hemeda, Hatim; Lenz, Michael; Abagnale, Giulio; Joussen, Sylvia; Denecke, Bernd; Sarić, Tomo; Zenke, Martin; Wagner, Wolfgang

    2014-09-01

    Standardization of mesenchymal stromal cells (MSCs) remains a major obstacle in regenerative medicine. Starting material and culture expansion affect cell preparations and render comparison between studies difficult. In contrast, induced pluripotent stem cell>s (iPSCs) assimilate toward a ground state and may therefore give rise to more standardized cell preparations. We reprogrammed MSCs into iPSCs, which were subsequently redifferentiated toward MSCs. These iPS-MSCs revealed similar morphology, immunophenotype, in vitro differentiation potential, and gene expression profiles as primary MSCs. However, iPS-MSCs were impaired in suppressing T cell proliferation. DNA methylation (DNAm) profiles of iPSCs maintained donor-specific characteristics, whereas tissue-specific, senescence-associated, and age-related DNAm patterns were erased during reprogramming. iPS-MSCs reacquired senescence-associated DNAm during culture expansion, but they remained rejuvenated with regard to age-related DNAm. Overall, iPS-MSCs are similar to MSCs, but they reveal incomplete reacquisition of immunomodulatory function and MSC-specific DNAm patterns-particularly of DNAm patterns associated with tissue type and aging. PMID:25241740

  4. Increasing cell culture population doublings for long-term growth of finite life span human cell cultures

    DOEpatents

    Stampfer, Martha R.; Garbe, James C.

    2016-06-28

    Cell culture media formulations for culturing human epithelial cells are herein described. Also described are methods of increasing population doublings in a cell culture of finite life span human epithelial cells and prolonging the life span of human cell cultures. Using the cell culture media disclosed alone and in combination with addition to the cell culture of a compound associated with anti-stress activity achieves extended growth of pre-stasis cells and increased population doublings and life span in human epithelial cell cultures.

  5. Increasing cell culture population doublings for long-term growth of finite life span human cell cultures

    SciTech Connect

    Stampfer, Martha R; Garbe, James C

    2015-02-24

    Cell culture media formulations for culturing human epithelial cells are herein described. Also described are methods of increasing population doublings in a cell culture of finite life span human epithelial cells and prolonging the life span of human cell cultures. Using the cell culture media disclosed alone and in combination with addition to the cell culture of a compound associated with anti-stress activity achieves extended growth of pre-stasis cells and increased population doublings and life span in human epithelial cell cultures.

  6. Longevity in space; experiment on the life span of Paramecium cell clone in space.

    PubMed

    Mogami, Y; Tokunaga, N; Baba, S A

    1999-01-01

    Life span is the most interesting and also the most important biologically relevant time to be investigated on the space station. As a model experiment, we proposed an investigation to assess the life span of clone generation of the ciliate Paramecium. In space, clone generation will be artificially started by conjugation or autogamy, and the life span of the cell populations in different gravitational fields (microgravity and onboard 1 x g control) will be precisely assessed in terms of fission age as compared with the clock time. In order to perform the space experiment including long-lasting culture and continuous measurement of cell division, we tested the methods of cell culture and of cell-density measurement, which will be available in closed environments under microgravity. The basic design of experimental hardware and a preliminary result of the cultivation procedure are described.

  7. Biological Effects of Culture Substrates on Human Pluripotent Stem Cell>s

    PubMed Central

    2016-01-01

    In recent years, as human pluripotent stem cell>s (hPSCs) have been commonly cultured in feeder-free conditions, a number of cell culture substrates have been applied or developed. However, the functional roles of these substrates in maintaining hPSC self-renewal remain unclear. Here in this review, we summarize the types of these substrates and their effect on maintaining hPSC self-renewal. Endogenous extracellular matrix (ECM) protein expression has been shown to be crucial in maintaining hPSC self-renewal. These ECM molecules interact with integrin cell-surface receptors and transmit their cellular signaling. We discuss the possible effect of integrin-mediated signaling pathways on maintaining hPSC self-renewal. Activation of integrin-linked kinase (ILK), which transmits ECM-integrin signaling to AKT (also known as protein kinase B), has been shown to be critical in maintaining hPSC self-renewal. Also, since naïve pluripotency has been widely recognized as an alternative pluripotent state of hPSCs, we discuss the possible effects of culture substrates and integrin signaling on naïve hPSCs based on the studies of mouse embryonic stem cells. Understanding the role of culture substrates in hPSC self-renewal and differentiation enables us to control hPSC behavior precisely and to establish scalable or microfabricated culture technologies for regenerative medicine and drug development. PMID:27656216

  8. Cell nonautonomous activation of flavin-containing monooxygenase promotes longevity and health span.

    PubMed

    Leiser, Scott F; Miller, Hillary; Rossner, Ryan; Fletcher, Marissa; Leonard, Alison; Primitivo, Melissa; Rintala, Nicholas; Ramos, Fresnida J; Miller, Dana L; Kaeberlein, Matt

    2015-12-11

    Stabilization of the hypoxia-inducible factor 1 (HIF-1) increases life span and health span in nematodes through an unknown mechanism. We report that neuronal stabilization of HIF-1 mediates these effects in Caenorhabditis elegans through a cell nonautonomous signal to the intestine, which results in activation of the xenobiotic detoxification enzyme flavin-containing monooxygenase-2 (FMO-2). This prolongevity signal requires the serotonin biosynthetic enzyme TPH-1 in neurons and the serotonin receptor SER-7 in the intestine. Intestinal FMO-2 is also activated by dietary restriction (DR) and is necessary for DR-mediated life-span extension, which suggests that this enzyme represents a point of convergence for two distinct longevity pathways. FMOs are conserved in eukaryotes and induced by multiple life span-extending interventions in mice, which suggests that these enzymes may play a critical role in promoting health and longevity across phyla.

  9. Blood volume and red cell life span (M113), part C

    NASA Technical Reports Server (NTRS)

    Johnson, P. C., Jr.

    1973-01-01

    Prechamber, in-chamber, and postchamber blood samples taken from Skylab simulation crewmembers did not indicate significant shortening of the red cell life span during the mission. This does not suggest that the space simulation environment could not be associated with red cell enzyme changes. It does show that any changes in enzymes were not sufficiently great to significantly shorten red cell survival. There was no evidence of bone marrow erythropoetic suppression nor was there any evidence of increased red cell destruction.

  10. Isolation and cultivation of naive-like human pluripotent stem cell>s based on HERVH expression.

    PubMed

    Wang, Jichang; Singh, Manvendra; Sun, Chuanbo; Besser, Daniel; Prigione, Alessandro; Ivics, Zoltán; Hurst, Laurence D; Izsvák, Zsuzsanna

    2016-02-01

    The ability to derive and stably maintain ground-state human pluripotent stem cell>s (hPSCs) that resemble the cells seen in vivo in the inner cell mass has the potential to be an invaluable tool for researchers developing stem cell-based therapies. To date, derivation of human naive-like pluripotent stem cell lines has been limited to a small number of lineages, and their long-term culturing remains problematic. We describe a protocol for genetic and phenotypic tagging, selecting and maintaining naive-like hPSCs. We tag hPSCs by GFP, expressed by the long terminal repeat (LTR7) of HERVH endogenous retrovirus. This simple and efficient protocol has been reproduced with multiple hPSC lines, including embryonic and induced pluripotent stem cell>s, and it takes ∼6 weeks. By using the reporter, homogeneous hPSC cultures can be derived, characterized and maintained for the long term by repeated re-sorting and re-plating steps. The HERVH-expressing cells have a similar, but nonidentical, expression pattern to other naive-like cells, suggesting that alternative pluripotent states might exist. PMID:26797457

  11. Fuzzy stochastic analysis of serviceability and ultimate limit states of two-span pedestrian steel bridge

    NASA Astrophysics Data System (ADS)

    Kala, Zdeněk; Sandovič, GiedrÄ--

    2012-09-01

    The paper deals with non-linear analysis of ultimate and serviceability limit states of two-span pedestrian steel bridge. The effects of random material and geometrical characteristics on limit states are analyzed. The Monte Carlo method was applied to stochastic analysis. For the serviceability limit state, also influence of fuzzy uncertainty of the limit deflection value on random characteristics of load capacity of variable action was studied. The results prove that, for the type of structure studied, the serviceability limit state is decisive from the point of view of design. The present paper opens a discussion on the use of stochastic analysis to verify the limit deflections given in the standards EUROCODES.

  12. Differentiation of pluripotent stem cell>s into hypothalamic and pituitary cells.

    PubMed

    Suga, Hidetaka

    2015-01-01

    The hypothalamic-pituitary system is essential to maintain life and control systemic homeostasis, but it is negatively affected by various diseases, leading to serious symptoms. Embryonic stem (ES) cells differentiate into neuroectodermal progenitors when cultured as floating aggregates under serum-free conditions. Recently, our colleagues have shown that strict removal of exogenous patterning factors during early differentiation steps induced efficient generation of rostral hypothalamic-like progenitors from mouse ES cell-derived neuroectodermal cells. The use of growth factor-free chemically defined medium was critical for this induction. The ES cell-derived hypothalamic-like progenitors generated rostral-dorsal hypothalamic neurons, especially magnocellular vasopressinergic neurons that release the hormone upon stimulation. Subsequently, we reported efficient self-formation of 3-dimensional adenohypophysis tissues in aggregate cultures of mouse ES cells. The ES cells were stimulated to differentiate into nonneural head ectoderm and hypothalamic neuroectoderm in adjacent layers within the aggregate and then treated with hedgehog. Self-organization of Rathke's pouch-like structures occurred at the interface of the two epithelia, as observed in vivo, and various endocrine cells including corticotrophs and somatotrophs were subsequently produced. The corticotrophs efficiently secreted adrenocorticotropic hormone in response to corticotropin-releasing hormone. Furthermore, when engrafted in vivo, these cells rescued the systemic glucocorticoid level in hypopituitary mice. Our present research aims are to prepare hypothalamic and pituitary tissues from human induced pluripotent stem cell>s and establish effective transplantation techniques with clinical applications. To replicate the complex and precise control of the hypothalamic-pituitary system, regenerative medicine using pluripotent cells may be a hopeful option. PMID:25428763

  13. Enhanced Cytotoxicity for Colon 26 Cells Using Doxorubicin-Loaded Sorbitan Monooleate (Span 80) Vesicles

    PubMed Central

    Hayashi, Keita; Tatsui, Tsuyoshi; Shimanouchi, Toshinori; Umakoshi, Hiroshi

    2013-01-01

    Span 80 (sorbitan monooleate) vesicles behaved differently from conventional phospholipid vesicles (liposomes) because the former had a more fluid interface. After doxorubicin hydrochloride (DOX) was encapsulated into the Span 80 vesicle (loading efficiency: 63 %), DOX-loaded Span 80 vesicles (DVs) were thereafter added to Colon 26 cells. It was suggested, from the flow cytometric analysis and confocal laser microscopic observation, that DVs directly deliver DOX into the cytoplasm of Colon 26 cells. DVs showed the different delivery manner from the DOX-loaded liposomes (DLs). It is considered that the difference of delivery manner between DVs and DLs resulted in the difference of cytotoxicity (IC50); i.e. IC50 values for DVs and DLs were 5 and > 30 μM, respectively. The results obtained herein would give the fundamental findings which can contribute to the improvement of formulation of conventional liposome-based carrier and its cytotoxicity. PMID:23411680

  14. Bilayer-Spanning DNA Nanopores with Voltage-Switching between Open and Closed State

    PubMed Central

    2014-01-01

    Membrane-spanning nanopores from folded DNA are a recent example of biomimetic man-made nanostructures that can open up applications in biosensing, drug delivery, and nanofluidics. In this report, we generate a DNA nanopore based on the archetypal six-helix-bundle architecture and systematically characterize it via single-channel current recordings to address several fundamental scientific questions in this emerging field. We establish that the DNA pores exhibit two voltage-dependent conductance states. Low transmembrane voltages favor a stable high-conductance level, which corresponds to an unobstructed DNA pore. The expected inner width of the open channel is confirmed by measuring the conductance change as a function of poly(ethylene glycol) (PEG) size, whereby smaller PEGs are assumed to enter the pore. PEG sizing also clarifies that the main ion-conducting path runs through the membrane-spanning channel lumen as opposed to any proposed gap between the outer pore wall and the lipid bilayer. At higher voltages, the channel shows a main low-conductance state probably caused by electric-field-induced changes of the DNA pore in its conformation or orientation. This voltage-dependent switching between the open and closed states is observed with planar lipid bilayers as well as bilayers mounted on glass nanopipettes. These findings settle a discrepancy between two previously published conductances. By systematically exploring a large space of parameters and answering key questions, our report supports the development of DNA nanopores for nanobiotechnology. PMID:25338165

  15. Generation of Hepatocytes from Pluripotent Stem Cell>s for Drug Screening and Developmental Modeling.

    PubMed

    Gieseck, Richard L; Vallier, Ludovic; Hannan, Nicholas R F

    2015-01-01

    Hepatocytes produced from the differentiation of human pluripotent stem cell>s can be used to study human development and liver disease, to investigate the toxicological response of novel drug candidates, and as an alternative source of primary cells for transplantation therapies. Here, we describe a method to produce hepatocytes by differentiating human pluripotent stem cell>s into definitive endoderm, patterning definitive endoderm into anterior definitive endoderm, specifying anterior definitive endoderm into hepatic endoderm, and differentiating hepatic endoderm into immature hepatocytes. These cells are further matured in either two-dimensional or three-dimensional culture conditions to produce cells capable of metabolizing xenobiotics and generating liver-specific proteins, such as albumin and alpha 1 antitrypsin. PMID:26272139

  16. Hematopoietic differentiation of pluripotent stem cell>s in culture.

    PubMed

    Mills, Jason A; Paluru, Prasuna; Weiss, Mitchell J; Gadue, Paul; French, Deborah L

    2014-01-01

    This chapter describes a two-dimensional "monolayer" system for differentiating human pluripotent stem cell>s (PSCs) into "primitive" hematopoietic progenitor cells (HPCs) resembling those produced in vivo by the early embryonic yolk sac. This experimental system utilizes defined conditions without serum or feeder cells. Cytokines are added sequentially to stimulate the formation of mesoderm and its subsequent patterning to hematopoietic progenitors. The HPCs produced by this protocol have multi-lineage potential (erythroid, megakaryocyte, and myeloid) and can be isolated as a homogeneous population for use in standard hematopoietic studies including liquid expansion to mature lineages and colony assays. In addition, the HPCs can be cryopreserved for distribution or analysis at later times. The HPCs generated by this protocol have been used successfully to better define intrinsic variation in hematopoietic potential between different PSC lines and to model human hematopoietic diseases using patient-derived induced pluripotent stem cell>s. PMID:25062629

  17. Ground States of Random Spanning Trees on a D-Wave 2X

    NASA Astrophysics Data System (ADS)

    Hall, J. S.; Hobl, L.; Novotny, M. A.; Michielsen, Kristel

    The performances of two D-Wave 2 machines (476 and 496 qubits) and of a 1097-qubit D-Wave 2X were investigated. Each chip has a Chimera interaction graph calG . Problem input consists of values for the fields hj and for the two-qubit interactions Ji , j of an Ising spin-glass problem formulated on calG . Output is returned in terms of a spin configuration {sj } , with sj = +/- 1 . We generated random spanning trees (RSTs) uniformly distributed over all spanning trees of calG . On the 476-qubit D-Wave 2, RSTs were generated on the full chip with Ji , j = - 1 and hj = 0 and solved one thousand times. The distribution of solution energies and the average magnetization of each qubit were determined. On both the 476- and 1097-qubit machines, four identical spanning trees were generated on each quadrant of the chip. The statistical independence of these regions was investigated. In another study, on the D-Wave 2X, one hundred RSTs with random Ji , j ∈ { - 1 , 1 } and hj = 0 were generated on the full chip. Each RST problem was solved one hundred times and the number of times the ground state energy was found was recorded. This procedure was repeated for square subgraphs, with dimensions ranging from 7 ×7 to 11 ×11. Supported in part by NSF Grants DGE-0947419 and DMR-1206233. D-Wave time provided by D-Wave Systems and by the USRA Quantum Artificial Intelligence Laboratory Research Opportunity.

  18. Generating human intestinal tissue from pluripotent stem cell>s in vitro.

    PubMed

    McCracken, Kyle W; Howell, Jonathan C; Wells, James M; Spence, Jason R

    2011-12-01

    Here we describe a protocol for generating 3D human intestinal tissues (called organoids) in vitro from human pluripotent stem cell>s (hPSCs). To generate intestinal organoids, pluripotent stem cell>s are first differentiated into FOXA2(+)SOX17(+) endoderm by treating the cells with activin A for 3 d. After endoderm induction, the pluripotent stem cell>s are patterned into CDX2(+) mid- and hindgut tissue using FGF4 and WNT3a. During this patterning step, 3D mid- or hindgut spheroids bud from the monolayer epithelium attached to the tissue culture dish. The 3D spheroids are further cultured in Matrigel along with prointestinal growth factors, and they proliferate and expand over 1-3 months to give rise to intestinal tissue, complete with intestinal mesenchyme and epithelium comprising all of the major intestinal cell types. To date, this is the only method for efficiently directing the differentiation of hPSCs into 3D human intestinal tissue in vitro. PMID:22082986

  19. 6. DETAIL OF VERTICAL LIFT SPAN AND FIXED SPAN IMMEDIATELY ...

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

    6. DETAIL OF VERTICAL LIFT SPAN AND FIXED SPAN IMMEDIATELY NORTH OF VERTICAL LIFT SPAN, LOOKING SOUTHEAST. - Shippingsport Bridge, Spanning Illinois River at State Route 51, La Salle, La Salle County, IL

  20. NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice.

    PubMed

    Zhang, Hongbo; Ryu, Dongryeol; Wu, Yibo; Gariani, Karim; Wang, Xu; Luan, Peiling; D'Amico, Davide; Ropelle, Eduardo R; Lutolf, Matthias P; Aebersold, Ruedi; Schoonjans, Kristina; Menzies, Keir J; Auwerx, Johan

    2016-06-17

    Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to senescence during aging. We demonstrate the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD(+)) and its effect on mitochondrial activity as a pivotal switch to modulate muscle SC (MuSC) senescence. Treatment with the NAD(+) precursor nicotinamide riboside (NR) induced the mitochondrial unfolded protein response and synthesis of prohibitin proteins, and this rejuvenated MuSCs in aged mice. NR also prevented MuSC senescence in the mdx (C57BL/10ScSn-Dmd(mdx)/J) mouse model of muscular dystrophy. We furthermore demonstrate that NR delays senescence of neural SCs and melanocyte SCs and increases mouse life span. Strategies that conserve cellular NAD(+) may reprogram dysfunctional SCs and improve life span in mammals. PMID:27127236

  1. Scalable topographies to support proliferation and Oct4 expression by human induced pluripotent stem cell>s

    PubMed Central

    Reimer, Andreas; Vasilevich, Aliaksei; Hulshof, Frits; Viswanathan, Priyalakshmi; van Blitterswijk, Clemens A.; de Boer, Jan; Watt, Fiona M.

    2016-01-01

    It is well established that topographical features modulate cell behaviour, including cell morphology, proliferation and differentiation. To define the effects of topography on human induced pluripotent stem cell>s (iPSC), we plated cells on a topographical library containing over 1000 different features in medium lacking animal products (xeno-free). Using high content imaging, we determined the effect of each topography on cell proliferation and expression of the pluripotency marker Oct4 24 h after seeding. Features that maintained Oct4 expression also supported proliferation and cell-cell adhesion at 24 h, and by 4 days colonies of Oct4-positive, Sox2-positive cells had formed. Computational analysis revealed that small feature size was the most important determinant of pluripotency, followed by high wave number and high feature density. Using this information we correctly predicted whether any given topography within our library would support the pluripotent state at 24 h. This approach not only facilitates the design of substrates for optimal human iPSC expansion, but also, potentially, identification of topographies with other desirable characteristics, such as promoting differentiation. PMID:26757610

  2. Single-spanning transmembrane domains in cell growth and cell-cell interactions

    PubMed Central

    Sawma, Paul; Duneau, Jean-Pierre; Khao, Jonathan; Hénin, Jélerôme; Bagnard, Dominique; Sturgis, James

    2010-01-01

    As a whole, integral membrane proteins represent about one third of sequenced genomes, and more than 50% of currently available drugs target membrane proteins, often cell surface receptors. Some membrane protein classes, with a defined number of transmembrane (TM) helices, are receiving much attention because of their great functional and pharmacological importance, such as G protein-coupled receptors possessing 7 TM segments. Although they represent roughly half of all membrane proteins, bitopic proteins (with only 1 TM helix) have so far been less well characterized. Though they include many essential families of receptors, such as adhesion molecules and receptor tyrosine kinases, many of which are excellent targets for biopharmaceuticals (peptides, antibodies, et al.). A growing body of evidence suggests a major role for interactions between TM domains of these receptors in signaling, through homo and heteromeric associations, conformational changes, assembly of signaling platforms, etc. Significantly, mutations within single domains are frequent in human disease, such as cancer or developmental disorders. This review attempts to give an overview of current knowledge about these interactions, from structural data to therapeutic perspectives, focusing on bitopic proteins involved in cell signaling. PMID:20543559

  3. Differentiation of human induced pluripotent stem cell>s to mature functional Purkinje neurons.

    PubMed

    Wang, Shuyan; Wang, Bin; Pan, Na; Fu, Linlin; Wang, Chaodong; Song, Gongru; An, Jing; Liu, Zhongfeng; Zhu, Wanwan; Guan, Yunqian; Xu, Zhi-Qing David; Chan, Piu; Chen, Zhiguo; Zhang, Y Alex

    2015-01-01

    It remains a challenge to differentiate human induced pluripotent stem cell>s (iPSCs) or embryonic stem (ES) cells to Purkinje cells. In this study, we derived iPSCs from human fibroblasts and directed the specification of iPSCs first to Purkinje progenitors, by adding Fgf2 and insulin to the embryoid bodies (EBs) in a time-sensitive manner, which activates the endogenous production of Wnt1 and Fgf8 from EBs that further patterned the cells towards a midbrain-hindbrain-boundary tissue identity. Neph3-positive human Purkinje progenitors were sorted out by using flow cytometry and cultured either alone or with granule cell precursors, in a 2-dimensional or 3-dimensional environment. However, Purkinje progenitors failed to mature further under above conditions. By co-culturing human Purkinje progenitors with rat cerebellar slices, we observed mature Purkinje-like cells with right morphology and marker expression patterns, which yet showed no appropriate membrane properties. Co-culture with human fetal cerebellar slices drove the progenitors to not only morphologically correct but also electrophysiologically functional Purkinje neurons. Neph3-posotive human cells could also survive transplantation into the cerebellum of newborn immunodeficient mice and differentiate to L7- and Calbindin-positive neurons. Obtaining mature human Purkinje cells in vitro has significant implications in studying the mechanisms of spinocerebellar ataxias and other cerebellar diseases. PMID:25782665

  4. Spanning Forests and the q-State Potts Model in the Limit q →0

    NASA Astrophysics Data System (ADS)

    Jacobsen, Jesper Lykke; Salas, Jesús; Sokal, Alan D.

    2005-06-01

    We study the q-state Potts model with nearest-neighbor coupling v=eβJ-1 in the limit q,v → 0 with the ratio w = v/q held fixed. Combinatorially, this limit gives rise to the generating polynomial of spanning forests; physically, it provides information about the Potts-model phase diagram in the neighborhood of (q,v) = (0,0). We have studied this model on the square and triangular lattices, using a transfer-matrix approach at both real and complex values of w. For both lattices, we have computed the symbolic transfer matrices for cylindrical strips of widths 2≤ L ≤ 10, as well as the limiting curves B of partition-function zeros in the complex w-plane. For real w, we find two distinct phases separated by a transition point w= w 0, where w0 =-1/4 (resp. w0=-0.1753 ± 0.0002) for the square (resp. triangular) lattice. For w>w0 we find a non-critical disordered phase that is compatible with the predicted asymptotic freedom as w → +∞. For w

  5. High-performance analysis of single interphase cells with custom DNA probes spanning translocation break points

    NASA Astrophysics Data System (ADS)

    Weier, Heinz-Ulli G.; Munne, S.; Lersch, Robert A.; Marquez, C.; Wu, J.; Pedersen, Roger A.; Fung, Jingly

    1999-06-01

    The chromatin organization of interphase cell nuclei, albeit an object of intense investigation, is only poorly understood. In the past, this has hampered the cytogenetic analysis of tissues derived from specimens where only few cells were actively proliferating or a significant number of metaphase cells could be obtained by induction of growth. Typical examples of such hard to analyze cell systems are solid tumors, germ cells and, to a certain extent, fetal cells such as amniocytes, blastomeres or cytotrophoblasts. Balanced reciprocal translocations that do not disrupt essential genes and thus do not led to disease symptoms exit in less than one percent of the general population. Since the presence of translocations interferes with homologue pairing in meiosis, many of these individuals experience problems in their reproduction, such as reduced fertility, infertility or a history of spontaneous abortions. The majority of translocation carriers enrolled in our in vitro fertilization (IVF) programs carry simple translocations involving only two autosomes. While most translocations are relatively easy to spot in metaphase cells, the majority of cells biopsied from embryos produced by IVF are in interphase and thus unsuitable for analysis by chromosome banding or FISH-painting. We therefore set out to analyze single interphase cells for presence or absence of specific translocations. Our assay, based on fluorescence in situ hybridization (FISH) of breakpoint-spanning DNA probes, detects translocations in interphase by visual microscopic inspection of hybridization domains. Probes are prepared so that they span a breakpoint and cover several hundred kb of DNA adjacent to the breakpoint. On normal chromosomes, such probes label a contiguous stretch of DNA and produce a single hybridization domain per chromosome in interphase cells. The translocation disrupts the hybridization domain and the resulting two fragments appear as physically separated hybridization domains in

  6. Grade Span.

    ERIC Educational Resources Information Center

    Renchler, Ron

    2000-01-01

    This issue reviews grade span, or grade configuration. Catherine Paglin and Jennifer Fager's "Grade Configuration: Who Goes Where?" provides an overview of issues and concerns related to grade spans and supplies profiles of eight Northwest schools with varying grade spans. David F. Wihry, Theodore Coladarci, and Curtis Meadow's "Grade Span and…

  7. Microtubule nucleation remote from centrosomes may explain how asters span large cells.

    PubMed

    Ishihara, Keisuke; Nguyen, Phuong A; Groen, Aaron C; Field, Christine M; Mitchison, Timothy J

    2014-12-16

    A major challenge in cell biology is to understand how nanometer-sized molecules can organize micrometer-sized cells in space and time. One solution in many animal cells is a radial array of microtubules called an aster, which is nucleated by a central organizing center and spans the entire cytoplasm. Frog (here Xenopus laevis) embryos are more than 1 mm in diameter and divide with a defined geometry every 30 min. Like smaller cells, they are organized by asters, which grow, interact, and move to precisely position the cleavage planes. It has been unclear whether asters grow to fill the enormous egg by the same mechanism used in smaller somatic cells, or whether special mechanisms are required. We addressed this question by imaging growing asters in a cell-free system derived from eggs, where asters grew to hundreds of microns in diameter. By tracking marks on the lattice, we found that microtubules could slide outward, but this was not essential for rapid aster growth. Polymer treadmilling did not occur. By measuring the number and positions of microtubule ends over time, we found that most microtubules were nucleated away from the centrosome and that interphase egg cytoplasm supported spontaneous nucleation after a time lag. We propose that aster growth is initiated by centrosomes but that asters grow by propagating a wave of microtubule nucleation stimulated by the presence of preexisting microtubules. PMID:25468969

  8. Engineering Strategies for the Formation of Embryoid Bodies from Human Pluripotent Stem Cell>s

    PubMed Central

    Pettinato, Giuseppe

    2015-01-01

    Human pluripotent stem cell>s (hPSCs) are powerful tools for regenerative therapy and studying human developmental biology, attributing to their ability to differentiate into many functional cell types in the body. The main challenge in realizing hPSC potential is to guide their differentiation in a well-controlled manner. One way to control the cell differentiation process is to recapitulate during in vitro culture the key events in embryogenesis to obtain the three developmental germ layers from which all cell types arise. To achieve this goal, many techniques have been tested to obtain a cellular cluster, an embryoid body (EB), from both mouse and hPSCs. Generation of EBs that are homogeneous in size and shape would allow directed hPSC differentiation into desired cell types in a more synchronous manner and define the roles of cell–cell interaction and spatial organization in lineage specification in a setting similar to in vivo embryonic development. However, previous success in uniform EB formation from mouse PSCs cannot be extrapolated to hPSCs possibly due to the destabilization of adherens junctions on cell surfaces during the dissociation into single cells, making hPSCs extremely vulnerable to cell death. Recently, new advances have emerged to form uniform human embryoid bodies (hEBs) from dissociated single cells of hPSCs. In this review, the existing methods for hEB production from hPSCs and the results on the downstream differentiation of the hEBs are described with emphases on the efficiency, homogeneity, scalability, and reproducibility of the hEB formation process and the yield in terminal differentiation. New trends in hEB production and directed differentiation are discussed. PMID:25900308

  9. Expansion and patterning of cardiovascular progenitors derived from human pluripotent stem cell>s.

    PubMed

    Birket, Matthew J; Ribeiro, Marcelo C; Verkerk, Arie O; Ward, Dorien; Leitoguinho, Ana Rita; den Hartogh, Sabine C; Orlova, Valeria V; Devalla, Harsha D; Schwach, Verena; Bellin, Milena; Passier, Robert; Mummery, Christine L

    2015-09-01

    The inability of multipotent cardiovascular progenitor cells (CPCs) to undergo multiple divisions in culture has precluded stable expansion of precursors of cardiomyocytes and vascular cells. This contrasts with neural progenitors, which can be expanded robustly and are a renewable source of their derivatives. Here we use human pluripotent stem cell>s bearing a cardiac lineage reporter to show that regulated MYC expression enables robust expansion of CPCs with insulin-like growth factor-1 (IGF-1) and a hedgehog pathway agonist. The CPCs can be patterned with morphogens, recreating features of heart field assignment, and controllably differentiated to relatively pure populations of pacemaker-like or ventricular-like cardiomyocytes. The cells are clonogenic and can be expanded for >40 population doublings while retaining the ability to differentiate into cardiomyocytes and vascular cells. Access to CPCs will allow precise recreation of elements of heart development in vitro and facilitate investigation of the molecular basis of cardiac fate determination. This technology is applicable for cardiac disease modeling, toxicology studies and tissue engineering. PMID:26192318

  10. Cellular Zinc Homeostasis Contributes to Neuronal Differentiation in Human Induced Pluripotent Stem Cell>s

    PubMed Central

    Pfaender, Stefanie; Föhr, Karl; Lutz, Anne-Kathrin; Putz, Stefan; Achberger, Kevin; Linta, Leonhard; Liebau, Stefan; Boeckers, Tobias M.; Grabrucker, Andreas M.

    2016-01-01

    Disturbances in neuronal differentiation and function are an underlying factor of many brain disorders. Zinc homeostasis and signaling are important mediators for a normal brain development and function, given that zinc deficiency was shown to result in cognitive and emotional deficits in animal models that might be associated with neurodevelopmental disorders. One underlying mechanism of the observed detrimental effects of zinc deficiency on the brain might be impaired proliferation and differentiation of stem cells participating in neurogenesis. Thus, to examine the molecular mechanisms regulating zinc metabolism and signaling in differentiating neurons, using a protocol for motor neuron differentiation, we characterized the expression of zinc homeostasis genes during neurogenesis using human induced pluripotent stem cell>s (hiPSCs) and evaluated the influence of altered zinc levels on the expression of zinc homeostasis genes, cell survival, cell fate, and neuronal function. Our results show that zinc transporters are highly regulated genes during neuronal differentiation and that low zinc levels are associated with decreased cell survival, altered neuronal differentiation, and, in particular, synaptic function. We conclude that zinc deficiency in a critical time window during brain development might influence brain function by modulating neuronal differentiation. PMID:27247802

  11. Characterizing Pluripotent Stem Cell>s Using the TaqMan® hPSC Scorecard(TM) Panel.

    PubMed

    Fergus, Jeffrey; Quintanilla, Rene; Lakshmipathy, Uma

    2016-01-01

    Rapid technological developments for the efficient generation of footprint-free induced pluripotent stem cell>s (iPSC) enabled the creation of patient-specific iPSC for downstream applications in drug discovery and regenerative medicine. However, the large number of iPSCs, generated from diverse genetic backgrounds using various methods and culture conditions, created a steep challenge for rapid characterization and a demand for standardized methods. Current methods rely on a combination of in vitro and in vivo cellular analyses based on the expression of markers of self-renewal and the ability of the cells to differentiate into cell types representative of the three germ layers as a confirmation of functional pluripotency. These methods, though informative and extensively used, are not ideal for parallel analyses of large numbers of samples and hence not amenable to high-throughput environments. Recently, genetic and epigenetic expression signatures were used to define and confirm cell states, thus providing a surrogate molecular assay that can potentially replace complex in vivo cellular assays such as teratoma formation. In this chapter, we describe a molecular assay for rapid characterization and standardization of pluripotent stem cell>s. The TaqMan(®) hPSC Scorecard™ Panel is a comprehensive gene expression real-time PCR assay that consists of 94 individual q-PCR assays comprised of a combination of control, housekeeping, self-renewal, and lineage-specific genes. The resulting expression data set is analyzed using cloud-based analysis software that compares the expression pattern against a reference standard composed of multiple functionally validated ESC and iPSC lines. This system was successfully used to test several ESC and iPSC lines in their undifferentiated states to confirm their signatures of self renewal, as well as their terminally differentiates states, via spontaneous differentiation and directed differentiation into specific

  12. Factors controlling the proliferative rate, final cell density, and life span of bovine vascular smooth muscle cells in culture.

    PubMed

    Gospodarowicz, D; Hirabayashi, K; Giguère, L; Tauber, J P

    1981-06-01

    Low density vascular smooth muscle (VSM) cell cultures maintained on extracellular-matrix(ECM)-coated dishes and plated in the presence of either plasma or serum will proliferate actively when serum-containing medium is replaced by a synthetic medium supplemented with three factors: high density lipoprotein (HDL, 250 micrograms protein/ml); insulin (2.5 micrograms/ml) or somatomedin C (10 ng/ml); and fibroblast growth factor (FGF, 100 ng/ml) or epidermal growth factor (EGF, 50 ng/ml). The omission of any of these three factors from the synthetic medium results in a lower growth rate of the cultures, as well as in a lower final cell density once cultures reach confluence. When cells are plated in the total absence of serum, transferrin (10 micrograms/ml) is also required to induce optimal cell growth. The effects of the substrate and medium supplements on the life span of VSM cultures have also been analyzed. Cultures maintained on plastic and exposed to medium supplemented with 5% bovine serum underwent 15 generations. However, when maintained on ECM-coated dishes the serum-fed cultures had a life span of at least 88 generations. Likewise, when cultures were maintained in a synthetic medium supplemented with HDL and either FGF or EGF, an effect on the tissue culture life span by the substrate was observed. Cultures maintained on plastic underwent 24 generations, whereas those maintained on ECM-coated dishes could be passaged repeatedly for 58 generations. These experiments demonstrate the influence of the ECM-substrate only in promoting cell growth but also in increasing the longevity of the cultures.

  13. Induced pluripotent stem cell>s restore function in a human cell loss model of open-angle glaucoma.

    PubMed

    Abu-Hassan, Diala W; Li, Xinbo; Ryan, Eileen I; Acott, Ted S; Kelley, Mary J

    2015-03-01

    Normally, trabecular meshwork (TM) and Schlemm's canal inner wall endothelial cells within the aqueous humor outflow pathway maintain intraocular pressure within a narrow safe range. Elevation in intraocular pressure, because of the loss of homeostatic regulation by these outflow pathway cells, is the primary risk factor for vision loss due to glaucomatous optic neuropathy. A notable feature associated with glaucoma is outflow pathway cell loss. Using controlled cell loss in ex vivo perfused human outflow pathway organ culture, we developed compelling experimental evidence that this level of cell loss compromises intraocular pressure homeostatic function. This function was restored by repopulation of the model with fresh TM cells. We then differentiated induced pluripotent stem cell>s (iPSCs) and used them to repopulate this cell depletion model. These differentiated cells (TM-like iPSCs) became similar to TM cells in both morphology and expression patterns. When transplanted, they were able to fully restore intraocular pressure homeostatic function. This successful transplantation of TM-like iPSCs establishes the conceptual feasibility of using autologous stem cells to restore intraocular pressure regulatory function in open-angle glaucoma patients, providing a novel alternative treatment option. PMID:25377070

  14. 5. VIEW OF SPAN ADJOINING SPAN TO THE NORTH OF ...

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

    5. VIEW OF SPAN ADJOINING SPAN TO THE NORTH OF THE VERTICAL LIFT SPAN (IN THE DISTANCE IS THE RECENTLY COMPLETED NEW STATE ROUTE 51 BRIDGE CROSSING THE ILLINOIS RIVER). - Shippingsport Bridge, Spanning Illinois River at State Route 51, La Salle, La Salle County, IL

  15. JNK/SAPK Signaling Is Essential for Efficient Reprogramming of Human Fibroblasts to Induced Pluripotent Stem Cell>s.

    PubMed

    Neganova, Irina; Shmeleva, Evgenija; Munkley, Jennifer; Chichagova, Valeria; Anyfantis, George; Anderson, Rhys; Passos, Joao; Elliott, David J; Armstrong, Lyle; Lako, Majlinda

    2016-05-01

    Reprogramming of somatic cells to the phenotypic state termed "induced pluripotency" is thought to occur through three consecutive stages: initiation, maturation, and stabilisation. The initiation phase is stochastic but nevertheless very important as it sets the gene expression pattern that permits completion of reprogramming; hence a better understanding of this phase and how this is regulated may provide the molecular cues for improving the reprogramming process. c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPKs) are stress activated MAPK kinases that play an essential role in several processes known to be important for successful completion of the initiation phase such as cellular proliferation, mesenchymal to epithelial transition (MET) and cell cycle regulation. In view of this, we postulated that manipulation of this pathway would have significant impacts on reprogramming of human fibroblasts to induced pluripotent stem cell>s. Accordingly, we found that key components of the JNK/SAPK signaling pathway increase expression as early as day 3 of the reprogramming process and continue to rise in reprogrammed cells throughout the initiation and maturation stages. Using both chemical inhibitors and RNA interference of MKK4, MKK7 and JNK1, we tested the role of JNK/SAPK signaling during the initiation stage of neonatal and adult fibroblast reprogramming. These resulted in complete abrogation of fully reprogrammed colonies and the emergence of partially reprogrammed colonies which disaggregated and were lost from culture during the maturation stage. Inhibition of JNK/SAPK signaling resulted in reduced cell proliferation, disruption of MET and loss of the pluripotent phenotype, which either singly or in combination prevented establishment of pluripotent colonies. Together these data provide new evidence for an indispensable role for JNK/SAPK signaling to overcome the well-established molecular barriers in human somatic cell induced

  16. Global indiscriminate methylation in cell-specific gene promoters following reprogramming into human induced pluripotent stem cell>s.

    PubMed

    Nissenbaum, Jonathan; Bar-Nur, Ori; Ben-David, Eyal; Benvenisty, Nissim

    2013-01-01

    Molecular reprogramming of somatic cells into human induced pluripotent stem cell>s (iPSCs) is accompanied by extensive changes in gene expression patterns and epigenetic marks. To better understand the link between gene expression and DNA methylation, we have profiled human somatic cells from different embryonic cell types (endoderm, mesoderm, and parthenogenetic germ cells) and the iPSCs generated from them. We show that reprogramming is accompanied by extensive DNA methylation in CpG-poor promoters, sparing CpG-rich promoters. Intriguingly, methylation in CpG-poor promoters occurred not only in downregulated genes, but also in genes that are not expressed in the parental somatic cells or their respective iPSCs. These genes are predominantly tissue-specific genes of other cell types from different lineages. Our results suggest a role of DNA methylation in the silencing of the somatic cell identity by global nonspecific methylation of tissue-specific genes from all lineages, regardless of their expression in the parental somatic cells. PMID:24371806

  17. Mixed emotions across the adult life span in the United States.

    PubMed

    Schneider, Stefan; Stone, Arthur A

    2015-06-01

    Mixed emotions involve the co-occurrence of positive and negative affect, such that people feel happy and sad at the same time. The purpose of the present study was to investigate age-related differences in the experience of mixed emotions across the adult life span in 2 nationally representative samples of U.S. residents. Data collected by the Princeton Affect and Time Survey (PATS, n = 3,948) and by the 2010 Wellbeing Module of the American Time Use Survey (ATUS, n = 12,828) were analyzed. In both surveys, respondents (aged 15 years or older) provided a detailed time diary about the preceding day and rated their happiness and sadness for 3 of the day's episodes. From these reports, 3 different indices of mixed emotions were derived. Results indicated small, but robust, increases in mixed emotions with age. Linear age increases were consistently evident in both PATS and ATUS, and replicated across the different indices of mixed emotions. There was no significant evidence for curvilinear age trends in either study. Several sociodemographic factors that could plausibly explain age-differences in mixed emotions (e.g., retirement, disability) did not alter the age-effects. The present study adds to the growing literature documenting vital changes in the complexity of emotional experience over the life span.

  18. Hydrogel microfluidics for the patterning of pluripotent stem cell>s.

    PubMed

    Cosson, S; Lutolf, M P

    2014-01-01

    Biomolecular signaling is of utmost importance in governing many biological processes such as the patterning of the developing embryo where biomolecules regulate key cell-fate decisions. In vivo, these factors are presented in a spatiotemporally tightly controlled fashion. Although state-of-the-art microfluidic technologies allow precise biomolecule delivery in time and space, long-term (stem) cell culture at the micro-scale is often far from ideal due to medium evaporation, limited space for cell growth or shear stress. To overcome these challenges, we here introduce a concept based on hydrogel microfluidics for decoupling conventional, macro-scale cell culture from precise biomolecule delivery through a gel layer. We demonstrate the spatiotemporally controlled neuronal commitment of mouse embryonic stem cells via delivery of retinoic acid gradients. This technique should be useful for testing the effect of dose and timing of biomolecules, singly or in combination, on stem cell fate. PMID:24662945

  19. MicroRNA-302 switch to identify and eliminate undifferentiated human pluripotent stem cell>s

    PubMed Central

    Parr, Callum J. C.; Katayama, Shota; Miki, Kenji; Kuang, Yi; Yoshida, Yoshinori; Morizane, Asuka; Takahashi, Jun; Yamanaka, Shinya; Saito, Hirohide

    2016-01-01

    The efficiency of pluripotent stem cell differentiation is highly variable, often resulting in heterogeneous populations that contain undifferentiated cells. Here we developed a sensitive, target-specific, and general method for removing undesired cells before transplantation. MicroRNA-302a-5p (miR-302a) is highly and specifically expressed in human pluripotent stem cell>s and gradually decreases to basal levels during differentiation. We synthesized a new RNA tool, miR-switch, as a live-cell reporter mRNA for miR-302a activity that can specifically detect human induced pluripotent stem cell>s (hiPSCs) down to a spiked level of 0.05% of hiPSCs in a heterogeneous population and can prevent teratoma formation in an in vivo tumorigenicity assay. Automated and selective hiPSC-elimination was achieved by controlling puromycin resistance using the miR-302a switch. Our system uniquely provides sensitive detection of pluripotent stem cell>s and partially differentiated cells. In addition to its ability to eliminate undifferentiated cells, miR-302a switch also holds great potential in investigating the dynamics of differentiation and/or reprograming of live-cells based on intracellular information. PMID:27608814

  20. Chromosome microduplication in somatic cells decreases the genetic stability of human reprogrammed somatic cells and results in pluripotent stem cell>s.

    PubMed

    Yu, Yang; Chang, Liang; Zhao, Hongcui; Li, Rong; Fan, Yong; Qiao, Jie

    2015-01-01

    Human pluripotent stem cell>s, including cloned embryonic and induced pluripotent stem cell>s, offer a limitless cellular source for regenerative medicine. However, their derivation efficiency is limited, and a large proportion of cells are arrested during reprogramming. In the current study, we explored chromosome microdeletion/duplication in arrested and established reprogrammed cells. Our results show that aneuploidy induced by somatic cell nuclear transfer technology is a key factor in the developmental failure of cloned human embryos and primary colonies from implanted cloned blastocysts and that expression patterns of apoptosis-related genes are dynamically altered. Overall, ~20%-53% of arrested primary colonies in induced plurpotent stem cells displayed aneuploidy, and upregulation of P53 and Bax occurred in all arrested primary colonies. Interestingly, when somatic cells with pre-existing chromosomal mutations were used as donor cells, no cloned blastocysts were obtained, and additional chromosomal mutations were detected in the resulting iPS cells following long-term culture, which was not observed in the two iPS cell lines with normal karyotypes. In conclusion, aneuploidy induced by the reprogramming process restricts the derivation of pluripotent stem cell>s, and, more importantly, pre-existing chromosomal mutations enhance the risk of genome instability, which limits the clinical utility of these cells. PMID:25965553

  1. Generation and characterization of functional cardiomyocytes derived from human T cell-derived induced pluripotent stem cell>s.

    PubMed

    Seki, Tomohisa; Yuasa, Shinsuke; Kusumoto, Dai; Kunitomi, Akira; Saito, Yuki; Tohyama, Shugo; Yae, Kojiro; Kishino, Yoshikazu; Okada, Marina; Hashimoto, Hisayuki; Takei, Makoto; Egashira, Toru; Kodaira, Masaki; Kuroda, Yusuke; Tanaka, Atsushi; Okata, Shinichiro; Suzuki, Tomoyuki; Murata, Mitsushige; Fujita, Jun; Fukuda, Keiichi

    2014-01-01

    Induced pluripotent stem cell>s (iPSCs) have been proposed as novel cell sources for genetic disease models and revolutionary clinical therapies. Accordingly, human iPSC-derived cardiomyocytes are potential cell sources for cardiomyocyte transplantation therapy. We previously developed a novel generation method for human peripheral T cell-derived iPSCs (TiPSCs) that uses a minimally invasive approach to obtain patient cells. However, it remained unknown whether TiPSCs with genomic rearrangements in the T cell receptor (TCR) gene could differentiate into functional cardiomyocyte in vitro. To address this issue, we investigated the morphology, gene expression pattern, and electrophysiological properties of TiPSC-derived cardiomyocytes differentiated by floating culture. RT-PCR analysis and immunohistochemistry showed that the TiPSC-derived cardiomyocytes properly express cardiomyocyte markers and ion channels, and show the typical cardiomyocyte morphology. Multiple electrode arrays with application of ion channel inhibitors also revealed normal electrophysiological responses in the TiPSC-derived cardiomyocytes in terms of beating rate and the field potential waveform. In this report, we showed that TiPSCs successfully differentiated into cardiomyocytes with morphology, gene expression patterns, and electrophysiological features typical of native cardiomyocytes. TiPSCs-derived cardiomyocytes obtained from patients by a minimally invasive technique could therefore become disease models for understanding the mechanisms of cardiac disease and cell sources for revolutionary cardiomyocyte therapies. PMID:24465630

  2. Targeted disruption of Pten in ovarian granulosa cells enhances ovulation and extends the life span of luteal cells.

    PubMed

    Fan, Heng-Yu; Liu, Zhilin; Cahill, Nicola; Richards, JoAnne S

    2008-09-01

    FSH activates the phosphatidylinositol-3 kinase (PI3K)/acute transforming retrovirus thymoma protein kinase pathway and thereby enhances granulosa cell differentiation in culture. To identify the physiological role of the PI3K pathway in vivo we disrupted the PI3K suppressor, Pten, in developing ovarian follicles. To selectively disrupt Pten expression in granulosa cells, Ptenfl/fl mice were mated with transgenic mice expressing cAMP response element recombinase driven by Cyp19 promoter (Cyp19-Cre). The resultant Pten mutant mice were fertile, ovulated more oocytes, and produced moderately more pups than control mice. These physiological differences in the Pten mutant mice were associated with hyperactivation of the PI3K/acute transforming retrovirus thymoma protein kinase pathway, decreased susceptibility to apoptosis, and increased proliferation of mutant granulosa cells. Strikingly, corpora lutea of the Pten mutant mice persisted longer than those of control mice. Although the follicular and luteal cell steroidogenesis in Ptenfl/fl;Cyp19-Cre mice was similar to controls, viable nonsteroidogenic luteal cells escaped structural luteolysis. These findings provide the novel evidence that Pten impacts the survival/life span of granulosa/luteal cells and that its loss not only results in the facilitated ovulation but also in the persistence of nonsteroidogenic luteal structures in the adult mouse ovary.

  3. Targeted Disruption of Pten in Ovarian Granulosa Cells Enhances Ovulation and Extends the Life Span of Luteal Cells

    PubMed Central

    Fan, Heng-Yu; Liu, Zhilin; Cahill, Nicola; Richards, JoAnne S.

    2008-01-01

    FSH activates the phosphatidylinositol-3 kinase (PI3K)/acute transforming retrovirus thymoma protein kinase pathway and thereby enhances granulosa cell differentiation in culture. To identify the physiological role of the PI3K pathway in vivo we disrupted the PI3K suppressor, Pten, in developing ovarian follicles. To selectively disrupt Pten expression in granulosa cells, Ptenfl/fl mice were mated with transgenic mice expressing cAMP response element recombinase driven by Cyp19 promoter (Cyp19-Cre). The resultant Pten mutant mice were fertile, ovulated more oocytes, and produced moderately more pups than control mice. These physiological differences in the Pten mutant mice were associated with hyperactivation of the PI3K/acute transforming retrovirus thymoma protein kinase pathway, decreased susceptibility to apoptosis, and increased proliferation of mutant granulosa cells. Strikingly, corpora lutea of the Pten mutant mice persisted longer than those of control mice. Although the follicular and luteal cell steroidogenesis in Ptenfl/fl;Cyp19-Cre mice was similar to controls, viable nonsteroidogenic luteal cells escaped structural luteolysis. These findings provide the novel evidence that Pten impacts the survival/life span of granulosa/luteal cells and that its loss not only results in the facilitated ovulation but also in the persistence of nonsteroidogenic luteal structures in the adult mouse ovary. PMID:18606860

  4. Switching between self-renewal and lineage commitment of human induced pluripotent stem cell>s via cell-substrate and cell-cell interactions on a dendrimer-immobilized surface.

    PubMed

    Kim, Mee-Hae; Kino-oka, Masahiro

    2014-07-01

    Understanding mechanisms that govern cell fate determination of human induced pluripotent stem cell>s (hiPSCs) could assist in maintenance of the undifferentiated state during cell expansion. We used polyamidoamine dendrimer surfaces with first-generation (G1), third-generation (G3) and fifth-generation (G5) of dendron structure in cultures of hiPSCs with SNL feeder cells. Cells on the G1 surface formed tightly packed colony with close cell-cell contacts during division and migration; those on the G3 surface exhibited loose or dispersed colony pattern by enhanced migration. On the G5 surface, formation of aggregated colony with ring-like structures occurred spontaneously. We found that the substrate-adsorbed fibronectin and feeder cell-secreted fibronectin appeared elevated levels with the varied generation numbers of dendrimer surfaces. This subsequently resulted in cell migration and in activation of paxillin of hiPSCs. Location-dependent expression of Rac1 induced rearrangement of E-cadherin-mediated cell-cell interactions on dendrimer surfaces, and was associated with alterations in the cell and colony morphology, and migratory behavior. Furthermore, caspase-3 occurred in apoptotic cells on dendrimer surfaces, concomitant with the loss of E-cadherin-mediated cell-cell interactions. Cells on the G1 surface were maintained in an undifferentiated state, while those on the G5 surface exhibited the early commitment to differentiation toward endodermal fates. We conclude that morphological changes associated with altered migration on the dendrimer surfaces were responsible for the coordinated regulation of balance between cell-cell and cell-substrate interactions, thereby switching their transition from self-renewal state to early endoderm differentiation in hiPSCs. PMID:24746960

  5. End state renal disease among Native Americanspan>s, 1983-86.

    PubMed Central

    Newman, J M; Marfin, A A; Eggers, P W; Helgerson, S D

    1990-01-01

    We used data reported to Medicare from 1983 through 1986 to determine the incidence of end-stage renal disease (ESRD) among Native Americans and Whites in the United States. The 1,075 Native American cases represented an annual incidence, age-adjusted to the White population, of 269 per million, 2.8 times the rate for Whites. Fifty-six percent of Native American cases and 27 percent of the White cases were attributed to diabetes, indicating that ESRD is a major problem. Diabetes control provides the greatest opportunity for prevention. PMID:2305914

  6. Carrier-specific breakpoint-spanning DNA probes: an approach to preimplantation genetic diagnosis in interphase cells.

    PubMed

    Cassel, M J; Munné, S; Fung, J; Weier, H U

    1997-09-01

    Carriers of chromosomal inversions or other balanced rearrangements represent a significant fraction of patients in in-vitro fertilization (IVF) programmes due to recurrent reproductive problems. In most cases, chromosomal imbalance in fertilized oocytes is incompatible with embryo survival leading to increased rates of spontaneous abortions. Assuming that a fraction of the germ cells is karyotypically normal, these patients would greatly benefit from efficient procedures for generation and use of breakpoint-specific DNA hybridization probes in preconception and preimplantation genetic diagnosis (PGD). We describe the generation of such patient-specific probes to discriminate between normal and aberrant chromosomes in interphase cells. First, a large insert DNA library was screened for probes that bind adjacent to the chromosomal breakpoints or span them. Then, probe and hybridization parameters were optimized using white blood cells from the carrier to increase in hybridization signal intensity and contrast. Finally, the probes were tested on target cells (typically polar bodies or blastomeres) and a decision about the colour labelling scheme was made, before the probes can be used for preconception or preimplantation genetic analysis. Thus, it was demonstrated that cells with known structural abnormalities could be detected, based on hybridization of breakpoint spanning yeast artificial chromosome (YAC) DNA probes in interphase cells.

  7. The potential of induced pluripotent stem cell>s in models of neurological disorders: implications on future therapy.

    PubMed

    Crook, Jeremy Micah; Wallace, Gordon; Tomaskovic-Crook, Eva

    2015-03-01

    There is an urgent need for new and advanced approaches to modeling the pathological mechanisms of complex human neurological disorders. This is underscored by the decline in pharmaceutical research and development efficiency resulting in a relative decrease in new drug launches in the last several decades. Induced pluripotent stem cell>s represent a new tool to overcome many of the shortcomings of conventional methods, enabling live human neural cell modeling of complex conditions relating to aberrant neurodevelopment, such as schizophrenia, epilepsy and autism as well as age-associated neurodegeneration. This review considers the current status of induced pluripotent stem cell-based modeling of neurological disorders, canvassing proven and putative advantages, current constraints, and future prospects of next-generation culture systems for biomedical research and translation. PMID:25664599

  8. Marmoset induced pluripotent stem cell>s: Robust neural differentiation following pretreatment with dimethyl sulfoxide.

    PubMed

    Qiu, Zhifang; Mishra, Anuja; Li, Miao; Farnsworth, Steven L; Guerra, Bernadette; Lanford, Robert E; Hornsby, Peter J

    2015-07-01

    The marmoset is an important nonhuman primate model for regenerative medicine. For experimental autologous cell therapy based on induced pluripotent (iPS) cells in the marmoset, cells must be able to undergo robust and reliable directed differentiation that will not require customization for each specific iPS cell clone. When marmoset iPS cells were aggregated in a hanging drop format for 3 days, followed by exposure to dual SMAD inhibitors and retinoic acid in monolayer culture for 3 days, we found substantial variability in the response of different iPS cell clones. However, when clones were pretreated with 0.05-2% dimethyl sulfoxide (DMSO) for 24 hours, all clones showed a very similar maximal response to the directed differentiation scheme. Peak responses were observed at 0.5% DMSO in two clones and at 1% DMSO in a third clone. When patterns of gene expression were examined by microarray analysis, hierarchical clustering showed very similar responses in all 3 clones when they were pretreated with optimal DMSO concentrations. The change in phenotype following exposure to DMSO and the 6 day hanging drop/monolayer treatment was confirmed by immunocytochemistry. Analysis of DNA content in DMSO-exposed cells indicated that it is unlikely that DMSO acts by causing cells to exit from the cell cycle. This approach should be generally valuable in the directed neural differentiation of pluripotent cells for experimental cell therapy. PMID:26070112

  9. Efficient hepatic differentiation of human induced pluripotent stem cell>s in a three-dimensional microscale culture.

    PubMed

    Zhang, Ran-Ran; Takebe, Takanori; Miyazaki, Leina; Takayama, Maho; Koike, Hiroyuki; Kimura, Masaki; Enomura, Masahiro; Zheng, Yun-Wen; Sekine, Keisuke; Taniguchi, Hideki

    2014-01-01

    Human induced pluripotent stem cell>s (iPSCs) represent a novel source of hepatocytes for drug development, disease modeling studies, and regenerative therapy for the treatment of liver diseases. A number of protocols for generating functional hepatocytes have been reported worldwide; however, reproducible and efficient differentiation remained challenging under conventional two-dimensional (2D) culture. In this study, we describe an efficient differentiation protocol for generating functional hepatocyte-like cells from human iPSC-derived homogenous hepatic endoderm cells combined with three-dimensional (3D) microscale culture system. First, hepatic endoderm cells (iPSC-HEs) were directly differentiated using two-step approaches, and then cultured in the 3D micropattern plate. Human iPSC-HEs quickly reaggregated and formed hundreds of round-shaped spheroids at day 4 of cell plating. The size distribution of iPSC-HEs derived spheroids was relatively uniform around 100-200 μm in diameter. After 14 days, iPSC-HEs efficiently differentiated into hepatocyte-like cells in terms of hepatic maker gene expression compared with conventional 2D approach. We conclude that our scalable and three-dimensional culture system would be one promising approach to generate a huge number of hepatocyte-like cells from human iPSCs aiming at future industrial and clinical applications. PMID:25173165

  10. Induced pluripotent stem cell>s for modeling neurological disorders.

    PubMed

    Russo, Fabiele B; Cugola, Fernanda R; Fernandes, Isabella R; Pignatari, Graciela C; Beltrão-Braga, Patricia C B

    2015-12-24

    Several diseases have been successfully modeled since the development of induced pluripotent stem cell (iPSC) technology in 2006. Since then, methods for increased reprogramming efficiency and cell culture maintenance have been optimized and many protocols for differentiating stem cell lines have been successfully developed, allowing the generation of several cellular subtypes in vitro. Gene editing technologies have also greatly advanced lately, enhancing disease-specific phenotypes by creating isogenic cell lines, allowing mutations to be corrected in affected samples or inserted in control lines. Neurological disorders have benefited the most from iPSC-disease modeling for its capability for generating disease-relevant cell types in vitro from the central nervous system, such as neurons and glial cells, otherwise only available from post-mortem samples. Patient-specific iPSC-derived neural cells can recapitulate the phenotypes of these diseases and therefore, considerably enrich our understanding of pathogenesis, disease mechanism and facilitate the development of drug screening platforms for novel therapeutic targets. Here, we review the accomplishments and the current progress in human neurological disorders by using iPSC modeling for Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal muscular atrophy, amyotrophic lateral sclerosis, duchenne muscular dystrophy, schizophrenia and autism spectrum disorders, which include Timothy syndrome, Fragile X syndrome, Angelman syndrome, Prader-Willi syndrome, Phelan-McDermid, Rett syndrome as well as Nonsyndromic Autism. PMID:26722648

  11. Cell specific radiation dosimetry in skeleton from life-span carcinogenesis studies. Final report

    SciTech Connect

    Webster, S.S.J.

    1993-04-05

    The osteogenic sarcoma is the dominant life-threatening pathology in lifespan studies of beagles exposed to alpha-emitting bone-seeking radionuclides. It was deduced from these studies that certain skeletal sites are more prone to develop tumors. This project sought to determine the bone cells at risk and their cell-specific radiation dose. The cell-specific radiation dose values are related to loss and high Ra-226 and Pu-239 induced osteogenic sarcoma sites, to test different dose response hypothesis and predict the extent of effects in humans.

  12. Cell specific radiation dosimetry in skeleton from life-span carcinogenesis studies

    SciTech Connect

    Webster, S.S.J.

    1993-04-05

    The osteogenic sarcoma is the dominant life-threatening pathology in lifespan studies of beagles exposed to alpha-emitting bone-seeking radionuclides. It was deduced from these studies that certain skeletal sites are more prone to develop tumors. This project sought to determine the bone cells at risk and their cell-specific radiation dose. The cell-specific radiation dose values are related to loss and high Ra-226 and Pu-239 induced osteogenic sarcoma sites, to test different dose response hypothesis and predict the extent of effects in humans.

  13. Cernunnos Deficiency Reduces Thymocyte Life Span and Alters the T Cell Repertoire in Mice and Humans

    PubMed Central

    Vera, Gabriella; Rivera-Munoz, Paola; Abramowski, Vincent; Malivert, Laurent; Lim, Annick; Bole-Feysot, Christine; Martin, Christelle; Florkin, Benoit; Latour, Sylvain; Revy, Patrick

    2013-01-01

    Cernunnos is a DNA repair factor of the nonhomologous end-joining machinery. Its deficiency in humans causes radiosensitive severe combined immune deficiency (SCID) with microcephaly, characterized in part by a profound lymphopenia. In contrast to the human condition, the immune system of Cernunnos knockout (KO) mice is not overwhelmingly affected. In particular, Cernunnos is dispensable during V(D)J recombination in lymphoid cells. Nevertheless, the viability of thymocytes is reduced in Cernunnos KO mice, owing to the chronic activation of a P53-dependent DNA damage response. This translates into a qualitative alteration of the T cell repertoire to one in which the most distal Vα and Jα segments are missing. This results in the contraction of discrete T cell populations, such as invariant natural killer T (iNKT) and mucosa-associated invariant T (MAIT) cells, in both humans and mice. PMID:23207905

  14. Confined 3D microenvironment regulates early differentiation in human pluripotent stem cell>s.

    PubMed

    Giobbe, Giovanni G; Zagallo, Monica; Riello, Massimo; Serena, Elena; Masi, Giulia; Barzon, Luisa; Di Camillo, Barbara; Elvassore, Nicola

    2012-12-01

    The therapeutic potential of human pluripotent stem (hPS) cells is threatened, among various problems, by the difficulty to homogenously direct cell differentiation into specific lineages. The transition from hPSC into committed differentiated cells is accompanied by secretome activity, remodeling of extracellular matrix and self-organization into germ layers. In this work, we aimed to investigate how different three-dimensional microenvironments regulate the early differentiation of the three germ layers in human embryonic stem (hES) cells derived embryoid bodies. In particular, a permeable, biocompatible, hydrogel microwell array was specifically designed for recreating a confined niche in which EB secreted molecules accumulate in accordance with hydrogel diffusional cut-off. Fluorescence recovery after photobleaching technique was performed to accurately evaluate hydrogel permeability, mesh size and diffusional cutoff for soluble molecules. Three different culture conditions of EB culture were analyzed: suspension, confinement in microwells of width/depth ratio 1:1 and 1:2. Results show that EBs cultured in microwells are viable and have comparable average size after 8 days culture. Whole genome microarrays show that significative differential gene expression was observed between suspension and confined EBs culture. In particular, EBs culture in microwells promotes the expression of genes involved in pattern specification processes, brain development, ectoderm and endoderm differentiation. On the contrary, suspension EBs express instead genes involved in mesoderm specification and heart development. These results suggest that local accumulation of EBs secreted molecules drives differentiation patterns, as confirmed by immunofluorescence of germ layer markers, in hydrogel confined EB culture from both hES cells and human induced pluripotent stem (hiPS) cells. Our findings highlight an additional potential role of biomaterial in controlling hPSC differentiation

  15. Are Mesenchymal Cells Indeed Pluripotent Stem Cell>s or Just Stromal Cells? OCT-4 and VSELs Biology Has Led to Better Understanding.

    PubMed

    Bhartiya, Deepa

    2013-01-01

    Stem cells have excited researchers because of their potential to regenerate. However, which stem cells will be the best candidate for regenerative medicine remains an enigma. Compared to pluripotent stem cell>s with associated risks of immune rejection and teratoma formation, adult stem cells especially the mesenchymal stem cells (MSCs) are hyped to be a suitable alternate since they also exhibit pluripotent properties. This review shows that there is a subpopulation of pluripotent very small embryonic-like stem cells (VSELs) among MSCs culture. The two populations differ from each other in expression pattern of OCT-4. VSELs exhibit nuclear OCT-4A, whereas the MSCs have cytoplasmic OCT-4B, similar to our earlier findings in testis and ovary. Pluripotent VSELs with nuclear OCT-4A exist in various adult body organs, and the immediate progenitors express cytoplasmic OCT-4B which is eventually lost as the cell differentiates further. To conclude it is essential to discriminate between nuclear and cytoplasmic OCT-4 expression and also to acknowledge the presence of VSELs. PMID:24187558

  16. Sickle Cell Disease: An Opportunity for Palliative Care across the Life Span

    PubMed Central

    Johnson, Bonnye; Mack, A. Kyle; Labotka, Richard; Molokie, Robert E.

    2010-01-01

    Sickle cell disease is a chronic illness that impacts patients physically and emotionally and can do so at an early age. An ecological model of palliative care that involves improved communication among the health care team, patients, and their families can be beneficial. Open and honest communication regarding advance care planning, disease management, relief of pain and other symptoms, and bereavement and grief are all important for the patient, family, and health care team. Given the multiple acute and chronic complications of sickle cell disease, an approach to care that is holistic and comprehensive may help to improve a patient’s biological function and the perceived health, functional status, and quality of life of the patient and family. PMID:20804884

  17. Murine cytomegalovirus with a deletion of genes spanning HindIII-J and -I displays altered cell and tissue tropism.

    PubMed

    Cavanaugh, V J; Stenberg, R M; Staley, T L; Virgin, H W; MacDonald, M R; Paetzold, S; Farrell, H E; Rawlinson, W D; Campbell, A E

    1996-03-01

    Murine cytomegalovirus (MCMV) gene products dispensable for growth in cell culture are likely to have important functions within the infected host, influencing tissue tropism, dissemination, or immunological responses against the virus. To identify such genes, our strategy was to delete large regions of the MCMV genome likely to contain genes nonessential for virus replication in NIH 3T3 cells. Mutant virus RV7 contained a deletion of 7.7 kb spanning portions of MCMV HindIII-J and -I. This virus grew comparably to wild-type (WT) virus in NIH 3T3 fibroblasts, primary embryo fibroblasts, and bone marrow macrophages. However, RV7 failed to replicate in target organs of immunocompetent BALB/c mice and severe combined immunodeficient mice, which are exquisitely sensitive to MCMV infection. This defect in vivo growth may be related to the observation that RV7 grew poorly in the peritoneal macrophage cell line IC-21, which is highly permissive for growth of WT MCMV. Two other mutant viruses with an insertion or smaller deletion in the region common to the RV7 deletion grew comparably to WT virus in the macrophage cell line and replicated in salivary gland tissue. The poor growth of RV7 in IC-21 cells was due to a block in immediate-early gene expression, as levels of RNA from immediate-early gene IE1 were reduced eightfold compared with levels for WT virus in macrophages infected with RV7. Consequently, levels of RNA from early and late genes were also reduced. The lower expression of IE1 in RV7-infected IC-21 macrophages was not due to defective entry of virus into the cells, as equal amounts of viral DNA were present in cells 3 h after infection with RV7 or WT MCMV. These studies demonstrate that deletion of sequences in HindIII-J and -I confer altered cell and tissue tropism. PMID:8627652

  18. Murine cytomegalovirus with a deletion of genes spanning HindIII-J and -I displays altered cell and tissue tropism.

    PubMed Central

    Cavanaugh, V J; Stenberg, R M; Staley, T L; Virgin, H W; MacDonald, M R; Paetzold, S; Farrell, H E; Rawlinson, W D; Campbell, A E

    1996-01-01

    Murine cytomegalovirus (MCMV) gene products dispensable for growth in cell culture are likely to have important functions within the infected host, influencing tissue tropism, dissemination, or immunological responses against the virus. To identify such genes, our strategy was to delete large regions of the MCMV genome likely to contain genes nonessential for virus replication in NIH 3T3 cells. Mutant virus RV7 contained a deletion of 7.7 kb spanning portions of MCMV HindIII-J and -I. This virus grew comparably to wild-type (WT) virus in NIH 3T3 fibroblasts, primary embryo fibroblasts, and bone marrow macrophages. However, RV7 failed to replicate in target organs of immunocompetent BALB/c mice and severe combined immunodeficient mice, which are exquisitely sensitive to MCMV infection. This defect in vivo growth may be related to the observation that RV7 grew poorly in the peritoneal macrophage cell line IC-21, which is highly permissive for growth of WT MCMV. Two other mutant viruses with an insertion or smaller deletion in the region common to the RV7 deletion grew comparably to WT virus in the macrophage cell line and replicated in salivary gland tissue. The poor growth of RV7 in IC-21 cells was due to a block in immediate-early gene expression, as levels of RNA from immediate-early gene IE1 were reduced eightfold compared with levels for WT virus in macrophages infected with RV7. Consequently, levels of RNA from early and late genes were also reduced. The lower expression of IE1 in RV7-infected IC-21 macrophages was not due to defective entry of virus into the cells, as equal amounts of viral DNA were present in cells 3 h after infection with RV7 or WT MCMV. These studies demonstrate that deletion of sequences in HindIII-J and -I confer altered cell and tissue tropism. PMID:8627652

  19. A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cell>s.

    PubMed

    Marchetto, Maria C N; Carromeu, Cassiano; Acab, Allan; Yu, Diana; Yeo, Gene W; Mu, Yangling; Chen, Gong; Gage, Fred H; Muotri, Alysson R

    2010-11-12

    Autism spectrum disorders (ASD) are complex neurodevelopmental diseases in which different combinations of genetic mutations may contribute to the phenotype. Using Rett syndrome (RTT) as an ASD genetic model, we developed a culture system using induced pluripotent stem cell>s (iPSCs) from RTT patients' fibroblasts. RTT patients' iPSCs are able to undergo X-inactivation and generate functional neurons. Neurons derived from RTT-iPSCs had fewer synapses, reduced spine density, smaller soma size, altered calcium signaling and electrophysiological defects when compared to controls. Our data uncovered early alterations in developing human RTT neurons. Finally, we used RTT neurons to test the effects of drugs in rescuing synaptic defects. Our data provide evidence of an unexplored developmental window, before disease onset, in RTT syndrome where potential therapies could be successfully employed. Our model recapitulates early stages of a human neurodevelopmental disease and represents a promising cellular tool for drug screening, diagnosis and personalized treatment. PMID:21074045

  20. Urine-derived induced pluripotent stem cell>s as a modeling tool to study rare human diseases

    PubMed Central

    Shi, Liang; Cui, Yazhou; Luan, Jing; Zhou, Xiaoyan; Han, Jinxiang

    2016-01-01

    Summary Rare diseases with a low prevalence are a key public health issue because the causes of those diseases are difficult to determine and those diseases lack a clearly established or curative treatment. Thus, investigating the molecular mechanisms that underlie the pathology of rare diseases and facilitating the development of novel therapies using disease models is crucial. Human induced pluripotent stem cell>s (iPSCs) are well suited to modeling rare diseases since they have the capacity for self-renewal and pluripotency. In addition, iPSC technology provides a valuable tool to generate patient-specific iPSCs. These cells can be differentiated into cell types that have been affected by a disease. These cells would circumvent ethical concerns and avoid immunological rejection, so they could be used in cell replacement therapy or regenerative medicine. To date, human iPSCs could have been generated from multiple donor sources, such as skin, adipose tissue, and peripheral blood. However, these cells are obtained via invasive procedures. In contrast, several groups of researchers have found that urine may be a better source for producing iPSCs from normal individuals or patients. This review discusses urinary iPSC (UiPSC) as a candidate for modeling rare diseases. Cells obtained from urine have overwhelming advantages compared to other donor sources since they are safely, affordably, and frequently obtained and they are readily obtained from patients. The use of iPSC-based models is also discussed. UiPSCs may prove to be a key means of modeling rare diseases and they may facilitate the treatment of those diseases in the future. PMID:27672542

  1. Differentiation of human limbal-derived induced pluripotent stem cell>s into limbal-like epithelium.

    PubMed

    Sareen, Dhruv; Saghizadeh, Mehrnoosh; Ornelas, Loren; Winkler, Michael A; Narwani, Kavita; Sahabian, Anais; Funari, Vincent A; Tang, Jie; Spurka, Lindsay; Punj, Vasu; Maguen, Ezra; Rabinowitz, Yaron S; Svendsen, Clive N; Ljubimov, Alexander V

    2014-09-01

    Limbal epithelial stem cell (LESC) deficiency (LSCD) leads to corneal abnormalities resulting in compromised vision and blindness. LSCD can be potentially treated by transplantation of appropriate cells, which should be easily expandable and bankable. Induced pluripotent stem cell>s (iPSCs) are a promising source of transplantable LESCs. The purpose of this study was to generate human iPSCs and direct them to limbal differentiation by maintaining them on natural substrata mimicking the native LESC niche, including feederless denuded human amniotic membrane (HAM) and de-epithelialized corneas. These iPSCs were generated with nonintegrating vectors from human primary limbal epithelial cells. This choice of parent cells was supposed to enhance limbal cell differentiation from iPSCs by partial retention of parental epigenetic signatures in iPSCs. When the gene methylation patterns were compared in iPSCs to parental LESCs using Illumina global methylation arrays, limbal-derived iPSCs had fewer unique methylation changes than fibroblast-derived iPSCs, suggesting retention of epigenetic memory during reprogramming. Limbal iPSCs cultured for 2 weeks on HAM developed markedly higher expression of putative LESC markers ABCG2, ΔNp63α, keratins 14, 15, and 17, N-cadherin, and TrkA than did fibroblast iPSCs. On HAM culture, the methylation profiles of select limbal iPSC genes (including NTRK1, coding for TrkA protein) became closer to the parental cells, but fibroblast iPSCs remained closer to parental fibroblasts. On denuded air-lifted corneas, limbal iPSCs even upregulated differentiated corneal keratins 3 and 12. These data emphasize the importance of the natural niche and limbal tissue of origin in generating iPSCs as a LESC source with translational potential for LSCD treatment. PMID:25069777

  2. SHARP OBLIQUE PERSPECTIVE OF DECK AND APPROACH SPANS ALONG WITH ...

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

    SHARP OBLIQUE PERSPECTIVE OF DECK AND APPROACH SPANS ALONG WITH PRINCIPLE CANTILEVER SPAN SHARP OBLIQUE PERSPECTIVE OF DECK AND APPROACH SPANS ALONG WITH PRINCIPLE CANTILEVER SPAN SHARP OBLIQUE PERSPECTIVE OF DECK AND APPROACH SPANS ALONG WITH PRINCIPLE CANTILEVER SPAN SHARP OBLIQUE PERSPECTIVE OF DECK AND APPROACH SPANS ALONG WITH PRINCIPLE CANTILEVER SPAN SHARP OBLIQUE PERSPECTIVE OF DECK AND APPROACH SPANS ALONG WITH PRINCIPLE CANTILEVER SPAN SHARP OBLIQUE PERSPECTIVE OF DECK AND APPROACH SPANS ALONG WITH PRINCIPLE CANTILEVER SPAN vSHARP OBLIQUE PERSPECTIVE OF DECK AND APPROACH SPANS ALONG WITH PRINCIPLE CANTILEVER SPAN SHARP OBLIQUE PERSPECTIVE OF DECK AND APPROACH SPANS ALONG WITH PRINCIPLE CANTILEVER SPAN SHARP OBLIQUE PERSPECTIVE OF DECK AND APPROACH SPANS ALONG WITH PRINCIPLE CANTILEVER SPAN - Snake River Bridge at Lyons' Ferry, State Route 261 spanning Snake River, Starbuck, Columbia County, WA

  3. 7. DETAIL OF LATERAL BRACING OF THROUGH TRUSS SPAN (THIS ...

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

    7. DETAIL OF LATERAL BRACING OF THROUGH TRUSS SPAN (THIS SPAN IS IMMEDIATELY SOUTH OF THE VERTICAL LIFT SPAN). - Shippingsport Bridge, Spanning Illinois River at State Route 51, La Salle, La Salle County, IL

  4. Beta-cell function, incretin effect, and incretin hormones in obese youth along the span of glucose tolerance from normal to prediabetes to Type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Using the hyperglycemic and euglycemic clamp, we demonstrated impaired Beta-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled Beta-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. Bet...

  5. The lysine residue in the membrane-spanning domain of the beta chain is necessary for cell surface expression of the T cell antigen receptor

    PubMed Central

    1988-01-01

    The TCR is a complex receptor composed of seven polypeptide chains consisting of a ligand-binding subunit, Ti, and a putative signal- transducing subunit, CD3. Phylogenetically conserved charged amino acid residues within the membrane-spanning domains present in all seven chains of the TCR have been proposed to be important in the association between Ti and CD3. Using a Ti beta chain-deficient mutant of the cell line Jurkat, site-directed mutagenesis and transfection of Ti beta chain cDNA was performed to assess the importance of the lysine residue at position 290 within the membrane-spanning domain of the Ti beta chain to expression of the TCR complex. These studies demonstrated that the lysine residue, and not simply conservation of either basic charge or secondary structure, is important at this position. PMID:2974063

  6. Full membrane spanning self-assembled monolayers as model systems for UHV-based studies of cell-penetrating peptides

    SciTech Connect

    Franz, Johannes; Graham, Daniel J.; Baio, Joe E.; Lelle, Marco; Peneva, Kalina; Müllen, Klaus; Castner, David G.; Weidner, Tobias

    2015-03-01

    Biophysical studies of the interaction of peptides with model membranes provide a simple yet effective approach to understand the transport of peptides and peptide based drug carriers across the cell membrane. Therein, the authors discuss the use of self-assembled monolayers fabricated from the full membrane-spanning thiol (FMST) 3-((14-((4'-((5-methyl-1-phenyl-35-(phytanyl)oxy-6,9,12,15,18,21,24,27,30,33,37-undecaoxa-2,3-dithiahenpentacontan-51-yl)oxy)-[1,1'-biphenyl]-4-yl)oxy)tetradecyl)oxy)-2-(phytanyl)oxy glycerol for ultrahigh vacuum (UHV) based experiments. UHV-based methods such as electron spectroscopy and mass spectrometry can provide important information about how peptides bind and interact with membranes, especially with the hydrophobic core of a lipid bilayer. Moreover, near-edge x-ray absorption fine structure spectra and x-ray photoelectron spectroscopy (XPS) data showed that FMST forms UHV-stable and ordered films on gold. XPS and time of flight secondary ion mass spectrometry depth profiles indicated that a proline-rich amphipathic cell-penetrating peptide, known as sweet arrow peptide is located at the outer perimeter of the model membrane.

  7. Generation of Functional Cardiomyocytes from the Synoviocytes of Patients with Rheumatoid Arthritis via Induced Pluripotent Stem Cell>s

    PubMed Central

    Lee, Jaecheol; Jung, Seung Min; Ebert, Antje D.; Wu, Haodi; Diecke, Sebastian; Kim, Youngkyun; Yi, Hyoju; Park, Sung-Hwan; Ju, Ji Hyeon

    2016-01-01

    Cardiovascular disease is a leading cause of morbidity in rheumatoid arthritis (RA) patients. This study aimed to generate and characterise cardiomyocytes from induced pluripotent stem cell>s (iPSCs) of RA patients. Fibroblast-like synoviocytes (FLSs) from patients with RA and osteoarthritis (OA) were successfully reprogrammed into RA-iPSCs and OA-iPSCs, respectively. The pluripotency of iPSCs was confirmed by quantitative reverse transcription-polymerase chain reaction and immunofluorescence staining. Established iPSCs were differentiated into cardiomyocytes using a small molecule-based monolayer differentiation protocol. Within 12 days of cardiac differentiation from patient-specific and control-iPSCs, spontaneously beating cardiomyocytes (iPSC-CMs) were observed. All iPSC-CMs exhibited a reliable sarcomeric structure stained with antibodies against cardiac markers and similar expression profiles of cardiac-specific genes. Intracellular calcium signalling was recorded to compare calcium-handling properties among cardiomyocytes differentiated from the three groups of iPSCs. RA-iPSC-CMs had a lower amplitude and a shorter duration of calcium transients than the control groups. Peak tangential stress and the maximum contractile rate were also decreased in RA-iPSC-CMs, suggesting that contractility was reduced. This study demonstrates the successful generation of functional cardiomyocytes from pathogenic synovial cells in RA patients through iPSC reprogramming. Research using RA-iPSC-CMs might provide an opportunity to investigate the pathophysiology of cardiac involvement in RA. PMID:27609119

  8. Controlling expansion and cardiomyogenic differentiation of human pluripotent stem cell>s in scalable suspension culture.

    PubMed

    Kempf, Henning; Olmer, Ruth; Kropp, Christina; Rückert, Michael; Jara-Avaca, Monica; Robles-Diaz, Diana; Franke, Annika; Elliott, David A; Wojciechowski, Daniel; Fischer, Martin; Roa Lara, Angelica; Kensah, George; Gruh, Ina; Haverich, Axel; Martin, Ulrich; Zweigerdt, Robert

    2014-12-01

    To harness the potential of human pluripotent stem cell>s (hPSCs), an abundant supply of their progenies is required. Here, hPSC expansion as matrix-independent aggregates in suspension culture was combined with cardiomyogenic differentiation using chemical Wnt pathway modulators. A multiwell screen was scaled up to stirred Erlenmeyer flasks and subsequently to tank bioreactors, applying controlled feeding strategies (batch and cyclic perfusion). Cardiomyogenesis was sensitive to the GSK3 inhibitor CHIR99021 concentration, whereas the aggregate size was no prevailing factor across culture platforms. However, in bioreactors, the pattern of aggregate formation in the expansion phase dominated subsequent differentiation. Global profiling revealed a culture-dependent expression of BMP agonists/antagonists, suggesting their decisive role in cell-fate determination. Furthermore, metallothionein was discovered as a potentially stress-related marker in hPSCs. In 100 ml bioreactors, the production of 40 million predominantly ventricular-like cardiomyocytes (up to 85% purity) was enabled that were directly applicable to bioartificial cardiac tissue formation. PMID:25454631

  9. Differentiation patterns of mouse embryonic stem cells and induced pluripotent stem cell>s into neurons.

    PubMed

    Nakamura, Mai; Kamishibahara, Yu; Kitazawa, Ayako; Kawaguchi, Hideo; Shimizu, Norio

    2016-05-01

    Mouse embryonic stem (ES) cells and induced pluripotent stem (iPS) cells have the ability to differentiate in vitro into various cell lineages including neurons. The differentiation of these cells into neurons has potential applications in regenerative medicine. Previously, we reported that a chick dorsal root ganglion (DRG)-conditioned medium (CM) promoted the differentiation of mouse ES and iPS cells into neurons. Here, we used real-time PCR to investigate the differentiation patterns of ES and iPS cells into neurons when DRG-CM was added. DRG-CM promoted the expression levels of βIII-tubulin gene (a marker of postmitotic neurons) in ES and iPS cells. ES cells differentiated into neurons faster than iPS cells, and the maximum peaks of gene expression involved in motor, sensory, and dopaminergic neurons were different. Rho kinase (ROCK) inhibitors could be very valuable at numerous stages in the production and use of stem cells in basic research and eventual cell-based therapies. Thus, we investigated whether the addition of a ROCK inhibitor Y-27632 and DRG-CM on the basis of the differentiation patterns promotes the neuronal differentiation of ES cells. When the ROCK inhibitor was added to the culture medium at the initial stages of cultivation, it stimulated the neuronal differentiation of ES cells more strongly than that stimulated by DRG-CM. Moreover, the combination of the ROCK inhibitor and DRG-CM promoted the neuronal differentiation of ES cells when the ROCK inhibitor was added to the culture medium at day 3. The ROCK inhibitor may be useful for promoting neuronal differentiation of ES cells. PMID:25354731

  10. Solid state cell with anolyte

    SciTech Connect

    Barnette, L. H.; Liang, C. C.

    1985-06-25

    A solid state cell having a solid cathode, a solid electrolyte, and a solid anolyte comprised of at least 50% by volume of ionically conductive materials such as the electrolye and 50% or less by volume of an active metal. The anolyte is either the cell anode or alternatively the anolyte is an additional structural member within said cell positioned between an anode, comprised of the same active metal, and the solid electrolyte.

  11. 1. View south. North elevation Walpole span, link span, ...

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

    1. View south. North elevation - Walpole span, link span, and Westminster span. - Walpole-Westminster Bridge, Spanning Connecticut River between Walpole, NH & Westminster, VT, Walpole, Cheshire County, NH

  12. 2. View northeast. South elevation Westminster span, link span, ...

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

    2. View northeast. South elevation - Westminster span, link span, Walpole span. - Walpole-Westminster Bridge, Spanning Connecticut River between Walpole, NH & Westminster, VT, Walpole, Cheshire County, NH

  13. State of the States: Fuel Cells in America

    SciTech Connect

    2011-06-15

    This 2011 report, written by Fuel Cells 2000 and partially funded by the U.S. Department of Energy's Fuel Cell Technologies Program, provides an update of fuel cell and hydrogen activity in the 50 states and District of Columbia. State activities reported include new policies and funding, recent and planned fuel cell and hydrogen installations, and recent activities by state industries and universities.

  14. Structural model for the organization of the transmembrane spans of the human red-cell anion exchanger (band 3; AE1).

    PubMed Central

    Groves, J D; Tanner, M J

    1999-01-01

    We have examined the functional co-assembly of non-complementary pairs of N- and C-terminal polypeptide fragments of the anion transport domain (b3mem) of human red-cell band 3. cDNA clones encoding non-contiguous pairs of fragments with one transmembrane (TM) region omitted, or overlapping pairs of fragments with between one and ten TM regions duplicated, were co-expressed in Xenopus oocytes and a cell-free translation system. Stilbene disulphonate-sensitive chloride uptake assays in oocytes revealed that the omission of any single TM region of b3mem except spans 6 and 7 caused a complete loss of functional expression. In contrast, co-expressed pairs of fragments overlapping a single TM region 5, 6, 7, 8, 9-10 or 11-12 retained a high level of functionality, whereas fragments overlapping the clusters of TM regions 2-5, 4-5, 5-8 and 8-10 also mediated some stilbene disulphonate-sensitive uptake. The co-assembly of N- or C-terminal fragments with intact band 3, b3mem or other fragments was examined by co-immunoprecipitation in non-denaturing detergent solutions by using monoclonal antibodies against the termini of b3mem. All the fragments, except for TM spans 13-14, co-immunoprecipitated with b3mem. The medium-sized N-terminal fragments comprising spans 1-6, 1-7 or 1-8 co-immunoprecipitated particularly strongly with the C-terminal fragments containing spans 8-14 or 9-14. The fragments comprising spans 1-4 or 1-12 co-immunoprecipitated less extensively than the other N-terminal fragments with either b3mem or C-terminal fragments. There is sufficient flexibility in the structure of b3mem to allow the inclusion of at least one duplicated TM span without a loss of function. We propose a working model for the organization of TM spans of dimeric band 3 based on current evidence. PMID:10585856

  15. Birthweight-specific infant mortality for native Americanspan>s compared with whites, six states, 1980.

    PubMed Central

    Vanlandingham, M J; Buehler, J W; Hogue, C J; Strauss, L T

    1988-01-01

    We used data from the National Infant Mortality Surveillance (NIMS) project to compare birthweights and birthweight-specific mortality risks among Native American and White infants. Because race categories in NIMS were limited to White, Black, and all, we studied six states in which greater than 85 per cent of newborns who were neither White nor Black were Native American. In these states, the infant mortality risk (IMR) among Native Americans was 15.3 deaths per 1,000 live births compared with 8.7 deaths among Whites, relative risk (RR) = 1.8 (95% CI = 1.5-2.0). The percentage of Native American infants with less than 2,500 g birthweights was 5.8 per cent versus 5.0 per cent for White infants. Birthweight-specific neonatal mortality risks were similar for the two race groups, but birthweight-specific postneonatal mortality risks (PNMRs) were more than three times as high among Native Americans compared with Whites for infants of greater than or equal to 2,500 g birthweight. PNMRs were elevated for most causes of death and for all categories for maternal age, educational attainment, trimester prenatal care began, and number of previous live births. Leading causes of postneonatal death among Native Americans of greater than or equal to 2,500 g birthweight were sudden infant death syndrome and infections. PMID:3354730

  16. Fuzzy approximate entropy analysis of resting state fMRI signal complexity across the adult life span.

    PubMed

    Sokunbi, Moses O; Cameron, George G; Ahearn, Trevor S; Murray, Alison D; Staff, Roger T

    2015-11-01

    In this study, we present a method for measuring functional magnetic resonance imaging (fMRI) signal complexity using fuzzy approximate entropy (fApEn) and compare it with the established sample entropy (SampEn). Here we use resting state fMRI dataset of 86 healthy adults (41 males) with age ranging from 19 to 85 years. We expect the complexity of the resting state fMRI signals measured to be consistent with the Goldberger/Lipsitz model for robustness where healthier (younger) and more robust systems exhibit more complexity in their physiological output and system complexity decrease with age. The mean whole brain fApEn demonstrated significant negative correlation (r = -0.472, p<0.001) with age. In comparison, SampEn produced a non-significant negative correlation (r = -0.099, p = 0.367). fApEn also demonstrated a significant (p < 0.05) negative correlation with age regionally (frontal, parietal, limbic, temporal and cerebellum parietal lobes). There was no significant correlation regionally between the SampEn maps and age. These results support the Goldberger/Lipsitz model for robustness and have shown that fApEn is potentially a sensitive new method for the complexity analysis of fMRI data.

  17. State of the States: Fuel Cells in America, 2010

    SciTech Connect

    Curtin, Sandra; Delmont, Elizabeth; Gangi, Jennifer

    2010-04-01

    This report, written by Fuel Cells 2000 and partially funded by the U.S. Department of Energy's Fuel Cell Technologies Program, provides a snapshot of fuel cell and hydrogen activity in the 50 states and District of Columbia. It features the top five fuel cell states (in alphabetical order): California, Connecticut, New York, Ohio, and South Carolina. State activities reported include supportive fuel cell and hydrogen policies, installations and demonstrations, road maps, and level of activism.

  18. Calendar life-span versus fission life-span of Paramecium aurelia.

    PubMed

    Smith-Sonneborn, J; Reed, J C

    1976-01-01

    The hypothesis that paramecia use fissions, not days, to measure length of cell life-span was investigated. Parallel cell lines were grown at 27 C and at 24 C. The daily fission rate of the cells at 24 C was lower than at 27 C. If the cells count fissions, not days, the life-span in fissions should remain unchanged, whereas the cell life-span in days should increase in the lines with reduced daily fission rate. The results showed a significant increase in cell life-span in days when the cells were cultivated for 70-100% of their life cycle at 24 C. The life-span as measured by fissions, however, remained unchanged regardless of the time of the life cycle when cells were shifted to 24 C. The data indicate that, as a model system for cellular aging, paramecia are comparable to cells which use cell doublings to measure life-span. PMID:1244399

  19. 3. VIEW NORTH SHOWING FIXED SPAN, COVERED SPAN, MOVEABLE TRANSITION ...

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

    3. VIEW NORTH SHOWING FIXED SPAN, COVERED SPAN, MOVEABLE TRANSITION SPAN AND PONTOON FLOATING SPAN - Lacey V. Murrow Memorial Floating Bridge, Spanning Lake Washington at I-90, Seattle, King County, WA

  20. Efficient endoderm induction from human pluripotent stem cell>s by logically directing signals controlling lineage bifurcations.

    PubMed

    Loh, Kyle M; Ang, Lay Teng; Zhang, Jingyao; Kumar, Vibhor; Ang, Jasmin; Auyeong, Jun Qiang; Lee, Kian Leong; Choo, Siew Hua; Lim, Christina Y Y; Nichane, Massimo; Tan, Junru; Noghabi, Monireh Soroush; Azzola, Lisa; Ng, Elizabeth S; Durruthy-Durruthy, Jens; Sebastiano, Vittorio; Poellinger, Lorenz; Elefanty, Andrew G; Stanley, Edouard G; Chen, Qingfeng; Prabhakar, Shyam; Weissman, Irving L; Lim, Bing

    2014-02-01

    Human pluripotent stem cell (hPSC) differentiation typically yields heterogeneous populations. Knowledge of signals controlling embryonic lineage bifurcations could efficiently yield desired cell types through exclusion of alternate fates. Therefore, we revisited signals driving induction and anterior-posterior patterning of definitive endoderm to generate a coherent roadmap for endoderm differentiation. With striking temporal dynamics, BMP and Wnt initially specified anterior primitive streak (progenitor to endoderm), yet, 24 hr later, suppressed endoderm and induced mesoderm. At lineage bifurcations, cross-repressive signals separated mutually exclusive fates; TGF-β and BMP/MAPK respectively induced pancreas versus liver from endoderm by suppressing the alternate lineage. We systematically blockaded alternate fates throughout multiple consecutive bifurcations, thereby efficiently differentiating multiple hPSC lines exclusively into endoderm and its derivatives. Comprehensive transcriptional and chromatin mapping of highly pure endodermal populations revealed that endodermal enhancers existed in a surprising diversity of "pre-enhancer" states before activation, reflecting the establishment of a permissive chromatin landscape as a prelude to differentiation. PMID:24412311

  1. Core promoter sequence of SEMG I spans between the two putative GATA-1 binding domains and is responsive to IL-4 and IL-6 in myeloma cells.

    PubMed

    Zhang, Yana; Wang, Zhiqing; Zhang, Jian; Lim, Seah H

    2009-01-01

    Semenogelin (SEMG) I is a cancer-testis antigen expressed in myeloma cells. SEMG I expression is upregulated by IL-4, IL-6 and 5-azacytidine. In this study, we set out to define the core promoter sequence needed for the expression of SEMG I in myeloma cells. We found that nucleotide sequences spanning the two putative GATA-1 binding domains are vital for the primary regulation of SEMG I promoter function while the other parts of the promoter sequence are responsible for the fine adjustment of the core promoter function. The core promoter sequence is responsive to the enhancing effect of IL-4 and IL-6. PMID:18602691

  2. Universal cardiac induction of human pluripotent stem cell>s in two and three-dimensional formats: implications for in vitro maturation.

    PubMed

    Zhang, Miao; Schulte, Jan Sebastian; Heinick, Alexander; Piccini, Ilaria; Rao, Jyoti; Quaranta, Roberto; Zeuschner, Dagmar; Malan, Daniela; Kim, Kee-Pyo; Röpke, Albrecht; Sasse, Philipp; Araúzo-Bravo, Marcos; Seebohm, Guiscard; Schöler, Hans; Fabritz, Larissa; Kirchhof, Paulus; Müller, Frank Ulrich; Greber, Boris

    2015-05-01

    Directed cardiac differentiation of human pluripotent stem cell>s (hPSCs) enables disease modeling, investigation of human cardiogenesis, as well as large-scale production of cardiomyocytes (CMs) for translational purposes. Multiple CM differentiation protocols have been developed to individually address specific requirements of these diverse applications, such as enhanced purity at a small scale or mass production at a larger scale. However, there is no universal high-efficiency procedure for generating CMs both in two-dimensional (2D) and three-dimensional (3D) culture formats, and undefined or complex media additives compromise functional analysis or cost-efficient upscaling. Using systematic combinatorial optimization, we have narrowed down the key requirements for efficient cardiac induction of hPSCs. This implied differentiation in simple serum and serum albumin-free basal media, mediated by a minimal set of signaling pathway manipulations at moderate factor concentrations. The method was applicable both to 2D and 3D culture formats as well as to independent hPSC lines. Global time-course gene expression analyses over extended time periods and in comparison with human heart tissue were used to monitor culture-induced maturation of the resulting CMs. This suggested that hPSC-CMs obtained with our procedure reach a rather stable transcriptomic state after approximately 4 weeks of culture. The underlying gene expression changes correlated well with a decline of immature characteristics as well as with a gain of structural and physiological maturation features within this time frame. These data link gene expression patterns of hPSC-CMs to functional readouts and thus define the cornerstones of culture-induced maturation. PMID:25639979

  3. SPAN: Ocean science

    NASA Technical Reports Server (NTRS)

    Thomas, Valerie L.; Koblinsky, Chester J.; Webster, Ferris; Zlotnicki, Victor; Green, James L.

    1987-01-01

    The Space Physics Analysis Network (SPAN) is a multi-mission, correlative data comparison network which links space and Earth science research and data analysis computers. It provides a common working environment for sharing computer resources, sharing computer peripherals, solving proprietary problems, and providing the potential for significant time and cost savings for correlative data analysis. This is one of a series of discipline-specific SPAN documents which are intended to complement the SPAN primer and SPAN Management documents. Their purpose is to provide the discipline scientists with a comprehensive set of documents to assist in the use of SPAN for discipline specific scientific research.

  4. State of the States. Fuel Cells in America 2012

    SciTech Connect

    Curtin, Sandra; Gangi, Jennifer; Skukowski, Ryan

    2012-09-01

    This report, written by Fuel Cells 2000 and partially funded by the U.S. Department of Energy's Fuel Cell Technologies Program, continues to build on the April 2010 State of the States report that provided a snapshot of fuel cell and hydrogen activity in the 50 states and District of Columbia. This update report provides more details on the progress and activities that happened since the second report, issued in June 2011. Details reported for each state include new policies and funding, recent and planned fuel cell and hydrogen installations, and recent activity by state industry and universities.

  5. Self-Organizing 3D Human Neural Tissue Derived from Induced Pluripotent Stem Cell>s Recapitulate Alzheimer’s Disease Phenotypes

    PubMed Central

    Raja, Waseem K.; Mungenast, Alison E.; Lin, Yuan-Ta; Ko, Tak; Abdurrob, Fatema; Seo, Jinsoo; Tsai, Li-Huei

    2016-01-01

    The dismal success rate of clinical trials for Alzheimer’s disease (AD) motivates us to develop model systems of AD pathology that have higher predictive validity. The advent of induced pluripotent stem cell>s (iPSCs) allows us to model pathology and study disease mechanisms directly in human neural cells from healthy individual as well as AD patients. However, two-dimensional culture systems do not recapitulate the complexity of neural tissue, and phenotypes such as extracellular protein aggregation are difficult to observe. We report brain organoids that use pluripotent stem cell>s derived from AD patients and recapitulate AD-like pathologies such as amyloid aggregation, hyperphosphorylated tau protein, and endosome abnormalities. These pathologies are observed in an age-dependent manner in organoids derived from multiple familial AD (fAD) patients harboring amyloid precursor protein (APP) duplication or presenilin1 (PSEN1) mutation, compared to controls. The incidence of AD pathology was consistent amongst several fAD lines, which carried different mutations. Although these are complex assemblies of neural tissue, they are also highly amenable to experimental manipulation. We find that treatment of patient-derived organoids with β- and γ-secretase inhibitors significantly reduces amyloid and tau pathology. Moreover, these results show the potential of this model system to greatly increase the translatability of pre-clinical drug discovery in AD. PMID:27622770

  6. SPAN: Astronomy and astrophysics

    NASA Technical Reports Server (NTRS)

    Thomas, Valerie L.; Green, James L.; Warren, Wayne H., Jr.; Lopez-Swafford, Brian

    1987-01-01

    The Space Physics Analysis Network (SPAN) is a multi-mission, correlative data comparison network which links science research and data analysis computers in the U.S., Canada, and Europe. The purpose of this document is to provide Astronomy and Astrophysics scientists, currently reachable on SPAN, with basic information and contacts for access to correlative data bases, star catalogs, and other astrophysic facilities accessible over SPAN.

  7. State of the States: Fuel Cells in America 2013

    SciTech Connect

    Curtin, Sandra; Gangi, Jennifer

    2013-10-31

    This October 2013 report, written by Fuel Cells 2000 and partially funded by the U.S. Department of Energy's Fuel Cell Technologies Office, continues to build on the April 2010 State of the States report that provided a snapshot of fuel cell and hydrogen activity in the 50 states and District of Columbia. This update report provides more details on the progress and activities that happened since the third report, issued in August 2012.

  8. 37. VIEW SOUTHWEST, CENTER SPAN OF THREE SPAN FRAME SHOWING ...

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

    37. VIEW SOUTHWEST, CENTER SPAN OF THREE SPAN FRAME SHOWING BRACING SYSTEM (SPAN 50) - Route 1 Extension, Southbound Viaduct, Spanning Conrail Yards, Wilson Avenue, Delancy Street, & South Street on Routes 1 & 9 Southbound, Newark, Essex County, NJ

  9. 4. View northwest. South elevation Walpole span, link span, ...

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

    4. View northwest. South elevation - Walpole span, link span, and Westminster span. Structure on east pier is stream level gauge station. - Walpole-Westminster Bridge, Spanning Connecticut River between Walpole, NH & Westminster, VT, Walpole, Cheshire County, NH

  10. 4. DETAIL VIEW FIXED SPAN INCLUDING TRUSS, MOVEABLE SPAN WHICH ...

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

    4. DETAIL VIEW FIXED SPAN INCLUDING TRUSS, MOVEABLE SPAN WHICH THE NEXT UNIT TO THE RIGHT, AND FIRST UNIT OF PONTOON FLOATING SPAN. - Lacey V. Murrow Memorial Floating Bridge, Spanning Lake Washington at I-90, Seattle, King County, WA

  11. 20. Vertical lift span, north tower, bascule span, and Warren ...

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

    20. Vertical lift span, north tower, bascule span, and Warren truss spans, facing north - Sault Ste. Marie International Railroad Bridge, Spanning Soo Locks at St. Marys Falls Canal, Sault Ste. Marie, Chippewa County, MI

  12. State of the States: Fuel Cells in America 2015

    SciTech Connect

    Curtin, Sandra; Jennifer, Gangi

    2015-12-17

    This December 2015 report, the sixth in a series, provides a comprehensive analysis of state activities supporting fuel cell and hydrogen technology, profiles of leading states, and a catalog of recent installations, policies, funding, and deployments around the country.

  13. The Cell Wall Protein Ecm33 of Candida albicans is Involved in Chronological Life Span, Morphogenesis, Cell Wall Regeneration, Stress Tolerance, and Host-Cell Interaction.

    PubMed

    Gil-Bona, Ana; Reales-Calderon, Jose A; Parra-Giraldo, Claudia M; Martinez-Lopez, Raquel; Monteoliva, Lucia; Gil, Concha

    2016-01-01

    Ecm33 is a glycosylphosphatidylinositol-anchored protein in the human pathogen Candida albicans. This protein is known to be involved in fungal cell wall integrity (CWI) and is also critical for normal virulence in the mouse model of hematogenously disseminated candidiasis, but its function remains unknown. In this work, several phenotypic analyses of the C. albicans ecm33/ecm33 mutant (RML2U) were performed. We observed that RML2U displays the inability of protoplast to regenerate the cell wall, activation of the CWI pathway, hypersensitivity to temperature, osmotic and oxidative stresses and a shortened chronological lifespan. During the exponential and stationary culture phases, nuclear and actin staining revealed the possible arrest of the cell cycle in RML2U cells. Interestingly, a "veil growth," never previously described in C. albicans, was serendipitously observed under static stationary cells. The cells that formed this structure were also observed in cornmeal liquid cultures. These cells are giant, round cells, without DNA, and contain large vacuoles, similar to autophagic cells observed in other fungi. Furthermore, RML2U was phagocytozed more than the wild-type strain by macrophages at earlier time points, but the damage caused to the mouse cells was less than with the wild-type strain. Additionally, the percentage of RML2U apoptotic cells after interaction with macrophages was fewer than in the wild-type strain.

  14. The Cell Wall Protein Ecm33 of Candida albicans is Involved in Chronological Life Span, Morphogenesis, Cell Wall Regeneration, Stress Tolerance, and Host–Cell Interaction

    PubMed Central

    Gil-Bona, Ana; Reales-Calderon, Jose A.; Parra-Giraldo, Claudia M.; Martinez-Lopez, Raquel; Monteoliva, Lucia; Gil, Concha

    2016-01-01

    Ecm33 is a glycosylphosphatidylinositol-anchored protein in the human pathogen Candida albicans. This protein is known to be involved in fungal cell wall integrity (CWI) and is also critical for normal virulence in the mouse model of hematogenously disseminated candidiasis, but its function remains unknown. In this work, several phenotypic analyses of the C. albicans ecm33/ecm33 mutant (RML2U) were performed. We observed that RML2U displays the inability of protoplast to regenerate the cell wall, activation of the CWI pathway, hypersensitivity to temperature, osmotic and oxidative stresses and a shortened chronological lifespan. During the exponential and stationary culture phases, nuclear and actin staining revealed the possible arrest of the cell cycle in RML2U cells. Interestingly, a “veil growth,” never previously described in C. albicans, was serendipitously observed under static stationary cells. The cells that formed this structure were also observed in cornmeal liquid cultures. These cells are giant, round cells, without DNA, and contain large vacuoles, similar to autophagic cells observed in other fungi. Furthermore, RML2U was phagocytozed more than the wild-type strain by macrophages at earlier time points, but the damage caused to the mouse cells was less than with the wild-type strain. Additionally, the percentage of RML2U apoptotic cells after interaction with macrophages was fewer than in the wild-type strain. PMID:26870022

  15. Dopaminergic neurons differentiating from LRRK2 G2019S induced pluripotent stem cell>s show early neuritic branching defects

    PubMed Central

    Borgs, Laurence; Peyre, Elise; Alix, Philippe; Hanon, Kevin; Grobarczyk, Benjamin; Godin, Juliette D.; Purnelle, Audrey; Krusy, Nathalie; Maquet, Pierre; Lefebvre, Philippe; Seutin, Vincent; Malgrange, Brigitte; Nguyen, Laurent

    2016-01-01

    Some mutations of the LRRK2 gene underlie autosomal dominant form of Parkinson’s disease (PD). The G2019S is a common mutation that accounts for about 2% of PD cases. To understand the pathophysiology of this mutation and its possible developmental implications, we developed an in vitro assay to model PD with human induced pluripotent stem cell>s (hiPSCs) reprogrammed from skin fibroblasts of PD patients suffering from the LRKK2 G2019S mutation. We differentiated the hiPSCs into neural stem cells (NSCs) and further into dopaminergic neurons. Here we show that NSCs bearing the mutation tend to differentiate less efficiently into dopaminergic neurons and that the latter exhibit significant branching defects as compared to their controls. PMID:27640816

  16. Long-term self-renewal of human pluripotent stem cell>s on peptide-decorated poly(OEGMA-co-HEMA) brushes under fully defined conditions.

    PubMed

    Deng, Y; Zhang, X; Zhao, X; Li, Q; Ye, Z; Li, Z; Liu, Y; Zhou, Y; Ma, H; Pan, G; Pei, D; Fang, J; Wei, S

    2013-11-01

    Realization of the full potential of human induced pluripotent stem cell>s (hiPSC) in clinical applications requires the development of well-defined culture conditions for their long-term growth and directed differentiation. This paper describes a novel fully defined synthetic peptide-decorated substrate that supports self-renewal of hiPSC in commercially available xeno-free, chemically defined medium. The Au surface was deposited by a poly(OEGMA-co-HEMA) film, using the surface-initiated polymerization method (SIP) with the further step of carboxylation. The hiPSC generated from umbilical cord mesenchymal cells were successfully cultured for 10 passages on the peptide-tethered poly(OEGMA-co-HEMA) brushes for the first time. Cells maintained their characteristic morphology, proliferation and expressed high levels of markers of pluripotency, similar to the cells cultured on Matrigel™. Moreover, the cell adhesion could be tuned by the pattern and peptide concentration on the substrate. This well-defined, xeno-free and safe substrate, which supports long-term proliferation and self-renewal of hiPSC, will not only help to accelerate the translational perspectives of hiPSC, but also provide a platform to elucidate the underlying molecular mechanisms that regulate stem cell proliferation and differentiation via SIP technology. PMID:23891809

  17. Genetically engineering self-organization of human pluripotent stem cell>s into a liver bud-like tissue using Gata6

    PubMed Central

    Guye, Patrick; Ebrahimkhani, Mohammad R.; Kipniss, Nathan; Velazquez, Jeremy J.; Schoenfeld, Eldi; Kiani, Samira; Griffith, Linda G.; Weiss, Ron

    2016-01-01

    Human induced pluripotent stem cell>s (hiPSCs) have potential for personalized and regenerative medicine. While most of the methods using these cells have focused on deriving homogenous populations of specialized cells, there has been modest success in producing hiPSC-derived organotypic tissues or organoids. Here we present a novel approach for generating and then co-differentiating hiPSC-derived progenitors. With a genetically engineered pulse of GATA-binding protein 6 (GATA6) expression, we initiate rapid emergence of all three germ layers as a complex function of GATA6 expression levels and tissue context. Within 2 weeks we obtain a complex tissue that recapitulates early developmental processes and exhibits a liver bud-like phenotype, including haematopoietic and stromal cells as well as a neuronal niche. Collectively, our approach demonstrates derivation of complex tissues from hiPSCs using a single autologous hiPSCs as source and generates a range of stromal cells that co-develop with parenchymal cells to form tissues. PMID:26732624

  18. Distinct MicroRNA Expression Signatures of Porcine Induced Pluripotent Stem Cell>s under Mouse and Human ESC Culture Conditions.

    PubMed

    Zhang, Wei; Zhong, Liang; Wang, Jing; Han, Jianyong

    2016-01-01

    It is well known that microRNAs play a very important role in regulating reprogramming, pluripotency and cell fate decisions. Porcine induced pluripotent stem cell>s (piPSCs) are now available for studying the pluripotent regulation network in pigs. Two types of piPSCs have been derived from human and mouse embryonic stem cell (ESC) culture conditions: hpiPSCs and mpiPSCs, respectively. The hpiPSCs were morphologically similar to human ESCs, and the mpiPSCs resembled mouse ESCs. However, our current understanding of the role of microRNAs in the development of piPSCs is still very limited. Here, we performed small RNA sequencing to profile the miRNA expression in porcine fibroblasts (pEFs), hpiPSCs and mpiPSCs. There were 22 differential expressed (DE) miRNAs down-regulated in both types of piPSCs compared with pEFs, such as ssc-miR-145-5p and ssc-miR-98. There were 27 DE miRNAs up-regulated in both types of piPSCs compared with pEFs. Among these up-regulated DE miRNAs in piPSCs, ssc-miR-217, ssc-miR-216, ssc-miR-142-5p, ssc-miR-182, ssc-miR-183 and ssc-miR-96-5p have much higher expression levels in mpiPSCs, while ssc-miR-106a, ssc-miR-363, ssc-miR-146b, ssc-miR-195, ssc-miR-497, ssc-miR-935 and ssc-miR-20b highly expressed in hpiPSCs. Quantitative stem-loop RT-PCR was performed to confirm selected DE miRNAs expression levels. The results were consistent with small RNA sequencing. Different expression patterns were observed for key miRNA clusters, such as the miR-17-92 cluster, the let-7 family, the miR-106a-363 cluster and the miR-182-183 cluster, in the mpiPSCs and hpiPSCs. Novel miRNAs were also predicted in this study, including a putative porcine miR-302 cluster: ssc_38503, ssc_38503 and ssc_38501 (which resemble human miR-302a and miR-302b) found in both types of piPSCs. The miR-106a-363 cluster and putative miR-302 cluster increased the reprogramming efficiency of pEFs. The study revealed significant differences in the miRNA signatures of hpiPSCs and

  19. Common chromosomal fragile site FRA16D sequence: identification of the FOR gene spanning FRA16D and homozygous deletions and translocation breakpoints in cancer cells.

    PubMed

    Ried, K; Finnis, M; Hobson, L; Mangelsdorf, M; Dayan, S; Nancarrow, J K; Woollatt, E; Kremmidiotis, G; Gardner, A; Venter, D; Baker, E; Richards, R I

    2000-07-01

    Fluorescence in situ hybridization of a tile path of DNA subclones has previously enabled the cyto-genetic definition of the minimal DNA sequence which spans the FRA16D common chromosomal fragile site, located at 16q23.2. Homozygous deletion of the FRA16D locus has been reported in adenocarcinomas of stomach, colon, lung and ovary. We have sequenced the 270 kb containing the FRA16D fragile site and the minimal homozygously deleted region in tumour cells. This sequence enabled localization of some of the tumour cell breakpoints to regions which contain AT-rich secondary structures similar to those associated with the FRA10B and FRA16B rare fragile sites. The FRA16D DNA sequence also led to the identification of an alternatively spliced gene, named FOR (fragile site FRA16D oxidoreductase), exons of which span both the fragile site and the minimal region of homozygous deletion. In addition, the complete DNA sequence of the FRA16D-containing FOR intron reveals no evidence of additional authentic transcripts. Alternatively spliced FOR transcripts (FOR I, FOR II and FOR III) encode proteins which share N-terminal WW domains and differ at their C-terminus, with FOR III having a truncated oxidoreductase domain. FRA16D-associated deletions selectively affect the FOR gene transcripts. Three out of five previously mapped translocation breakpoints in multiple myeloma are also located within the FOR gene. FOR is therefore the principle genetic target for DNA instability at 16q23.2 and perturbation of FOR function is likely to contribute to the biological consequences of DNA instability at FRA16D in cancer cells. PMID:10861292

  20. Glycomic Characterization of Induced Pluripotent Stem Cell>s Derived from a Patient Suffering from Phosphomannomutase 2 Congenital Disorder of Glycosylation (PMM2-CDG).

    PubMed

    Thiesler, Christina T; Cajic, Samanta; Hoffmann, Dirk; Thiel, Christian; van Diepen, Laura; Hennig, René; Sgodda, Malte; Weiβmann, Robert; Reichl, Udo; Steinemann, Doris; Diekmann, Ulf; Huber, Nicolas M B; Oberbeck, Astrid; Cantz, Tobias; Kuss, Andreas W; Körner, Christian; Schambach, Axel; Rapp, Erdmann; Buettner, Falk F R

    2016-04-01

    PMM2-CDG, formerly known as congenital disorder of glycosylation-Ia (CDG-Ia), is caused by mutations in the gene encoding phosphomannomutase 2 (PMM2). This disease is the most frequent form of inherited CDG-diseases affecting protein N-glycosylation in human. PMM2-CDG is a multisystemic disease with severe psychomotor and mental retardation. In order to study the pathophysiology of PMM2-CDG in a human cell culture model, we generated induced pluripotent stem cell>s (iPSCs) from fibroblasts of a PMM2-CDG-patient (PMM2-iPSCs). Expression of pluripotency factors andin vitrodifferentiation into cell types of the three germ layers was unaffected in the analyzed clone PMM2-iPSC-C3 compared with nondiseased human pluripotent stem cell>s (hPSCs), revealing no broader influence of the PMM2 mutation on pluripotency in cell culture. Analysis of gene expression by deep-sequencing did not show obvious differences in the transcriptome between PMM2-iPSC-C3 and nondiseased hPSCs. By multiplexed capillary gel electrophoresis coupled to laser induced fluorescence detection (xCGE-LIF) we could show that PMM2-iPSC-C3 exhibit the common hPSC N-glycosylation pattern with high-mannose-type N-glycans as the predominant species. However, phosphomannomutase activity of PMM2-iPSC-C3 was 27% compared with control hPSCs and lectin staining revealed an overall reduced protein glycosylation. In addition, quantitative assessment of N-glycosylation by xCGE-LIF showed an up to 40% reduction of high-mannose-type N-glycans in PMM2-iPSC-C3, which was in concordance to the observed reduction of the Glc3Man9GlcNAc2 lipid-linked oligosaccharide compared with control hPSCs. Thus we could model the PMM2-CDG disease phenotype of hypoglycosylation with patient derived iPSCsin vitro Knock-down ofPMM2by shRNA in PMM2-iPSC-C3 led to a residual activity of 5% and to a further reduction of the level of N-glycosylation. Taken together we have developed human stem cell-based cell culture models with

  1. Utility of Induced Pluripotent Stem Cell>s for the Study and Treatment of Genetic Diseases: Focus on Childhood Neurological Disorders

    PubMed Central

    Barral, Serena; Kurian, Manju A.

    2016-01-01

    The study of neurological disorders often presents with significant challenges due to the inaccessibility of human neuronal cells for further investigation. Advances in cellular reprogramming techniques, have however provided a new source of human cells for laboratory-based research. Patient-derived induced pluripotent stem cell>s (iPSCs) can now be robustly differentiated into specific neural subtypes, including dopaminergic, inhibitory GABAergic, motorneurons and cortical neurons. These neurons can then be utilized for in vitro studies to elucidate molecular causes underpinning neurological disease. Although human iPSC-derived neuronal models are increasingly regarded as a useful tool in cell biology, there are a number of limitations, including the relatively early, fetal stage of differentiated cells and the mainly two dimensional, simple nature of the in vitro system. Furthermore, clonal variation is a well-described phenomenon in iPSC lines. In order to account for this, robust baseline data from multiple control lines is necessary to determine whether a particular gene defect leads to a specific cellular phenotype. Over the last few years patient-derived neural cells have proven very useful in addressing several mechanistic questions related to central nervous system diseases, including early-onset neurological disorders of childhood. Many studies report the clinical utility of human-derived neural cells for testing known drugs with repurposing potential, novel compounds and gene therapies, which then can be translated to clinical reality. iPSCs derived neural cells, therefore provide great promise and potential to gain insight into, and treat early-onset neurological disorders. PMID:27656126

  2. Bridge Types: Suspension Bridge Spans, Section AA; Cantilever Truss Spans, ...

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

    Bridge Types: Suspension Bridge Spans, Section A-A; Cantilever Truss Spans, Section B-B; Through Truss Spans, Section C-C; Deck Truss Spans, Section D-D - San Francisco Oakland Bay Bridge, Spanning San Francisco Bay, San Francisco, San Francisco County, CA

  3. Insulin-like growth factor-I extends in vitro replicative life span of skeletal muscle satellite cells by enhancing G1/S cell cycle progression via the activation of phosphatidylinositol 3'-kinase/Akt signaling pathway

    NASA Technical Reports Server (NTRS)

    Chakravarthy, M. V.; Abraha, T. W.; Schwartz, R. J.; Fiorotto, M. L.; Booth, F. W.

    2000-01-01

    Interest is growing in methods to extend replicative life span of non-immortalized stem cells. Using the insulin-like growth factor I (IGF-I) transgenic mouse in which the IGF-I transgene is expressed during skeletal muscle development and maturation prior to isolation and during culture of satellite cells (the myogenic stem cells of mature skeletal muscle fibers) as a model system, we elucidated the underlying molecular mechanisms of IGF-I-mediated enhancement of proliferative potential of these cells. Satellite cells from IGF-I transgenic muscles achieved at least five additional population doublings above the maximum that was attained by wild type satellite cells. This IGF-I-induced increase in proliferative potential was mediated via activation of the phosphatidylinositol 3'-kinase/Akt pathway, independent of mitogen-activated protein kinase activity, facilitating G(1)/S cell cycle progression via a down-regulation of p27(Kip1). Adenovirally mediated ectopic overexpression of p27(Kip1) in exponentially growing IGF-I transgenic satellite cells reversed the increase in cyclin E-cdk2 kinase activity, pRb phosphorylation, and cyclin A protein abundance, thereby implicating an important role for p27(Kip1) in promoting satellite cell senescence. These observations provide a more complete dissection of molecular events by which increased local expression of a growth factor in mature skeletal muscle fibers extends replicative life span of primary stem cells than previously known.

  4. Insulin-like growth factor-I extends in vitro replicative life span of skeletal muscle satellite cells by enhancing G1/S cell cycle progression via the activation of phosphatidylinositol 3'-kinase/Akt signaling pathway.

    PubMed

    Chakravarthy, M V; Abraha, T W; Schwartz, R J; Fiorotto, M L; Booth, F W

    2000-11-17

    Interest is growing in methods to extend replicative life span of non-immortalized stem cells. Using the insulin-like growth factor I (IGF-I) transgenic mouse in which the IGF-I transgene is expressed during skeletal muscle development and maturation prior to isolation and during culture of satellite cells (the myogenic stem cells of mature skeletal muscle fibers) as a model system, we elucidated the underlying molecular mechanisms of IGF-I-mediated enhancement of proliferative potential of these cells. Satellite cells from IGF-I transgenic muscles achieved at least five additional population doublings above the maximum that was attained by wild type satellite cells. This IGF-I-induced increase in proliferative potential was mediated via activation of the phosphatidylinositol 3'-kinase/Akt pathway, independent of mitogen-activated protein kinase activity, facilitating G(1)/S cell cycle progression via a down-regulation of p27(Kip1). Adenovirally mediated ectopic overexpression of p27(Kip1) in exponentially growing IGF-I transgenic satellite cells reversed the increase in cyclin E-cdk2 kinase activity, pRb phosphorylation, and cyclin A protein abundance, thereby implicating an important role for p27(Kip1) in promoting satellite cell senescence. These observations provide a more complete dissection of molecular events by which increased local expression of a growth factor in mature skeletal muscle fibers extends replicative life span of primary stem cells than previously known.

  5. Control of adhesion of human induced pluripotent stem cell>s to plasma-patterned polydimethylsiloxane coated with vitronectin and γ-globulin.

    PubMed

    Yamada, Ryotaro; Hattori, Koji; Tachikawa, Saoko; Tagaya, Motohiro; Sasaki, Toru; Sugiura, Shinji; Kanamori, Toshiyuki; Ohnuma, Kiyoshi

    2014-09-01

    Human induced pluripotent stem cell>s (hiPSCs) are a promising source of cells for medical applications. Recently, the development of polydimethylsiloxane (PDMS) microdevices to control the microenvironment of hiPSCs has been extensively studied. PDMS surfaces are often treated with low-pressure air plasma to facilitate protein adsorption and cell adhesion. However, undefined molecules present in the serum and extracellular matrix used to culture cells complicate the study of cell adhesion. Here, we studied the effects of vitronectin and γ-globulin on hiPSC adhesion to plasma-treated and untreated PDMS surfaces under defined culture conditions. We chose these proteins because they have opposite properties: vitronectin mediates hiPSC attachment to hydrophilic siliceous surfaces, whereas γ-globulin is adsorbed by hydrophobic surfaces and does not mediate cell adhesion. Immunostaining showed that, when applied separately, vitronectin and γ-globulin were adsorbed by both plasma-treated and untreated PDMS surfaces. In contrast, when PDMS surfaces were exposed to a mixture of the two proteins, vitronectin was preferentially adsorbed onto plasma-treated surfaces, whereas γ-globulin was adsorbed onto untreated surfaces. Human iPSCs adhered to the vitronectin-rich plasma-treated surfaces but not to the γ-globulin-rich untreated surfaces. On the basis of these results, we used perforated masks to prepare plasma-patterned PDMS substrates, which were then used to pattern hiPSCs. The patterned hiPSCs expressed undifferentiated-cell markers and did not escape from the patterned area for at least 7 days. The patterned PDMS could be stored for up to 6 days before hiPSCs were plated. We believe that our results will be useful for the development of hiPSC microdevices. PMID:24656306

  6. Controlled Growth and the Maintenance of Human Pluripotent Stem Cell>s by Cultivation with Defined Medium on Extracellular Matrix-Coated Micropatterned Dishes.

    PubMed

    Takenaka, Chiemi; Miyajima, Hiroshi; Yoda, Yusuke; Imazato, Hideo; Yamamoto, Takako; Gomi, Shinichi; Ohshima, Yasuhiro; Kagawa, Kenichi; Sasaki, Tetsuji; Kawamata, Shin

    2015-01-01

    Here, we introduce a new serum-free defined medium (SPM) that supports the cultivation of human pluripotent stem cell>s (hPSCs) on recombinant human vitronectin-N (rhVNT-N)-coated dishes after seeding with either cell clumps or single cells. With this system, there was no need for an intervening sequential adaptation process after moving hPSCs from feeder layer-dependent conditions. We also introduce a micropatterned dish that was coated with extracellular matrix by photolithographic technology. This procedure allowed the cultivation of hPSCs on 199 individual rhVNT-N-coated small round spots (1 mm in diameter) on each 35-mm polystyrene dish (termed "patterned culture"), permitting the simultaneous formation of 199 uniform high-density small-sized colonies. This culture system supported controlled cell growth and maintenance of undifferentiated hPSCs better than dishes in which the entire surface was coated with rhVNT-N (termed "non-patterned cultures"). Non-patterned cultures produced variable, unrestricted cell proliferation with non-uniform cell growth and uneven densities in which we observed downregulated expression of some self-renewal-related markers. Comparative flow cytometric studies of the expression of pluripotency-related molecules SSEA-3 and TRA-1-60 in hPSCs from non-patterned cultures and patterned cultures supported this concept. Patterned cultures of hPSCs allowed sequential visual inspection of every hPSC colony, giving an address and number in patterned culture dishes. Several spots could be sampled for quality control tests of production batches, thereby permitting the monitoring of hPSCs in a single culture dish. Our new patterned culture system utilizing photolithography provides a robust, reproducible and controllable cell culture system and demonstrates technological advantages for the mass production of hPSCs with process quality control. PMID:26115194

  7. Effects of Integrating and Non-Integrating Reprogramming Methods on Copy Number Variation and Genomic Stability of Human Induced Pluripotent Stem Cell>s.

    PubMed

    Kang, Xiangjin; Yu, Qian; Huang, Yuling; Song, Bing; Chen, Yaoyong; Gao, Xingcheng; He, Wenyin; Sun, Xiaofang; Fan, Yong

    2015-01-01

    Human-induced pluripotent stem cell>s (iPSCs) are derived from differentiated somatic cells using defined factors and provide a renewable source of autologous cells for cell therapy. Many reprogramming methods have been employed to generate human iPSCs, including the use of integrating vectors and non-integrating vectors. Maintenance of the genomic integrity of iPSCs is highly desirable if the cells are to be used in clinical applications. Here, using the Affymetrix Cytoscan HD array, we investigated the genomic aberration profiles of 19 human cell lines: 5 embryonic stem cell (ESC) lines, 6 iPSC lines derived using integrating vectors ("integrating iPSC lines"), 6 iPSC lines derived using non-integrating vectors ("non-integrating iPSC lines"), and the 2 parental cell lines from which the iPSCs were derived. The genome-wide copy number variation (CNV), loss of heterozygosity (LOH) and mosaicism patterns of integrating and non-integrating iPSC lines were investigated. The maximum sizes of CNVs in the genomes of the integrating iPSC lines were 20 times higher than those of the non-integrating iPSC lines. Moreover, the total number of CNVs was much higher in integrating iPSC lines than in other cell lines. The average numbers of novel CNVs with a low degree of overlap with the DGV and of likely pathogenic CNVs with a high degree of overlap with the ISCA (International Symposium on Computer Architecture) database were highest in integrating iPSC lines. Different single nucleotide polymorphisms (SNP) calls revealed that, using the parental cell genotype as a reference, integrating iPSC lines displayed more single nucleotide variations and mosaicism than did non-integrating iPSC lines. This study describes the genome stability of human iPSCs generated using either a DNA-integrating or non-integrating reprogramming method, of the corresponding somatic cells, and of hESCs. Our results highlight the importance of using a high-resolution method to monitor genomic

  8. View of approach span and movable span, looking southeast from ...

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

    View of approach span and movable span, looking southeast from navy land. Note that navigational channel exists only on north side of movable span. - Naval Supply Annex Stockton, Rough & Ready Island, Stockton, San Joaquin County, CA

  9. EAST END FROM MID SPAN OF EASTERN SPAN (THREE DIFFERENT ...

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

    EAST END FROM MID SPAN OF EASTERN SPAN (THREE DIFFERENT TRUSSES, EAST SOUTHEAST 110 DEGREES) - Honey Run Bridge, Spanning Butte Creek, bypassed section of Honey Run Road (originally Carr Hill Road), Paradise, Butte County, CA

  10. 23. Span 1, detail view, central section of span front ...

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

    23. Span 1, detail view, central section of span front below; view to south. - Fifth Street Bridge, Spanning MBTA Fitchburg Commuter Rail Line tracks, Conrail Fitchburg Secondary Line & North Nashua River, Fitchburg, Worcester County, MA

  11. 2. Skew Span on left to Span 3 on right ...

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

    2. Skew Span on left to Span 3 on right from north bank-up river. - Monongahela Connecting Railroad Company, Hot Metal Bridge, Spanning Monongahela River at mile post 3.1, Pittsburgh, Allegheny County, PA

  12. 4. From Skew Span to portal on span 1 looking ...

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

    4. From Skew Span to portal on span 1 looking up grade toward the south end. - Monongahela Connecting Railroad Company, Hot Metal Bridge, Spanning Monongahela River at mile post 3.1, Pittsburgh, Allegheny County, PA

  13. 11. Span 2 foreground, Span 3 beyondunderneath from riverbank vicinity ...

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

    11. Span 2- foreground, Span 3 beyond-underneath from riverbank vicinity Pier 1 toward Pier 2 in river. - Monongahela Connecting Railroad Company, Main Bridge, Spanning Monongahela River at mile post 3.1, Pittsburgh, Allegheny County, PA

  14. 5. From Span 6 to portal on span 5 looking ...

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

    5. From Span 6 to portal on span 5 looking down grade toward north end. - Monongahela Connecting Railroad Company, Hot Metal Bridge, Spanning Monongahela River at mile post 3.1, Pittsburgh, Allegheny County, PA

  15. 3. Span 4 on right to Skew Span on leftfrom ...

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

    3. Span 4 on right to Skew Span on left-from south bank-up river. - Monongahela Connecting Railroad Company, Hot Metal Bridge, Spanning Monongahela River at mile post 3.1, Pittsburgh, Allegheny County, PA

  16. 25. Spans 25, underview of Span 4 and western elevation ...

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

    25. Spans 2-5, underview of Span 4 and western elevation of Pier 4; view to northeast. - Fifth Street Bridge, Spanning MBTA Fitchburg Commuter Rail Line tracks, Conrail Fitchburg Secondary Line & North Nashua River, Fitchburg, Worcester County, MA

  17. 22. VIEW OF FIXED SPAN SUBSTRUCTURE, EAST SPAN, SHOWING CANTILEVEREDBEAM ...

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

    22. VIEW OF FIXED SPAN SUBSTRUCTURE, EAST SPAN, SHOWING CANTILEVERED-BEAM SIDEWALK SUPPORTS, LONGITUDINAL GIRDER AND TRANSVERSE ROADBED BEAMS, LOOKING SOUTHEAST - Congress Street Bascule Bridge, Spanning Fort Point Channel at Congress Street, Boston, Suffolk County, MA

  18. Development and function of human cerebral cortex neural networks from pluripotent stem cell>s in vitro.

    PubMed

    Kirwan, Peter; Turner-Bridger, Benita; Peter, Manuel; Momoh, Ayiba; Arambepola, Devika; Robinson, Hugh P C; Livesey, Frederick J

    2015-09-15

    A key aspect of nervous system development, including that of the cerebral cortex, is the formation of higher-order neural networks. Developing neural networks undergo several phases with distinct activity patterns in vivo, which are thought to prune and fine-tune network connectivity. We report here that human pluripotent stem cell (hPSC)-derived cerebral cortex neurons form large-scale networks that reflect those found in the developing cerebral cortex in vivo. Synchronised oscillatory networks develop in a highly stereotyped pattern over several weeks in culture. An initial phase of increasing frequency of oscillations is followed by a phase of decreasing frequency, before giving rise to non-synchronous, ordered activity patterns. hPSC-derived cortical neural networks are excitatory, driven by activation of AMPA- and NMDA-type glutamate receptors, and can undergo NMDA-receptor-mediated plasticity. Investigating single neuron connectivity within PSC-derived cultures, using rabies-based trans-synaptic tracing, we found two broad classes of neuronal connectivity: most neurons have small numbers (<10) of presynaptic inputs, whereas a small set of hub-like neurons have large numbers of synaptic connections (>40). These data demonstrate that the formation of hPSC-derived cortical networks mimics in vivo cortical network development and function, demonstrating the utility of in vitro systems for mechanistic studies of human forebrain neural network biology. PMID:26395144

  19. Nox2 contributes to the arterial endothelial specification of mouse induced pluripotent stem cell>s by upregulating Notch signaling

    PubMed Central

    Kang, Xueling; Wei, Xiangxiang; Wang, Xinhong; Jiang, Li; Niu, Cong; Zhang, Jianyi; Chen, Sifeng; Meng, Dan

    2016-01-01

    Reactive oxygen species (ROS) have a crucial role in stem-cell differentiation; however, the mechanisms by which ROS regulate the differentiation of stem cells into endothelial cells (ECs) are unknown. Here, we determine the role of ROS produced by NADPH oxidase 2 (Nox2) in the endothelial-lineage specification of mouse induced-pluripotent stem cell>s (miPSCs). When wild-type (WT) and Nox2-knockout (Nox2−/−) miPSCs were differentiated into ECs (miPSC-ECs), the expression of endothelial markers, arterial endothelial markers, pro-angiogenic cytokines, and Notch pathway components was suppressed in the Nox2−/− cells but increased in both WT and Nox2−/− miPSCs when Nox2 expression was upregulated. Higher levels of Nox2 expression increased Notch signaling and arterial EC differentiation, and this increase was abolished by the inhibition of ROS generation or by the silencing of Notch1 expression. Nox2 deficiency was associated with declines in the survival and angiogenic potency of miPSC-ECs, and capillary and arterial density were lower in the ischemic limbs of mice after treatment with Nox2−/− miPSC-ECs than WT miPSC-EC treatment. Taken together, these observations indicate that Nox2-mediated ROS production promotes arterial EC specification in differentiating miPSCs by activating the Notch signaling pathway and contributes to the angiogenic potency of transplanted miPSC-derived ECs. PMID:27642005

  20. Assessing state stem cell programs in the United States: how has state funding affected publication trends?

    PubMed

    Alberta, Hillary B; Cheng, Albert; Jackson, Emily L; Pjecha, Matthew; Levine, Aaron D

    2015-02-01

    Several states responded to federal funding limitations placed on human embryonic stem cell research and the potential of the field by creating state stem cell funding programs, yet little is known about the impact of these programs. Here we examine how state programs have affected publication trends in four states.

  1. 78. VIEW SHOWING PLACEMENT OF LIFE SPAN SHOE ON PIER ...

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

    78. VIEW SHOWING PLACEMENT OF LIFE SPAN SHOE ON PIER 6, LOOKING NORTH, March 5, 1935 - Sacramento River Bridge, Spanning Sacramento River at California State Highway 275, Sacramento, Sacramento County, CA

  2. Barrel view from center span, looking east. Waterville Bridge, ...

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

    Barrel view from center span, looking east. - Waterville Bridge, Spanning Swatara Creek at Appalachian Trail (moved from Little Pine Creek at State Route 44, Waterville, Lycoming County), Green Point, Lebanon County, PA

  3. 20. DETAIL VIEW OF MOVABLE SPAN MACHINERY UNDER GRID DECK ...

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

    20. DETAIL VIEW OF MOVABLE SPAN MACHINERY UNDER GRID DECK AT CENTRAL CONCRETE SUPPORT PEDESTAL, SHOWING DRIVE GEARS, ELECTRIC MOTOR AND STEEL BEAMS (taken in January 1984) - Sharptown Bridge, Spanning Nanticoke River, State Route 313, Sharptown, Wicomico County, MD

  4. 1. GENERAL VIEW LOOKING EAST, SHOWING REINFORCED CONCRETE BRIDGE SPANNING ...

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

    1. GENERAL VIEW LOOKING EAST, SHOWING REINFORCED CONCRETE BRIDGE SPANNING SIMPSON CREEK. - Bridgeport Lamp Chimney Company, Simpson Creek Bridge, Spanning Simpson Creek, State Route 58 vicinity, Bridgeport, Harrison County, WV

  5. 31. DETAIL VIEW OF MOVABLE SPAN, UPPER TRUSS GUSSET PLATE, ...

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

    31. DETAIL VIEW OF MOVABLE SPAN, UPPER TRUSS GUSSET PLATE, CONNECTION OF VERTICAL AND HORIZONTAL MEMBERS AT BRIDGE TENDER'S MOUSE (taken in December 1983) - Sharptown Bridge, Spanning Nanticoke River, State Route 313, Sharptown, Wicomico County, MD

  6. 4. DETAIL OF VERTICAL LIFT SPAN SHOWING CONCRETE PIERS, LIFT ...

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

    4. DETAIL OF VERTICAL LIFT SPAN SHOWING CONCRETE PIERS, LIFT TOWERS, AND THROUGH TRUSS, LOOKING SOUTHEAST. - Shippingsport Bridge, Spanning Illinois River at State Route 51, La Salle, La Salle County, IL

  7. 6. View southeast, west elevation, showing north arch span abutment ...

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

    6. View southeast, west elevation, showing north arch span abutment and central pier with nose on upstream side - Edna Dean Proctor Bridge, Spanning Contoacook River at State Route 114, Henniker, Merrimack County, NH

  8. 36. DETAIL, ALTERNATE DESIGN USING THROUGH ARCH SPANS Pencil drawing ...

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

    36. DETAIL, ALTERNATE DESIGN USING THROUGH ARCH SPANS Pencil drawing by project architect Alfred Eichler, ca. 1934. - Sacramento River Bridge, Spanning Sacramento River at California State Highway 275, Sacramento, Sacramento County, CA

  9. Modeling human retinal development with patient-specific induced pluripotent stem cell>s reveals multiple roles for visual system homeobox 2.

    PubMed

    Phillips, M Joseph; Perez, Enio T; Martin, Jessica M; Reshel, Samantha T; Wallace, Kyle A; Capowski, Elizabeth E; Singh, Ruchira; Wright, Lynda S; Clark, Eric M; Barney, Patrick M; Stewart, Ron; Dickerson, Sarah J; Miller, Michael J; Percin, E Ferda; Thomson, James A; Gamm, David M

    2014-06-01

    Human induced pluripotent stem cell>s (hiPSCs) have been shown to differentiate along the retinal lineage in a manner that mimics normal mammalian development. Under certain culture conditions, hiPSCs form optic vesicle-like structures (OVs), which contain proliferating progenitors capable of yielding all neural retina (NR) cell types over time. Such observations imply conserved roles for regulators of retinogenesis in hiPSC-derived cultures and the developing embryo. However, whether and to what extent this assumption holds true has remained largely uninvestigated. We examined the role of a key NR transcription factor, visual system homeobox 2 (VSX2), using hiPSCs derived from a patient with microphthalmia caused by an R200Q mutation in the VSX2 homeodomain region. No differences were noted between (R200Q)VSX2 and sibling control hiPSCs prior to OV generation. Thereafter, (R200Q)VSX2 hiPSC-OVs displayed a significant growth deficit compared to control hiPSC-OVs, as well as increased production of retinal pigmented epithelium at the expense of NR cell derivatives. Furthermore, (R200Q)VSX2 hiPSC-OVs failed to produce bipolar cells, a distinctive feature previously observed in Vsx2 mutant mice. (R200Q)VSX2 hiPSC-OVs also demonstrated delayed photoreceptor maturation, which could be overcome via exogenous expression of wild-type VSX2 at early stages of retinal differentiation. Finally, RNAseq analysis on isolated hiPSC-OVs implicated key transcription factors and extracellular signaling pathways as potential downstream effectors of VSX2-mediated gene regulation. Our results establish hiPSC-OVs as versatile model systems to study retinal development at stages not previously accessible in humans and support the bona fide nature of hiPSC-OV-derived retinal progeny. PMID:24532057

  10. Overexpression of hsp27 Rescued Neuronal Cell Death and Reduction in Life- and Health-Span in Drosophila melanogaster Against Prolonged Exposure to Dichlorvos.

    PubMed

    Pandey, Ashutosh; Saini, Sanjay; Khatoon, Rehana; Sharma, Divya; Narayan, Gopeshwar; Kar Chowdhuri, Debapratim

    2016-07-01

    Long-term exposure to dichlorvos (O,O-dimethyl-2,2-dichlorovinyl phosphate (DDVP), an organophosphate pesticide) is reported to exert neurotoxicity, i.e., generation of reactive oxygen species (ROS), oxidative damage, and neuronal cell death along with life- and health-span reduction in nontarget organisms including humans. However, studies on genetic modulation towards neuroprotection against prolonged DDVP exposure are elusive. Hsp27 (a small heat shock protein) is involved in various cellular processes and thus has attained emphasis as a therapeutic target. We aimed to examine the protective effect of hsp27 overexpression against prolonged DDVP exposure using an in vivo model Drosophila melanogaster. Flies were exposed to 15.0 ng/ml DDVP for a prolonged period to examine neuronal cell death, locomotor performance, and lifespan. After prolonged exposure, cell death, ROS level, glutathione depletion, nicotinamide adenine dinucleotide phosphate level (NADPH), glucose-6-phosphate dehydrogenase (G6PD), and thioredoxin reductase (TrxR) activities were examined in fly brain tissues at different days of age (days 10, 20, and 30). Flies with ubiquitous overexpression of hsp27 showed better resistance (improved lifespan and locomotor performance) in comparison to that targeted to motor neurons and nervous system. These flies also exhibited lesser intracellular ROS level and glutathione depletion by restoring G6PD activity, NADPH level, and TrxR activity in their brains thereby resisted neuronal cell death. Conversely, hsp27 knockdown flies exhibited reversal of the above endpoints. The study evidenced the neuroprotective efficacy of hsp27 overexpression against prolonged DDVP exposure and favored Hsp27 as a therapeutic target towards achieving better organismal (including human) health against long-term chemical exposure.

  11. [Prolongation of the mitotic life span of diploid human glia cells in a quantitative cell culture system by centrophenoxine (author's transl)].

    PubMed

    Rodemann, H P; Bayreuther, K

    1979-01-01

    The accumulation of lipofuscin in postmitotic and reversible postmitotic cells of animals and man is an age correlated process. The mechanism of the lipofuscin accumulation and the function of lipofuscin in the aging cell is not fully understood. The accumulation of lipofuscin in vivo and in vitro can be slowed down by the action of centrophenoxine (Helfergin). Diploid cells are the only reversible postmitotic cells of man that have a genetically determined limited cell division capacity and accumulate lipofuscin in the process of the cellular aging in a quantitative cell culture system in vitro. The treatment of diploid human glia cells with centrophenoxine results in increasing the cell division capacity by 30--40% in vitro. The data demonstrate that the centrophenoxine induced inhibition of lipofuscin accumulation has a positive influence on the cell metabolism and the mitotic division capacity and causes a delay of the cellular aging of the human glia cells in vitro.

  12. Span efficiency in hawkmoths.

    PubMed

    Henningsson, Per; Bomphrey, Richard J

    2013-07-01

    Flight in animals is the result of aerodynamic forces generated as flight muscles drive the wings through air. Aerial performance is therefore limited by the efficiency with which momentum is imparted to the air, a property that can be measured using modern techniques. We measured the induced flow fields around six hawkmoth species flying tethered in a wind tunnel to assess span efficiency, ei, and from these measurements, determined the morphological and kinematic characters that predict efficient flight. The species were selected to represent a range in wingspan from 40 to 110 mm (2.75 times) and in mass from 0.2 to 1.5 g (7.5 times) but they were similar in their overall shape and their ecology. From high spatio-temporal resolution quantitative wake images, we extracted time-resolved downwash distributions behind the hawkmoths, calculating instantaneous values of ei throughout the wingbeat cycle as well as multi-wingbeat averages. Span efficiency correlated positively with normalized lift and negatively with advance ratio. Average span efficiencies for the moths ranged from 0.31 to 0.60 showing that the standard generic value of 0.83 used in previous studies of animal flight is not a suitable approximation of aerodynamic performance in insects. PMID:23658113

  13. Span efficiency in hawkmoths

    PubMed Central

    Henningsson, Per; Bomphrey, Richard J.

    2013-01-01

    Flight in animals is the result of aerodynamic forces generated as flight muscles drive the wings through air. Aerial performance is therefore limited by the efficiency with which momentum is imparted to the air, a property that can be measured using modern techniques. We measured the induced flow fields around six hawkmoth species flying tethered in a wind tunnel to assess span efficiency, ei, and from these measurements, determined the morphological and kinematic characters that predict efficient flight. The species were selected to represent a range in wingspan from 40 to 110 mm (2.75 times) and in mass from 0.2 to 1.5 g (7.5 times) but they were similar in their overall shape and their ecology. From high spatio-temporal resolution quantitative wake images, we extracted time-resolved downwash distributions behind the hawkmoths, calculating instantaneous values of ei throughout the wingbeat cycle as well as multi-wingbeat averages. Span efficiency correlated positively with normalized lift and negatively with advance ratio. Average span efficiencies for the moths ranged from 0.31 to 0.60 showing that the standard generic value of 0.83 used in previous studies of animal flight is not a suitable approximation of aerodynamic performance in insects. PMID:23658113

  14. Differentiation from human pluripotent stem cell>s of cortical neurons of the superficial layers amenable to psychiatric disease modeling and high-throughput drug screening.

    PubMed

    Boissart, C; Poulet, A; Georges, P; Darville, H; Julita, E; Delorme, R; Bourgeron, T; Peschanski, M; Benchoua, A

    2013-01-01

    Cortical neurons of the superficial layers (II-IV) represent a pivotal neuronal population involved in the higher cognitive functions of the human and are particularly affected by psychiatric diseases with developmental manifestations such as schizophrenia and autism. Differentiation protocols of human pluripotent stem cell>s (PSC) into cortical neurons have been achieved, opening the way to in vitro modeling of neuropsychiatric diseases. However, these protocols commonly result in the asynchronous production of neurons typical for the different layers of the cortex within an extended period of culture, thus precluding the analysis of specific subtypes of neurons in a standardized manner. Addressing this issue, we have successfully captured a stable population of self-renewing late cortical progenitors (LCPs) that synchronously and massively differentiate into glutamatergic cortical neurons of the upper layers. The short time course of differentiation into neurons of these progenitors has made them amenable to high-throughput assays. This has allowed us to analyze the capability of LCPs at differentiating into post mitotic neurons as well as extending and branching neurites in response to a collection of selected bioactive molecules. LCPs and cortical neurons of the upper layers were successfully produced from patient-derived-induced PSC, indicating that this system enables functional studies of individual-specific cortical neurons ex vivo for disease modeling and therapeutic purposes. PMID:23962924

  15. Sexual Conflict, Life Span, and Aging

    PubMed Central

    Adler, Margo I.; Bonduriansky, Russell

    2014-01-01

    The potential for sexual conflict to influence the evolution of life span and aging has been recognized for more than a decade, and recent work also suggests that variation in life span and aging can influence sexually antagonistic coevolution. However, empirical exploration of these ideas is only beginning. Here, we provide an overview of the ideas and evidence linking inter- and intralocus sexual conflicts with life span and aging. We aim to clarify the conceptual basis of this research program, examine the current state of knowledge, and suggest key questions for further investigation. PMID:24938876

  16. Sexual conflict, life span, and aging.

    PubMed

    Adler, Margo I; Bonduriansky, Russell

    2014-08-01

    The potential for sexual conflict to influence the evolution of life span and aging has been recognized for more than a decade, and recent work also suggests that variation in life span and aging can influence sexually antagonistic coevolution. However, empirical exploration of these ideas is only beginning. Here, we provide an overview of the ideas and evidence linking inter- and intralocus sexual conflicts with life span and aging. We aim to clarify the conceptual basis of this research program, examine the current state of knowledge, and suggest key questions for further investigation. PMID:24938876

  17. Defining cell types and states with single-cell genomics

    PubMed Central

    Trapnell, Cole

    2015-01-01

    A revolution in cellular measurement technology is under way: For the first time, we have the ability to monitor global gene regulation in thousands of individual cells in a single experiment. Such experiments will allow us to discover new cell types and states and trace their developmental origins. They overcome fundamental limitations inherent in measurements of bulk cell population that have frustrated efforts to resolve cellular states. Single-cell genomics and proteomics enable not only precise characterization of cell state, but also provide a stunningly high-resolution view of transitions between states. These measurements may finally make explicit the metaphor that C.H. Waddington posed nearly 60 years ago to explain cellular plasticity: Cells are residents of a vast “landscape” of possible states, over which they travel during development and in disease. Single-cell technology helps not only locate cells on this landscape, but illuminates the molecular mechanisms that shape the landscape itself. However, single-cell genomics is a field in its infancy, with many experimental and computational advances needed to fully realize its full potential. PMID:26430159

  18. Organization, structure, and function of 95 kb of DNA spanning the murine T-cell receptor C alpha/C delta region.

    PubMed

    Koop, B F; Wilson, R K; Wang, K; Vernooij, B; Zallwer, D; Kuo, C L; Seto, D; Toda, M; Hood, L

    1992-08-01

    We have analyzed the organization, structure, and function of the murine T-cell receptor C alpha/C delta region. This region spans 94.6 kb of DNA and contains the C alpha and C delta genes, as well as the V delta 5, J delta 2, and 50 different J alpha gene segments. Within this sequence we have identified 15 new J alpha gene segments, 40 new 5' RNA splice signals, and 40 new DNA rearrangement signals for the J alpha gene segments. The murine C alpha/C delta sequence contains an exceptionally high level of coding sequence with over 5.7% of the total sequence found in the exons. This is much more than that found in the beta-globin locus and the HPRT locus. Using the sequence data obtained from the C alpha/C delta region, we have designed simple assays to test for J alpha gene segment transcription and to determine the level of polymorphism for simple repeat sequences among different inbred strains of mice using the polymerase chain reaction. Furthermore, comparisons of this 95 kb of sequence with the available sequence from homologous regions of other species have led to the identification of a highly conserved sequence that is present throughout vertebrates and in the mouse binds lymphocyte-specific nuclear proteins. Comparisons of a 10-kb region, which includes the C alpha gene in human and mouse, average 66% sequence similarity. These studies support the contention that large-scale DNA sequencing projects of homologous regions of mouse and human will provide powerful new tools for studying the biology and evolution of loci such as the T-cell receptor and for identifying and posing new questions about the functions of conserved sequences.

  19. Chromatin States Accurately Classify Cell Differentiation Stages

    PubMed Central

    Larson, Jessica L.; Yuan, Guo-Cheng

    2012-01-01

    Gene expression is controlled by the concerted interactions between transcription factors and chromatin regulators. While recent studies have identified global chromatin state changes across cell-types, it remains unclear to what extent these changes are co-regulated during cell-differentiation. Here we present a comprehensive computational analysis by assembling a large dataset containing genome-wide occupancy information of 5 histone modifications in 27 human cell lines (including 24 normal and 3 cancer cell lines) obtained from the public domain, followed by independent analysis at three different representations. We classified the differentiation stage of a cell-type based on its genome-wide pattern of chromatin states, and found that our method was able to identify normal cell lines with nearly 100% accuracy. We then applied our model to classify the cancer cell lines and found that each can be unequivocally classified as differentiated cells. The differences can be in part explained by the differential activities of three regulatory modules associated with embryonic stem cells. We also found that the “hotspot” genes, whose chromatin states change dynamically in accordance to the differentiation stage, are not randomly distributed across the genome but tend to be embedded in multi-gene chromatin domains, and that specialized gene clusters tend to be embedded in stably occupied domains. PMID:22363642

  20. Cell mechanics and human disease states

    NASA Astrophysics Data System (ADS)

    Suresh, Subra

    2006-03-01

    This presentation will provide summary of our very recent studies exploring the effects of biochemical factors, influenced by foreign organisms or in vivo processes, on intracellular structural reorganization, single-cell mechanical response and motility of a population of cells in the context of two human diseases: malaria induced by Plasmodium falciparum merozoites that invade red blood cells, and gastrointestinal cancer metastasis involving epithelial cells. In both cases, particular attention will be devoted to systematic changes induced in specific molecular species in response to controlled alterations in disease state. The role of critical proteins in influencing the mechanical response of human red bloods during the intra-erythrocytic development of P. falciparum merozoites has also been assessed quantitatively using specific protein knock-out experiments by recourse to gene inactivation methods. Single-cell mechanical response characterization entails such tools as optical tweezers and mechanical plate stretchers whereas cell motility assays and cell-population biorheology characterization involves microfluidic channels. The experimental studies are accompanied by three-dimensional computational simulations at the continuum and mesoscopic scales of cell deformation. An outcome of such combined experimental and computational biophysical studies is the realization of how chemical factors influence single-cell mechanical response, cytoadherence, the biorheology of a large population of cells through microchannels representative of in vivo conditions, and the onset and progression of disease states.

  1. 6. VIEW OF APPROACH SPAN AND MAIN SPAN OF THE ...

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

    6. VIEW OF APPROACH SPAN AND MAIN SPAN OF THE ACCESS BRIDGE AND INTAKE PIER, LOOKING SOUTHWEST. - Sacramento River Water Treatment Plant Intake Pier & Access Bridge, Spanning Sacramento River approximately 175 feet west of eastern levee on river; roughly .5 mile downstream from confluence of Sacramento & American Rivers, Sacramento, Sacramento County, CA

  2. View of approach span and movable span, looking southeast from ...

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

    View of approach span and movable span, looking southeast from navy land. Note that navigational channel exists only on north side of movable span. - Naval Supply Annex Stockton, Daggett Road Bridge, Daggett Road traversing Burns Cut Off, Stockton, San Joaquin County, CA

  3. 56. VIEW SOUTH, WEST SIDE AT CANTILEVER SPAN (SPAN 70) ...

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

    56. VIEW SOUTH, WEST SIDE AT CANTILEVER SPAN (SPAN 70) SHOWING FACADE, DOUBLE CROSS BRACING AT COLUMNS, AND CONCRETE BASE - Route 1 Extension, Southbound Viaduct, Spanning Conrail Yards, Wilson Avenue, Delancy Street, & South Street on Routes 1 & 9 Southbound, Newark, Essex County, NJ

  4. Underside from northeast. Waterville Bridge, Spanning Swatara Creek at ...

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

    Underside from northeast. - Waterville Bridge, Spanning Swatara Creek at Appalachian Trail (moved from Little Pine Creek at State Route 44, Waterville, Lycoming County), Green Point, Lebanon County, PA

  5. Differentiation and Molecular Properties of Mesenchymal Stem Cells Derived from Murine Induced Pluripotent Stem Cell>s Derived on Gelatin or Collagen

    PubMed Central

    Obara, Chizuka; Takizawa, Kazuya; Tomiyama, Kenichi; Hazawa, Masaharu; Saotome-Nakamura, Ai; Gotoh, Takaya; Yasuda, Takeshi

    2016-01-01

    The generation of induced-pluripotential stem cells- (iPSCs-) derived mesenchymal stem cells (iMSCs) is an attractive and promising approach for preparing large, uniform batches of applicable MSCs that can serve as an alternative cell source of primary MSCs. Appropriate culture surfaces may influence their growth and differentiation potentials during iMSC derivation. The present study compared molecular properties and differentiation potential of derived mouse iPS-MSCs by deriving on gelatin or collagen-coated surfaces. The cells were derived by a one-step method and expressed CD73 and CD90, but CD105 was downregulated in iMSCs cultured only on gelatin-coated plates with increasing numbers of passages. A pairwise scatter analysis revealed similar expression of MSC-specific genes in iMSCs derived on gelatin and on collagen surfaces as well as in primary mouse bone marrow MSCs. Deriving iMSCs on gelatin and collagen dictated their osteogenic and adipose differentiation potentials, respectively. Derived iMSCs on gelatin upregulated Bmp2 and Lif prior to induction of osteogenic or adipose differentiation, while PPARγ was upregulated by deriving on collagen. Our results suggest that extracellular matrix components such as gelatin biases generated iMSC differentiation potential towards adipose or bone tissue in their derivation process via up- or downregulation of these master genes. PMID:27642306

  6. Non-integrating episomal plasmid-based reprogramming of human amniotic fluid stem cells into induced pluripotent stem cell>s in chemically defined conditions.

    PubMed

    Slamecka, Jaroslav; Salimova, Lilia; McClellan, Steven; van Kelle, Mathieu; Kehl, Debora; Laurini, Javier; Cinelli, Paolo; Owen, Laurie; Hoerstrup, Simon P; Weber, Benedikt

    2016-01-01

    Amniotic fluid stem cells (AFSC) represent an attractive potential cell source for fetal and pediatric cell-based therapies. However, upgrading them to pluripotency confers refractoriness toward senescence, higher proliferation rate and unlimited differentiation potential. AFSC were observed to rapidly and efficiently reacquire pluripotency which together with their easy recovery makes them an attractive cell source for reprogramming. The reprogramming process as well as the resulting iPSC epigenome could potentially benefit from the unspecialized nature of AFSC. iPSC derived from AFSC also have potential in disease modeling, such as Down syndrome or β-thalassemia. Previous experiments involving AFSC reprogramming have largely relied on integrative vector transgene delivery and undefined serum-containing, feeder-dependent culture. Here, we describe non-integrative oriP/EBNA-1 episomal plasmid-based reprogramming of AFSC into iPSC and culture in fully chemically defined xeno-free conditions represented by vitronectin coating and E8 medium, a system that we found uniquely suited for this purpose. The derived AF-iPSC lines uniformly expressed a set of pluripotency markers Oct3/4, Nanog, Sox2, SSEA-1, SSEA-4, TRA-1-60, TRA-1-81 in a pattern typical for human primed PSC. Additionally, the cells formed teratomas, and were deemed pluripotent by PluriTest, a global expression microarray-based in-silico pluripotency assay. However, we found that the PluriTest scores were borderline, indicating a unique pluripotent signature in the defined condition. In the light of potential future clinical translation of iPSC technology, non-integrating reprogramming and chemically defined culture are more acceptable. PMID:26654216

  7. Polysulfone membranes coated with polymerized 3,4-dihydroxy-l-phenylalanine are a versatile and cost-effective synthetic substrate for defined long-term cultures of human pluripotent stem cell>s.

    PubMed

    Kandasamy, Karthikeyan; Narayanan, Karthikeyan; Ni, Ming; Du, Chan; Wan, Andrew C A; Zink, Daniele

    2014-06-01

    Clinical and industrial applications of human pluripotent stem cell>s (hPSC) require large amounts of cells that have been expanded under defined conditions. Labor-intensive techniques and ill-defined or expensive compounds and substrates are not applicable. Here we describe a chemically defined synthetic substrate consisting of polysulfone (PSF) membranes coated with polymerized 3,4-dihydroxy-l-phenylalanine (DOPA). DOPA/PSF is inexpensive and can be easily produced at various shapes and sizes. DOPA/PSF supports long-term self-renewal of undifferentiated human embryonic (hESC) and human induced pluripotent stem cell>s (hiPSC) under defined conditions. Pluripotency is maintained for at least 10 passages. Adhesion of hPSC to DOPA/PSF is mainly mediated by a specific integrin heterodimer. Proliferation and gene expression patterns on DOPA/PSF and control substrates are comparable. Labor-intensive cultivation methods and use of serum or coating with proteins are not required. Together, these features make DOPA/PSF attractive for applications where large-scale expansion of human pluripotent stem cell>s under defined conditions is essential. PMID:24762265

  8. High temperature solid state storage cell

    DOEpatents

    Rea, Jesse R.; Kallianidis, Milton; Kelsey, G. Stephen

    1983-01-01

    A completely solid state high temperature storage cell comprised of a solid rechargeable cathode such as TiS.sub.2, a solid electrolyte which remains solid at the high temperature operating conditions of the cell and which exhibits high ionic conductivity at such elevated temperatures such as an electrolyte comprised of lithium iodide, and a solid lithium or other alkali metal alloy anode (such as a lithium-silicon alloy) with 5-50% by weight of said anode being comprised of said solid electrolyte.

  9. SPAN - Terminal sterilization process analysis program

    NASA Technical Reports Server (NTRS)

    1969-01-01

    Computer program, SPAN, measures the dry heat thermal sterilization process applied to a planetary capsule and calculates the time required for heat application, steady state conditions, and cooling. The program is based on the logarithmic survival of micro-organisms. Temperature profiles must be input on tape.

  10. SPAN C - Terminal sterilization process analysis program

    NASA Technical Reports Server (NTRS)

    1969-01-01

    Computer program, SPAN-C, measures the dry heat thermal sterilization process applied to a planetary capsule and calculates the time required for heat application, steady state conditions, and cooling. The program is based on the logarithmic survival of micro-organisms. Temperature profiles must be input on cards.

  11. The Impact of School-to-School Transitions on Academic Achievement: An Analysis of Various Grade-Span Configurations Utilized by Public School Districts in New York State

    ERIC Educational Resources Information Center

    DelViscio, James J.

    2013-01-01

    At the beginning of the 20th century, there were essentially two types of organizational structures for primary and secondary education in the United States. There were either one-room K-12 schools or in larger systems K-8 buildings feeding into four-year high schools. Despite numerous experiments since then in reconfiguring schools resulting in a…

  12. Pluripotent states of human embryonic stem cells.

    PubMed

    Chen, Yifei; Lai, Dongmei

    2015-02-01

    Since human embryonic stem cells (hESCs) were first isolated and successfully cultured in vitro, the pluripotent potential of hESCs has been underestimated. The pluripotency of mouse embryonic stem cells (mESCs) can be categorized as naïve and primed, depending on their corresponding in vivo developing phases. mESC morphology differs at distinct pluripotent states, which differ in signaling dependence, gene expression, epigenetic features, and developmental potential. hESCs resemble mouse stem cells at primed pluripotency, and consequently are believed to correspond to a later developmental stage in vivo than mESCs. Nevertheless, recent studies indicate that a naïve state of pluripotency may exist in hESCs, and the pluripotency of hESCs also can be enhanced by genetic modification or optimized culture systems. These findings provide novel insight into the properties and differentiation potential of hESCs. Here, we review the recent advances in characterization of ESC states and investigate the mechanisms regulating hESC pluripotency. PMID:25393391

  13. A Newly Defined and Xeno-Free Culture Medium Supports Every-Other-Day Medium Replacement in the Generation and Long-Term Cultivation of Human Pluripotent Stem Cell>s

    PubMed Central

    Scotty Cadet, Jean; Shah, Kevan; Walde, Amy; Tran, Huan; Kovarcik, Don Paul; Clarke, Diana; Fellner, Thomas

    2016-01-01

    Human pluripotent stem cell>s (hPSCs) present an unprecedented opportunity to advance human health by offering an alternative and renewable cell resource for cellular therapeutics and regenerative medicine. The present demand for high quality hPSCs for use in both research and clinical studies underscores the need to develop technologies that will simplify the cultivation process and control variability. Here we describe the development of a robust, defined and xeno-free hPSC medium that supports reliable propagation of hPSCs and generation of human induced pluripotent stem cell>s (hiPSCs) from multiple somatic cell types; long-term serial subculturing of hPSCs with every-other-day (EOD) medium replacement; and banking fully characterized hPSCs. The hPSCs cultured in this medium for over 40 passages are genetically stable, retain high expression levels of the pluripotency markers TRA-1-60, TRA-1-81, Oct-3/4 and SSEA-4, and readily differentiate into ectoderm, mesoderm and endoderm. Importantly, the medium plays an integral role in establishing a cGMP-compliant process for the manufacturing of hiPSCs that can be used for generation of clinically relevant cell types for cell replacement therapy applications. PMID:27606941

  14. Span graphics display utilities handbook, first edition

    NASA Technical Reports Server (NTRS)

    Gallagher, D. L.; Green, J. L.; Newman, R.

    1985-01-01

    The Space Physics Analysis Network (SPAN) is a computer network connecting scientific institutions throughout the United States. This network provides an avenue for timely, correlative research between investigators, in a multidisciplinary approach to space physics studies. An objective in the development of SPAN is to make available direct and simplified procedures that scientists can use, without specialized training, to exchange information over the network. Information exchanges include raw and processes data, analysis programs, correspondence, documents, and graphite images. This handbook details procedures that can be used to exchange graphic images over SPAN. The intent is to periodically update this handbook to reflect the constantly changing facilities available on SPAN. The utilities described within reflect an earnest attempt to provide useful descriptions of working utilities that can be used to transfer graphic images across the network. Whether graphic images are representative of satellite servations or theoretical modeling and whether graphics images are of device dependent or independent type, the SPAN graphics display utilities handbook will be the users guide to graphic image exchange.

  15. Susquehanna River Bridge swing span. Havre de Grace, Hareford Co., ...

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

    Susquehanna River Bridge swing span. Havre de Grace, Hareford Co., MD. Sec. 1201, MP 60.07. - Northeast Railroad Corridor, Amtrak route between District of Columbia/Maryland state line & Maryland/Delaware state line, Baltimore, Independent City, MD

  16. A human iPSC model of Ligase IV deficiency reveals an important role for NHEJ-mediated-DSB repair in the survival and genomic stability of induced pluripotent stem cell>s and emerging haematopoietic progenitors.

    PubMed

    Tilgner, K; Neganova, I; Moreno-Gimeno, I; Al-Aama, J Y; Burks, D; Yung, S; Singhapol, C; Saretzki, G; Evans, J; Gorbunova, V; Gennery, A; Przyborski, S; Stojkovic, M; Armstrong, L; Jeggo, P; Lako, M

    2013-08-01

    DNA double strand breaks (DSBs) are the most common form of DNA damage and are repaired by non-homologous-end-joining (NHEJ) or homologous recombination (HR). Several protein components function in NHEJ, and of these, DNA Ligase IV is essential for performing the final 'end-joining' step. Mutations in DNA Ligase IV result in LIG4 syndrome, which is characterised by growth defects, microcephaly, reduced number of blood cells, increased predisposition to leukaemia and variable degrees of immunodeficiency. In this manuscript, we report the creation of a human induced pluripotent stem cell (iPSC) model of LIG4 deficiency, which accurately replicates the DSB repair phenotype of LIG4 patients. Our findings demonstrate that impairment of NHEJ-mediated-DSB repair in human iPSC results in accumulation of DSBs and enhanced apoptosis, thus providing new insights into likely mechanisms used by pluripotent stem cell>s to maintain their genomic integrity. Defects in NHEJ-mediated-DSB repair also led to a significant decrease in reprogramming efficiency of human cells and accumulation of chromosomal abnormalities, suggesting a key role for NHEJ in somatic cell reprogramming and providing insights for future cell based therapies for applications of LIG4-iPSCs. Although haematopoietic specification of LIG4-iPSC is not affected per se, the emerging haematopoietic progenitors show a high accumulation of DSBs and enhanced apoptosis, resulting in reduced numbers of mature haematopoietic cells. Together our findings provide new insights into the role of NHEJ-mediated-DSB repair in the survival and differentiation of progenitor cells, which likely underlies the developmental abnormalities observed in many DNA damage disorders. In addition, our findings are important for understanding how genomic instability arises in pluripotent stem cell>s and for defining appropriate culture conditions that restrict DNA damage and result in ex vivo expansion of stem cells with intact

  17. Characterizing PCDH19 in human induced pluripotent stem cell>s (iPSCs) and iPSC-derived developing neurons: emerging role of a protein involved in controlling polarity during neurogenesis

    PubMed Central

    Compagnucci, Claudia; Petrini, Stefania; Higuraschi, Norimichi; Trivisano, Marina; Specchio, Nicola; Hirose, Shinichi; Bertini, Enrico; Terracciano, Alessandra

    2015-01-01

    PCDH19 (Protocadherin 19), a member of the cadherin superfamily, is involved in the pathogenic mechanism of an X-linked model of neurological disease. The biological function of PCHD19 in human neurons and during neurogenesis is currently unknown. Therefore, we decided to use the model of the induced pluripotent stem cell>s (iPSCs) to characterize the location and timing of expression of PCDH19 during cortical neuronal differentiation. Our data show that PCDH19 is expressed in pluripotent cells before differentiation in a homogeneous pattern, despite its localization is often limited to one pole of the cell. During neuronal differentiation, positional information on the progenitor cells assumes an important role in acquiring polarization. The proper control of the cell orientation ensures a fine balancing between symmetric (giving rise to two progenitor sister cells) versus asymmetric (giving rise to one progenitor cell and one newborn neuron) division. This process results in the polar organization of the neural tube with a lumen indicating the basal part of the polarized neuronal progenitor cell; in the iPSC model the cells are organized in the ‘neural rosette’ and interestingly, PCDH19 is located at the center of the rosette, with other well-known markers of the lumen (N-cadherin and ZO-1). These data suggest that PCDH19 has a role in instructing the apico-basal polarity of the progenitor cells, thus regulating the development of a properly organized human brain. PMID:26450854

  18. 17. DETAIL VIEW OF MOVABLE SPAN MACHINERY, OUTER FIXED GEAR ...

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

    17. DETAIL VIEW OF MOVABLE SPAN MACHINERY, OUTER FIXED GEAR RING AND ROLLERS ON CENTER CONCRETE PEDESTAL; THE TWO DRIVE GEARS MESH INTO THIS RING TO TURN BASCULE (taken in January 1984) - Sharptown Bridge, Spanning Nanticoke River, State Route 313, Sharptown, Wicomico County, MD

  19. 18. DETAIL VIEW OF MOVABLE SPAN UNDER GRID DECK, ONE ...

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

    18. DETAIL VIEW OF MOVABLE SPAN UNDER GRID DECK, ONE OF TWO DRIVE GEARS ON NORTH SIDE OF PEDESTAL THAT MESHES INTO FIXED GEAR RING, SET INTO TOP OF CENTER CONCRETE PEDESTAL, LOOKING SOUTHEAST (taken in March 1984) - Sharptown Bridge, Spanning Nanticoke River, State Route 313, Sharptown, Wicomico County, MD

  20. View of plate girder spans at north end, looking west ...

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

    View of plate girder spans at north end, looking west from beneath state route 18 bridge (which lies along previous alignment of Pittsburgh, Fort Wayne & Chicago Railway). - Pittsburgh, Fort Wayne & Chicago Railway, Beaver River Bridge, Spanning Beaver River along line of Second Avenue, New Brighton, Beaver County, PA

  1. 35. ALTERNATE DESIGN USING THROUGH ARCH SPANS, WITH ARCH REPEATED ...

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

    35. ALTERNATE DESIGN USING THROUGH ARCH SPANS, WITH ARCH REPEATED BETWEEN TOWER LEGS, AND ASHLAR MASONRY WALLS AND PYLONS Pen-and-ink drawing by project architect Alfred Eichler, 1934. - Sacramento River Bridge, Spanning Sacramento River at California State Highway 275, Sacramento, Sacramento County, CA

  2. Human fibroblast commitment to a senescence-like state in response to histone deacetylase inhibitors is cell cycle dependent.

    PubMed Central

    Ogryzko, V V; Hirai, T H; Russanova, V R; Barbie, D A; Howard, B H

    1996-01-01

    Human diploid fibroblasts (HDF) complete a limited number of cell divisions before entering a growth arrest state that is termed replicative senescence. Two histone deacetylase inhibitors, sodium butyrate and trichostatin A, dramatically reduce the HDF proliferative life span in a manner that is dependent on one or more cell doublings in the presence of these agents. Cells arrested and subsequently released from histone deacetylase inhibitors display markers of senescence and exhibit a persistent G1 block but remain competent to initiate a round of DNA synthesis in response to simian virus 40 T antigen. Average telomere length in prematurely arrested cells is greater than in senescent cells, reflecting a lower number of population doublings completed by the former. Taken together, these results support the view that one component of HDF senescence mimics a cell cycle-dependent drift in differentiation state and that propagation of HDF in histone deacetylase inhibitors accentuates this component. PMID:8756678

  3. Molecular control of steady-state dendritic cell maturation and immune homeostasis.

    PubMed

    Hammer, Gianna Elena; Ma, Averil

    2013-01-01

    Dendritic cells (DCs) are specialized sentinels responsible for coordinating adaptive immunity. This function is dependent upon coupled sensitivity to environmental signs of inflammation and infection to cellular maturation-the programmed alteration of DC phenotype and function to enhance immune cell activation. Although DCs are thus well equipped to respond to pathogens, maturation triggers are not unique to infection. Given that immune cells are exquisitely sensitive to the biological functions of DCs, we now appreciate that multiple layers of suppression are required to restrict the environmental sensitivity, cellular maturation, and even life span of DCs to prevent aberrant immune activation during the steady state. At the same time, steady-state DCs are not quiescent but rather perform key functions that support homeostasis of numerous cell types. Here we review these functions and molecular mechanisms of suppression that control steady-state DC maturation. Corruption of these steady-state operatives has diverse immunological consequences and pinpoints DCs as potent drivers of autoimmune and inflammatory disease.

  4. Semi-span model testing in the National Transonic Facility

    NASA Technical Reports Server (NTRS)

    Chokani, Ndaona; Milholen, William E., II

    1993-01-01

    obtain data on the expected complex flow field in the near wall region. This status report summarizes the progress to date on developing the semi-span geometry definition suitable for generating structured grids for the computational research. In addition, the progress on evaluating three state-of-the-art Navier-Stokes codes is presented.

  5. Barrel view from southwest. Waterville Bridge, Spanning Swatara Creek ...

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

    Barrel view from southwest. - Waterville Bridge, Spanning Swatara Creek at Appalachian Trail (moved from Little Pine Creek at State Route 44, Waterville, Lycoming County), Green Point, Lebanon County, PA

  6. Detail of lower chord connections Waterville Bridge, Spanning Swatara ...

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

    Detail of lower chord connections - Waterville Bridge, Spanning Swatara Creek at Appalachian Trail (moved from Little Pine Creek at State Route 44, Waterville, Lycoming County), Green Point, Lebanon County, PA

  7. Detail of east corner post. Waterville Bridge, Spanning Swatara ...

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

    Detail of east corner post. - Waterville Bridge, Spanning Swatara Creek at Appalachian Trail (moved from Little Pine Creek at State Route 44, Waterville, Lycoming County), Green Point, Lebanon County, PA

  8. Lower connections from south. Waterville Bridge, Spanning Swatara Creek ...

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

    Lower connections from south. - Waterville Bridge, Spanning Swatara Creek at Appalachian Trail (moved from Little Pine Creek at State Route 44, Waterville, Lycoming County), Green Point, Lebanon County, PA

  9. Detail elevation of truss from southeast. Waterville Bridge, Spanning ...

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

    Detail elevation of truss from southeast. - Waterville Bridge, Spanning Swatara Creek at Appalachian Trail (moved from Little Pine Creek at State Route 44, Waterville, Lycoming County), Green Point, Lebanon County, PA

  10. 104. Connecticut River Bridge draw span. Old Lyme, New London ...

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

    104. Connecticut River Bridge draw span. Old Lyme, New London Co., CT. Sec. 4209, MP 106.89. - Northeast Railroad Corridor, Amtrak Route between New York/Connecticut & Connecticut/Rhode Island State Lines, New Haven, New Haven County, CT

  11. 103. Connecticut River Bridge draw span. Old Lyme, New London ...

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

    103. Connecticut River Bridge draw span. Old Lyme, New London Co., CT. Sec. 4209, MP 106.89. - Northeast Railroad Corridor, Amtrak Route between New York/Connecticut & Connecticut/Rhode Island State Lines, New Haven, New Haven County, CT

  12. Life Span Well-Being

    ERIC Educational Resources Information Center

    Wolf, Mary Alice

    2005-01-01

    This chapter, rooted in life span developmental research and theory, examines domains of subjective well-being: emotional, social, and psychological. What is the impact of these domains on the learner's experience of education? It invites the reader to consider implications for learning through the use of learners' narratives.

  13. A yeast artificial chromosome contig that spans the RB1-D13S31 interval on human chromosome 13 and encompasses the frequently deleted region in B-cell chronic lymphocytic leukemia

    SciTech Connect

    Hawthorn, L.; Roberts, T.; Cowell, J.K.

    1995-12-10

    Abnormalities involving chromosome 13 have been a reported as the only cytogenetic change in B-cell chronic lymphocytic leukemia (BCLL). Deletions are the most common cytogenetic abnormality and always involve 13q14, but when translocations are seen, the consistent breakpoint is always in 13q14. It is now established that deletions, distal to the RB1 gene in 13q14, are invariably associated with these translocations. We have recently described the smallest such deletion from a series of rearrangements from these tumors isolated in somatic cell hybrids, which spans approximately 1 Mb. In this report, we present the results of a series of a chromosome walking experiments using YACs and have been able to span this small deletion, which must contain the gene that is frequently deleted in BCLL. Four probes from 13q14 (RB1-mgg15-D13S25-D13S31) were used to isolate corresponding YACs for each of the markers. The chromosomal location of these YACs was verified using FISH, which also demonstrated their nonchimeric nature. Vectorette end rescue was then used to demonstrate the overlap of the YACs and to isolate new clones to complete the contig. The extremes of the contig were shown to cross the chromosome 13 translocation breakpoints isolated in somatic cell hybrids that carry the derivatives of chromosome 13 involved in the smallest BCLL deletion. This YAC contig covers the entire deletion and will prove a valuable resource to begin isolating genes from this region. In addition, we have isolated YACs corresponding to the RB1 locus, which extends the contig over a 3.8-cM distance on the chromosome. 25 refs., 1 fig., 1 tab.

  14. Ovarian hormone level alterations during rat post-reproductive life-span influence CD8 + T-cell homeostasis

    PubMed Central

    Arsenović-Ranin, Nevena; Kosec, Duško; Nacka-Aleksić, Mirjana; Pilipović, Ivan; Stojić-Vukanić, Zorica; Djikić, Jasmina; Bufan, Biljana

    2015-01-01

    The study examined the putative role of ovarian hormones in shaping of rat peripheral T-cell compartment during post-reproductive period. In 20-month-old rats ovariectomized (Ox) at the very end of reproductive period, thymic output, cellularity and composition of major TCRαβ + peripheral blood lymphocyte and splenocyte subsets were analyzed. Ovariectomy led to the enlargement of CD8 + peripheral blood lymphocyte and splenocyte subpopulations. This reflected: (i) a more efficient thymic generation of CD8 + cells as indicated by increased number of CD4+CD8 + double positive and the most mature CD4-CD8+TCRαβhigh thymocytes and CD8 + recent thymic emigrants (RTEs) in peripheral blood, but not in the spleen of Ox rats, and (ii) the expansion of CD8 + memory/activated peripheral blood lymphocytes and splenocytes. The latter was consistent with a greater frequency of proliferating cells among freshly isolated memory/activated CD8 + peripheral blood lymphocytes and splenocytes and increased proliferative response of CD8 + splenocytes to stimulation with plate-bound anti-CD3 antibody. The former could be related to the rise in splenic IL-7 and IL-15 mRNA expression. Although ovariectomy affected the overall number of CD4 + T cells in none of the examined compartments, it increased CD4+FoxP3 + peripheral blood lymphocyte and splenocyte counts by enhancing their generation in periphery. Collectively, the results suggest that ovariectomy-induced long-lasting disturbances in ovarian hormone levels (mirrored in diminished progesterone serum level in 20-month-old rats) affects both thymic CD8 + cell generation and peripheral homeostasis and leads to the expansion of CD4+FoxP3 + cells in the periphery, thereby enhancing autoreactive cell control on account of immune system efficacy to combat infections and tumors. PMID:25716018

  15. The New Federalism: State Policies Regarding Embryonic Stem Cell Research.

    PubMed

    Acosta, Nefi D; Golub, Sidney H

    2016-09-01

    Stem cell policy in the United States is an amalgam of federal and state policies. The scientific development of human pluripotent embryonic stem cells (ESCs) triggered a contentious national stem cell policy debate during the administration of President George W. Bush. The Bush "compromise" that allowed federal funding to study only a very limited number of ESC derived cell lines did not satisfy either the researchers or the patient advocates who saw great medical potential being stifled. Neither more restrictive legislation nor expansion of federal funding proved politically possible and the federal impasse opened the door for a variety of state-based experiments. In 2004, California became the largest and most influential state venture into stem cell research by passing "Prop 71," a voter initiative that created a new stem cell agency and funded it with $3 billion. Several states followed suit with similar programs to protect the right of investigators to do stem cell research and in some cases to invest state funding in such projects. Other states devised legislation to restrict stem cell research and in five states, criminal penalties were included. Thus, the US stem cell policy is a patchwork of multiple, often conflicting, state and federal policies. PMID:27587447

  16. The New Federalism: State Policies Regarding Embryonic Stem Cell Research.

    PubMed

    Acosta, Nefi D; Golub, Sidney H

    2016-09-01

    Stem cell policy in the United States is an amalgam of federal and state policies. The scientific development of human pluripotent embryonic stem cells (ESCs) triggered a contentious national stem cell policy debate during the administration of President George W. Bush. The Bush "compromise" that allowed federal funding to study only a very limited number of ESC derived cell lines did not satisfy either the researchers or the patient advocates who saw great medical potential being stifled. Neither more restrictive legislation nor expansion of federal funding proved politically possible and the federal impasse opened the door for a variety of state-based experiments. In 2004, California became the largest and most influential state venture into stem cell research by passing "Prop 71," a voter initiative that created a new stem cell agency and funded it with $3 billion. Several states followed suit with similar programs to protect the right of investigators to do stem cell research and in some cases to invest state funding in such projects. Other states devised legislation to restrict stem cell research and in five states, criminal penalties were included. Thus, the US stem cell policy is a patchwork of multiple, often conflicting, state and federal policies.

  17. The SPAN cookbook: A practical guide to accessing SPAN

    NASA Technical Reports Server (NTRS)

    Mason, Stephanie; Tencati, Ronald D.; Stern, David M.; Capps, Kimberly D.; Dorman, Gary; Peters, David J.

    1990-01-01

    This is a manual for remote users who wish to send electronic mail messages from the Space Physics Analysis Network (SPAN) to scientific colleagues on other computer networks and vice versa. In several instances more than one gateway has been included for the same network. Users are provided with an introduction to each network listed with helpful details about accessing the system and mail syntax examples. Also included is information on file transfers, remote logins, and help telephone numbers.

  18. Fuel Cell Technologies: State And Perspectives

    NASA Astrophysics Data System (ADS)

    Sammes, Nigel; Smirnova, Alevtina; Vasylyev, Oleksandr

    Fuel Cells have become a potentially highly efficient sustainable source of energy and electricity for an ever-demanding power hungry world. The two main types of fuel cells ripe for commercialisation are the high temperature solid oxide fuel cell (SOFC) and the low temperature polymer electrolyte membrane fuel cell (PEM). The commercial uses of which include, but are not limited to, military, stand-by power, commercial and industrial, and remoter power. However, all aspects of the electricity market are being considered.

  19. Insights on the design of free-spanning pipelines.

    PubMed

    Drago, M; Mattioli, M; Bruschi, R; Vitali, L

    2015-01-28

    The design of free-spanning pipelines is performed with the aim of ensuring their integrity against permanent loads generated by seabed roughness, functional loads induced by internal pressure and temperature, and dynamic loads induced by marine currents and direct wave action. In particular, a load and resistance factored design is applied that focuses on extreme environmental loads, and a fatigue limit state approach is applied as a consequence of free-span dynamics due to vortex shedding-induced vibration and direct wave action. The pipeline free-span scenario can be permanent, when generated by seabed roughness, or characterized by short- to long-term evolution, when generated by seabed mobility and scouring in shallow waters. Free-span analysis is generally a task involving a number of disciplines and should be carried out using a multidisciplinary approach. The paper illustrates various themes related to free-span analysis: (i) free-span scenarios, (ii) characterization of the environment from deep to shallow water related to proper seabed properties, (iii) hydrodynamic load regimes, (iv) pipeline free-span design assessment aiming to reduce overstress and fatigue damage, (v) erodible seabed mobility and local scour, and (vi) some experiences of inspection surveys chosen as representative of a free-spanning pipeline in sandy soils. PMID:25512589

  20. Exploring the Dimensionality of Digit Span

    ERIC Educational Resources Information Center

    Bowden, Stephen C.; Petrauskas, Vilija M.; Bardenhagen, Fiona J.; Meade, Catherine E.; Simpson, Leonie C.

    2013-01-01

    The Digit Span subtest from the Wechsler Scales is used to measure Freedom from Distractibility or Working Memory. Some published research suggests that Digit Span forward should be interpreted differently from Digit Span backward. The present study explored the dimensionality of the Wechsler Memory Scale-III Digit Span (forward and backward)…

  1. Loneliness across the life span.

    PubMed

    Qualter, Pamela; Vanhalst, Janne; Harris, Rebecca; Van Roekel, Eeske; Lodder, Gerine; Bangee, Munirah; Maes, Marlies; Verhagen, Maaike

    2015-03-01

    Most people have experienced loneliness and have been able to overcome it to reconnect with other people. In the current review, we provide a life-span perspective on one component of the evolutionary theory of loneliness-a component we refer to as the reaffiliation motive (RAM). The RAM represents the motivation to reconnect with others that is triggered by perceived social isolation. Loneliness is often a transient experience because the RAM leads to reconnection, but sometimes this motivation can fail, leading to prolonged loneliness. We review evidence of how aspects of the RAM change across development and how these aspects can fail for different reasons across the life span. We conclude with a discussion of age-appropriate interventions that may help to alleviate prolonged loneliness. PMID:25910393

  2. Loneliness across the life span.

    PubMed

    Qualter, Pamela; Vanhalst, Janne; Harris, Rebecca; Van Roekel, Eeske; Lodder, Gerine; Bangee, Munirah; Maes, Marlies; Verhagen, Maaike

    2015-03-01

    Most people have experienced loneliness and have been able to overcome it to reconnect with other people. In the current review, we provide a life-span perspective on one component of the evolutionary theory of loneliness-a component we refer to as the reaffiliation motive (RAM). The RAM represents the motivation to reconnect with others that is triggered by perceived social isolation. Loneliness is often a transient experience because the RAM leads to reconnection, but sometimes this motivation can fail, leading to prolonged loneliness. We review evidence of how aspects of the RAM change across development and how these aspects can fail for different reasons across the life span. We conclude with a discussion of age-appropriate interventions that may help to alleviate prolonged loneliness.

  3. Self-assembling peptide nanofiber scaffolds enhance dopaminergic differentiation of mouse pluripotent stem cell>s in 3-dimensional culture.

    PubMed

    Ni, Na; Hu, Yaohua; Ren, Huixia; Luo, Chuanming; Li, Peng; Wan, Jian-Bo; Su, Huanxing

    2013-01-01

    Dopaminergic differentiation of embryonic stem cells (ESCs) gains more and more attention worldwide owing to its potential use for neurorestorative therapy for the treatment of Parkinson's disease. The conventional 2D cell culture on petri dishes with various animal derived substrata such as collagen gels, laminin, and Matrigel is widely used to induce dopaminergic differentiation and it may limit the efficiency in the generation of dopaminergic neurons from ESCs and prevent their application for human therapies. Here, we reported that a self-assembling peptide made from natural amino acids has a property to generate a true 3D environment for dopaminergic differentiation. Mouse ESCs (R1) and mouse iPSCs (TTF-1) embedded in RADA16-I peptide-derived nanofiber scaffolds led to a marked increase in dopaminergic differentiation compared to the laminin-coated 2D culture or Matrigel-encapsulated 3D culture. These differentiated neurons expressed specific dopaminergic markers and produced appropriate patterns of action potential firing. Consistent with the increase in the number of dopaminergic neurons differentiated from R1 or TTF-1 in the self-assembling peptide nanofiber scaffold (SAPNS), both the expression levels of genes that involve in dopaminergic differentiation and maturation and the dopamine release in SAPNS culture were significantly elevated. The results of the study suggest that SAPNS provides a promising 3D culture system for dopaminergic differentiation. PMID:24376815

  4. Enumeration of Spanning Trees on Generalized Pseudofractal Networks

    NASA Astrophysics Data System (ADS)

    Xiao, Jinmei; Zhang, Jingyuan; Sun, Weigang

    2015-05-01

    In this paper, we calculate the number of spanning trees on two families of generalized pseudo- fractal networks with two controllable parameters. The initial state is a complete graph with an arbitrary number of nodes as a generalization of a triangle. In the subsequent steps, each existing edge (newly produced edge) gives birth to finite new nodes. Using the electrically equivalent transformations, we obtain the changes of edge weights of corresponding equivalent networks and derive the relationships for enumerating spanning trees between original networks and transformed networks. Finally, we obtain closed-form formulas for the number of spanning trees, which is verified by numerical simulations.

  5. 12. DETAIL VIEW OF BRIDGE, SHOWING SPRING LINE OF SPANS ...

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

    12. DETAIL VIEW OF BRIDGE, SHOWING SPRING LINE OF SPANS FROM CROWN OF MID-CHANNEL PIER, PAIRED COLUMNS SUPPORTING DECK, ARCHED WINDOW RAILING, LOOKING WEST-NORTHWEST FROM EUREKA SOUTHERN RAILROAD BRIDGE. CABLES VISIBLE IN BACKGROUND ARE EARTHQUAKE RESTRAINERS RETROFITTED TO 1952 HIGHWAY BRIDGE, WHICH FUNCTIONED AS DESIGNED IN APRIL 1992 TEMBLOR - Van Duzen River Bridge, Spanning Van Duzen River at CA State Highway 101, Alton, Humboldt County, CA

  6. Multistage carcinogenesis modeling including cell cycle and DNA damage states

    NASA Astrophysics Data System (ADS)

    Hazelton, W.; Moolgavkar, S.

    The multistage clonal expansion model of carcinogenesis is generalized to include cell cycle states and corresponding DNA damage states with imperfect repair for normal and initiated stem cells. Initiated cells may undergo transformation to a malignant state, eventually leading to cancer incidence or death. The model allows oxidative or radiation induced DNA damage, checkpoint delay, DNA repair, apoptosis, and transformation rates to depend on the cell cycle state or DNA damage state of normal and initiated cells. A probability generating function approach is used to represent the time dependent probability distribution for cells in all states. The continuous time coupled Markov system representing this joint distribution satisfies a partial differential equation (pde). Time dependent survival and hazard functions are found through numerical solution of the characteristic equations for the pde. Although the hazard and survival can be calculated numerically, number and size distributions of pre-malignant lesions from models that are developed will be approximated through simulation. We use the model to explore predictions for hazard and survival as parameters representing cell cycle regulation and arrest are modified. Modification of these parameters may influence rates for cell division, apoptosis and malignant transformation that are important in carcinogenesis. We also explore enhanced repair that may be important for low-dose hypersensitivity and adaptive response, and degradation of repair processes or loss of checkpoint control that may drive genetic instability.

  7. The organelle of differentiation in embryos: the cell state splitter.

    PubMed

    Gordon, Natalie K; Gordon, Richard

    2016-01-01

    The cell state splitter is a membraneless organelle at the apical end of each epithelial cell in a developing embryo. It consists of a microfilament ring and an intermediate filament ring subtending a microtubule mat. The microtubules and microfilament ring are in mechanical opposition as in a tensegrity structure. The cell state splitter is bistable, perturbations causing it to contract or expand radially. The intermediate filament ring provides metastability against small perturbations. Once this snap-through organelle is triggered, it initiates signal transduction to the nucleus, which changes gene expression in one of two readied manners, causing its cell to undergo a step of determination and subsequent differentiation. The cell state splitter also triggers the cell state splitters of adjacent cells to respond, resulting in a differentiation wave. Embryogenesis may be represented then as a bifurcating differentiation tree, each edge representing one cell type. In combination with the differentiation waves they propagate, cell state splitters explain the spatiotemporal course of differentiation in the developing embryo. This review is excerpted from and elaborates on "Embryogenesis Explained" (World Scientific Publishing, Singapore, 2016). PMID:26965444

  8. Novel Low Temperature Solid State Fuel Cells

    SciTech Connect

    Chen, Chonglin; Nash, Patrick; Liu, Jian; Collins, Gregory

    2010-03-23

    We have successfully fabricated (PrBa)Co2O5+δ and (LaBa)Co2O5+δ epitaxial thin film on various single crystal substrates. Physical and electrochemical properties characterizations were carried out. Highly conductive oxygen-deficient double perovskite LnBaCo2O5+ thin films were grown on single crystal (001) SrTiO3 (STO), (001) MgO, (001) LaAlO3 and (110) NdGaO3} substrate by pulsed laser deposition. Microstructure studies from synchrotron X-ray diffraction and Transmission electron microscopy. High temperature transport properties was carried in different atmosphere (O2,Air, N2) up to ~900K. Resistance response of (LaBa)Co2O5+δ epitaxial thin film was characterized in oxygen, nitrogen and 4% hydrogen over a wide range of temperature from 400 C up to 800 C. To determine the electrode performance and oxygen exchange kinetics of PrBaCo2O5+δ, multi-layered thin film based half cell was deposited on LaAlO3(001) substrate. The temperature dependence of the resistance of this half cell structure was characterized by electrochemical impedance spectroscopy (EIS) within different temperature and gas environments. Anode supported fuel cells, with GCO:YSZ multilayer thin film as electrolyte and PBCO thin film as electrode, are fabricated on tape casted NiO/YSZ substrate. Full cell performance is characterized up to 800 C.

  9. Newer approaches in increasing life span.

    PubMed

    Dhar, H L

    1999-09-01

    Based on ideal conditions technical life span of human kind is approximately 110-120 years. Although number of studies including calorie restriction and antiparkinsonism drug (deprenyl) have indicated increased life span in animals, it is premature to expect them to increase life span in man. However, current studies like activation of immune system with DHEA in man and anticipation of antioxidant therapy contributing to increased life span are encouraging. Practice of meditation particularly TM and balanced diet might be contributory.

  10. Life-Span Learning: A Developmental Perspective

    ERIC Educational Resources Information Center

    Thornton, James E.

    2003-01-01

    The article discusses learning as embedded processes of development and aging, and as social activity over the life course. The concept of life-span learning is proposed and outlined to discuss these processes as aspects of and propositions in life-span development and aging theory. Life-span learning processes arise and continuously develop in a…

  11. C-SPAN Networks: Professors' Guide.

    ERIC Educational Resources Information Center

    C-SPAN in the Classroom, 1993

    1993-01-01

    The intention of this guide is to serve as a forum for college faculty members to share ideas and articles about using C-SPAN programming in college classrooms and in academic research. The first article, "C-SPAN as a 'Lecture Launcher'" (Stephen Frantzich) illustrates how well-chosen segments of C-SPAN programming can be used to stimulate…

  12. Center for Cell Research, Pennsylvania State University

    NASA Technical Reports Server (NTRS)

    Cronin, Mike

    1991-01-01

    A brief review of Genentech, Inc., is presented. Additionally, the Physiological Systems Experiment (PSE-01) is discussed in terms of its development history. The PSE-01 was developed to investigate the bone wasting, muscle wasting, and immune cell dysfunction that occur in microgravity conditions. Specifically, a number of human disorders are associated with maladaptive changes in bone, muscle, and immune function. The physiological adjustments that the body makes in response to space flight can be monitored and may aid in the discovery of new protein forms and patterns. This research may also provide strategies for protecting the health of flight crews enduring prolonged space flight. Results are discussed.

  13. Spanning Tree Calculations on D-Wave 2 Machines

    NASA Astrophysics Data System (ADS)

    Novotny, M. A.; Hobl, Q. L.; Hall, J. S.; Michielsen, K.

    2016-02-01

    Calculations on D-Wave machines are presented, both for the 500-qubit and the 1000-qubit machines. Results are presented for spanning trees on the available K4,4 Chimera graphs of both machines. Comparing trees of approximately the same size, the frequency of finding the ground state for the 1000-qubit machine is significantly improved over the 500- qubit older generation machine. Spanning trees are difficult problems for solution by adiabatic quantum computers, so the enhanced frequency of finding the ground state for newer machine generations and larger machines is encouraging for this immature technology.

  14. Mechanism for multiplicity of steady states with distinct cell concentration in continuous culture of mammalian cells.

    PubMed

    Yongky, Andrew; Lee, Jongchan; Le, Tung; Mulukutla, Bhanu Chandra; Daoutidis, Prodromos; Hu, Wei-Shou

    2015-07-01

    Continuous culture for the production of biopharmaceutical proteins offers the possibility of steady state operations and thus more consistent product quality and increased productivity. Under some conditions, multiplicity of steady states has been observed in continuous cultures of mammalian cells, wherein with the same dilution rate and feed nutrient composition, steady states with very different cell and product concentrations may be reached. At those different steady states, cells may exhibit a high glycolysis flux with high lactate production and low cell concentration, or a low glycolysis flux with low lactate and high cell concentration. These different steady states, with different cell concentration, also have different productivity. Developing a mechanistic understanding of the occurrence of steady state multiplicity and devising a strategy to steer the culture toward the desired steady state is critical. We establish a multi-scale kinetic model that integrates a mechanistic intracellular metabolic model and cell growth model in a continuous bioreactor. We show that steady state multiplicity exists in a range of dilution rate in continuous culture as a result of the bistable behavior in glycolysis. The insights from the model were used to devise strategies to guide the culture to the desired steady state in the multiple steady state region. The model provides a guideline principle in the design of continuous culture processes of mammalian cells.

  15. Development of Semi-Span Model Test Techniques

    NASA Technical Reports Server (NTRS)

    Pulnam, L. Elwood (Technical Monitor); Milholen, William E., II; Chokani, Ndaona; McGhee, Robert J.

    1996-01-01

    A computational investigation was performed to support the development of a semi-span model test capability in the NASA Langley Research Center's National Transonic Facility. This capability is desirable for the testing of advanced subsonic transport aircraft at full-scale Reynolds numbers. A state-of-the-art three-dimensional Navier-Stokes solver was used to examine methods to improve the flow over a semi-span configuration. First, a parametric study is conducted to examine the influence of the stand-off height on the flow over the semi-span model. It is found that decreasing the stand-off height, below the maximum fuselage radius, improves the aerodynamic characteristics of the semi-span model. Next, active sidewall boundary layer control techniques are examined. Juncture region blowing jets, upstream tangential blowing, and sidewall suction are found to improve the flow over the aft portion of the semi-span model. Both upstream blowing and suction are found to reduce the sidewall boundary layer separation. The resulting near surface streamline patterns are improved, and found to be quite similar to the full-span results. Both techniques however adversely affect the pitching moment coefficient.

  16. 1. From north bankup riverSpan 2 on left to Span ...

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

    1. From north bank-up river-Span 2 on left to Span 6 on right. Coke Plant in distance (under Span 3). - Monongahela Connecting Railroad Company, Hot Metal Bridge, Spanning Monongahela River at mile post 3.1, Pittsburgh, Allegheny County, PA

  17. Extended attention span training system

    NASA Technical Reports Server (NTRS)

    Pope, Alan T.; Bogart, Edward H.

    1991-01-01

    Attention Deficit Disorder (ADD) is a behavioral disorder characterized by the inability to sustain attention long enough to perform activities such as schoolwork or organized play. Treatments for this disorder include medication and brainwave biofeedback training. Brainwave biofeedback training systems feed back information to the trainee showing him how well he is producing the brainwave pattern that indicates attention. The Extended Attention Span Training (EAST) system takes the concept a step further by making a video game more difficult as the player's brainwaves indicate that attention is waning. The trainee can succeed at the game only by maintaining an adequate level of attention. The EAST system is a modification of a biocybernetic system that is currently being used to assess the extent to which automated flight management systems maintain pilot engagement. This biocybernetic system is a product of a program aimed at developing methods to evaluate automated flight deck designs for compatibility with human capabilities. The EAST technology can make a contribution in the fields of medical neuropsychology and neurology, where the emphasis is on cautious, conservative treatment of youngsters with attention disorders.

  18. Synthetic recombinase-based state machines in living cells.

    PubMed

    Roquet, Nathaniel; Soleimany, Ava P; Ferris, Alyssa C; Aaronson, Scott; Lu, Timothy K

    2016-07-22

    State machines underlie the sophisticated functionality behind human-made and natural computing systems that perform order-dependent information processing. We developed a recombinase-based framework for building state machines in living cells by leveraging chemically controlled DNA excision and inversion operations to encode states in DNA sequences. This strategy enables convenient readout of states (by sequencing and/or polymerase chain reaction) as well as complex regulation of gene expression. We validated our framework by engineering state machines in Escherichia coli that used one, two, or three chemical inputs to control up to 16 DNA states. These state machines were capable of recording the temporal order of all inputs and performing multi-input, multi-output control of gene expression. We also developed a computational tool for the automated design of gene regulation programs using recombinase-based state machines. Our scalable framework should enable new strategies for recording and studying how combinational and temporal events regulate complex cell functions and for programming sophisticated cell behaviors. PMID:27463678

  19. Synthetic recombinase-based state machines in living cells.

    PubMed

    Roquet, Nathaniel; Soleimany, Ava P; Ferris, Alyssa C; Aaronson, Scott; Lu, Timothy K

    2016-07-22

    State machines underlie the sophisticated functionality behind human-made and natural computing systems that perform order-dependent information processing. We developed a recombinase-based framework for building state machines in living cells by leveraging chemically controlled DNA excision and inversion operations to encode states in DNA sequences. This strategy enables convenient readout of states (by sequencing and/or polymerase chain reaction) as well as complex regulation of gene expression. We validated our framework by engineering state machines in Escherichia coli that used one, two, or three chemical inputs to control up to 16 DNA states. These state machines were capable of recording the temporal order of all inputs and performing multi-input, multi-output control of gene expression. We also developed a computational tool for the automated design of gene regulation programs using recombinase-based state machines. Our scalable framework should enable new strategies for recording and studying how combinational and temporal events regulate complex cell functions and for programming sophisticated cell behaviors.

  20. Derivation of novel human ground state naive pluripotent stem cells.

    PubMed

    Gafni, Ohad; Weinberger, Leehee; Mansour, Abed AlFatah; Manor, Yair S; Chomsky, Elad; Ben-Yosef, Dalit; Kalma, Yael; Viukov, Sergey; Maza, Itay; Zviran, Asaf; Rais, Yoach; Shipony, Zohar; Mukamel, Zohar; Krupalnik, Vladislav; Zerbib, Mirie; Geula, Shay; Caspi, Inbal; Schneir, Dan; Shwartz, Tamar; Gilad, Shlomit; Amann-Zalcenstein, Daniela; Benjamin, Sima; Amit, Ido; Tanay, Amos; Massarwa, Rada; Novershtern, Noa; Hanna, Jacob H

    2013-12-12

    Mouse embryonic stem (ES) cells are isolated from the inner cell mass of blastocysts, and can be preserved in vitro in a naive inner-cell-mass-like configuration by providing exogenous stimulation with leukaemia inhibitory factor (LIF) and small molecule inhibition of ERK1/ERK2 and GSK3β signalling (termed 2i/LIF conditions). Hallmarks of naive pluripotency include driving Oct4 (also known as Pou5f1) transcription by its distal enhancer, retaining a pre-inactivation X chromosome state, and global reduction in DNA methylation and in H3K27me3 repressive chromatin mark deposition on developmental regulatory gene promoters. Upon withdrawal of 2i/LIF, naive mouse ES cells can drift towards a primed pluripotent state resembling that of the post-implantation epiblast. Although human ES cells share several molecular features with naive mouse ES cells, they also share a variety of epigenetic properties with primed murine epiblast stem cells (EpiSCs). These include predominant use of the proximal enhancer element to maintain OCT4 expression, pronounced tendency for X chromosome inactivation in most female human ES cells, increase in DNA methylation and prominent deposition of H3K27me3 and bivalent domain acquisition on lineage regulatory genes. The feasibility of establishing human ground state naive pluripotency in vitro with equivalent molecular and functional features to those characterized in mouse ES cells remains to be defined. Here we establish defined conditions that facilitate the derivation of genetically unmodified human naive pluripotent stem cells from already established primed human ES cells, from somatic cells through induced pluripotent stem (iPS) cell reprogramming or directly from blastocysts. The novel naive pluripotent cells validated herein retain molecular characteristics and functional properties that are highly similar to mouse naive ES cells, and distinct from conventional primed human pluripotent cells. This includes competence in the generation

  1. Methionine restriction beyond life-span extension.

    PubMed

    Ables, Gene P; Hens, Julie R; Nichenametla, Sailendra N

    2016-01-01

    Dietary methionine restriction (MR) extends life span across species via various intracellular regulatory mechanisms. In rodents, MR induces resistance against adiposity, improves hepatic glucose metabolism, preserves cardiac function, and reduces body size, all of which can affect the onset of age-related diseases. Recent studies have shown that MR-affected biomarkers, such as fibroblast growth factor 21, adiponectin, leptin, cystathionine β synthase, and insulin-like growth factor 1, can potentially alter physiology. The beneficial effects of MR could be explained in part by its ability to reduce mitochondrial oxidative stress. Studies have revealed that MR can reduce reactive oxygen species that damage cells and promote cancer progression. It has been demonstrated that either MR or the targeting of specific genes in the methionine cycle could induce cell apoptosis while decreasing proliferation in several cancer models. The complete mechanism underlying the actions of MR on the cell cycle during cancer has not been fully elucidated. Epigenetic mechanisms, such as methylation and noncoding RNAs, are also possible downstream effectors of MR; future studies should help to elucidate some of these mechanisms. Despite evidence that changes in dietary methionine can affect epigenetics, it remains unknown whether epigenetics is a mechanism in MR. This review summarizes research on MR and its involvement in metabolism, cancer, and epigenetics.

  2. Skeletal muscle stem cells adopt a dormant cell state post mortem and retain regenerative capacity.

    PubMed

    Latil, Mathilde; Rocheteau, Pierre; Châtre, Laurent; Sanulli, Serena; Mémet, Sylvie; Ricchetti, Miria; Tajbakhsh, Shahragim; Chrétien, Fabrice

    2012-01-01

    The accessibility to stem cells from healthy or diseased individuals, and the maintenance of their potency are challenging issues for stem cell biology. Here we report the isolation of viable and functional skeletal myogenic cells from humans up to 17 days, and mice up to 14 days post mortem, much longer beyond previous reports. Muscle stem cells are enriched in post mortem tissue, suggesting a selective survival advantage compared with other cell types. Transplantation of mouse muscle and haematopoietic stem cells regenerates tissues robustly. Cellular quiescence contributes to this cell viability where cells adopt a reversible dormant state characterized by reduced metabolic activity, a prolonged lag phase before the first cell division, elevated levels of reactive oxygen species and a transcriptional status less primed for commitment. Finally, severe hypoxia, or anoxia is critical for maintaining stem cell viability and regenerative capacity. Thus, these cells provide a useful resource for studying stem cell biology.

  3. Defining the functional states of Th17 cells

    PubMed Central

    Lee, Youjin; Kuchroo, Vijay

    2015-01-01

    The molecular mechanisms governing T helper (Th) cell differentiation and function have revealed a complex network of transcriptional and protein regulators. Cytokines not only initiate the differentiation of CD4 Th cells into subsets but also influence the identity, plasticity and effector function of a T cell. Of the subsets, Th17 cells, named for producing interleukin 17 (IL-17) as their signature cytokine, secrete a cohort of other cytokines, including IL-22, IL-21, IL-10, IL-9, IFNγ, and GM-CSF.  In recent years, Th17 cells have emerged as key players in host defense against both extracellular pathogens and fungal infections, but they have also been implicated as one of the main drivers in the pathogenesis of autoimmunity, likely mediated in part by the cytokines that they produce. Advances in high throughput genomic sequencing have revealed unexpected heterogeneity in Th17 cells and, as a consequence, may have tremendous impact on our understanding of their functional diversity. The assortment in gene expression may also identify different functional states of Th17 cells. This review aims to understand the interplay between the cytokine regulators that drive Th17 cell differentiation and functional states in Th17 cells. PMID:27006754

  4. Cell kinetics of GM-CFC in the steady state

    SciTech Connect

    Hagan, M.P.; MacVittie, T.J.; Dodgen, D.P.

    1985-07-01

    The kinetics of cell turnover for myeloid/monocyte cells that form colonies in agar (GM-CFC) were measured through the progressive increase in their sensitivity to 313-nm light during a period of cell labeling with BrdCyd. Two components of cell killing with distinctly separate labeling kinetics revealed both the presence of two generations within the GM-CFC compartment and the properties of the kinetics of the precursors of the GM-CFC. These precursors of the GM-CFC were not assayable in a routine GM-CFC assay when pregnant mouse uterus extract and mouse L-cell-conditioned medium were used to stimulate colony formation but were revealed by the labeling kinetics of the assayable GM-CFC. Further, these precursor cells appeared to enter the assayable GM-CFC population from a noncycling state. This was evidenced by the failure of the majority of these cells to incorporate BrdCyd during five days of infusion. The half-time for cell turnover within this precursor compartment was measured to be approximately 5.5 days. Further, these normally noncycling cells proliferated rapidly in response to endotoxin. High-proliferative-potential colony-forming cells (HPP-CFC) were tested as a candidate for this precursor population. The results of the determination of the kinetics for these cells showed that the HPP-CFC exist largely in a Go state, existing at an average rate of once every four days. The slow turnover time for these cells and their response to endotoxin challenge are consistent with a close relationship between the HPP-CFC and the Go pool of cells that is the direct precursor of the GM-CFC.

  5. Relationship between Grade Span Configuration and Academic Achievement

    ERIC Educational Resources Information Center

    Dove, Mary Jane; Pearson, L. Carolyn; Hooper, Herbert

    2010-01-01

    The relationship between grade span configuration and academic achievement of 6th-grade students as measured by the Arkansas Benchmark Examination, which is the approved NCLB criterion-referenced annual assessment, was examined. The results of a one-between two-within analysis of variance for the 3-year state-wide study of 6th graders' combined…

  6. Cloning and Variation of Ground State Intestinal Stem Cells

    PubMed Central

    Wang, Xia; Yamamoto, Yusuke; Wilson, Lane H.; Zhang, Ting; Howitt, Brooke; Farrow, Melissa A.; Kern, Florian; Ning, Gang; Hong, Yue; Khor, Chiea Chuen; Chevalier, Benoit; Bertrand, Denis; Wu, Lingyan; Nagarajan, Niranjan; Sylvester, Francisco A.; Hyams, Jeffrey S.; Devers, Thomas; Bronson, Roderick; Lacy, D. Borden; Ho, Khek Yu; Crum, Christopher P.; McKeon, Frank; Xian, Wa

    2016-01-01

    Summary Stem cells of the gastrointestinal tract, pancreas, liver, and other columnar epithelia collectively resist cloning in their elemental states. Here we demonstrate the cloning and propagation of highly clonogenic, “ground state” stem cells of the human intestine and colon. We show that derived stem cell pedigrees sustain limited copy number and sequence variation despite extensive serial passaging and display exquisitely precise, cell-autonomous commitment to epithelial differentiation consistent with their origins along the intestinal tract. This developmentally patterned and epigenetically maintained commitment of stem cells likely enforces the functional specificity of the adult intestinal tract. Using clonally-derived colonic epithelia, we show that toxins A or B of the enteric pathogen C. difficile recapitulate the salient features of pseudomembranous colitis. The stability of the epigenetic commitment programs of these stem cells, coupled with their unlimited replicative expansion and maintained clonogenicity, suggests certain advantages for their use in disease modeling and regenerative medicine. PMID:26040716

  7. Patentability of Stem Cells in the United States.

    PubMed

    Fendrick, Sarah E; Zuhn, Donald L

    2015-08-20

    Until recently, the patentability of stem cells was well established within the judicial and statutory framework in the United States. However, the shifting landscape of patent law, particularly with regard to patent-eligible subject matter under 35 U.S.C. §101, presents new challenges to the patentability of stem cells. In this paper, we discuss the legal precedent that paved the way for stem cell patents, including Diamond v. Chakrabarty and In re Bergy. Additionally, we review recent Supreme Court cases and recent guidance issued by the U.S. Patent and Trademark Office that impose new limitations on patent-eligible subject matter and thereby threaten the patentability of stem cells in the United States.

  8. An engineered dimeric protein pore that spans adjacent lipid bilayers

    PubMed Central

    Mantri, Shiksha; Sapra, K. Tanuj; Cheley, Stephen; Sharp, Thomas H.; Bayley, Hagan

    2013-01-01

    The bottom-up construction of artificial tissues is an underexplored area of synthetic biology. An important challenge is communication between constituent compartments of the engineered tissue and between the engineered tissue and additional compartments, including extracellular fluids, further engineered tissue and living cells. Here we present a dimeric transmembrane pore that can span two adjacent lipid bilayers and thereby allow aqueous compartments to communicate. Two heptameric staphylococcal α-hemolysin (αHL) pores were covalently linked in an aligned cap-to-cap orientation. The structure of the dimer, (α7)2, was confirmed by biochemical analysis, transmission electron microscopy (TEM) and single-channel electrical recording. We show that one of two β barrels of (α7)2 can insert into the lipid bilayer of a small unilamellar vesicle, while the other spans a planar lipid bilayer. (α7)2 pores spanning two bilayers were also observed by TEM. PMID:23591892

  9. Single-cell ChIP-seq reveals cell subpopulations defined by chromatin state

    PubMed Central

    Rotem, Assaf; Ram, Oren; Shoresh, Noam; Sperling, Ralph A.; Goren, Alon; Weitz, David A.; Bernstein, Bradley E.

    2015-01-01

    Chromatin profiling provides a versatile means to investigate functional genomic elements and their regulation. However, current methods yield ensemble profiles that are insensitive to cell-to-cell variation. Here we combine microfluidics, DNA barcoding and sequencing to collect chromatin data at single-cell resolution. We demonstrate the utility of the technology by assaying thousands of individual cells, and using the data to deconvolute a mixture of ES cells, fibroblasts and hematopoietic progenitors into high-quality chromatin state maps for each cell type. The data from each single cell is sparse, comprising on the order of 1000 unique reads. However, by assaying thousands of ES cells, we identify a spectrum of sub-populations defined by differences in chromatin signatures of pluripotency and differentiation priming. We corroborate these findings by comparison to orthogonal single-cell gene expression data. Our method for single-cell analysis reveals aspects of epigenetic heterogeneity not captured by transcriptional analysis alone. PMID:26458175

  10. Radio-frequency-modulated Rydberg states in a vapor cell

    NASA Astrophysics Data System (ADS)

    Miller, S. A.; Anderson, D. A.; Raithel, G.

    2016-05-01

    We measure strong radio-frequency (RF) electric fields using rubidium Rydberg atoms prepared in a room-temperature vapor cell as field sensors. Electromagnetically induced transparency is employed as an optical readout. We RF-modulate the 60{{{S}}}1/2 and 58{{{D}}}5/2 Rydberg states with 50 and 100 MHz fields, respectively. For weak to moderate RF fields, the Rydberg levels become Stark-shifted, and sidebands appear at even multiples of the driving frequency. In high fields, the adjacent hydrogenic manifold begins to intersect the shifted levels, providing rich spectroscopic structure suitable for precision field measurements. A quantitative description of strong-field level modulation and mixing of S and D states with hydrogenic states is provided by Floquet theory. Additionally, we estimate the shielding of DC electric fields in the interior of the glass vapor cell.

  11. 3. View west. North elevation Walpole span in foreground, ...

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

    3. View west. North elevation - Walpole span in foreground, link span; Westminster span in background. - Walpole-Westminster Bridge, Spanning Connecticut River between Walpole, NH & Westminster, VT, Walpole, Cheshire County, NH

  12. 8. General view of movable span from water level, showing ...

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

    8. General view of movable span from water level, showing piers turntable, movable span, parts of west land span and east viaduct. VIEW NORTHEAST - Broadway Bridge, Spanning Foundry Street, MBTA Yard, Fort Point Channel, & Lehigh Street, Boston, Suffolk County, MA

  13. 2. DETAIL VIEW OF ON RIGHT FOREGROUND FIXED SPAN TO ...

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

    2. DETAIL VIEW OF ON RIGHT FOREGROUND FIXED SPAN TO TRANSITIONAL MOVEABLE SPAN TO FLOATING SPAN IN MIDDLEGROUND - Lacey V. Murrow Memorial Floating Bridge, Spanning Lake Washington at I-90, Seattle, King County, WA

  14. Biophysical regulation of epigenetic state and cell reprogramming

    NASA Astrophysics Data System (ADS)

    Downing, Timothy L.; Soto, Jennifer; Morez, Constant; Houssin, Timothee; Fritz, Ashley; Yuan, Falei; Chu, Julia; Patel, Shyam; Schaffer, David V.; Li, Song

    2013-12-01

    Biochemical factors can help reprogram somatic cells into pluripotent stem cells, yet the role of biophysical factors during reprogramming is unknown. Here, we show that biophysical cues, in the form of parallel microgrooves on the surface of cell-adhesive substrates, can replace the effects of small-molecule epigenetic modifiers and significantly improve reprogramming efficiency. The mechanism relies on the mechanomodulation of the cells’ epigenetic state. Specifically, decreased histone deacetylase activity and upregulation of the expression of WD repeat domain 5 (WDR5)—a subunit of H3 methyltranferase—by microgrooved surfaces lead to increased histone H3 acetylation and methylation. We also show that microtopography promotes a mesenchymal-to-epithelial transition in adult fibroblasts. Nanofibrous scaffolds with aligned fibre orientation produce effects similar to those produced by microgrooves, suggesting that changes in cell morphology may be responsible for modulation of the epigenetic state. These findings have important implications in cell biology and in the optimization of biomaterials for cell-engineering applications.

  15. Multidimensional solid-state NMR spectroscopy of plant cell walls.

    PubMed

    Wang, Tuo; Phyo, Pyae; Hong, Mei

    2016-09-01

    Plant biomass has become an important source of bio-renewable energy in modern society. The molecular structure of plant cell walls is difficult to characterize by most atomic-resolution techniques due to the insoluble and disordered nature of the cell wall. Solid-state NMR (SSNMR) spectroscopy is uniquely suited for studying native hydrated plant cell walls at the molecular level with chemical resolution. Significant progress has been made in the last five years to elucidate the molecular structures and interactions of cellulose and matrix polysaccharides in plant cell walls. These studies have focused on primary cell walls of growing plants in both the dicotyledonous and grass families, as represented by the model plants Arabidopsis thaliana, Brachypodium distachyon, and Zea mays. To date, these SSNMR results have shown that 1) cellulose, hemicellulose, and pectins form a single network in the primary cell wall; 2) in dicot cell walls, the protein expansin targets the hemicellulose-enriched region of the cellulose microfibril for its wall-loosening function; and 3) primary wall cellulose has polymorphic structures that are distinct from the microbial cellulose structures. This article summarizes these key findings, and points out future directions of investigation to advance our fundamental understanding of plant cell wall structure and function.

  16. Multidimensional solid-state NMR spectroscopy of plant cell walls.

    PubMed

    Wang, Tuo; Phyo, Pyae; Hong, Mei

    2016-09-01

    Plant biomass has become an important source of bio-renewable energy in modern society. The molecular structure of plant cell walls is difficult to characterize by most atomic-resolution techniques due to the insoluble and disordered nature of the cell wall. Solid-state NMR (SSNMR) spectroscopy is uniquely suited for studying native hydrated plant cell walls at the molecular level with chemical resolution. Significant progress has been made in the last five years to elucidate the molecular structures and interactions of cellulose and matrix polysaccharides in plant cell walls. These studies have focused on primary cell walls of growing plants in both the dicotyledonous and grass families, as represented by the model plants Arabidopsis thaliana, Brachypodium distachyon, and Zea mays. To date, these SSNMR results have shown that 1) cellulose, hemicellulose, and pectins form a single network in the primary cell wall; 2) in dicot cell walls, the protein expansin targets the hemicellulose-enriched region of the cellulose microfibril for its wall-loosening function; and 3) primary wall cellulose has polymorphic structures that are distinct from the microbial cellulose structures. This article summarizes these key findings, and points out future directions of investigation to advance our fundamental understanding of plant cell wall structure and function. PMID:27552739

  17. Metastable primordial germ cell-like state induced from mouse embryonic stem cells by Akt activation

    SciTech Connect

    Yamano, Noriko; Kimura, Tohru; Watanabe-Kushima, Shoko; Shinohara, Takashi; Nakano, Toru

    2010-02-12

    Specification to primordial germ cells (PGCs) is mediated by mesoderm-induction signals during gastrulation. We found that Akt activation during in vitro mesodermal differentiation of embryonic stem cells (ESCs) generated self-renewing spheres with differentiation states between those of ESCs and PGCs. Essential regulators for PGC specification and their downstream germ cell-specific genes were expressed in the spheres, indicating that the sphere cells had commenced differentiation to the germ lineage. However, the spheres did not proceed to spermatogenesis after transplantation into testes. Sphere cell transfer to the original feeder-free ESC cultures resulted in chaotic differentiation. In contrast, when the spheres were cultured on mouse embryonic fibroblasts or in the presence of ERK-cascade and GSK3 inhibitors, reversion to the ESC-like state was observed. These results indicate that Akt signaling promotes a novel metastable and pluripotent state that is intermediate to those of ESCs and PGCs.

  18. Single-cell states in the estrogen response of breast cancer cell lines.

    PubMed

    Casale, Francesco Paolo; Giurato, Giorgio; Nassa, Giovanni; Armond, Jonathan W; Oates, Chris J; Corá, Davide; Gamba, Andrea; Mukherjee, Sach; Weisz, Alessandro; Nicodemi, Mario

    2014-01-01

    Estrogen responsive breast cancer cell lines have been extensively studied to characterize transcriptional patterns in hormone-responsive tumors. Nevertheless, due to current technological limitations, genome-wide studies have typically been limited to population averaged data. Here we obtain, for the first time, a characterization at the single-cell level of the states and expression signatures of a hormone-starved MCF-7 cell system responding to estrogen. To do so, we employ a recently proposed model that allows for dissecting single-cell states from time-course microarray data. We show that within 32 hours following stimulation, MCF-7 cells traverse, most likely, six states, with a faster early response followed by a progressive deceleration. We also derive the genome-wide transcriptional profiles of such single-cell states and their functional characterization. Our results support a scenario where estrogen promotes cell cycle progression by controlling multiple, sequential regulatory steps, whose single-cell events are here identified. PMID:24586334

  19. Single-Cell States in the Estrogen Response of Breast Cancer Cell Lines

    PubMed Central

    Casale, Francesco Paolo; Giurato, Giorgio; Nassa, Giovanni; Armond, Jonathan W.; Oates, Chris J.; Corá, Davide; Gamba, Andrea; Mukherjee, Sach; Weisz, Alessandro; Nicodemi, Mario

    2014-01-01

    Estrogen responsive breast cancer cell lines have been extensively studied to characterize transcriptional patterns in hormone-responsive tumors. Nevertheless, due to current technological limitations, genome-wide studies have typically been limited to population averaged data. Here we obtain, for the first time, a characterization at the single-cell level of the states and expression signatures of a hormone-starved MCF-7 cell system responding to estrogen. To do so, we employ a recently proposed model that allows for dissecting single-cell states from time-course microarray data. We show that within 32 hours following stimulation, MCF-7 cells traverse, most likely, six states, with a faster early response followed by a progressive deceleration. We also derive the genome-wide transcriptional profiles of such single-cell states and their functional characterization. Our results support a scenario where estrogen promotes cell cycle progression by controlling multiple, sequential regulatory steps, whose single-cell events are here identified. PMID:24586334

  20. MR-04DICER REGULATES GLIOMA STEM CELL STATE

    PubMed Central

    Singh, Sanjay; Burrell, Kelly; Alamhabspour, Amir; Agnihotri, Sameer; Vartanian, Alenoush; Jalali, Shahrzad; Gumin, Joy; Sulman, Erik; Lang, Frederick; Zadeh, Gelareh

    2014-01-01

    The role of cancer stem cells in tumor formation and tumor heterogeneity is currently one of the most researched topics in cancer biology, and microRNAs likely have functional relevance in regulation of critical genes and parameters implicated in glioma stem cell (GSC) behavior and differentiation. To address this, we investigated global role of microRNA in GSCs, focusing on DICER, which regulates double-stranded RNA processing for microRNA biogenesis. Analysis of data from the Cancer Genome Atlas (TCGA) database suggests that high Dicer expression level is correlated with better prognosis of GBM patients. Gene signatures correlated with DICER expression levels suggest DICER/miRNA mediated mechanisms potentially regulate a multitude of cellular pathways in GBMs. Immunohistochemistry analysis of GBM tissue microarray reveals that of 54 tumor samples, 26 (48%) of GBM patients have low or undetectable levels of DICER1 protein, indicating frequent inactivation in high grade glioma. To characterize this functionally, we utilized various in vitro approaches, including exposure to hypoxia, to characterize the GSC properties after knockdown of DICER (GSCs did not have significant variation in endogenous DICER levels). Using three different GSC lines, we found in all cases with Dicer knockdown resulted in increased proliferation of three independent GSC lines with concomitant decrease in levels of stem cell markers (Sox2, Bmi1 etc.), a phenotype observed even upon exposure to hypoxia, a state that is known to preserve and promote the stem-like cell phenotype. Results from self-renewal assays as well as expression profiling show that GSCs with depleted levels of Dicer lose stem cell characteristics and acquire a progenitor-cell like state. Our results highlight the role of DICER as potential regulators of GSC stem-like versus progenitor-like state.

  1. Atomic structure of interface states in silicon heterojunction solar cells.

    PubMed

    George, B M; Behrends, J; Schnegg, A; Schulze, T F; Fehr, M; Korte, L; Rech, B; Lips, K; Rohrmüller, M; Rauls, E; Schmidt, W G; Gerstmann, U

    2013-03-29

    Combining orientation dependent electrically detected magnetic resonance and g tensor calculations based on density functional theory we assign microscopic structures to paramagnetic states involved in spin-dependent recombination at the interface of hydrogenated amorphous silicon crystalline silicon (a-Si:H/c-Si) heterojunction solar cells. We find that (i) the interface exhibits microscopic roughness, (ii) the electronic structure of the interface defects is mainly determined by c-Si, (iii) we identify the microscopic origin of the conduction band tail state in the a-Si:H layer, and (iv) present a detailed recombination mechanism.

  2. Solid-State High-Temperature Power Cells

    NASA Technical Reports Server (NTRS)

    Whitacre, Jay; West, William

    2008-01-01

    All-solid-state electrochemical power cells have been fabricated and tested in a continuing effort to develop batteries for instruments for use in environments as hot as 500 C. Batteries of this type are needed for exploration of Venus, and could be used on Earth for such applications as measuring physical and chemical conditions in geothermal and oil wells, processing furnaces, and combustion engines. In the state-of-the-art predecessors of the present solid-state power cells, fully packaged molten eutectic salts are used as electrolytes. The molten-salt-based cells can be susceptible to significant amounts of self-discharge and corrosion when used for extended times at elevated temperatures. In contrast, all-solid-state cells such as the present ones are expected to be capable of operating for many days at temperatures up to 500 C, without significant self-discharge. The solid-state cell described here includes a cathode made of FeS2, an electrolyte consisting of a crystalline solid solution of equimolar amounts of Li3PO4 and Li4SiO4, and an anode made of an alloy of Li and Si (see figure). The starting material for making the solid electrolyte is a stoichiometric mixture of Li3PO4, SiO2, and Li3CO2. This mixture is ball-milled, then calcined for two hours at a temperature of 1,100 C, then placed in a die atop the cathode material. Next, the layers in the die are squeezed together at a pressure between 60 and 120 MPa for one hour at a temperature of 600 C to form a unitary structure comprising the solid electrolyte and cathode bonded together. Finally, the lithium-alloy anode is pressure-bonded to the solid electrolyte layer, using an intermediate layer of pure lithium. In one test of a cell of this type, a discharge rate of about 1 mA per gram of cathode material was sustained for 72 hours at a temperature of about 460 C. This is about three times the discharge rate required to support some of the longer duration Venus-exploration mission scenarios.

  3. Cell state-specific metabolic dependency in hematopoiesis and leukemogenesis

    PubMed Central

    Wang, Ying-Hua; Israelsen, William J.; Lee, Dongjun; Yu, Vionnie W.C.; Jeanson, Nathaniel T.; Clish, Clary B; Cantley, Lewis C.; Heiden, Matthew G. Vander; Scadden, David T.

    2014-01-01

    SUMMARY The balance between oxidative and non-oxidative glucose metabolism is essential for a number of pathophysiological processes. By deleting enzymes that affect aerobic glycolysis with different potencies, we examine how modulating glucose metabolism specifically affects hematopoietic and leukemic cell populations. We find that deficiency in the M2 pyruvate kinase isoform (PKM2) reduces levels of metabolic intermediates important for biosynthesis and impairs progenitor function without perturbing hematopoietic stem cells (HSC), whereas lactate dehydrogenase-A (LDHA) deletion significantly inhibits the function of both HSC and progenitors during hematopoiesis. In contrast, leukemia initiation by transforming alleles putatively affecting either HSC or progenitors is inhibited in the absence of either PKM2 or LDHA, indicating that the cell state-specific responses to metabolic manipulation in hematopoiesis do not apply to the setting of leukemia. This finding suggests that fine-tuning the level of glycolysis may be therapeutically explored for treating leukemia while preserving HSC function. PMID:25215489

  4. 52. Virginia Route 666. This single span structure, built in ...

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

    52. Virginia Route 666. This single span structure, built in 1962, is an example of a spandrel arch grade separation structure with a roman arch over a state secondary road. The bridge is constructed of reinforced concrete, backfilled with earth and has a thick stone veneer. Looking east-northeast at elevation. - Blue Ridge Parkway, Between Shenandoah National Park & Great Smoky Mountains, Asheville, Buncombe County, NC

  5. Conditionally reprogrammed cells represent a stem-like state of adult epithelial cells

    PubMed Central

    Suprynowicz, Frank A.; Upadhyay, Geeta; Krawczyk, Ewa; Kramer, Sarah C.; Hebert, Jess D.; Liu, Xuefeng; Yuan, Hang; Cheluvaraju, Chaitra; Clapp, Phillip W.; Boucher, Richard C.; Kamonjoh, Christopher M.; Randell, Scott H.; Schlegel, Richard

    2012-01-01

    The combination of irradiated fibroblast feeder cells and Rho kinase inhibitor, Y-27632, conditionally induces an indefinite proliferative state in primary mammalian epithelial cells. These conditionally reprogrammed cells (CRCs) are karyotype-stable and nontumorigenic. Because self-renewal is a recognized property of stem cells, we investigated whether Y-27632 and feeder cells induced a stem-like phenotype. We found that CRCs share characteristics of adult stem cells and exhibit up-regulated expression of α6 and β1 integrins, ΔNp63α, CD44, and telomerase reverse transcriptase, as well as decreased Notch signaling and an increased level of nuclear β-catenin. The induction of CRCs is rapid (occurs within 2 d) and results from reprogramming of the entire cell population rather than the selection of a minor subpopulation. CRCs do not overexpress the transcription factor sets characteristic of embryonic or induced pluripotent stem cells (e.g., Sox2, Oct4, Nanog, or Klf4). The induction of CRCs is also reversible, and removal of Y-27632 and feeders allows the cells to differentiate normally. Thus, when CRCs from ectocervical epithelium or tracheal epithelium are placed in an air–liquid interface culture system, the cervical cells form a well differentiated stratified squamous epithelium, whereas the tracheal cells form a ciliated airway epithelium. We discuss the diagnostic and therapeutic opportunities afforded by a method that can generate adult stem-like cells in vitro without genetic manipulation. PMID:23169653

  6. Reconstructing dynamic molecular states from single-cell time series.

    PubMed

    Huang, Lirong; Pauleve, Loic; Zechner, Christoph; Unger, Michael; Hansen, Anders S; Koeppl, Heinz

    2016-09-01

    The notion of state for a system is prevalent in the quantitative sciences and refers to the minimal system summary sufficient to describe the time evolution of the system in a self-consistent manner. This is a prerequisite for a principled understanding of the inner workings of a system. Owing to the complexity of intracellular processes, experimental techniques that can retrieve a sufficient summary are beyond our reach. For the case of stochastic biomolecular reaction networks, we show how to convert the partial state information accessible by experimental techniques into a full system state using mathematical analysis together with a computational model. This is intimately related to the notion of conditional Markov processes and we introduce the posterior master equation and derive novel approximations to the corresponding infinite-dimensional posterior moment dynamics. We exemplify this state reconstruction approach using both in silico data and single-cell data from two gene expression systems in Saccharomyces cerevisiae, where we reconstruct the dynamic promoter and mRNA states from noisy protein abundance measurements. PMID:27605167

  7. Air Force Ni-H2 cell test program: State of Charge test

    NASA Technical Reports Server (NTRS)

    Moore, Bruce; Smellie, Douglas

    1995-01-01

    Nickel-Hydrogen cells are being cycled under a LEO (low earth orbit) test regime to examine the benefits of operating the cells at lower States of Charge (SOC) than typically used. A group of four cells are cycled using a voltage limiting charge regime that limits the State of Charge that the cells are allowed to reach. The test cells are then compared to identical cells being cycled at or near 100% State of Charge using a constant current charge regime.

  8. Device and Method for Continuously Equalizing the Charge State of Lithium Ion Battery Cells

    NASA Technical Reports Server (NTRS)

    Schwartz, Paul D. (Inventor); Martin, Mark N. (Inventor); Roufberg, Lewis M. (Inventor)

    2015-01-01

    A method of equalizing charge states of individual cells in a battery includes measuring a previous cell voltage for each cell, measuring a previous shunt current for each cell, calculating, based on the previous cell voltage and the previous shunt current, an adjusted cell voltage for each cell, determining a lowest adjusted cell voltage from among the calculated adjusted cell voltages, and calculating a new shunt current for each cell.

  9. Modulation of red cell metabolism by states of decreased activation: comparison between states.

    PubMed

    Jevning, R; Wilson, A F; Pirkle, H; Guich, S; Walsh, R N

    1985-11-01

    Marked decline of red cell metabolism has been described during the acute state of decreased activation associated with the stylized mental technique of transcendental meditation (TM) in long-term meditators (5-10 years regular elicitation, TM instructors). It is not known whether unstylized rest is accompanied by a similar effect and it is not known what effector(s) may contribute to red cell metabolic changes in these states. In the present study ordinary, unstylized rest was found to be accompanied by small increase of red cell glycolytic rate. Apparently, either repeated elicitation of TM behavior or some special feature of this practice become associated with new mechanisms of metabolic control than those previously in operation. Although the data of this study do not permit isolation of the precise psychological determinants of this effect, the range of possible physiological effectors can be delimited. Blood pH, PCO2, PO2, and phosphate can be eliminated as significant for red cell metabolic control during both TM and rest, and based upon related studies, several known hormones such as insulin, T3, T4, arginine vasopressin, oxytocin, prolactin and growth hormone can also be eliminated as responsible effector(s).

  10. The Relationship of Role-Based, Task-Based, Boundary-Spanning, and Conflict-Mediating Stress Experienced by New York State Special Education Administrators and Emotional Exhaustion, Depersonalization, and Personal Accomplishment

    ERIC Educational Resources Information Center

    Ambrosini, MaryAnn

    2013-01-01

    Given the challenges faced in ensuring the needs of students with disabilities are met in the midst of fiscal constraints, increasing litigation, meeting adequate yearly progress and compliance with State regulations, special education administrators are more at risk for burnout than ever before. Burnout is characterized by a high degree of…

  11. Transcriptomic profiling of human embryonic stem cells upon cell cycle manipulation during pluripotent state dissolution.

    PubMed

    Gonzales, Kevin Andrew Uy; Liang, Hongqing

    2015-12-01

    While distinct cell cycle structures have been known to correlate with pluripotent or differentiated cell states [1], there is no evidence on how the cell cycle machinery directly contributes to human embryonic stem cell (hESC) pluripotency. We established a determinant role of cell cycle machineries on the pluripotent state by demonstrating that the specific perturbation of the S and G2 phases can prevent pluripotent state dissolution (PSD) [2]. Active mechanisms in these phases, such as the DNA damage checkpoint and Cyclin B1, promote the pluripotent state [2]. To understand the mechanisms behind the effect on PSD by these pathways in hESCs, we performed comprehensive gene expression analysis by time-course microarray experiments. From these datasets, we observed expression changes in genes involved in the TGFβ signaling pathway, which has a well-established role in hESC maintenance [3], [4], [5]. The microarray data have been deposited in NCBI's Gene Expression Omnibus (GEO) and can be accessed through GEO Series accession numbers GSE62062 and GSE63215.

  12. Anomalous oxidation states in oxide multilayers for fuel cell applications

    SciTech Connect

    Perkins, James; Fearn, Sarah; Cook, S. N.; Srinivasan, R.; Rouleau, Christopher M; Christen, Hans M; West, G. D.; Morris, R. J. H.; Fraser, H. L.; Skinner, Stephen; Kilner, John; McComb, David

    2010-01-01

    Significant interest has been directed towards interface enhanced ionic conductivity. Advanced analytical techniques including electron microscopy (TEM/STEM), electron energy loss spectroscopy (EELS), and secondary ion mass spectrometry (SIMS) have been used to characterize CeO2/Ce0.85Sm0.15O2 multilayer thin films grown by pulsed laser deposition. High quality growth is observed, but ionic conductivity measured by impedance spectroscopy and 18O tracer experiments is consistent with bulk materials. EELS analysis reveals the unusual situation of layers containing only Ce(IV) adjacent to layers containing both Ce(III) and Ce(IV). Post oxygen annealing induced oxygen diffusion and mixed oxidation states in both layers, but only in the vicinity of low angle grain boundaries perpendicular to the layers. The implications of this remarkable metastability of Ce oxidation states on the design of novel electrolytes for solid oxide fuel cells is discussed.

  13. The Impact of Boundary Spanning Scholarly Publications and Patents

    PubMed Central

    Shi, Xiaolin; Adamic, Lada A.; Tseng, Belle L.; Clarkson, Gavin S.

    2009-01-01

    Background Human knowledge and innovation are recorded in two media: scholarly publication and patents. These records not only document a new scientific insight or new method developed, but they also carefully cite prior work upon which the innovation is built. Methodology We quantify the impact of information flow across fields using two large citation dataset: one spanning over a century of scholarly work in the natural sciences, social sciences and humanities, and second spanning a quarter century of United States patents. Conclusions We find that a publication's citing across disciplines is tied to its subsequent impact. In the case of patents and natural science publications, those that are cited at least once are cited slightly more when they draw on research outside of their area. In contrast, in the social sciences, citing within one's own field tends to be positively correlated with impact. PMID:19688087

  14. Minimizing travel claims cost with minimal-spanning tree model

    NASA Astrophysics Data System (ADS)

    Jamalluddin, Mohd Helmi; Jaafar, Mohd Azrul; Amran, Mohd Iskandar; Ainul, Mohd Sharizal; Hamid, Aqmar; Mansor, Zafirah Mohd; Nopiah, Zulkifli Mohd

    2014-06-01

    Travel demand necessitates a big expenditure in spending, as has been proven by the National Audit Department (NAD). Every year the auditing process is carried out throughout the country involving official travel claims. This study focuses on the use of the Spanning Tree model to determine the shortest path to minimize the cost of the NAD's official travel claims. The objective is to study the possibility of running a network based in the Kluang District Health Office to eight Rural Clinics in Johor state using the Spanning Tree model applications for optimizing travelling distances and make recommendations to the senior management of the Audit Department to analyze travelling details before an audit is conducted. Result of this study reveals that there were claims of savings of up to 47.4% of the original claims, over the course of the travel distance.

  15. Cell receptor and surface ligand density effects on dynamic states of adhering circulating tumor cells.

    PubMed

    Zheng, Xiangjun; Cheung, Luthur Siu-Lun; Schroeder, Joyce A; Jiang, Linan; Zohar, Yitshak

    2011-10-21

    Dynamic states of cancer cells moving under shear flow in an antibody-functionalized microchannel are investigated experimentally and theoretically. The cell motion is analyzed with the aid of a simplified physical model featuring a receptor-coated rigid sphere moving above a solid surface with immobilized ligands. The motion of the sphere is described by the Langevin equation accounting for the hydrodynamic loadings, gravitational force, receptor-ligand bindings, and thermal fluctuations; the receptor-ligand bonds are modeled as linear springs. Depending on the applied shear flow rate, three dynamic states of cell motion have been identified: (i) free motion, (ii) rolling adhesion, and (iii) firm adhesion. Of particular interest is the fraction of captured circulating tumor cells, defined as the capture ratio, via specific receptor-ligand bonds. The cell capture ratio decreases with increasing shear flow rate with a characteristic rate. Based on both experimental and theoretical results, the characteristic flow rate increases monotonically with increasing either cell-receptor or surface-ligand density within certain ranges. Utilizing it as a scaling parameter, flow-rate dependent capture ratios for various cell-surface combinations collapse onto a single curve described by an exponential formula.

  16. Boundary Spanning Leadership Practices for Population Health.

    PubMed

    Shirey, Maria R; White-Williams, Connie

    2015-09-01

    This department highlights change management strategies that may be successful in strategically planning and executing organizational change initiatives. In this article, the authors discuss boundary spanning leadership practices for achieving the Triple Aim of simultaneously improving the health of populations, improving the patient experience, and reducing per-capita cost of health care. Drawing on experience with an existing population-focused heart failure clinic borne of an academic-practice partnership, the authors discuss boundary spanning leadership practices aimed at achieving the Triple Aim concept and its intended design. PMID:26301546

  17. 47. DRAW SPAN OVER PASSAIC RIVER Drawing No. 54 General ...

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

    47. DRAW SPAN OVER PASSAIC RIVER Drawing No. 54 General Details of Wedge Operating Machinery for Draw Span Scale 1-1/2'=1'; April 1897 - Jackson Street Bridge, Spanning Passaic River, Newark, Essex County, NJ

  18. 347. Caltrans, Photographer April 10, 1935 "500 FT. SPANS"; VIEW ...

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

    347. Caltrans, Photographer April 10, 1935 "500 FT. SPANS"; VIEW OF THROUGH TRUSS (500 FT. SPANS) UNDER CONSTRUCTION. 7-613 - San Francisco Oakland Bay Bridge, Spanning San Francisco Bay, San Francisco, San Francisco County, CA

  19. Interior view of eastern lift span, with decking above, looking ...

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

    Interior view of eastern lift span, with decking above, looking back from center of span, toward lift mechanism area. - Arlington Memorial Bridge, Spanning Potomac River between Lincoln Memorial & Arlington National Cemetery, Washington, District of Columbia, DC

  20. 3. GENERAL ELEVATION, FROM THE NORTH, SHOWING ENTIRE BASCULE SPAN ...

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

    3. GENERAL ELEVATION, FROM THE NORTH, SHOWING ENTIRE BASCULE SPAN AND FOCUSING ON FIXED SPAN IN FOREGROUND - Seddon Island Scherzer Rolling Lift Bridge, Spanning Garrison Channel from Tampa to Seddon Island, Tampa, Hillsborough County, FL

  1. Detail, south (breslau) approach span, from west, showing end block ...

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

    Detail, south (breslau) approach span, from west, showing end block and railing at approach span - Breslau Bridge, Spanning North Branch of Susquehanna River at Hannover Street, Plymouth, Luzerne County, PA

  2. 21. VIEW SOUTHWEST, DETAIL OF TRANSITION FROM CONCRETE SPAN TO ...

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

    21. VIEW SOUTHWEST, DETAIL OF TRANSITION FROM CONCRETE SPAN TO STEEL SPAN AT PIER NUMBER 116 - Route 1 Extension, South Street Viaduct, Spanning Conrail & Wheeler Point Road at South Street, Newark, Essex County, NJ

  3. 12. DETAIL OF UNDERSIDE OF NORTH APPROACH SPANS, SHOWING ROADWAY ...

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

    12. DETAIL OF UNDERSIDE OF NORTH APPROACH SPANS, SHOWING ROADWAY DECK AND APPROACH SPAN PIERS. VIEW TO SOUTHEAST. - Navajo Bridge, Spanning Colorado River at U.S. Highway 89 Alternate, Page, Coconino County, AZ

  4. 11. View underside of draw span, with fender in foreground ...

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

    11. View underside of draw span, with fender in foreground and concrete deck spans and pile visible at rear, looking northeast - Colonel Alexander Scammell Memorial Bridge, Spanning Bellamy River at U.S. Route 4, Dover, Strafford County, NH

  5. 13. OBLIQUE OF UNDERSIDE OF SOUTH TRUSS SPAN, SOUTH APPROACH ...

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

    13. OBLIQUE OF UNDERSIDE OF SOUTH TRUSS SPAN, SOUTH APPROACH SPAN, AND SOUTH PIER, SHOWING FLOOR SYSTEM AND BEARINGS. LOOKING NORTH. - Flintville Bridge, Spanning Broad Creek at Flintville Road (Maryland Route 623), Castleton, Harford County, MD

  6. 2. WEST ELEVATION, SHOWING ENTIRE STRUCTURE: PENNSYLVANIA TRUSS MAIN SPANS ...

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

    2. WEST ELEVATION, SHOWING ENTIRE STRUCTURE: PENNSYLVANIA TRUSS MAIN SPANS AND PONY TRUSS APPROACH SPANS - Coraopolis Bridge, Spanning Ohio River back channel at Ferree Street & Grand Avenue, Coraopolis, Allegheny County, PA

  7. 10. DETAIL, SOUTHEAST SPAN THROUGH CANAL, VIEW BLOCKED BY STEEL, ...

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

    10. DETAIL, SOUTHEAST SPAN THROUGH CANAL, VIEW BLOCKED BY STEEL, CLAD COUNTER WEIGHT, WATER SPAN RAISED OUT OF VIEW - Cape Cod Canal Lift Bridge, Spanning Cape Cod Canal, Buzzards Bay, Barnstable County, MA

  8. 42. SOUTH SIDE OF COOPER RIVER SPAN WITH PEARMAN BRIDGE ...

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

    42. SOUTH SIDE OF COOPER RIVER SPAN WITH PEARMAN BRIDGE IN FOREGROUN, VIEW NORTHWEST TOWARDS TWIN CREEK SPAN AND DRUM ISLAND - Grace Memorial Bridge, U.S. Highway 17 spanning Cooper River & Town Creek , Charleston, Charleston County, SC

  9. 40. UNDERSIDE OF TOWN CREEK SPAN (LEFT) AND PEARMAN BRIDE ...

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

    40. UNDERSIDE OF TOWN CREEK SPAN (LEFT) AND PEARMAN BRIDE (RIGHT) FROM BENEATH BRIDGES, FACING EAST TOWARDS COOPER RIVER SPAN - Grace Memorial Bridge, U.S. Highway 17 spanning Cooper River & Town Creek , Charleston, Charleston County, SC

  10. 41. OBLIQUE VIEW OF NORTH SIDE OF COOPER RIVER SPAN ...

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

    41. OBLIQUE VIEW OF NORTH SIDE OF COOPER RIVER SPAN WITH PEARMAN BRIDGE AND TOWN CREEK SPAN IN BACKGROUND, VIEW WEST TOWARDS CHARLESTON - Grace Memorial Bridge, U.S. Highway 17 spanning Cooper River & Town Creek , Charleston, Charleston County, SC

  11. 2. THREEQUARTER VIEW FROM ADJACENT ACCESS ROAD SHOWING THREE SPANS ...

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

    2. THREE-QUARTER VIEW FROM ADJACENT ACCESS ROAD SHOWING THREE SPANS AND NORTHWEST APPROACH SPANS, LOOKING SOUTHEAST - Red River Bridge, Spanning Red River at U.S. Highway 82, Garland, Miller County, AR

  12. General closeup view of the swing span bridge in the ...

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

    General close-up view of the swing span bridge in the close position, looking upriver. The pivot/center pier is positioned in the center of Tennessee River. Note: Each arm of the continuous swing span acts as simple spans. The total span over four (4) supports is partially continuous-- the middle panel at the center pier is continuous for bending moments, but discontinuous for shears. - Bridgeport Swing Span Bridge, Spanning Tennessee River, Bridgeport, Jackson County, AL

  13. Full Scale Span Load Distribution on a Tapered Wing with Split Flaps of Various Spans

    NASA Technical Reports Server (NTRS)

    Parsons, John F; Silverstein, Abe

    1937-01-01

    Pressure-distribution tests were conducted in the full-scale wind tunnel on a 2:1 tapered U.S.A. 45 airfoil equipped with 20 percent chord split trailing-edge flaps of various spans. A special installation was employed in the tests utilizing a half-span airfoil mounted vertically above a reflection plane. The airfoil has a constant chord center section and rounded tips and is tapered in thickness from 18 percent c at the root to 9 percent c at the tip. The aerodynamic characteristics, given by the usual dimension less coefficients, are presented graphically as functions of flap span and angle of attack as well as by semispan load diagrams. The results indicate, in general, that only a relatively small increase in the normal-force coefficient is to be expected by extending the flap span of an airfoil-flap combination, similar to the one tested, beyond 70 percent of the wing span.

  14. Manganese oxidation state mediates toxicity in PC12 cells

    SciTech Connect

    Reaney, S.H. . E-mail: stevereaney@hotmail.com; Smith, D.R.

    2005-06-15

    The role of the manganese (Mn) oxidation state on cellular Mn uptake and toxicity is not well understood. Therefore, undifferentiated PC12 cells were exposed to 0-200 {mu}M Mn(II)-chloride or Mn(III)-pyrophosphate for 24 h, after which cellular manganese levels were measured along with measures of cell viability, function, and cytotoxicity (trypan blue exclusion, medium lactate dehydrogenase (LDH), 8-isoprostanes, cellular ATP, dopamine, serotonin, H-ferritin, transferrin receptor (TfR), Mn-superoxide dismutase (MnSOD), and copper-zinc superoxide dismutase (CuZnSOD) protein levels). Exposures to Mn(III) >10 {mu}M produced 2- to 5-fold higher cellular manganese levels than equimolar exposures to Mn(II). Cell viability and ATP levels both decreased at the highest Mn(II) and Mn(III) exposures (150-200 {mu}M), while Mn(III) exposures produced increases in LDH activity at lower exposures ({>=}50 {mu}M) than did Mn(II) (200 {mu}M only). Mn(II) reduced cellular dopamine levels more than Mn(III), especially at the highest exposures (50% reduced at 200 {mu}M Mn(II)). In contrast, Mn(III) produced a >70% reduction in cellular serotonin at all exposures compared to Mn(II). Different cellular responses to Mn(II) exposures compared to Mn(III) were also observed for H-ferritin, TfR, and MnSOD protein levels. Notably, these differential effects of Mn(II) versus Mn(III) exposures on cellular toxicity could not simply be accounted for by the different cellular levels of manganese. These results suggest that the oxidation state of manganese exposures plays an important role in mediating manganese cytotoxicity.

  15. Maintenance of DNA methylation level in SV40-infected human fibroblasts during their in vitro limited proliferative life span.

    PubMed

    Matsumura, T; Hunter, J L; Farooq, M; Holliday, R

    1989-09-01

    Methylation level as expressed by the molar ratio of 5-methylcytosine content to the combined content of cytosine and 5-methylcytosine was determined by HPLC and uv adsorption of cellular DNA extracted from SV40-infected and pretransformed MRC-5 human diploid fibroblasts (HDFs) during their limited in vitro life span. The level decreased slightly during early passages, and then was maintained within a certain range in the subsequent pretransformed stage of serial passages. When HDFs were treated with 5-aza-2'-deoxycytidine (5-aza-CdR) at an effective concentration shortly after the SV40 infection, the level decreased and then increased or was maintained again within a certain range in the subsequent pretransformed state. The proliferative life span potential of SV40-infected HDFs was not significantly decreased by the 5-aza-CdR treatment. These results are in contrast to the established observations for uninfected HDFs, that methylation level decreases during serial passages, and that, after treatment with 5-aza-CdR, the level, as well as the proliferative life span, is decreased in comparison to untreated populations. These results show that SV40-infected pretransformed HDFs are in an intermediate state between normal finite growth and an established permanent line, in that they retain limited in vitro cell proliferation, while acquiring the ability to maintain methylation levels.

  16. The Vegetative State and Stem Cells: Therapeutic Considerations

    PubMed Central

    Hazell, Alan S.

    2016-01-01

    The vegetative state (VS), also known as “unresponsive wakefulness syndrome,” is considered one of the most devastating outcomes of acquired brain injury. While diagnosis of this condition is generally well-defined clinically, patients often appear to be awake despite an absence of behavioral signs of awareness, which to the family can be confusing, leading them to believe the loved one is aware of their surroundings. This inequality of agreement can be very distressing. Currently, no cure for the VS is available; as a result, patients may remain in this condition for the rest of their lives, which in some cases amount to decades. Recent advances in stem cell approaches for the treatment of other neurological conditions may now provide an opportunity to intervene in this syndrome. This mini review will address the development of VS, its diagnosis, affected cerebral structures, and the underlying basis of how stem cells can offer therapeutic promise that would take advantage of the often long-term features associated with this maladie to effect a repair of the severely damaged circuitry. In addition, current limitations of this treatment strategy, including a lack of animal models, few long-term clinical studies that might identify benefits of stem cell treatment, and the potential for development of tumors are considered.

  17. The Vegetative State and Stem Cells: Therapeutic Considerations.

    PubMed

    Hazell, Alan S

    2016-01-01

    The vegetative state (VS), also known as "unresponsive wakefulness syndrome," is considered one of the most devastating outcomes of acquired brain injury. While diagnosis of this condition is generally well-defined clinically, patients often appear to be awake despite an absence of behavioral signs of awareness, which to the family can be confusing, leading them to believe the loved one is aware of their surroundings. This inequality of agreement can be very distressing. Currently, no cure for the VS is available; as a result, patients may remain in this condition for the rest of their lives, which in some cases amount to decades. Recent advances in stem cell approaches for the treatment of other neurological conditions may now provide an opportunity to intervene in this syndrome. This mini review will address the development of VS, its diagnosis, affected cerebral structures, and the underlying basis of how stem cells can offer therapeutic promise that would take advantage of the often long-term features associated with this maladie to effect a repair of the severely damaged circuitry. In addition, current limitations of this treatment strategy, including a lack of animal models, few long-term clinical studies that might identify benefits of stem cell treatment, and the potential for development of tumors are considered. PMID:27602016

  18. The Vegetative State and Stem Cells: Therapeutic Considerations

    PubMed Central

    Hazell, Alan S.

    2016-01-01

    The vegetative state (VS), also known as “unresponsive wakefulness syndrome,” is considered one of the most devastating outcomes of acquired brain injury. While diagnosis of this condition is generally well-defined clinically, patients often appear to be awake despite an absence of behavioral signs of awareness, which to the family can be confusing, leading them to believe the loved one is aware of their surroundings. This inequality of agreement can be very distressing. Currently, no cure for the VS is available; as a result, patients may remain in this condition for the rest of their lives, which in some cases amount to decades. Recent advances in stem cell approaches for the treatment of other neurological conditions may now provide an opportunity to intervene in this syndrome. This mini review will address the development of VS, its diagnosis, affected cerebral structures, and the underlying basis of how stem cells can offer therapeutic promise that would take advantage of the often long-term features associated with this maladie to effect a repair of the severely damaged circuitry. In addition, current limitations of this treatment strategy, including a lack of animal models, few long-term clinical studies that might identify benefits of stem cell treatment, and the potential for development of tumors are considered. PMID:27602016

  19. State of the art: stem cells in equine regenerative medicine.

    PubMed

    Lopez, M J; Jarazo, J

    2015-03-01

    According to Greek mythology, Prometheus' liver grew back nightly after it was removed each day by an eagle as punishment for giving mankind fire. Hence, contrary to popular belief, the concept of tissue and organ regeneration is not new. In the early 20th century, cell culture and ex vivo organ preservation studies by Alexis Carrel, some with famed aviator Charles Lindbergh, established a foundation for much of modern regenerative medicine. While early beliefs and discoveries foreshadowed significant accomplishments in regenerative medicine, advances in knowledge within numerous scientific disciplines, as well as nano- and micromolecular level imaging and detection technologies, have contributed to explosive advances over the last 20 years. Virtually limitless preparations, combinations and applications of the 3 major components of regenerative medicine, namely cells, biomaterials and bioactive molecules, have created a new paradigm of future therapeutic options for most species. It is increasingly clear, however, that despite significant parallels among and within species, there is no 'one-size-fits-all' regenerative therapy. Likewise, a panacea has yet to be discovered that completely reverses the consequences of time, trauma and disease. Nonetheless, there is no question that the promise and potential of regenerative medicine have forever altered medical practices. The horse is a relative newcomer to regenerative medicine applications, yet there is already a large body of work to incorporate novel regenerative therapies into standard care. This review focuses on the current state and potential future of stem cells in equine regenerative medicine. PMID:24957845

  20. State of the art: stem cells in equine regenerative medicine.

    PubMed

    Lopez, M J; Jarazo, J

    2015-03-01

    According to Greek mythology, Prometheus' liver grew back nightly after it was removed each day by an eagle as punishment for giving mankind fire. Hence, contrary to popular belief, the concept of tissue and organ regeneration is not new. In the early 20th century, cell culture and ex vivo organ preservation studies by Alexis Carrel, some with famed aviator Charles Lindbergh, established a foundation for much of modern regenerative medicine. While early beliefs and discoveries foreshadowed significant accomplishments in regenerative medicine, advances in knowledge within numerous scientific disciplines, as well as nano- and micromolecular level imaging and detection technologies, have contributed to explosive advances over the last 20 years. Virtually limitless preparations, combinations and applications of the 3 major components of regenerative medicine, namely cells, biomaterials and bioactive molecules, have created a new paradigm of future therapeutic options for most species. It is increasingly clear, however, that despite significant parallels among and within species, there is no 'one-size-fits-all' regenerative therapy. Likewise, a panacea has yet to be discovered that completely reverses the consequences of time, trauma and disease. Nonetheless, there is no question that the promise and potential of regenerative medicine have forever altered medical practices. The horse is a relative newcomer to regenerative medicine applications, yet there is already a large body of work to incorporate novel regenerative therapies into standard care. This review focuses on the current state and potential future of stem cells in equine regenerative medicine.

  1. Interior room within eastern lift span, showing auxiliary electric and ...

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

    Interior room within eastern lift span, showing auxiliary electric and gas generators. - Connecticut Avenue Bridge, Spans Rock Creek & Potomac Parkway at Connecticut Avenue, Washington, District of Columbia, DC

  2. 2. DETAIL VIEW OF MIDDLE ARCH SPAN, LOOKING NORTHWEST. ...

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

    2. DETAIL VIEW OF MIDDLE ARCH SPAN, LOOKING NORTHWEST. - Cumberland & Pennsylvania Railroad, Wills Creek Bridge, Spanning Wills Creek 587 feet West of Eckhart Junction, Cumberland, Allegany County, MD

  3. Perspective view of span over French Creek and east abutment, ...

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

    Perspective view of span over French Creek and east abutment, looking NW. - Pennsylvania Railroad, French Creek Trestle, Spanning French Creek, north of Paradise Street, Phoenixville, Chester County, PA

  4. Interior of lift mechanism area of eastern lift span, looking ...

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

    Interior of lift mechanism area of eastern lift span, looking northwest. - Arlington Memorial Bridge, Spanning Potomac River between Lincoln Memorial & Arlington National Cemetery, Washington, District of Columbia, DC

  5. Interior room within eastern lift span, showing auxiliary electric generator. ...

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

    Interior room within eastern lift span, showing auxiliary electric generator. - Arlington Memorial Bridge, Spanning Potomac River between Lincoln Memorial & Arlington National Cemetery, Washington, District of Columbia, DC

  6. EXTERIOR VIEW, LOOKING WEST, WITH CENTER SPAN EXTENDING ACROSS WARRIOR ...

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

    EXTERIOR VIEW, LOOKING WEST, WITH CENTER SPAN EXTENDING ACROSS WARRIOR RIVER. - Gulf, Mobile & Ohio Railroad Bridge, Spans Black Warrior River between Northport & Tuscaloosa, Tuscaloosa, Tuscaloosa County, AL

  7. Identification of Trap States in Perovskite Solar Cells.

    PubMed

    Baumann, Andreas; Väth, Stefan; Rieder, Philipp; Heiber, Michael C; Tvingstedt, Kristofer; Dyakonov, Vladimir

    2015-06-18

    Thermally stimulated current (TSC) measurements are used to characterize electronic trap states in methylammonium lead iodide perovsite solar cells. Several TSC peaks were observed over the temperature range from 20 K to room temperature. To elucidate the origins of these peaks, devices with various organic charge transport layers and devices without transport layers were tested. Two peaks appear at very low temperatures, indicating shallow trap states that are mainly attributed to the PCBM/C60 electron transport bilayer. However, two additional peaks appear at higher temperatures, that is, they are deeper in energy, and are assigned to the perovskite layer. At around T = 163 K, a sharp peak, also present in the dark TSC measurements, is assigned to the orthorhombic-tetragonal phase transition in the perovskite. However, a peak at around T = 191 K is assigned to trap states with activation energies of around 500 meV but with a rather low concentration of 1 × 10(21) m(-3). PMID:26266616

  8. Life-Span Development of Affective Relationships.

    ERIC Educational Resources Information Center

    Takahashi, Keiko

    This paper presents a model of affective relationships and a review of a number of empirical studies based on the model. The fundamental aim of the model is to describe the life-span development of affective relationships, which are measured in terms of an individual's representation of a variety of significant interpersonal relationships. These…

  9. Sensorimotor Synchronization across the Life Span

    ERIC Educational Resources Information Center

    Drewing, Knut; Aschersleben, Gisa; Li, Shu-Chen

    2006-01-01

    The present study investigates the contribution of general processing resources as well as other more specific factors to the life-span development of sensorimotor synchronization and its component processes. Within a synchronization tapping paradigm, a group of 286 participants, 6 to 88 years of age, were asked to synchronize finger taps with…

  10. Improving spanning trees by upgrading nodes

    SciTech Connect

    Krumke, S.O.; Noltemeier, H.; Wirth, H.C.

    1997-01-16

    We study budget constrained optimal network upgrading problems. Such problems aim at finding optimal strategies for improving a network under some cost measure subject to certain budget constraints. A general problem in this setting is the following. We are given an edge weighted graph G = (V, E) where nodes represent processors and edges represent bidirectional communication links. The processor at a node v {element_of} V can be upgraded at a cost of c(v). Such an upgrade reduces the delay of each link emanating from v. The goal is to find a minimum cost set of nodes to be upgraded so that the resulting network has the best performance with respect to some measure. We consider the problem under two measures, namely, the weight of a minimum spanning tree and the bottleneck weight of a minimum bottleneck spanning tree. We present approximation and hardness results for the problem. Our results are tight to within constant factors. We also show that these approximation algorithms can be used to construct good approximation algorithms for the dual versions of the problems where there is a budget constraint on the upgrading cost and the objectives are minimum weight spanning tree and minimum bottleneck weight spanning tree respectively.

  11. Spatial Abilities across the Adult Life Span

    ERIC Educational Resources Information Center

    Borella, Erika; Meneghetti, Chiara; Ronconi, Lucia; De Beni, Rossana

    2014-01-01

    The study investigates age-related effects across the adult life span on spatial abilities (testing subabilities based on a distinction between spatial visualization, mental rotation, and perspective taking) and spatial self-assessments. The sample consisted of 454 participants (223 women and 231 men) from 20 to 91 years of age. Results showed…

  12. Dentulous appliance for upper anterior edentulous span.

    PubMed

    Chalakkal, Paul; Devi, Ramisetty Sabitha; Srinivas, G Vijay; Venkataramana, Pammi

    2013-12-01

    This article discusses about a fixed dentulous appliance that was constructed to replace the primary upper anterior edentulous span in a four year old girl. It constituted a design, whereby the maxillary primary second molars were used to support the appliance through bands and a wire that contained an acrylic flange bearing trimmed acrylic teeth, anteriorly. The appliance was functionally and aesthetically compliant.

  13. Higher respiratory activity decreases mitochondrial reactive oxygen release and increases life span in Saccharomyces cerevisiae.

    PubMed

    Barros, Mario H; Bandy, Brian; Tahara, Erich B; Kowaltowski, Alicia J

    2004-11-26

    Increased replicative longevity in Saccharomyces cerevisiae because of calorie restriction has been linked to enhanced mitochondrial respiratory activity. Here we have further investigated how mitochondrial respiration affects yeast life span. We found that calorie restriction by growth in low glucose increased respiration but decreased mitochondrial reactive oxygen species production relative to oxygen consumption. Calorie restriction also enhanced chronological life span. The beneficial effects of calorie restriction on mitochondrial respiration, reactive oxygen species release, and replicative and chronological life span could be mimicked by uncoupling agents such as dinitrophenol. Conversely, chronological life span decreased in cells treated with antimycin (which strongly increases mitochondrial reactive oxygen species generation) or in yeast mutants null for mitochondrial superoxide dismutase (which removes superoxide radicals) and for RTG2 (which participates in retrograde feedback signaling between mitochondria and the nucleus). These results suggest that yeast aging is linked to changes in mitochondrial metabolism and oxidative stress and that mild mitochondrial uncoupling can increase both chronological and replicative life span.

  14. How to conceptualize catalytic cycles? The energetic span model.

    PubMed

    Kozuch, Sebastian; Shaik, Sason

    2011-02-15

    A computational study of a catalytic cycle generates state energies (the E-representation), whereas experiments lead to rate constants (the k-representation). Based on transition state theory (TST), these are equivalent representations. Nevertheless, until recently, there has been no simple way to calculate the efficiency of a catalytic cycle, that is, its turnover frequency (TOF), from a theoretically obtained energy profile. In this Account, we introduce the energetic span model that enables one to evaluate TOFs in a straightforward manner and in affinity with the Curtin-Hammett principle. As shown herein, the model implies a change in our kinetic concepts. Analogous to Ohm's law, the catalytic chemical current (the TOF) can be defined by a chemical potential (independent of the mechanism) divided by a chemical resistance (dependent on the mechanism and the nature of the catalyst). This formulation is based on Eyring's TST and corresponds to a steady-state regime. In many catalytic cycles, only one transition state and one intermediate determine the TOF. We call them the TOF-determining transition state (TDTS) and the TOF-determining intermediate (TDI). These key states can be located, from among the many states available to a catalytic cycle, by assessing the degree of TOF control (X(TOF)); this last term resembles the structure-reactivity coefficient in classical physical organic chemistry. The TDTS-TDI energy difference and the reaction driving force define the energetic span (δE) of the cycle. Whenever the TDTS appears after the TDI, δE is the energy difference between these two states; when the opposite is true, we must also add the driving force to this difference. Having δE, the TOF is expressed simply in the Arrhenius-Eyring fashion, wherein δE serves as the apparent activation energy of the cycle. An important lesson from this model is that neither one transition state nor one reaction step possess all the kinetic information that determines the

  15. Development of Semi-Span Model Test Techniques

    NASA Technical Reports Server (NTRS)

    Milholen, William E., II; Chokani, Ndaona; McGhee, Robert J.

    1996-01-01

    A computational investigation was performed to support the development of a semispan model test capability in the NASA Langley Research Center's National Transonic Facility. This capability is desirable for the testing of advanced subsonic transport aircraft at full-scale Reynolds numbers. A state-of-the-art three-dimensional Navier-Stokes solver was used to examine methods to improve the flow over a semi-span configuration. First, a parametric study is conducted to examine the influence of the stand-off height on the flow over the semispan model. It is found that decreasing the stand-off height, below the maximum fuselage radius, improves the aerodynamic characteristics of the semi-span model. Next, active sidewall boundary layer control techniques are examined. Juncture region blowing jets, upstream tangential blowing, and sidewall suction are found to improve the flow over the aft portion of the semispan model. Both upstream blowing and suction are found to reduce the sidewall boundary layer separation. The resulting near surface streamline patterns are improved, and found to be quite similar to the full-span results. Both techniques however adversely affect the pitching moment coefficient.

  16. A murine-ES like state facilitates transgenesis and homologous recombination in human pluripotent stem cells

    PubMed Central

    Buecker, Christa; Chen, Hsu-Hsin; Polo, Jose; Daheron, Laurence; Bu, Lei; Barakat, Tahsin Stefan; Okwieka, Patricia; Porter, Andrew; Gribnau, Joost; Hochedlinger, Konrad; Geijsen, Niels

    2010-01-01

    Murine embryonic stem cells have been shown to exist in two functionally distinct pluripotent states, embryonic stem cells (ES cell)- and epiblast stem cells (EpiSCs), which are defined by the culture growth factor conditions. Human ES cells appear to exist in an epiblast-like state, which in comparison to their murine counterparts, is relatively difficult to propagate and manipulate. As a result, gene targeting is difficult and to-date only a handful of human knock-in or knock-out cell lines exist. We explored whether an alternative stem cell state exists for human stem cells as well, and demonstrate that manipulation of the growth factor milieu allows the derivation of a novel human stem cell type that displays morphological, molecular and functional properties of murine ES cells and facilitates gene targeting. As such, the murine ES-like state provides a powerful tool for the generation of recombinant human pluripotent stem cell lines. PMID:20569691

  17. Systematic drug perturbations on cancer cells reveal diverse exit paths from proliferative state.

    PubMed

    Zhou, Joseph X; Isik, Zerrin; Xiao, Caide; Rubin, Irit; Kauffman, Stuart A; Schroeder, Michael; Huang, Sui

    2016-02-16

    During a cell state transition, cells travel along trajectories in a gene expression state space. This dynamical systems framework complements the traditional concept of molecular pathways that drive cell phenotype switching. To expose the structure that hinders cancer cells from exiting robust proliferative state, we assessed the perturbation capacity of a drug library and identified 16 non-cytotoxic compounds that stimulate MCF7 breast cancer cells to exit from proliferative state to differentiated state. The transcriptome trajectories triggered by these drugs diverged, then converged. Chemical structures and drug targets of these compounds overlapped minimally. However, a network analysis of targeted pathways identified a core signaling pathway--indicating common stress-response and down-regulation of STAT1 before differentiation. This multi-trajectory analysis explores the cells' state transition with a multitude of perturbations in combination with traditional pathway analysis, leading to an encompassing picture of the dynamics of a therapeutically desired cell-state switching.

  18. Systematic drug perturbations on cancer cells reveal diverse exit paths from proliferative state

    PubMed Central

    Xiao, Caide; Rubin, Irit; Kauffman, Stuart A.; Schroeder, Michael; Huang, Sui

    2016-01-01

    During a cell state transition, cells travel along trajectories in a gene expression state space. This dynamical systems framework complements the traditional concept of molecular pathways that drive cell phenotype switching. To expose the structure that hinders cancer cells from exiting robust proliferative state, we assessed the perturbation capacity of a drug library and identified 16 non-cytotoxic compounds that stimulate MCF7 breast cancer cells to exit from proliferative state to differentiated state. The transcriptome trajectories triggered by these drugs diverged, then converged. Chemical structures and drug targets of these compounds overlapped minimally. However, a network analysis of targeted pathways identified a core signaling pathway - indicating common stress-response and down-regulation of STAT1 before differentiation. This multi-trajectory analysis explores the cells' state transition with a multitude of perturbations in combination with traditional pathway analysis, leading to an encompassing picture of the dynamics of a therapeutically desired cell-state switching. PMID:26871731

  19. Single-Cell-State Culture of Human Pluripotent Stem Cells Increases Transfection Efficiency

    PubMed Central

    Nii, Takenobu; Kohara, Hiroshi; Marumoto, Tomotoshi; Sakuma, Tetsushi; Yamamoto, Takashi; Tani, Kenzaburo

    2016-01-01

    Abstract Efficient gene transfer into human pluripotent stem cells (hPSCs) holds great promise for regenerative medicine and pharmaceutical development. In the past decade, various methods were developed for gene transfer into hPSCs; however, hPSCs form tightly packed colonies, making gene transfer difficult. In this study, we established a stable culture method of hPSCs at a single-cell state to reduce cell density and investigated gene transfection efficiency followed by gene editing efficiency. hPSCs cultured in a single-cell state were transfected using nonliposomal transfection reagents with plasmid DNA or mRNA encoding enhanced green fluorescent protein. We found that most cells (DNA > 90%; mRNA > 99%) were transfected without the loss of undifferentiated PSC marker expression or pluripotency. Moreover, we demonstrated an efficient gene editing method using transcription activator-like effector nucleases (TALENs) targeting the adenomatous polyposis coli (APC) gene. Our new method may improve hPSC gene transfer techniques, thus facilitating their use for human regenerative medicine. PMID:27257519

  20. Improved design and construction of large-span culverts

    NASA Astrophysics Data System (ADS)

    Webb, Mark Cottington

    A comprehensive review was made of the design and construction of flexible metal and rigid reinforced concrete large-span culverts, past documented field experience of monitored culvert performance, and culvert failures. Full-scale field testing of a flexible metal and a reinforced concrete large-span culvert was conducted and the results compared with finite element computer analyses. Based on this work recommendations for improved design and construction of large-span culverts were developed. The review of metal culvert design and construction practice revealed numerous differences among current methods as well as deficiencies. Proposed design limit states were identified and discussed for improved practice. An improved earth load thrust prediction model was developed based on past analytical work considering the flexural rigidity of the structure relative to the surrounding soil, in addition to other factors. The design curves for arching factors were extended to cover a wider range of structural backfill width conditions and shallower burial. Also, a proposed construction procedure was outlined to control construction moments based on deflection limits as a function of the expected level of construction control. None of the existing methods explicitly deals with large-span reinforced concrete culvert design and construction practice. Therefore, a proposed design approach for these culverts was outlined. Construction practice was based on recommendations from the manufacturers. The review of failure cases showed that most failures of large-span metal culverts occurred as a result of poor backfill procedures and/or poor backfill material selection. Other causes were excessive construction loads and invert uplift. Excessive deformation was the most common limit state reached before or at failure. Furthermore, significant variations in structural response may occur over time after construction. Therefore, better construction provisions and control are needed

  1. Racial disparities in hematopoietic cell transplantation in the United States.

    PubMed

    Majhail, N S; Nayyar, S; Santibañez, M E Burton; Murphy, E A; Denzen, E M

    2012-11-01

    Hematopoietic cell transplantation (HCT) is a highly specialized, expensive and resource-intense medical procedure that can be associated with racial disparities. We review the prevailing literature on racial disparities in HCT in the United States and describe areas for future research and interventions. We discuss the complexity of interpreting race as a biological and social determinant of disease in biomedical research, especially as it relates to HCT. In the United States, race is often a surrogate for socioeconomic, education and health insurance status. We also discuss some of the nuances to consider while reviewing the literature on racial disparities. Disparities by race exist in three areas related to HCT: donor availability, access to HCT and outcomes of HCT. African-Americans/Blacks have a lower likelihood of finding an unrelated donor. Race and ethnicity definitions are country-specific and reconciling race data can represent significant challenges to unrelated donor registries worldwide. African-Americans/Blacks do not have the same access to autologous and allogeneic HCT as Whites. Racial disparities in outcomes of HCT are more prevalent among allogeneic HCT than autologous HCT recipients. More research is required to understand the biological, social, cultural, medical and financial aspects of race that may influence access to HCT and survival after transplantation. Better understanding of racial disparities will minimize inequities, inform health policy, guide development of interventions targeted to eliminate disparities and ensure equitable access to HCT for all populations.

  2. Detail of center of swing span rotation. Forty (40) rods ...

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

    Detail of center of swing span rotation. Forty (40) rods radiate out from a center cap stand (like spokes on a bicycle) and hold 40 20-inch diameter wheels onto a rim bearing circular track on which they roll when swing span is opened and closed. - Bridgeport Swing Span Bridge, Spanning Tennessee River, Bridgeport, Jackson County, AL

  3. 93. View showing erection traveler erecting 190 foot span over ...

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

    93. View showing erection traveler erecting 190 foot span over Southern Pacific Company's main line track. This is the last span of the steel approach to the main bridge spans. - Carquinez Bridge, Spanning Carquinez Strait at Interstate 80, Vallejo, Solano County, CA

  4. 4. North portal of Skew Span looking south and leading ...

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

    4. North portal of Skew Span looking south and leading to Span 1 Main Bridge on the left and Span 1 Hot Metal Bridge on the right. - Monongahela Connecting Railroad Company, Main Bridge, Spanning Monongahela River at mile post 3.1, Pittsburgh, Allegheny County, PA

  5. 9. VIEW SHOWING JUNCTION OF CONCRETE EAST APPROACH SPAN WITH ...

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

    9. VIEW SHOWING JUNCTION OF CONCRETE EAST APPROACH SPAN WITH STEEL SPAN, LOOKING NORTH. NOTE ROCKING CAST STEEL SHOE ATTACHED TO PIER TO ALLOW FOR EXPANSION OF STEEL SPAN - Jensen Bridge, Spanning Green River at Town of Jensen, Jensen, Uintah County, UT

  6. Ocular pseudoexfoliation syndrome and life span

    PubMed Central

    Slettedal, Jon Klokk; Sandvik, Leiv; Ringvold, Amund

    2015-01-01

    Background To compare life span of persons with and without ocular pseudoexfoliation syndrome (PES). Methods The study is based on an epidemiological survey conducted in Sør-Trøndelag county, Norway, in 1985–86. All inhabitants over 64 years of age (2109 individuals) were invited. Mortality information was obtained from The Norwegian Institute of Public Health in 2014, by which time 99% of the participants were deceased. Results When adjusting for age and gender, life span was not statistically different in persons with and without PES. Following the diagnosis of PES, patients' survival was up to, and beyond, 30 years. Conclusions Our observations suggest that, despite all the systemic aberrations reported in persons with ocular PES, none or only marginal functional changes are caused in extraocular organs and tissues. The present study supports the notion that systemic PES is not a life-threatening condition. PMID:26288849

  7. The Cost of Uncertain Life Span*

    PubMed Central

    Edwards, Ryan D.

    2012-01-01

    A considerable amount of uncertainty surrounds the length of human life. The standard deviation in adult life span is about 15 years in the U.S., and theory and evidence suggest it is costly. I calibrate a utility-theoretic model of preferences over length of life and show that one fewer year in standard deviation is worth about half a mean life year. Differences in the standard deviation exacerbate cross-sectional differences in life expectancy between the U.S. and other industrialized countries, between rich and poor countries, and among poor countries. Accounting for the cost of life-span variance also appears to amplify recently discovered patterns of convergence in world average human well-being. This is partly for methodological reasons and partly because unconditional variance in human length of life, primarily the component due to infant mortality, has exhibited even more convergence than life expectancy. PMID:22368324

  8. Optimal decomposable witnesses without the spanning property

    NASA Astrophysics Data System (ADS)

    Augusiak, Remigiusz; Sarbicki, Gniewomir; Lewenstein, Maciej

    2011-11-01

    One of the unsolved problems in the characterization of the optimal entanglement witnesses is the existence of optimal witnesses acting on bipartite Hilbert spaces Hm,n=Cm⊗Cn such that the product vectors obeying =0 do not span Hm,n. So far, the only known examples of such witnesses were found among indecomposable witnesses, one of them being the witness corresponding to the Choi map. However, it remains an open question whether decomposable witnesses exist without the property of spanning. Here we answer this question affirmatively, providing systematic examples of such witnesses. Then, we generalize some of the recently obtained results on the characterization of 2⊗n optimal decomposable witnesses [R. Augusiak , J. Phys. APLRAAN1751-811310.1088/1751-8113/44/21/212001 44, 212001 (2011)] to finite-dimensional Hilbert spaces Hm,n with m,n≥3.

  9. Methionine restriction and life-span control.

    PubMed

    Lee, Byung Cheon; Kaya, Alaattin; Gladyshev, Vadim N

    2016-01-01

    Dietary restriction (DR) without malnutrition is associated with longevity in various organisms. However, it has also been shown that reduced calorie intake is often ineffective in extending life span. Selecting optimal dietary regimens for DR studies is complicated, as the same regimen may lead to different outcomes depending on genotype and environmental factors. Recent studies suggested that interventions such as moderate protein restriction with or without adequate nutrition (e.g., particular amino acids or carbohydrates) may have additional beneficial effects mediated by certain metabolic and hormonal factors implicated in the biology of aging, regardless of total calorie intake. In particular, it was shown that restriction of a single amino acid, methionine, can mimic the effects of DR and extend life span in various model organisms. We discuss the beneficial effects of a methionine-restricted diet, the molecular pathways involved, and the use of this regimen in longevity interventions.

  10. Optimal decomposable witnesses without the spanning property

    SciTech Connect

    Augusiak, Remigiusz; Sarbicki, Gniewomir; Lewenstein, Maciej

    2011-11-15

    One of the unsolved problems in the characterization of the optimal entanglement witnesses is the existence of optimal witnesses acting on bipartite Hilbert spaces H{sub m,n}=C{sup m} x C{sup n} such that the product vectors obeying =0 do not span H{sub m,n}. So far, the only known examples of such witnesses were found among indecomposable witnesses, one of them being the witness corresponding to the Choi map. However, it remains an open question whether decomposable witnesses exist without the property of spanning. Here we answer this question affirmatively, providing systematic examples of such witnesses. Then, we generalize some of the recently obtained results on the characterization of 2 x n optimal decomposable witnesses [R. Augusiak et al., J. Phys. A 44, 212001 (2011)] to finite-dimensional Hilbert spaces H{sub m,n} with m,n{>=}3.

  11. Activation of the methylation cycle in cells reprogrammed into a stem cell-like state

    PubMed Central

    Bosch-Barrera, Joaquim; Alarcón, Tomás; Joven, Jorge; Menendez, Javier A.

    2015-01-01

    Generation of induced pluripotent stem (iPS) cells and cancer biogenesis share similar metabolic switches. Most studies have focused on how the establishment of a cancer-like glycolytic phenotype is necessary for the optimal routing of somatic cells for achieving stemness. However, relatively little effort has been dedicated towards elucidating how one-carbon (1C) metabolism is retuned during acquisition of stem cell identity. Here we used ultra-high pressure liquid chromatography coupled to an electrospray ionization source and a triple-quadrupole mass spectrometer [UHPLC-ESI-QqQ-MS/MS] to quantitatively examine the methionine/folate bi-cyclic 1C metabolome during nuclear reprogramming of somatic cells into iPS cells. iPS cells optimize the synthesis of the universal methyl donor S-adenosylmethionine (SAM), apparently augment the ability of the redox balance regulator NADPH in SAM biosynthesis, and greatly increase their methylation potential by triggering a high SAM:S-adenosylhomocysteine (SAH) ratio. Activation of the methylation cycle in iPS cells efficiently prevents the elevation of homocysteine (Hcy), which could alter global DNA methylation and induce mitochondrial toxicity, oxidative stress and inflammation. In this regard, the methyl donor choline is also strikingly accumulated in iPS cells, suggesting perhaps an overactive intersection of the de novo synthesis of choline with the methionine-Hcy cycle. Activation of methylogenesis and maintenance of an optimal SAM:Hcy ratio might represent an essential function of 1C metabolism to provide a labile pool of methyl groups and NADPH-dependent redox products required for successfully establishing and maintaining an embryonic-like DNA methylation imprint in stem cell states. PMID:26909364

  12. Attitudes Toward Death Across the Life Span.

    ERIC Educational Resources Information Center

    Maiden, Robert; Walker, Gail

    To understand the change and development of people's attitudes toward death over the life span, a 62-item attitude questionnaire on death and dying was administered to 90 adults. Participants included five females and five males in each of nine age categories: 18-20, 20-24, 25-29, 30-34, 35-39, 40-49, 50-59, 60-64, and 65 or older. Participants…

  13. Dentulous Appliance for Upper Anterior Edentulous Span

    PubMed Central

    Chalakkal, Paul; Devi, Ramisetty Sabitha; Srinivas, G. Vijay; Venkataramana, Pammi

    2013-01-01

    This article discusses about a fixed dentulous appliance that was constructed to replace the primary upper anterior edentulous span in a four year old girl. It constituted a design, whereby the maxillary primary second molars were used to support the appliance through bands and a wire that contained an acrylic flange bearing trimmed acrylic teeth, anteriorly. The appliance was functionally and aesthetically compliant. PMID:24551736

  14. Vision in Flies: Measuring the Attention Span.

    PubMed

    Koenig, Sebastian; Wolf, Reinhard; Heisenberg, Martin

    2016-01-01

    A visual stimulus at a particular location of the visual field may elicit a behavior while at the same time equally salient stimuli in other parts do not. This property of visual systems is known as selective visual attention (SVA). The animal is said to have a focus of attention (FoA) which it has shifted to a particular location. Visual attention normally involves an attention span at the location to which the FoA has been shifted. Here the attention span is measured in Drosophila. The fly is tethered and hence has its eyes fixed in space. It can shift its FoA internally. This shift is revealed using two simultaneous test stimuli with characteristic responses at their particular locations. In tethered flight a wild type fly keeps its FoA at a certain location for up to 4s. Flies with a mutation in the radish gene, that has been suggested to be involved in attention-like mechanisms, display a reduced attention span of only 1s.

  15. Vision in Flies: Measuring the Attention Span.

    PubMed

    Koenig, Sebastian; Wolf, Reinhard; Heisenberg, Martin

    2016-01-01

    A visual stimulus at a particular location of the visual field may elicit a behavior while at the same time equally salient stimuli in other parts do not. This property of visual systems is known as selective visual attention (SVA). The animal is said to have a focus of attention (FoA) which it has shifted to a particular location. Visual attention normally involves an attention span at the location to which the FoA has been shifted. Here the attention span is measured in Drosophila. The fly is tethered and hence has its eyes fixed in space. It can shift its FoA internally. This shift is revealed using two simultaneous test stimuli with characteristic responses at their particular locations. In tethered flight a wild type fly keeps its FoA at a certain location for up to 4s. Flies with a mutation in the radish gene, that has been suggested to be involved in attention-like mechanisms, display a reduced attention span of only 1s. PMID:26848852

  16. Vision in Flies: Measuring the Attention Span

    PubMed Central

    Koenig, Sebastian; Wolf, Reinhard; Heisenberg, Martin

    2016-01-01

    A visual stimulus at a particular location of the visual field may elicit a behavior while at the same time equally salient stimuli in other parts do not. This property of visual systems is known as selective visual attention (SVA). The animal is said to have a focus of attention (FoA) which it has shifted to a particular location. Visual attention normally involves an attention span at the location to which the FoA has been shifted. Here the attention span is measured in Drosophila. The fly is tethered and hence has its eyes fixed in space. It can shift its FoA internally. This shift is revealed using two simultaneous test stimuli with characteristic responses at their particular locations. In tethered flight a wild type fly keeps its FoA at a certain location for up to 4s. Flies with a mutation in the radish gene, that has been suggested to be involved in attention-like mechanisms, display a reduced attention span of only 1s. PMID:26848852

  17. Spanning trees and the Eurozone crisis

    NASA Astrophysics Data System (ADS)

    Dias, João

    2013-12-01

    The sovereign debt crisis in the euro area has not yet been solved and recent developments in Spain and Italy have further deteriorated the situation. In this paper we develop a new approach to analyze the ongoing Eurozone crisis. Firstly, we use Maximum Spanning Trees to analyze the topological properties of government bond rates’ dynamics. Secondly, we combine the information given by both Maximum and Minimum Spanning Trees to obtain a measure of market dissimilarity or disintegration. Thirdly, we extend this measure to include a convenient distance not limited to the interval [0, 2]. Our empirical results show that Maximum Spanning Tree gives an adequate description of the separation of the euro area into two distinct groups: those countries strongly affected by the crisis and those that have remained resilient during this period. The measures of market dissimilarity also reveal a persistent separation of these two groups and, according to our second measure, this separation strongly increased during the period July 2009-March 2012.

  18. Spanning tree generating functions and Mahler measures

    NASA Astrophysics Data System (ADS)

    Guttmann, Anthony J.; Rogers, Mathew D.

    2012-12-01

    We define the notion of a spanning tree generating function (STGF) ∑anzn, which gives the spanning tree constant when evaluated at z = 1, and gives the lattice Green function (LGF) when differentiated. By making use of known results for logarithmic Mahler measures of certain Laurent polynomials, and proving new results, we express the STGFs as hypergeometric functions for all regular two and three dimensional lattices (and one higher-dimensional lattice). This gives closed form expressions for the spanning tree constants for all such lattices, which were previously largely unknown in all but one three-dimensional case. We show for all lattices that these can also be represented as Dirichlet L-series. Making the connection between STGFs and LGFs produces integral identities and hypergeometric connections, some of which appear to be new. This article is part of ‘Lattice models and integrability’, a special issue of Journal of Physics A: Mathematical and Theoretical in honour of F Y Wu's 80th birthday.

  19. Sox10 Regulates Stem/Progenitor and Mesenchymal Cell States in Mammary Epithelial Cells.

    PubMed

    Dravis, Christopher; Spike, Benjamin T; Harrell, J Chuck; Johns, Claire; Trejo, Christy L; Southard-Smith, E Michelle; Perou, Charles M; Wahl, Geoffrey M

    2015-09-29

    To discover mechanisms that mediate plasticity in mammary cells, we characterized signaling networks that are present in the mammary stem cells responsible for fetal and adult mammary development. These analyses identified a signaling axis between FGF signaling and the transcription factor Sox10. Here, we show that Sox10 is specifically expressed in mammary cells exhibiting the highest levels of stem/progenitor activity. This includes fetal and adult mammary cells in vivo and mammary organoids in vitro. Sox10 is functionally relevant, as its deletion reduces stem/progenitor competence whereas its overexpression increases stem/progenitor activity. Intriguingly, we also show that Sox10 overexpression causes mammary cells to undergo a mesenchymal transition. Consistent with these findings, Sox10 is preferentially expressed in stem- and mesenchymal-like breast cancers. These results demonstrate a signaling mechanism through which stem and mesenchymal states are acquired in mammary cells and suggest therapeutic avenues in breast cancers for which targeted therapies are currently unavailable. PMID:26365194

  20. Digit Span is (mostly) related linearly to general intelligence: Every extra bit of span counts.

    PubMed

    Gignac, Gilles E; Weiss, Lawrence G

    2015-12-01

    Historically, Digit Span has been regarded as a relatively poor indicator of general intellectual functioning (g). In fact, Wechsler (1958) contended that beyond an average level of Digit Span performance, there was little benefit to possessing a greater memory span. Although Wechsler's position does not appear to have ever been tested empirically, it does appear to have become clinical lore. Consequently, the purpose of this investigation was to test Wechsler's contention on the Wechsler Adult Intelligence Scale-Fourth Edition normative sample (N = 1,800; ages: 16 - 69). Based on linear and nonlinear contrast analyses of means, as well as linear and nonlinear bifactor model analyses, all 3 Digit Span indicators (LDSF, LDSB, and LDSS) were found to exhibit primarily linear associations with FSIQ/g. Thus, the commonly held position that Digit Span performance beyond an average level is not indicative of greater intellectual functioning was not supported. The results are discussed in light of the increasing evidence across multiple domains that memory span plays an important role in intellectual functioning.

  1. Showing partial side view of swing span in closed position. ...

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

    Showing partial side view of swing span in closed position. The two (2) arms act as simple spans, a small amount of negative bending is accommodated by the continous top and bottom truss chords due to a continuous condition. Note the inclined end post of each of the simple spans, the operator's house, center/pivot pier and the pivotal pole-line pole placed atop of bridge. - Bridgeport Swing Span Bridge, Spanning Tennessee River, Bridgeport, Jackson County, AL

  2. Endosomal protein sorting and autophagy genes contribute to the regulation of yeast life span.

    PubMed

    Longo, Valter D; Nislow, Corey; Fabrizio, Paola

    2010-11-01

    Accumulating evidence from various organisms points to a role for autophagy in the regulation of life span. By performing a genome-wide screen to identify novel life span determinants in Saccharomyces cerevisiae, we have obtained further insights into the autophagy-related and -unrelated degradation processes that may be important for preventing cellular senescence. The generation of multivesicular bodies and their fusion with the vacuole in the endosomal pathway emerged as novel cell functions involved in yeast chronological survival and longevity extension.

  3. Differentiation state determines neural effects on microvascular endothelial cells

    SciTech Connect

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

    2012-10-01

    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: Black-Right-Pointing-Pointer Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell proliferation. Black-Right-Pointing-Pointer Neural progenitor cells, not dorsal root ganglion neurons, regulate microvascular endothelial cell migration. Black-Right-Pointing-Pointer Neural progenitor cells and dorsal root ganglion neurons do not effect microvascular endothelial tube formation. Black-Right-Pointing-Pointer Dorsal root ganglion neurons, not neural progenitor cells, regulate

  4. T suppressor cells are required for the maintenance of the antigen-induced B-cell unresponsive state in humans

    SciTech Connect

    Benveniste, E.; Stevens, R.H.

    1983-04-01

    Tetanus toxoid immunization of humans generates circulating B cells which secrete IgG anti-tetanus toxoid antibodies (IgG-Tet) when stimulated in vitro with T cells and pokeweed mitogen (PWM). A unique property of these cells is the inhibition of maturation into antibody-secreting plasma cells following a 1-hr in vitro pulse with tetanus toxoid. Studies were undertaken to determine if different T-cell subsets could modulate the in vitro generated B-cell unresponsive state. The addition of OKT4+/OKT8- cells to antigen-treated B cells resulted in a partial reversal of the antigen-induced inhibition of IgG-Tet synthesis. The addition of OKT4-/OKT8+ cells to the treated B cells caused a suppression of IgG-Tet synthesis comparable to that seen in cultures containing unfractionated T cells. These results indicate that (1) the B-cell unresponsive state generated by antigen treatment is not absolute, (2) the degree of B-cell unresponsiveness results from a balance of suppressor and helper signals, and (3) T-suppressor cells need to be present to induce and maintain the B-cell unresponsive state.

  5. Temperature spans for growth: Hypothesis and discussion

    SciTech Connect

    Wiegel, J. )

    1990-01-01

    In recent years the upper and lower temperature limits for growth of pure cultures of microorganisms have been extended at least to 110C and [minus]14C, respectively. There are no organisms which grow at both 0C and 100C and, therefore, organisms are grouped according to their ranges of growth temperatures. Thus, the questions of importance are: (1) What is the widest temperature range (temperature span) over which a single organism can grow and (2) How much can one alter the temperature spans of an organism The concept of cryptic thermophiles' is used to explain some of the published data on the latter question. A wider temperature range can be very important for organisms in various ways, since it makes an organism more versatile with regard to changes in the environment. Also, it enables the organism to utilize a wider range of ecological niches. Some aerobic and anaerobic extreme thermophiles will grow within a span of more than 40C. Furthermore, such organisms are regarded suitable for biotechnological applications as well. The following hypothesis is presented and discussed: these organisms have two sets of key enzymes, and their synthesis is regulated by temperature. Such organisms are capable of growing in two different ranges, such as the mesophilic and thermophilic ranges. The hypothesis is based on the fact that these bacteria exhibit broken Arrhenius plots, and is illustrated with 'temperature tolerant extreme thermophiles' as the major example. However, the hypothesis is not restricted to this group, but it also applicable to the 'temperature tolerant thermophiles and mesophiles'.

  6. Battery system and method for sensing and balancing the charge state of battery cells

    NASA Technical Reports Server (NTRS)

    Davies, Francis J. (Inventor)

    2012-01-01

    A battery system utilizes a plurality of transformers interconnected with the battery cells. The transformers each have at least one transformer core operable for magnetization in at least a first magnetic state with a magnetic flux in a first direction and a second magnetic state with a magnetic flux in a second direction. The transformer cores retain the first magnetic state and the second magnetic state without current flow through said plurality of transformers. Circuitry is utilized for switching a selected transformer core between the first and second magnetic states to sense voltage and/or balance particular cells or particular banks of cells.

  7. In situ solid-state NMR spectroscopy of electrochemical cells: batteries, supercapacitors, and fuel cells.

    PubMed

    Blanc, Frédéric; Leskes, Michal; Grey, Clare P

    2013-09-17

    Electrochemical cells, in the form of batteries (or supercapacitors) and fuel cells, are efficient devices for energy storage and conversion. These devices show considerable promise for use in portable and static devices to power electronics and various modes of transport and to produce and store electricity both locally and on the grid. For example, high power and energy density lithium-ion batteries are being developed for use in hybrid electric vehicles where they improve the efficiency of fuel use and help to reduce greenhouse gas emissions. To gain insight into the chemical reactions involving the multiple components (electrodes, electrolytes, interfaces) in the electrochemical cells and to determine how cells operate and how they fail, researchers ideally should employ techniques that allow real-time characterization of the behavior of the cells under operating conditions. This Account reviews the recent use of in situ solid-state NMR spectroscopy, a technique that probes local structure and dynamics, to study these devices. In situ NMR studies of lithium-ion batteries are performed on the entire battery, by using a coin cell design, a flat sealed plastic bag, or a cylindrical cell. The battery is placed inside the NMR coil, leads are connected to a potentiostat, and the NMR spectra are recorded as a function of state of charge. (7)Li is used for many of these experiments because of its high sensitivity, straightforward spectral interpretation, and relevance to these devices. For example, (7)Li spectroscopy was used to detect intermediates formed during electrochemical cycling such as LixC and LiySiz species in batteries with carbon and silicon anodes, respectively. It was also used to observe and quantify the formation and growth of metallic lithium microstructures, which can cause short circuits and battery failure. This approach can be utilized to identify conditions that promote dendrite formation and whether different electrolytes and additives can help

  8. Empowerment, span of control, and safety performance in work teams after workforce reduction.

    PubMed

    Hechanova-Alampay, R; Beehr, T A

    2001-10-01

    Relationships of empowerment and span of control with 2 safety measures (unsafe behaviors and accidents) were investigated among 24 workgroups comprising 531 employees of a large chemical company in 3 U.S. states. The company recently implemented a reengineering process. Data were from an anonymous survey (unsafe behaviors), company records (accidents, span of control), and trained expert raters (empowerment). Span of control (positively) and level of empowerment (negatively) correlated with both measures of poor safety performance, but only empowerment predicted unique variance in safety criteria. Together, these structural measures predicted one third of the variance in safety measures. Structural variables such as span of control and team empowerment have been largely overlooked in past safety research but can be important.

  9. Steady state model for polymer light-emitting electrochemical cells

    SciTech Connect

    Smith, D.L.

    1997-03-01

    A model is presented for the steady state operation of polymer light-emitting electrochemical cells (LECs). An LEC consists of a luminescent and ionically conducting polymer, with an ionic salt added to provide ions necessary for p-type and n-type doping, sandwiched between two electrodes. Upon applying a sufficiently large voltage bias, the ions are spatially separated forming an electrical junction. Electrons injected from the n-type side of the junction recombine with holes injected from the p-type side of the junction emitting light. We first describe the LEC at zero bias in which electric fields may occur in charge double layers near the contacts but in which there is a charge neutral, field free region in the device center which has an equal density of anions and cations and essentially no electrons or holes. A threshold voltage for junction formation is found, which depends on the polymer energy gap, the dissociation free energy of the salt, and the added salt density. It is generally somewhat smaller than the polymer energy gap. Below threshold, an applied bias changes the electric fields in the double charge layers near the contacts but the device center remains field free and essentially no current flows. Above threshold, the ions become spatially separated, a junction forms, and current begins to flow. Part of the applied voltage, above threshold, falls in the contact region and is necessary to establish the junction by electrochemical doping and part of the applied voltage falls across the junction. We describe the structure of the junction, which is quite different from that of a conventional p-n junction, including the spatial profiles of the electrons, holes, and ions, and the electrostatic potential. We discuss the current-voltage and capacitance-voltage characteristics of the LECs and show how they depend on the material parameters. {copyright} {ital 1997 American Institute of Physics.}

  10. Chromatin states modify network motifs contributing to cell-specific functions

    PubMed Central

    Zhao, Hongying; Liu, Tingting; Liu, Ling; Zhang, Guanxiong; Pang, Lin; Yu, Fulong; Fan, Huihui; Ping, Yanyan; Wang, Li; Xu, Chaohan; Xiao, Yun; Li, Xia

    2015-01-01

    Epigenetic modification can affect many important biological processes, such as cell proliferation and apoptosis. It can alter chromatin conformation and contribute to gene regulation. To investigate how chromatin states associated with network motifs, we assembled chromatin state-modified regulatory networks by combining 269 ChIP-seq data and chromatin states in four cell types. We found that many chromatin states were significantly associated with network motifs, especially for feedforward loops (FFLs). These distinct chromatin state compositions contribute to different expression levels and translational control of targets in FFLs. Strikingly, the chromatin state-modified FFLs were highly cell-specific and, to a large extent, determined cell-selective functions, such as the embryonic stem cell-specific bivalent modification-related FFL with an important role in poising developmentally important genes for expression. Besides, comparisons of chromatin state-modified FFLs between cancerous/stem and primary cell lines revealed specific type of chromatin state alterations that may act together with motif structural changes cooperatively contribute to cell-to-cell functional differences. Combination of these alterations could be helpful in prioritizing candidate genes. Together, this work highlights that a dynamic epigenetic dimension can help network motifs to control cell-specific functions. PMID:26169043

  11. Single Cell Mass Cytometry for Analysis of Immune System Functional States

    PubMed Central

    Bjornson, Zach B.; Nolan, Garry P.; Fantl, Wendy J.

    2013-01-01

    Single cell mass cytometry facilitates high-dimensional, quantitative analysis of the effects of bioactive molecules on cell populations at single-cell resolution. Datasets are generated with antibody panels (upwards of 40) in which each antibody is conjugated to a polymer chelated with a stable metal isotope, usually in the Lanthanide series of the periodic table. Isotope labelled antibodies recognize surface markers to delineate cell types and intracellular signaling molecules to provide a measure of the network state—and thereby demarcating multiple cell state functions such as apoptosis, DNA damage and cell cycle. By measuring all these parameters simultaneously, the signaling state of an individual cell can be measured at its network state. This review will cover the basics of mass cytometry as well as outline steps already taken to allow it to stand aside traditional fluorescence based cytometry in the immunologist’s analytical arsenal in their study of immune states during infection. PMID:23999316

  12. Regulation of cell function by the cellular hydration state.

    PubMed

    Häussinger, D; Lang, F; Gerok, W

    1994-09-01

    Cellular hydration can change within minutes under the influence of hormones, nutrients, and oxidative stress. Such short-term modulation of cell volume within a narrow range acts per se as a potent signal which modifies cellular metabolism and gene expression. It appears that cell swelling and cell shrinkage lead to certain opposite patterns of cellular metabolic function. Apparently, hormones and amino acids can trigger those patterns simply by altering cell volume. Thus alterations of cellular hydration may represent another important mechanism for metabolic control and act as another second or third messenger linking cell function to hormonal and environmental alterations.

  13. 95. PHOTOCOPY OF DRAWING, SPAN 1, DETAILS OF TURNTABLE MACHINERY, ...

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

    95. PHOTOCOPY OF DRAWING, SPAN 1, DETAILS OF TURNTABLE MACHINERY, 3/4' and 1 1/2' = 1' (CENTER CONE, RADIAL STRUT RING, TRACK, ROLLERS, PINION GEARS) - Keokuk & Hamilton Bridge, Spanning Mississippi River, Keokuk, Lee County, IA

  14. 37. DRAW SPAN PASSAIC RIVER NEWARK 18M90; Sheet ...

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

    37. DRAW SPAN - PASSAIC RIVER - NEWARK 18-M-90; Sheet No. 9 Details of Portal Struts and Brackets; P, B1 and B2 Scale 1'=1'; February 1897 - Jackson Street Bridge, Spanning Passaic River, Newark, Essex County, NJ

  15. Detail view of operator's housing, northwest corner of bascule span ...

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

    Detail view of operator's housing, northwest corner of bascule span - Old Young's Bay Bridge, Spanning Young's Bay at Milepoint 6.89 on Warrenton-Astoria Highway (Highway No. 9), Astoria, Clatsop County, OR

  16. Detail view of operator's housing, northeast corner of bascule span ...

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

    Detail view of operator's housing, northeast corner of bascule span - Old Young's Bay Bridge, Spanning Young's Bay at Milepoint 6.89 on Warrenton-Astoria Highway (Highway No. 9), Astoria, Clatsop County, OR

  17. Interior room within eastern lift span, showing auxiliary electric and ...

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

    Interior room within eastern lift span, showing auxiliary electric and gas generators. - Arlington Memorial Bridge, Spanning Potomac River between Lincoln Memorial & Arlington National Cemetery, Washington, District of Columbia, DC

  18. 9. Detail of truss work on southwesternmost span, looking northnortheast ...

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

    9. Detail of truss work on southwesternmost span, looking north-northeast - Bridge No. 4800, Spanning Minnesota River on Trunk Highway 4 between Brown & Nicollet Counties, Sleepy Eye, Brown County, MN

  19. 14. Oblique detail; understructure beneath short span used for docking ...

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

    14. Oblique detail; understructure beneath short span used for docking fishing boats, north of northen pillar, from northwest. - Puente Ferroviario San Antonio, Spanning San Antonio Channel at PR-1, San Juan, San Juan Municipio, PR

  20. 3. LOOKING NORTH TO STREET ACROSS SPAN FROM INTERIOR. NOTE ...

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

    3. LOOKING NORTH TO STREET ACROSS SPAN FROM INTERIOR. NOTE TIMBER PANELS NOT ORIGINAL TO DESIGN. - South High Street Bridge, South High Street, spanning Little Juniata Creek, Duncannon, Perry County, PA

  1. 57. Long distance view looking E at Brooklyn side span, ...

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

    57. Long distance view looking E at Brooklyn side span, anchorage and approach. Jet Lowe, photographer, 1982. - Brooklyn Bridge, Spanning East River between Park Row, Manhattan and Sands Street, Brooklyn, New York County, NY

  2. 59. Night view looking W at Brooklyn side span and ...

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

    59. Night view looking W at Brooklyn side span and anchorage. Jet Lowe, photographer, 1982. - Brooklyn Bridge, Spanning East River between Park Row, Manhattan and Sands Street, Brooklyn, New York County, NY

  3. 24. View looking NE at Brooklyn Tower showing approach span. ...

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

    24. View looking NE at Brooklyn Tower showing approach span. Jet Lowe, photographer, 1982. - Brooklyn Bridge, Spanning East River between Park Row, Manhattan and Sands Street, Brooklyn, New York County, NY

  4. View of West end of central lift span truss web ...

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

    View of West end of central lift span truss web of Tensaw River Bridge, showing web brace of lift girder superstructure, looking west - Tensaw River Lift Bridge, Spanning Tensaw River at U.S. Highway 90, Mobile, Mobile County, AL

  5. Detail of moveable span over navigation channel of Fort Point ...

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

    Detail of moveable span over navigation channel of Fort Point Channel showing fender remanent. View west - New York, New Haven & Hartford Railroad, Fort Point Channel Rolling Lift Bridge, Spanning Fort Point Channel, Boston, Suffolk County, MA

  6. 32. DETAIL VIEW OF PIVOT SPAN TURNTABLE, SHOWING MORTISE GEAR, ...

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

    32. DETAIL VIEW OF PIVOT SPAN TURNTABLE, SHOWING MORTISE GEAR, GEAR SHAFT, DRIVE GEAR AND BULL GEAR, LOOKING SOUTHEAST - Alton Bridge, Spanning Mississippi River between IL & MO, Alton, Madison County, IL

  7. 14. DETAIL OF SECOND NORTH APPROACH SPAN, SHOWING STEEL PIERS ...

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

    14. DETAIL OF SECOND NORTH APPROACH SPAN, SHOWING STEEL PIERS AND CANTILEVERED CONCRETE PEDESTAL. VIEW TO SOUTH. - Navajo Bridge, Spanning Colorado River at U.S. Highway 89 Alternate, Page, Coconino County, AZ

  8. 57. VIEW WEST, DETAIL OF CANTILEVER SPAN SHOWING OVERHANG FRAMING ...

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

    57. VIEW WEST, DETAIL OF CANTILEVER SPAN SHOWING OVERHANG FRAMING AND UNDERSIDE FRAMING - Route 1 Extension, Southbound Viaduct, Spanning Conrail Yards, Wilson Avenue, Delancy Street, & South Street on Routes 1 & 9 Southbound, Newark, Essex County, NJ

  9. Detail, pier and underside of deck at truss span 2 ...

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

    Detail, pier and underside of deck at truss span 2 from below and north, showing floor system configuration, lower chords and cantilevered sidewalk - Breslau Bridge, Spanning North Branch of Susquehanna River at Hannover Street, Plymouth, Luzerne County, PA

  10. 44. Detail, bridge land span outboard girder brackets carrying utility ...

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

    44. Detail, bridge land span outboard girder brackets carrying utility conduit. Structure rests on granite blocks mounted on granite piers. - Broadway Bridge, Spanning Foundry Street, MBTA Yard, Fort Point Channel, & Lehigh Street, Boston, Suffolk County, MA

  11. 1. GENERAL ELEVATION, FROM THE NORTHWEST, SHOWING ENTIRE BASCULE SPAN ...

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

    1. GENERAL ELEVATION, FROM THE NORTHWEST, SHOWING ENTIRE BASCULE SPAN OF THE SCHERZER ROLLING LIFT BRIDGE - Seddon Island Scherzer Rolling Lift Bridge, Spanning Garrison Channel from Tampa to Seddon Island, Tampa, Hillsborough County, FL

  12. 39. DETAIL AERIAL VIEW LOOKING AT 210' 9' LIFT SPAN ...

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

    39. DETAIL AERIAL VIEW LOOKING AT 210' 9' LIFT SPAN TOWER SHEAVES SHOWING 1 SET WITH AND 1 SET WITHOUT SHEAVE HOODS - Central Railroad of New Jersey, Newark Bay Lift Bridge, Spanning Newark Bay, Newark, Essex County, NJ

  13. Interior view of lift mechanism area of eastern lift span ...

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

    Interior view of lift mechanism area of eastern lift span looking south, showing trunion gears at left and right, and counterweight above. - Arlington Memorial Bridge, Spanning Potomac River between Lincoln Memorial & Arlington National Cemetery, Washington, District of Columbia, DC

  14. View of central lift span truss web of Tensaw River ...

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

    View of central lift span truss web of Tensaw River Bridge, showing support girders for life house, looking east - Tensaw River Lift Bridge, Spanning Tensaw River at U.S. Highway 90, Mobile, Mobile County, AL

  15. Interior view of lift mechanism area of eastern lift span, ...

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

    Interior view of lift mechanism area of eastern lift span, showing trunion gears at left and right, and counterweight above. - Arlington Memorial Bridge, Spanning Potomac River between Lincoln Memorial & Arlington National Cemetery, Washington, District of Columbia, DC

  16. 6. DETAIL VIEW OF 210' 9' LIFT SPAN TOWER SHEAVES ...

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

    6. DETAIL VIEW OF 210' 9' LIFT SPAN TOWER SHEAVES AND BEARINGS WITH HOUSING AND SHEAVE HOODS REMOVED - Central Railroad of New Jersey, Newark Bay Lift Bridge, Spanning Newark Bay, Newark, Essex County, NJ

  17. 9. VIEW LOOKING SOUTHWEST SHOWING TOP OF LIFT SPAN AND ...

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

    9. VIEW LOOKING SOUTHWEST SHOWING TOP OF LIFT SPAN AND MACHINERY HOUSE; ADJACENT RAILROAD LIFT-BRIDGE TO THE RIGHT. - Carter Road Lift Bridge, Spanning Cuyahoga River at Carter Road, Cleveland, Cuyahoga County, OH

  18. Interior view of eastern lift span, looking south, showing internal ...

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

    Interior view of eastern lift span, looking south, showing internal truss work. River visible below through chain-link fence. - Arlington Memorial Bridge, Spanning Potomac River between Lincoln Memorial & Arlington National Cemetery, Washington, District of Columbia, DC

  19. Interior view of eastern lift span, looking south, showing internal ...

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

    Interior view of eastern lift span, looking south, showing internal truss work. - Arlington Memorial Bridge, Spanning Potomac River between Lincoln Memorial & Arlington National Cemetery, Washington, District of Columbia, DC

  20. INTERIOR OF WEST SPAN LOOKING WEST (SHADOW OF VERTICAL LAPS ...

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

    INTERIOR OF WEST SPAN LOOKING WEST (SHADOW OF VERTICAL LAPS PLACED ON ZONE III; ASPHALT ZONE IX) - Honey Run Bridge, Spanning Butte Creek, bypassed section of Honey Run Road (originally Carr Hill Road), Paradise, Butte County, CA

  1. ELEVATION NORTHEAST BY 30 DEGREES, WEST SECTIONS OF SPAN COVERED ...

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

    ELEVATION NORTHEAST BY 30 DEGREES, WEST SECTIONS OF SPAN COVERED BY OVERGROWTH - Honey Run Bridge, Spanning Butte Creek, bypassed section of Honey Run Road (originally Carr Hill Road), Paradise, Butte County, CA

  2. SWING BRIDGE AT CENTER OF SPAN. DRUM, ALTHOUGH NOT VISIBLE, ...

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

    SWING BRIDGE AT CENTER OF SPAN. DRUM, ALTHOUGH NOT VISIBLE, IS AT CENTER OF PICTURE. - Northern Avenue Swing Bridge, Spanning Fort Point Channel at boundary between Boston & South Boston, Boston, Suffolk County, MA

  3. 17. DETAIL OF FIRST NORTH APPROACH SPAN, SHOWING PIER, ENDPOST, ...

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

    17. DETAIL OF FIRST NORTH APPROACH SPAN, SHOWING PIER, ENDPOST, UPPER AND LOWER CHORDS AND DIAGONALS. VIEW TO SOUTH. - Navajo Bridge, Spanning Colorado River at U.S. Highway 89 Alternate, Page, Coconino County, AZ

  4. 13. Underside Span 1, Hot Metal Bridge on right toward ...

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

    13. Underside Span 1, Hot Metal Bridge on right toward Pier 1. - Monongahela Connecting Railroad Company, Hot Metal Bridge, Spanning Monongahela River at mile post 3.1, Pittsburgh, Allegheny County, PA

  5. VIEW LOOKING SOUTH SHOWING BACK SPAN SIDE OF NEW YORK ...

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

    VIEW LOOKING SOUTH SHOWING BACK SPAN SIDE OF NEW YORK TOWER, WORKERS ARE INSPECTING SUSPENDER SADDLES AND CABLES. - George Washington Bridge, Spanning Hudson River between Manhattan & Fort Lee, NJ, New York County, NY

  6. VIEW LOOKING SOUTHEAST SHOWING BACK SPAN SIDE OF NEW YORK ...

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

    VIEW LOOKING SOUTHEAST SHOWING BACK SPAN SIDE OF NEW YORK TOWER, WORKERS ARE INSPECTING SUSPENDER SADDLES AND CABLES - George Washington Bridge, Spanning Hudson River between Manhattan & Fort Lee, NJ, New York County, NY

  7. 50. VIEW LOOKING SOUTHEAST SHOWING BACK SPAN SIDE OF NEW ...

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

    50. VIEW LOOKING SOUTHEAST SHOWING BACK SPAN SIDE OF NEW YORK TOWER, WORKERS ARE INSPECTING SUSPENDER SADDLES AND CABLES - George Washington Bridge, Spanning Hudson River between Manhattan & Fort Lee, NJ, New York County, NY

  8. 10. EAST ELEVATION OF VERTICAL LIFT SPAN AND MACHINERY HOUSE. ...

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

    10. EAST ELEVATION OF VERTICAL LIFT SPAN AND MACHINERY HOUSE. - Pittsburgh, Fort Wayne & Chicago Railway, Calumet River Bridge, Spanning Calumet River, east of Chicago Skyway (I-90), Chicago, Cook County, IL

  9. 3. VIEW OF WEST SIDE, SHOWING SECOND VERTICAL SUPPORT (SPAN ...

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

    3. VIEW OF WEST SIDE, SHOWING SECOND VERTICAL SUPPORT (SPAN 1), CHANNELS, CROSS BRACING, AND CONNECTION DETAIL, LOOKING SOUTHWEST - McCann Road Bridge, Spanning Thornapple River at McCann Road, Hastings, Barry County, MI

  10. 7. PAIRED END POSTS AT MID SPAN SHOWING CONNECTION OF ...

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

    7. PAIRED END POSTS AT MID SPAN SHOWING CONNECTION OF DIAGONAL TENSION MEMBERS WITH ANCHOR CASTING - Baltimore & Ohio Railroad, Bollman Truss Bridge, Spanning Little Patuxent River, Savage, Howard County, MD

  11. 44. Fixed Span, Floor Beam, Lower Chord Connection, Vertical Tension ...

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

    44. Fixed Span, Floor Beam, Lower Chord Connection, Vertical Tension Member Connection at 2R; looking WNW. - Pacific Shortline Bridge, U.S. Route 20,spanning Missouri River, Sioux City, Woodbury County, IA

  12. 43. Fixed Span, Detail of Floor Beam, Lower Chord Connection, ...

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

    43. Fixed Span, Detail of Floor Beam, Lower Chord Connection, Vertical Tension Member connection at 5L; looking NNW. - Pacific Shortline Bridge, U.S. Route 20,spanning Missouri River, Sioux City, Woodbury County, IA

  13. 48. Fixed Span, Detail of Pinned Connection between End Post ...

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

    48. Fixed Span, Detail of Pinned Connection between End Post & First Segment of Top Chord (Vertical Tension Member goes to 2L); looking E. - Pacific Shortline Bridge, U.S. Route 20,spanning Missouri River, Sioux City, Woodbury County, IA

  14. 17. PAIRED END POSTS AT MID SPAN SHOWING CONNECTION OF ...

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

    17. PAIRED END POSTS AT MID SPAN SHOWING CONNECTION OF DIAGONAL TENSION MEMBERS WITH ANCHOR CASTING. - Baltimore & Ohio Railroad, Bollman Truss Bridge, Spanning Little Patuxent River, Savage, Howard County, MD

  15. 20. Third approach span, comparing pier types and showing guardrail ...

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

    20. Third approach span, comparing pier types and showing guardrail and connection to arch spring point, looking east - U.S. Route 1 Nottoway River Bridge, U.S. Route 1 spanning Nottoway River, McKenney, Dinwiddie County, VA

  16. 26. Southern approach span showing detail plan, elevation, and existing ...

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

    26. Southern approach span showing detail plan, elevation, and existing views for pier and abutment structural changes required after flood of December 1955. - Moody Bridge, Spanning South Fork Eel River, Garberville, Humboldt County, CA

  17. 21. Southern approach span plan and elevation views for pier ...

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

    21. Southern approach span plan and elevation views for pier and abutment structural changes required after flood of December 1955 on Moody Bridge. - Moody Bridge, Spanning South Fork Eel River, Garberville, Humboldt County, CA

  18. Interior view of fixed end of northernmost truss span, looking ...

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

    Interior view of fixed end of northernmost truss span, looking due south. - Pittsburgh, Fort Wayne & Chicago Railway, Beaver River Bridge, Spanning Beaver River along line of Second Avenue, New Brighton, Beaver County, PA

  19. Detail view of fixed end of northernmost truss span. ...

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

    Detail view of fixed end of northernmost truss span. - Pittsburgh, Fort Wayne & Chicago Railway, Beaver River Bridge, Spanning Beaver River along line of Second Avenue, New Brighton, Beaver County, PA

  20. Perspective view showing 850 plate girder span directly over creek, ...

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

    Perspective view showing 85-0 plate girder span directly over creek, looking west. - New York, Chicago & St. Louis Railroad, Elk Creek Trestle, Spanning Elk Creek, south of Elk Park Road, Lake City, Erie County, PA

  1. Detail view of 850 plate girder span directly over creek, ...

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

    Detail view of 85-0 plate girder span directly over creek, looking west. - New York, Chicago & St. Louis Railroad, Elk Creek Trestle, Spanning Elk Creek, south of Elk Park Road, Lake City, Erie County, PA

  2. 45. OBLIQUE VIEW OF NORTH SIDE OF COOPER RIVER SPAN, ...

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

    45. OBLIQUE VIEW OF NORTH SIDE OF COOPER RIVER SPAN, PIER 7, 8, AND 9, FACING SOUTHEAST FROM WATER - Grace Memorial Bridge, U.S. Highway 17 spanning Cooper River & Town Creek , Charleston, Charleston County, SC

  3. 24. OBLIQUE VIEW OF SOUTH SIDE OF COOPER RIVER SPAN ...

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

    24. OBLIQUE VIEW OF SOUTH SIDE OF COOPER RIVER SPAN FROM CHANNEL BELOW, PEARMAN BRIDGE ON RIGHT, FACING EAST - Grace Memorial Bridge, U.S. Highway 17 spanning Cooper River & Town Creek , Charleston, Charleston County, SC

  4. 14. PLANAR VIEW OF SOUTH SIDE OF COOPER RIVER SPAN ...

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

    14. PLANAR VIEW OF SOUTH SIDE OF COOPER RIVER SPAN WITH PEARMAN BRIDGE IN FOREGROUND, FACING NORTH FROM WATER - Grace Memorial Bridge, U.S. Highway 17 spanning Cooper River & Town Creek , Charleston, Charleston County, SC

  5. 44. UNDERSIDE OF COOPER RIVER SPAN, WITH PEARMAN BRIDGE ON ...

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

    44. UNDERSIDE OF COOPER RIVER SPAN, WITH PEARMAN BRIDGE ON LEFT, FACING WEST TOWARDS CHARLESTON - Grace Memorial Bridge, U.S. Highway 17 spanning Cooper River & Town Creek , Charleston, Charleston County, SC

  6. 48. OBLIQUE VIEW OF SOUTH SIDE OF COOPER RIVER SPAN, ...

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

    48. OBLIQUE VIEW OF SOUTH SIDE OF COOPER RIVER SPAN, PEARMAN BRIDGE ON RIGHT, FACING EAST TOWARDS MOUNT PLEASANT FROM BRIDGE - Grace Memorial Bridge, U.S. Highway 17 spanning Cooper River & Town Creek , Charleston, Charleston County, SC

  7. 46. OBLIQUE VIEW OF SOUTH SIDE OF COOPER RIVER SPAN, ...

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

    46. OBLIQUE VIEW OF SOUTH SIDE OF COOPER RIVER SPAN, PIER 9, FACING NORTHEAST FROM WATER - Grace Memorial Bridge, U.S. Highway 17 spanning Cooper River & Town Creek , Charleston, Charleston County, SC

  8. 21. OBLIQUE VIEW OF NORTH SIDE OF COOPER RIVER SPAN ...

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

    21. OBLIQUE VIEW OF NORTH SIDE OF COOPER RIVER SPAN FROM RANGE MARKER NEAR DRUM ISLAND, FACING SOUTHEAST - Grace Memorial Bridge, U.S. Highway 17 spanning Cooper River & Town Creek , Charleston, Charleston County, SC

  9. 43. UNDERSIDE OF PEARMAN BRIDGE, WITH COOPER RIVER SPAN ON ...

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

    43. UNDERSIDE OF PEARMAN BRIDGE, WITH COOPER RIVER SPAN ON RIGHT, FACING WEST TOWARDS CHARLESTON - Grace Memorial Bridge, U.S. Highway 17 spanning Cooper River & Town Creek , Charleston, Charleston County, SC

  10. 30. SOUTH SIDE OF COOPER RIVER CANTILEVER SPAN FROM WATER, ...

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

    30. SOUTH SIDE OF COOPER RIVER CANTILEVER SPAN FROM WATER, FACING WEST TOWARDS DRUM ISLAND - Grace Memorial Bridge, U.S. Highway 17 spanning Cooper River & Town Creek , Charleston, Charleston County, SC

  11. 20. OBLIQUE VIEW OF NORTH SIDE OF COOPER RIVER SPAN ...

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

    20. OBLIQUE VIEW OF NORTH SIDE OF COOPER RIVER SPAN FROM EAST SHORE OF DRUM ISLAND, FACING SOUTHEAST - Grace Memorial Bridge, U.S. Highway 17 spanning Cooper River & Town Creek , Charleston, Charleston County, SC

  12. 5. EAST SPAN, FROM SOUTH, SHOWING STRUCTURAL CONFIGURATION, INCLUDING POLYGONAL ...

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

    5. EAST SPAN, FROM SOUTH, SHOWING STRUCTURAL CONFIGURATION, INCLUDING POLYGONAL TOP CHORD, TRUSS PANELS, EAST ABUTMENT, AND CENTRAL PIER - Glendale Road Bridge, Spanning Deep Creek Lake on Glendale Road, McHenry, Garrett County, MD

  13. 7. Underside of span, details of deck, stringers, floor beams, ...

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

    7. Underside of span, details of deck, stringers, floor beams, bottom-lateral bracing, and north abutment; looking north - Bridge No. 92101, Spanning Pike River at County Highway 373, Embarrass, St. Louis County, MN

  14. FIXED END OF MIDDLE SPAN. WESTERN SIDE SHOWING WELDING OF ...

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

    FIXED END OF MIDDLE SPAN. WESTERN SIDE SHOWING WELDING OF TOP PLATE ADDED TO STRENGTHEN THE BRIDGE. - Spile Bridge Road Bridge, Spanning Black Lake Outlie at Spile Bridge Road, Oswegatchie, St. Lawrence County, NY

  15. Detail of expansion bearing shoe of Span No. 1 on ...

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

    Detail of expansion bearing shoe of Span No. 1 on Abutment No. 1, view to south - Gillespie Dam Bridge, Spanning Gila River on Old US 80 Highway, south of Gillespie Dam, Arlington, Maricopa County, AZ

  16. EXTERIOR VIEW, LOOKING WEST, WITH CENTER SPAN EXTENDING ACROSS WARRIOR ...

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

    EXTERIOR VIEW, LOOKING WEST, WITH CENTER SPAN EXTENDING ACROSS WARRIOR RIVER AND COAL BARGES (LEFT). - Gulf, Mobile & Ohio Railroad Bridge, Spans Black Warrior River between Northport & Tuscaloosa, Tuscaloosa, Tuscaloosa County, AL

  17. 20. WEST CONFEDERATE AVENUE BRIDGE SPANNING CODON'S RUN, ARCH DETAIL ...

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

    20. WEST CONFEDERATE AVENUE BRIDGE SPANNING CODON'S RUN, ARCH DETAIL SHOWING BRICK ARCH FOR MAIN SPAN AND STONE VOUSSOIRS. VIEW W. - Gettysburg National Military Park Tour Roads, Gettysburg, Adams County, PA

  18. 6. Main span (parker through truss, detail of floor system ...

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

    6. Main span (parker through truss, detail of floor system and bottom lateral bracing; looking northwest. - Bridge 4666, Minnesota Trunk Highway 19 spanning Minnesota River, North Redwood, Redwood County, MN

  19. 8. Approach spans (two warren pony trusses), west side, detail ...

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

    8. Approach spans (two warren pony trusses), west side, detail of lower chords and pier no. 2 (west pier); looking south. - Bridge 4666, Minnesota Trunk Highway 19 spanning Minnesota River, North Redwood, Redwood County, MN

  20. 4. Main span (parker through truss), south end, detail of ...

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

    4. Main span (parker through truss), south end, detail of web members and sway bracing; looking west. - Bridge 4666, Minnesota Trunk Highway 19 spanning Minnesota River, North Redwood, Redwood County, MN

  1. 33. DETAIL VIEW OF PIVOT SPAN TURNTABLE, SHOWING BEVEL AND ...

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

    33. DETAIL VIEW OF PIVOT SPAN TURNTABLE, SHOWING BEVEL AND MORTISE GEARS, GEAR SHAFT, DRIVE GEAR AND BULL GEAR, LOOKING NORTHEAST - Alton Bridge, Spanning Mississippi River between IL & MO, Alton, Madison County, IL

  2. CLOSEUP VIEW OF PORTION OF SIMPLE THROUGH TRUSS SPAN LOOKING ...

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

    CLOSE-UP VIEW OF PORTION OF SIMPLE THROUGH TRUSS SPAN LOOKING UP AND NORTHEAST. - Huey P. Long Bridge, Spanning Mississippi River approximately midway between nine & twelve mile points upstream from & west of New Orleans, Jefferson, Jefferson Parish, LA

  3. Distinct mechanical behavior of HEK293 cells in adherent and suspended states.

    PubMed

    Haghparast, Seyed Mohammad Ali; Kihara, Takanori; Miyake, Jun

    2015-01-01

    The mechanical features of individual animal cells have been regarded as indicators of cell type and state. Previously, we investigated the surface mechanics of cancer and normal stromal cells in adherent and suspended states using atomic force microscopy. Cancer cells possessed specific mechanical and actin cytoskeleton features that were distinct from normal stromal cells in adherent and suspended states. In this paper, we report the unique mechanical and actin cytoskeletal features of human embryonic kidney HEK293 cells. Unlike normal stromal and cancer cells, the surface stiffness of adherent HEK293 cells was very low, but increased after cell detachment from the culture surface. Induced actin filament depolymerization revealed that the actin cytoskeleton was the underlying source of the stiffness in suspended HEK293 cells. The exclusive mechanical response of HEK293 cells to perturbation of the actin cytoskeleton resembled that of adherent cancer cells and suspended normal stromal cells. Thus, with respect to their special cell-surface mechanical features, HEK293 cells could be categorized into a new class distinct from normal stromal and cancer cells.

  4. Study on Cloud Security Based on Trust Spanning Tree Protocol

    NASA Astrophysics Data System (ADS)

    Lai, Yingxu; Liu, Zenghui; Pan, Qiuyue; Liu, Jing

    2015-09-01

    Attacks executed on Spanning Tree Protocol (STP) expose the weakness of link layer protocols and put the higher layers in jeopardy. Although the problems have been studied for many years and various solutions have been proposed, many security issues remain. To enhance the security and credibility of layer-2 network, we propose a trust-based spanning tree protocol aiming at achieving a higher credibility of LAN switch with a simple and lightweight authentication mechanism. If correctly implemented in each trusted switch, the authentication of trust-based STP can guarantee the credibility of topology information that is announced to other switch in the LAN. To verify the enforcement of the trusted protocol, we present a new trust evaluation method of the STP using a specification-based state model. We implement a prototype of trust-based STP to investigate its practicality. Experiment shows that the trusted protocol can achieve security goals and effectively avoid STP attacks with a lower computation overhead and good convergence performance.

  5. Correcting deep spans in subsea pipelines

    SciTech Connect

    Sinclair, M.

    1985-11-01

    A diverless pipeline trenching system unique in nature and working method is described. The system is a highly effective tool for pipeline trenching and particularly for span correction. The system is a 90-ton ROV neutrally buoyant and employing a cutter suction principle to soil excavation. The cutter excavates on one side of the pipe to a controllable depth of cut with respect to the pipe. A combination of single and multipass cutting is possible. The trenching machine operates through an umbilical cable with the mother vessel. The neutrally buoyant machine is flown down to the seafloor by means of eight propellers. A sensor package is used to locate the pipeline and the machine clamps onto the pipe using it as a track during trenching. The specially developed handling system, based on a 130-ton U-frame with umbilical heave compensating unit, allows for operation and deployment in up to three meter significant wave height.

  6. Galactic Archaeology and Minimum Spanning Trees

    NASA Astrophysics Data System (ADS)

    MacFarlane, B. A.; Gibson, B. K.; Flynn, C. M. L.

    2016-10-01

    Chemical tagging of stellar debris from disrupted open clusters and associations underpins the science cases for next-generation multi-object spectroscopic surveys. As part of the Galactic Archaeology project TraCD (Tracking Cluster Debris), a preliminary attempt at reconstructing the birth clouds of now phase-mixed thin disk debris is undertaken using a parametric minimum spanning tree (MST) approach. Empirically-motivated chemical abundance pattern uncertainties (for a 10-dimensional chemistry-space) are applied to NBODY6-realized stellar associations dissolved into a background sea of field stars, all evolving in a Milky Way potential. We demonstrate that significant population reconstruction degeneracies appear when the abundance uncertainties approach ˜0.1 dex and the parameterized MST approach is employed; more sophisticated methodologies will be required to ameliorate these degeneracies.

  7. Ballooning Stability of Separatrix Spanning Modes

    NASA Astrophysics Data System (ADS)

    Myra, J. R.; Baver, D. A.; D'Ippolito, D. A.; Umansky, M. V.; Lodestro, L. L.; Goldston, R. J.; Nichols, J. H.

    2013-10-01

    The ideal ballooning stability of the near-separatrix tokamak plasma and its possible relation to the Greenwald density limit, as discussed in, motivates the present work. We consider a sequence of CORSICA-generated equilibrium shapes with varying elongation and examine the marginal stability of infinite-n and finite-n separatrix-spanning modes using the 2DX and ArbiTER eigenvalue codes. The elongation scaling of the result provides a test of the proposed density-limit theory. A new computationally efficient technique for dealing with the phase variation of moderate-n modes across the branch cut in field-line following coordinates will also be discussed. Work supported by US DOE grants DE-FG02-97ER54392 and DE-SC0006562.

  8. How The Genome Got a Life Span

    PubMed Central

    Lappé, Martine; Landecker, Hannah

    2015-01-01

    In the space of little more than a decade, ideas of the human genome have shifted significantly, with the emergence of the notion that the genome an individual changes with development, age, disease, environmental inputs, and time. This paper examines the emergence of the genome with a life span, one that experiences drift, instability and mutability, and a host of other temporal changes. We argue that developments in chromatin biology have provided the basis for this genomic embodiment of experience and exposure. We analyze how time has come to matter for the genome through chromatin, providing analysis of examples in which the human life course is being explored as a set of material changes to chromatin. A genome with a lifespan aligns the molecular and the experiential in new ways, shifting ideas of life stages, their interrelation, and the temporality of health and disease. PMID:26213491

  9. NSI directed to continue SPAN's functions

    NASA Technical Reports Server (NTRS)

    Rounds, Fred

    1991-01-01

    During a series of network management retreats in June and July 1990, representatives from NASA Headquarters Codes O and S agreed on networking roles and responsibilities for their respective organizations. The representatives decided that NASA Science Internet (NSI) will assume management of both the Space Physics Analysis Network (SPAN) and the NASA Science Network (NSN). SPAN is now known as the NSI/DECnet, and NSN is now known as the NSI/IP. Some management functions will be distributed between Ames Research Center (ARC) and Goddard Space Flight Center (GSFC). NSI at ARC has the lead role for requirements generation and networking engineering. Advanced Applications and the Network Information Center is being developed at GSFC. GSFC will lead the NSI User Services, but NSI at Ames will continue to provide the User Services during the transition. The transition will be made as transparent as possible for the users. DECnet service will continue, but is now directly managed by NSI at Ames. NSI will continue to work closely with routing center managers at other NASA centers, and has formed a transition team to address the change in management. An NSI/DECnet working group had also been formed as a separate engineering group within NSI to plan the transition to Phase 5, DECnet's approach to Open System Integration (OSI). Transition is not expected for a year or more due to delays in produce releases. Plans to upgrade speeds in tail circuits and the backbone are underway. The proposed baseline service for new connections is up to 56 Kbps; 9.6 Kbps lines will gradually be upgraded as requirements dictate. NSI is in the process of consolidating protocol traffic, tail circuits, and the backbone. Currently NSI's backbone is fractional T1; NSI will go to full T1 service as soon as it is feasible.

  10. Turning Simple Span into Complex Span: Time for Decay or Interference from Distractors?

    ERIC Educational Resources Information Center

    Lewandowsky, Stephan; Geiger, Sonja M.; Morrell, Daniel B.; Oberauer, Klaus

    2010-01-01

    We investigated the effects of the duration and type of to-be-articulated distractors during encoding of a verbal list into short-term memory (STM). Distractors and to-be-remembered items alternated during list presentation, as in the complex-span task that underlies much of working-memory research. According to an interference model of STM, known…

  11. 16. DETAIL OF END OF SWING SPAN (LEFT) AND SOUTH ...

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

    16. DETAIL OF END OF SWING SPAN (LEFT) AND SOUTH END OF NORTH STATIONARY SPAN REVEALING IRON SKID AND SWING BALANCE SUPPORT WHEEL. NOTE CHAIN USED TO HOLD BRIDGE IN PLACE - Maurice River Pratt Through-Truss Swing Bridge, Spanning Maurice River, Mauricetown, Cumberland County, NJ

  12. 28. Spans 25, detail view, easternmost diaphragm between southern and ...

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

    28. Spans 2-5, detail view, easternmost diaphragm between southern and central lines of spandrel arches of Span 5; view to west. - Fifth Street Bridge, Spanning MBTA Fitchburg Commuter Rail Line tracks, Conrail Fitchburg Secondary Line & North Nashua River, Fitchburg, Worcester County, MA

  13. 27. Spans 25, detail view, eastern spring of northern arch ...

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

    27. Spans 2-5, detail view, eastern spring of northern arch rib of Span 5 at east abutment, showing exposed structural steel; view to southwest. - Fifth Street Bridge, Spanning MBTA Fitchburg Commuter Rail Line tracks, Conrail Fitchburg Secondary Line & North Nashua River, Fitchburg, Worcester County, MA

  14. 24. Span 1, detail view, floor beams, northern sidewalk and ...

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

    24. Span 1, detail view, floor beams, northern sidewalk and parapet at eastern end of span, from below; view to southeast. - Fifth Street Bridge, Spanning MBTA Fitchburg Commuter Rail Line tracks, Conrail Fitchburg Secondary Line & North Nashua River, Fitchburg, Worcester County, MA

  15. 25. Central tension lock looking straight down, south span is ...

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

    25. Central tension lock looking straight down, south span is to the left, north span to the right. there are three tension locks just below road level. - Henry Ford Bridge, Spanning Cerritos Channel, Los Angeles-Long Beach Harbor, Los Angeles, Los Angeles County, CA

  16. 17. END OF SWING SPAN (LEFT) AND SOUTH END OF ...

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

    17. END OF SWING SPAN (LEFT) AND SOUTH END OF NORTH STATIONARY. CLOSE UP REVAEALS DETAILS OF THE IRON SKID AND SWING BALANCED SUPPORT WHEEL. ALSO ROD AND PINTON LOCK (NOT OPERATING). NOTE CHAIN TO HOLD SWING SPAN IN POSITION, - Maurice River Pratt Through-Truss Swing Bridge, Spanning Maurice River, Mauricetown, Cumberland County, NJ

  17. Spanning can be prevented, corrected in deeper water

    SciTech Connect

    Beckmann, M.M.; Hale, J.R.; Lamison, C.W. )

    1991-12-23

    Analysis and correction of subsea pipeline spans are becoming more important as pipelay operations move into the deeper waters of the U.S. Gulf of Mexico. Careful rout selection may prevent spanning. This article sets forth methods for eliminating spans during design or correcting those which occur despite careful design.

  18. p63 Inhibits Extravillous Trophoblast Migration and Maintains Cells in a Cytotrophoblast Stem Cell-Like State

    PubMed Central

    Li, Yingchun; Moretto-Zita, Matteo; Leon-Garcia, Sandra; Parast, Mana M.

    2015-01-01

    Proper differentiation of placental epithelial cells, called trophoblast, is required for implantation. Early during placentation, trophoblast cell columns help anchor the developing embryo in the uterine wall. Although proximally continuous with villous cytotrophoblast (CTB) distally, these cells differentiate into invasive extravillous trophoblast. We previously reported that p63, a p53 family member, is highly expressed in proliferative villous CTB and required for induction of the trophoblast lineage in human pluripotent stem cells. We now further explore its function in human trophoblast by using both primary CTB from the early placenta and established trophoblast cell lines. We show that p63 is expressed in epidermal growth factor receptor-positive CTB and that its expression decreases with differentiation into HLA-G+ extravillous trophoblast. In trophoblast cell lines, p63 is expressed in JEG3 cells but absent from HTR8 cells. Overexpression of p63 in both cell lines enhances cell proliferation and significantly reduces cell migration; conversely, down-regulation of p63 in JEG3 cells reduces cell proliferation and restores cell migration. Analysis of epithelial-to-mesenchymal transition, cell adhesion, and matrix degradation pathways shows that p63 blocks epithelial-to-mesenchymal transition, promotes a CTB-specific cell adhesion profile, and inhibits expression of matrix metalloproteinases. Taken together, these data show that p63 maintains the proliferative CTB state, at least partially through regulation of epithelial-to-mesenchymal transition, cell adhesion, and matrix degradation pathways. PMID:25307348

  19. Novel Molecular Insights into Classical and Alternative Activation States of Microglia as Revealed by Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC)-based Proteomics*

    PubMed Central

    Bell-Temin, Harris; Culver-Cochran, Ashley E.; Chaput, Dale; Carlson, Christina M.; Kuehl, Melanie; Burkhardt, Brant R.; Bickford, Paula C.; Liu, Bin; Stevens, Stanley M.

    2015-01-01

    Microglia, the resident immune cells of the brain, have been shown to display a complex spectrum of roles that span from neurotrophic to neurotoxic depending on their activation status. Microglia can be classified into four stages of activation, M1, which most closely matches the classical (pro-inflammatory) activation stage, and the alternative activation stages M2a, M2b, and M2c. The alternative activation stages have not yet been comprehensively analyzed through unbiased, global-scale protein expression profiling. In this study, BV2 mouse immortalized microglial cells were stimulated with agonists specific for each of the four stages and total protein expression for 4644 protein groups was quantified using SILAC-based proteomic analysis. After validating induction of the various stages through a targeted cytokine assay and Western blotting of activation states, the data revealed novel insights into the similarities and differences between the various states. The data identify several protein groups whose expression in the anti-inflammatory, pro-healing activation states are altered presumably to curtail inflammatory activation through differential protein expression, in the M2a state including CD74, LYN, SQST1, TLR2, and CD14. The differential expression of these proteins promotes healing, limits phagocytosis, and limits activation of reactive nitrogen species through toll-like receptor cascades. The M2c state appears to center around the down-regulation of a key member in the formation of actin-rich phagosomes, SLP-76. In addition, the proteomic data identified a novel activation marker, DAB2, which is involved in clathrin-mediated endocytosis and is significantly different between M2a and either M1 or M2b states. Western blot analysis of mouse primary microglia stimulated with the various agonists of the classical and alternative activation states revealed a similar trend of DAB2 expression compared with BV2 cells. PMID:26424600

  20. Novel Molecular Insights into Classical and Alternative Activation States of Microglia as Revealed by Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC)-based Proteomics.

    PubMed

    Bell-Temin, Harris; Culver-Cochran, Ashley E; Chaput, Dale; Carlson, Christina M; Kuehl, Melanie; Burkhardt, Brant R; Bickford, Paula C; Liu, Bin; Stevens, Stanley M

    2015-12-01

    Microglia, the resident immune cells of the brain, have been shown to display a complex spectrum of roles that span from neurotrophic to neurotoxic depending on their activation status. Microglia can be classified into four stages of activation, M1, which most closely matches the classical (pro-inflammatory) activation stage, and the alternative activation stages M2a, M2b, and M2c. The alternative activation stages have not yet been comprehensively analyzed through unbiased, global-scale protein expression profiling. In this study, BV2 mouse immortalized microglial cells were stimulated with agonists specific for each of the four stages and total protein expression for 4644 protein groups was quantified using SILAC-based proteomic analysis. After validating induction of the various stages through a targeted cytokine assay and Western blotting of activation states, the data revealed novel insights into the similarities and differences between the various states. The data identify several protein groups whose expression in the anti-inflammatory, pro-healing activation states are altered presumably to curtail inflammatory activation through differential protein expression, in the M2a state including CD74, LYN, SQST1, TLR2, and CD14. The differential expression of these proteins promotes healing, limits phagocytosis, and limits activation of reactive nitrogen species through toll-like receptor cascades. The M2c state appears to center around the down-regulation of a key member in the formation of actin-rich phagosomes, SLP-76. In addition, the proteomic data identified a novel activation marker, DAB2, which is involved in clathrin-mediated endocytosis and is significantly different between M2a and either M1 or M2b states. Western blot analysis of mouse primary microglia stimulated with the various agonists of the classical and alternative activation states revealed a similar trend of DAB2 expression compared with BV2 cells.

  1. State Ballots on Stem Cells and Race Are Decided

    ERIC Educational Resources Information Center

    Wiedeman, Reeves

    2008-01-01

    This article reports that a state ballot measure to ban affirmative-action programs based on race, gender, and national origin at public colleges and other state agencies was defeated. Colorado voters narrowly rejected such a referendum last week by a razor-thin margin that took two days to become official. Voters in Nebraska, however, took the…

  2. State of the science of blood cell labeling

    SciTech Connect

    Srivastava, S.C.; Straub, R.F.

    1989-01-01

    Blood cell labeling can be considered a science in as far as it is based on precise knowledge and can be readily reproduced. This benchmark criterion is applied to all current cell labeling modalities and their relative merits and deficiencies are discussed. Mechanisms are given where they are known as well as labeling yields, label stability, and cell functionality. The focus is on the methodology and its suitability to the clinical setting rather than on clinical applications per se. Clinical results are cited only as proof of efficacy of the various methods. The emphasis is on technetium as the cell label, although comparisons are made between technetium and indium, and all blood cells are covered. 52 refs., 6 figs., 7 tabs.

  3. Detailed view of one (1) end of the swing span, ...

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

    Detailed view of one (1) end of the swing span, supported on a rest pier, with the span in the closed position and in the train operational mode. Note the end truss bearing where a steel wedge is in the driven position to complete the end bearing arrangement. The wedges are power-driven through the machinery crank arms shown, thus forcing the ends of the swing span truss upward. Note: The top of the old stone pies has been encased with a concrete collar to hold stone masonry together and strengthen truss bearing points. - Bridgeport Swing Span Bridge, Spanning Tennessee River, Bridgeport, Jackson County, AL

  4. Reflections on the current status of the national sickle cell disease program in the United States.

    PubMed

    Scott, R B

    1979-07-01

    Some clouds of concern now appear on the horizon for the national sickle cell disease program. There is flagging general attention by the black population and a dilution of interest in and visibility of the sickle cell problem brought about by political maneuvering to bring the program under the legislative umbrella of many other genetic diseases (which occur predominantly in Caucasians). In addition, the federal program has recently phased-out six comprehensive sickle cell centers and imposed budgetary cutbacks in the remaining centers. The victims of this disease, the black population in general, and the researchers and investigators who seek ways to bring this disease under control need reassurance from the current national administration that the sickle cell program will not be permitted to die a slow death from financial attrition, attenuation of interest, and skillful neglect leading to the phasing-out of another "minority project." The national sickle cell program, in the relatively short span of six years, has made significant and notable progress not only in research endeavor but also in improved patient care and community-wide education. In this context, certainly, the positive aspects of the national sickle cell disease program continue to far outweigh any negative ones.(1)

  5. Reflections on the current status of the national sickle cell disease program in the United States.

    PubMed

    Scott, R B

    1979-07-01

    Some clouds of concern now appear on the horizon for the national sickle cell disease program. There is flagging general attention by the black population and a dilution of interest in and visibility of the sickle cell problem brought about by political maneuvering to bring the program under the legislative umbrella of many other genetic diseases (which occur predominantly in Caucasians). In addition, the federal program has recently phased-out six comprehensive sickle cell centers and imposed budgetary cutbacks in the remaining centers. The victims of this disease, the black population in general, and the researchers and investigators who seek ways to bring this disease under control need reassurance from the current national administration that the sickle cell program will not be permitted to die a slow death from financial attrition, attenuation of interest, and skillful neglect leading to the phasing-out of another "minority project." The national sickle cell program, in the relatively short span of six years, has made significant and notable progress not only in research endeavor but also in improved patient care and community-wide education. In this context, certainly, the positive aspects of the national sickle cell disease program continue to far outweigh any negative ones.(1) PMID:529329

  6. Activity of synchronized cells of a steady-state biofilm recirculated reactor during xenobiotic biodegradation.

    PubMed Central

    Ascon-Cabrera, M A; Thomas, D; Lebeault, J M

    1995-01-01

    The maintenance of a steady-state biofilm in a continuous-flow fixed-bed reactor, as a consequence of the reproduction-detachment of cells (an interfacial cell physiology phenomenon of steady-state biofilm) during the biodegradation of 2,4,6-trichlorophenol by Pseudomonas cells, was determined. After cell adhesion on an open-pore glass support, the biofilm was formed in a packed-bed recirculated reactor. After the steady-state biofilm was reached, the mechanisms of the interfacial cell detachment (at the biofilm-liquid interface) were determined. It was established that (i) the hydrophobicity of immobilized sessile cells (parent cells) increased (from 50 to 80%) as the dilution rate increased, while the hydrophobicity of detached suspended cells (daughter cells) remained constant (about 45%); and (ii) the immediately detached suspended cells showed a synchronized growth in about three generations. These results indicate that (i) the immobilized sessile and suspended detached cells grew synchronically at the end and at the beginning of the cell cycle, respectively; and (ii) the hydrophobicity difference of immobilized sessile and suspended detached cells permitted the cells detachment. Therefore, it is probable that independent of shear stress (due to recirculated flow), the synchronized growth and hydrophobicity of cells (which vary during the cell cycle) are the main factors permitting the maintenance of a steady-state xenobiotic-degrading biofilm reactor (in which the overall accumulation of biofilm is determined by the average growth rate of the biofilm cells minus the rate of detachment of cells from the biofilm). PMID:7793923

  7. Neuroendocrine and pharmacological manipulations to assess how caloric restriction increases life span.

    PubMed

    Mobbs, C V; Bray, G A; Atkinson, R L; Bartke, A; Finch, C E; Maratos-Flier, E; Crawley, J N; Nelson, J F

    2001-03-01

    As part of an effort to review current understanding of the mechanisms by which caloric restriction (CR) extends maximum life span, the authors of the present review were requested to develop a list of key issues concerning the potential role of neuroendocrine systems in mediating these effects. It has long been hypothesized that failure of specific neuroendocrine functions during aging leads to key age-related systemic and physiological failures, and more recently it has been postulated that physiological neuroendocrine responses to CR may increase life span. However, although the acute neuroendocrine responses to fasting have been well studied, it is not clear that these responses are necessarily identical to those observed in response to the chronic moderate (30% to 50% reduction) CR that increases maximum life span. Therefore the recommendations of this panel fall into two categories. First, further characterization of neuroendocrine responses to CR over the entire life span is needed. Second, rigorous interventional studies are needed to test the extent to which neuroendocrine responses to CR mediate the effects of CR on life span, or alternatively if CR protects the function of essential neuroendocrine cells whose impairment reduces life span. Complementary studies using rodent models, nonhuman primates, and humans will be essential to assess the generality of elucidated mechanisms, and to determine if such mechanisms might apply to humans. PMID:12088210

  8. Capacitance determination of interfacial states in CuInSe2 solar cells

    NASA Astrophysics Data System (ADS)

    Tavakolian, H.; Sites, J. R.

    Interfacial state densities of polycrystalline CdS/CuInSe2 solar cells were deduced from the frequency dispersion found in capacitance measurements. Cells from ARCO Solar, Boeing and IEC all showed interfacial states with a wide range of time constants and zero bias densities at the Fermi level in the junction of 10 to the 10th to 10 to the 11th states/sq cm/eV. In reverse bias, with larger depletion regions, the measured interfacial state densities are reduced. The time constants of the states apparently shift to larger values at reduced temperatures, smaller ones at elevated temperatures.

  9. Recent progress of SPAN towards neutrino mass spectroscopy

    NASA Astrophysics Data System (ADS)

    Masuda, T.; Hara, H.; Miyamoto, Y.; Sasao, N.; Tanaka, M.; Uetake, S.; Yoshimi, A.; Yoshimura, K.; Yoshimura, M.

    2016-05-01

    SPAN (Spectroscopy of Atomic Neutrino) project aims to determine the absolute neutrino mass. The process we plan to use is a cooperative de-excitation of atoms in a metastable level emitting a neutrino pair associated with a photon. The photon energy spectrum of this process contains information on the absolute mass of neutrino. Key items of this experiment are a rate amplification using macro-coherence in a target medium in case of plural particles emission and an external triggering of the emission in order to scan the spectrum. We have demonstrated the rate amplification in two-photon emission from para-hydrogen gas which was coherently excited to its first vibrationally excited state. The coherence in the medium was generated by irradiating two driving laser pulses. The emission was stimulated by irradiating a mid-infrared laser pulse. The enhancement factor of more than 1018 with respect to the spontaneous emission was achieved. This paper briefly summarizes the results.

  10. Emotional Egocentricity Bias Across the Life-Span

    PubMed Central

    Riva, Federica; Triscoli, Chantal; Lamm, Claus; Carnaghi, Andrea; Silani, Giorgia

    2016-01-01

    In our daily lives, we often have to quickly estimate the emotions of our conspecifics in order to have successful social interactions. While this estimation process seems quite easy when we are ourselves in a neutral or equivalent emotional state, it has recently been shown that in case of incongruent emotional states between ourselves and the others, our judgments can be biased. This phenomenon, introduced to the literature with the term Emotional Egocentricity Bias (EEB), has been found to occur in young adults and, to a greater extent, in children. However, how the EEB changes across the life-span from adolescence to old age has been largely unexplored. In this study, we recruited 114 female participants subdivided in four cohorts (adolescents, young adults, middle-aged adults, older adults) to examine EEB age-related changes. Participants were administered with a recently developed paradigm which, by making use of visuo-tactile stimulation that elicits conflicting feelings in paired participants, allows the valid and reliable exploration of the EEB. Results highlighted a U-shape relation between age and EEB, revealing enhanced emotional egocentricity in adolescents and older adults compared to young and middle-aged adults. These results are in line with the neuroscientific literature which has recently shown that overcoming the EEB is associated with a greater activation of a portion of the parietal lobe, namely the right Supramarginal Gyrus (rSMG). This is an area that reaches full maturation by the end of adolescence and goes through an early decay. Thus, the age-related changes of the EEB could be possibly due to the life-span development of the rSMG. This study is the first one to show the quadratic relation between age and the EEB and set a milestone for further research exploring the neural correlates of the life-span development of the EEB. Future studies are needed in order to generalize these results to the male population and to explore gender

  11. Maintenance of an undifferentiated state of human induced pluripotent stem cells through migration-dependent regulation of the balance between cell-cell and cell-substrate interactions.

    PubMed

    Kim, Mee-Hae; Kino-oka, Masahiro

    2015-06-01

    We present an outlook on the current strategies for maintaining and culturing human induced pluripotent stem cells (hiPSCs) in an undifferentiated state without affecting their pluripotency. First, cell structures and function are described in relation to interactions between hiPSCs and their surroundings. Second, the phenomenon of spontaneous deviation from undifferentiated hiPSCs in cultures with feeder cells is addressed, with a summary of current topics that are of particular interest to our studies. The key regulatory factors that can contribute to the growth and maintenance of undifferentiated hiPSCs are also discussed, with a summary of recent work toward a culture strategy to control hiPSC fate through balancing cell-cell and cell-substrate interactions. Finally, we discuss culture process design in our previous studies with respect to maintaining and expanding cultures of undifferentiated and pluripotent hiPSCs. We focus on the regulation of migration-dependent balance between cell-cell and cell-substrate interactions. This review offers novel insights into the regulation and processing of stem cells for research in regenerative medicine.

  12. The cell monolayer trajectory from the system state point of view.

    PubMed

    Stys, Dalibor; Vanek, Jan; Nahlik, Tomas; Urban, Jan; Cisar, Petr

    2011-10-01

    Time-lapse microscopic movies are being increasingly utilized for understanding the derivation of cell states and predicting cell future. Often, fluorescence and other types of labeling are not available or desirable, and cell state-definitions based on observable structures must be used. We present the methodology for cell behavior recognition and prediction based on the short term cell recurrent behavior analysis. This approach has theoretical justification in non-linear dynamics theory. The methodology is based on the general stochastic systems theory which allows us to define the cell states, trajectory and the system itself. We introduce the usage of a novel image content descriptor based on information contribution (gain) by each image point for the cell state characterization as the first step. The linkage between the method and the general system theory is presented as a general frame for cell behavior interpretation. We also discuss extended cell description, system theory and methodology for future development. This methodology may be used for many practical purposes, ranging from advanced, medically relevant, precise cell culture diagnostics to very utilitarian cell recognition in a noisy or uneven image background. In addition, the results are theoretically justified. PMID:21879106

  13. The cell monolayer trajectory from the system state point of view.

    PubMed

    Stys, Dalibor; Vanek, Jan; Nahlik, Tomas; Urban, Jan; Cisar, Petr

    2011-10-01

    Time-lapse microscopic movies are being increasingly utilized for understanding the derivation of cell states and predicting cell future. Often, fluorescence and other types of labeling are not available or desirable, and cell state-definitions based on observable structures must be used. We present the methodology for cell behavior recognition and prediction based on the short term cell recurrent behavior analysis. This approach has theoretical justification in non-linear dynamics theory. The methodology is based on the general stochastic systems theory which allows us to define the cell states, trajectory and the system itself. We introduce the usage of a novel image content descriptor based on information contribution (gain) by each image point for the cell state characterization as the first step. The linkage between the method and the general system theory is presented as a general frame for cell behavior interpretation. We also discuss extended cell description, system theory and methodology for future development. This methodology may be used for many practical purposes, ranging from advanced, medically relevant, precise cell culture diagnostics to very utilitarian cell recognition in a noisy or uneven image background. In addition, the results are theoretically justified.

  14. Longevity: potential life span and health span enhancement through practice of the basic yoga meditation regimen.

    PubMed

    Bushell, William C

    2009-08-01

    This chapter briefly reviews recent psychological, physiological, molecular biological, and anthropological research which has important implications, both direct and indirect, for the recognition and understanding of the potential life span and health span enhancing effects of the basic yoga meditational regimen. This regimen consists of meditation, yogic breath control practices, physical exercises (of both a postural- and movement-based, including aerobic nature), and dietary practices. While each of these component categories exhibit variations in different schools, lineages, traditions, and cultures, the focus of this chapter is primarily on basic forms of relaxation meditation and breath control, as well as postural and aerobic physical exercises (e.g., yogic prostration regimens, see below), and a standard form of yogic or ascetic diet, all of which constitute a basic form of regimen found in many if not most cultures, though with variations.

  15. Single-cell gene expression profiling and cell state dynamics: collecting data, correlating data points and connecting the dots.

    PubMed

    Marr, Carsten; Zhou, Joseph X; Huang, Sui

    2016-06-01

    Single-cell analyses of transcript and protein expression profiles-more precisely, single-cell resolution analysis of molecular profiles of cell populations-have now entered the center stage with widespread applications of single-cell qPCR, single-cell RNA-Seq and CyTOF. These high-dimensional population snapshot techniques are complemented by low-dimensional time-resolved, microscopy-based monitoring methods. Both fronts of advance have exposed a rich heterogeneity of cell states within uniform cell populations in many biological contexts, producing a new kind of data that has triggered computational analysis methods for data visualization, dimensionality reduction, and cluster (subpopulation) identification. The next step is now to go beyond collecting data and correlating data points: to connect the dots, that is, to understand what actually underlies the identified data patterns. This entails interpreting the 'clouds of points' in state space as a manifestation of the underlying molecular regulatory network. In that way control of cell state dynamics can be formalized as a quasi-potential landscape, as first proposed by Waddington. We summarize key methods of data acquisition and computational analysis and explain the principles that link the single-cell resolution measurements to dynamical systems theory.

  16. ω-6 Polyunsaturated fatty acids extend life span through the activation of autophagy

    PubMed Central

    O'Rourke, Eyleen J.; Kuballa, Petric; Xavier, Ramnik; Ruvkun, Gary

    2013-01-01

    Adaptation to nutrient scarcity depends on the activation of metabolic programs to efficiently use internal reserves of energy. Activation of these programs in abundant food regimens can extend life span. However, the common molecular and metabolic changes that promote adaptation to nutritional stress and extend life span are mostly unknown. Here we present a response to fasting, enrichment of ω-6 polyunsaturated fatty acids (PUFAs), which promotes starvation resistance and extends Caenorhabditis elegans life span. Upon fasting, C. elegans induces the expression of a lipase, which in turn leads to an enrichment of ω-6 PUFAs. Supplementing C. elegans culture media with these ω-6 PUFAs increases their resistance to starvation and extends their life span in conditions of food abundance. Supplementation of C. elegans or human epithelial cells with these ω-6 PUFAs activates autophagy, a cell recycling mechanism that promotes starvation survival and slows aging. Inactivation of C. elegans autophagy components reverses the increase in life span conferred by supplementing the C. elegans diet with these fasting-enriched ω-6 PUFAs. We propose that the salubrious effects of dietary supplementation with ω-3/6 PUFAs (fish oils) that have emerged from epidemiological studies in humans may be due to a similar activation of autophagic programs. PMID:23392608

  17. ω-6 Polyunsaturated fatty acids extend life span through the activation of autophagy.

    PubMed

    O'Rourke, Eyleen J; Kuballa, Petric; Xavier, Ramnik; Ruvkun, Gary

    2013-02-15

    Adaptation to nutrient scarcity depends on the activation of metabolic programs to efficiently use internal reserves of energy. Activation of these programs in abundant food regimens can extend life span. However, the common molecular and metabolic changes that promote adaptation to nutritional stress and extend life span are mostly unknown. Here we present a response to fasting, enrichment of ω-6 polyunsaturated fatty acids (PUFAs), which promotes starvation resistance and extends Caenorhabditis elegans life span. Upon fasting, C. elegans induces the expression of a lipase, which in turn leads to an enrichment of ω-6 PUFAs. Supplementing C. elegans culture media with these ω-6 PUFAs increases their resistance to starvation and extends their life span in conditions of food abundance. Supplementation of C. elegans or human epithelial cells with these ω-6 PUFAs activates autophagy, a cell recycling mechanism that promotes starvation survival and slows aging. Inactivation of C. elegans autophagy components reverses the increase in life span conferred by supplementing the C. elegans diet with these fasting-enriched ω-6 PUFAs. We propose that the salubrious effects of dietary supplementation with ω-3/6 PUFAs (fish oils) that have emerged from epidemiological studies in humans may be due to a similar activation of autophagic programs.

  18. ω-6 Polyunsaturated fatty acids extend life span through the activation of autophagy.

    PubMed

    O'Rourke, Eyleen J; Kuballa, Petric; Xavier, Ramnik; Ruvkun, Gary

    2013-02-15

    Adaptation to nutrient scarcity depends on the activation of metabolic programs to efficiently use internal reserves of energy. Activation of these programs in abundant food regimens can extend life span. However, the common molecular and metabolic changes that promote adaptation to nutritional stress and extend life span are mostly unknown. Here we present a response to fasting, enrichment of ω-6 polyunsaturated fatty acids (PUFAs), which promotes starvation resistance and extends Caenorhabditis elegans life span. Upon fasting, C. elegans induces the expression of a lipase, which in turn leads to an enrichment of ω-6 PUFAs. Supplementing C. elegans culture media with these ω-6 PUFAs increases their resistance to starvation and extends their life span in conditions of food abundance. Supplementation of C. elegans or human epithelial cells with these ω-6 PUFAs activates autophagy, a cell recycling mechanism that promotes starvation survival and slows aging. Inactivation of C. elegans autophagy components reverses the increase in life span conferred by supplementing the C. elegans diet with these fasting-enriched ω-6 PUFAs. We propose that the salubrious effects of dietary supplementation with ω-3/6 PUFAs (fish oils) that have emerged from epidemiological studies in humans may be due to a similar activation of autophagic programs. PMID:23392608

  19. Multiplexed immunofluorescence delineates proteomic cancer cell states associated with metabolism

    PubMed Central

    Sood, Anup; Miller, Alexandra M.; Brogi, Edi; Sui, Yunxia; Armenia, Joshua; McDonough, Elizabeth; Santamaria-Pang, Alberto; Stamper, Aleksandra; Campos, Carl; Pang, Zhengyu; Li, Qing; Port, Elisa; Graeber, Thomas G.; Schultz, Nikolaus; Ginty, Fiona; Larson, Steven M.

    2016-01-01

    The phenotypic diversity of cancer results from genetic and nongenetic factors. Most studies of cancer heterogeneity have focused on DNA alterations, as technologies for proteomic measurements in clinical specimen are currently less advanced. Here, we used a multiplexed immunofluorescence staining platform to measure the expression of 27 proteins at the single-cell level in formalin-fixed and paraffin-embedded samples from treatment-naive stage II/III human breast cancer. Unsupervised clustering of protein expression data from 638,577 tumor cells in 26 breast cancers identified 8 clusters of protein coexpression. In about one-third of breast cancers, over 95% of all neoplastic cells expressed a single protein coexpression cluster. The remaining tumors harbored tumor cells representing multiple protein coexpression clusters, either in a regional distribution or intermingled throughout the tumor. Tumor uptake of the radiotracer 18F-fluorodeoxyglucose was associated with protein expression clusters characterized by hormone receptor loss, PTEN alteration, and HER2 gene amplification. Our study demonstrates an approach to generate cellular heterogeneity metrics in routinely collected solid tumor specimens and integrate them with in vivo cancer phenotypes. PMID:27182557

  20. Arsenite maintains germinative state in cultured human epidermal cells

    SciTech Connect

    Patterson, Timothy J.; Reznikova, Tatiana V.; Phillips, Marjorie A.; Rice, Robert H. . E-mail: rhrice@ucdavis.edu

    2005-08-22

    Arsenic is a well-known carcinogen for human skin, but its mechanism of action and proximal macromolecular targets remain to be elucidated. In the present study, low micromolar concentrations of sodium arsenite maintained the proliferative potential of epidermal keratinocytes, decreasing their exit from the germinative compartment under conditions that promote differentiation of untreated cells. This effect was observed in suspension and in post-confluent surface cultures as measured by colony-forming ability and by proportion of rapidly adhering colony-forming cells. Arsenite-treated cultures exhibited elevated levels of {beta}1-integrin and {beta}-catenin, two proteins enriched in cells with high proliferative potential. Levels of phosphorylated (inactive) glycogen synthase kinase 3{beta} were higher in the treated cultures, likely accounting for the increased levels of transcriptionally available {beta}-catenin. These findings suggest that arsenic could have co-carcinogenic and tumor co-promoting activities in the epidermis as a result of increasing the population and persistence of germinative cells targeted by tumor initiators and promoters. These findings also identify a critical signal transduction pathway meriting further exploration in pursuit of this phenomenon.

  1. "Minimax Length Links" of a Dissimilarity Matrix and Minimum Spanning Trees.

    ERIC Educational Resources Information Center

    Carroll, J. Douglas

    1995-01-01

    A theorem is proved stating that the set of all "minimax links," defined as links minimizing, over paths, the maximum length of links in any path connecting a pair of objects comprising nodes in an undirected weighted graph, comprises the union of all minimum spanning trees of that graph. (Author/SLD)

  2. Teaching about September 11th and Its Aftermath. C-SPAN in the Classroom.

    ERIC Educational Resources Information Center

    C-SPAN, Washington, DC.

    The events of and since September 11, 2001 have had an immeasurable impact on all facets of people's lives, especially in the United States. The loss of human life, threatened public safety, and the impact of a military response are just some of the issues concerning U.S. citizens and public officials. This C-SPAN in the Classroom series offers…

  3. Heroin addiction and the Wechsler Digit Span test.

    PubMed

    Keiser, T W; Lowy, D

    1980-01-01

    There is some evidence that a Wechsler Digit Span scaled score well above the means of an individual's other WAIS subtest scores is diagnostically significant. Such positive Digit Span scatter seems to be a correlate of an interpersonal detachment syndrome characterized by superficial relationships and anhedonia. Negative scatter of Digit Span scaled scores considerably below the mean of other WAIS subtest scores have been viewed by some investigators as indicating depressive symptoms. Forty-two heroin addicts were compared with 41 neurotic depressive patients. The former group attained significantly higher average positive Digit Span scatter. Since heroin addicts appear more interpersonally distant and anhedonic for non-drug-related experiences, this finding was according to expectation. Digit Span scaled scores alone did not differentiate the groups. Digit Span scatter scores are clearly more desirable than scaled scores in the search for cognitive correlates of personality variables.

  4. The complex genetic architecture of Drosophila life span.

    PubMed

    Leips, Jeff; Mackay, Trudy F C

    2002-01-01

    Continuous phenotypic variation in life span results from segregating genetic variation at multiple loci, the environmental sensitivity of expression of these loci, and the history of environmental variation experienced by the organism throughout its life. We have mapped quantitative trait loci (QTL) that produce variation in the life span of mated Drosophila melanogaster using a panel of recombinant inbred lines (RIL) that were backcrossed to the parental strains from which they were derived. Five QTL were identified that influence mated life span, three were male-specific, one was female-specific, and one affected life span in both sexes. The additive allelic effects and dominance of QTL were highly sex-specific. One pair of QTL also exhibited significant epistatic effects on life span. We summarize all of the QTL mapping data for Drosophila life span, and outline future prospects for disentangling the genetic and environmental influences on this trait.

  5. Detail of lift wire rope attachment to lift span at ...

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

    Detail of lift wire rope attachment to lift span at southeast corner. Note rope-adjustment turnbuckle with strap keepers to prevent its rotation, which could pull the bridge out of alignment. A single rope and light-gauge attachment at each corner were adequate for lifting the span because most of its weight was balanced by the two counterweights. - Potomac Edison Company, Chesapeake & Ohio Canal Bridge, Spanning C & O Canal South of U.S. 11, Williamsport, Washington County, MD

  6. State-of-the-Art Fuel Cell Voltage Durability Status: Spring 2013 Composite Data Products

    SciTech Connect

    Kurtz, J.; Sprik, S.; Saur, G.; Peters, M.; Post, M.; Ainscough, C.

    2013-05-01

    This presentation from the U.S. Department of Energy's National Renewable Energy Laboratory includes composite data products (CDPs) produced in 2013 for state-of-the-art fuel cell voltage durability status.

  7. Solid oxide fuel cells in the United States

    NASA Astrophysics Data System (ADS)

    Hooie, Diane Traub

    This paper presents an overview of the solid-oxide fuel cell program being undertaken in the US. This program addresses both intermediate and high temperature fuel cells as well as a variety of configurations including planar/monolithic, and tubular. These projects also address a variety of issues such as material compatibility, life/degradation, fuel compatibility, and system scaleup and integration. The primary applications currently being developed is for power generation but a variety of other potential applications, such as transportation, are being considered. The funding for these projects is provided through a variety of sources including the US Government (primarily Departments of Energy, Transportation, and Defense), the Electric Power Research Institute (EPRI), the Gas Research Institute (GRI), and industry.

  8. Electromagnetic fields mediate efficient cell reprogramming into a pluripotent state.

    PubMed

    Baek, Soonbong; Quan, Xiaoyuan; Kim, Soochan; Lengner, Christopher; Park, Jung-Keug; Kim, Jongpil

    2014-10-28

    Life on Earth is constantly exposed to natural electromagnetic fields (EMFs), and it is generally accepted that EMFs may exert a variety of effects on biological systems. Particularly, extremely low-frequency electromagnetic fields (EL-EMFs) affect biological processes such as cell development and differentiation; however, the fundamental mechanisms by which EMFs influence these processes remain unclear. Here we show that EMF exposure induces epigenetic changes that promote efficient somatic cell reprogramming to pluripotency. These epigenetic changes resulted from EMF-induced activation of the histone lysine methyltransferase Mll2. Remarkably, an EMF-free system that eliminates Earth's naturally occurring magnetic field abrogates these epigenetic changes, resulting in a failure to undergo reprogramming. Therefore, our results reveal that EMF directly regulates dynamic epigenetic changes through Mll2, providing an efficient tool for epigenetic reprogramming including the acquisition of pluripotency. PMID:25248035

  9. 4. Threefourths view of span 2 and 1. Showing timber ...

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

    4. Three-fourths view of span 2 and 1. Showing timber deck resting on the floor stringers. Also note differences in stringer floor beam construction. In span 1, the stringers are connected to the side of the floor beams. Spans 2 and 3 the stringer bear on top of the floor beam. Also note non-continuous eye bar construction through the panel points on the bottom chord. - Bridge No. 33.3, Spanning Elk River at Milepost JC-33.3, Fayetteville, Lincoln County, TN

  10. Mathematical analysis of steady-state solutions in compartment and continuum models of cell polarization.

    PubMed

    Zheng, Zhenzhen; Chou, Ching-Shan; Yi, Tau-Mu; Nie, Qing

    2011-10-01

    Cell polarization, in which substances previously uniformly distributed become asymmetric due to external or/and internal stimulation, is a fundamental process underlying cell mobility, cell division, and other polarized functions. The yeast cell S. cerevisiae has been a model system to study cell polarization. During mating, yeast cells sense shallow external spatial gradients and respond by creating steeper internal gradients of protein aligned with the external cue. The complex spatial dynamics during yeast mating polarization consists of positive feedback, degradation, global negative feedback control, and cooperative effects in protein synthesis. Understanding such complex regulations and interactions is critical to studying many important characteristics in cell polarization including signal amplification, tracking dynamic signals, and potential trade-off between achieving both objectives in a robust fashion. In this paper, we study some of these questions by analyzing several models with different spatial complexity: two compartments, three compartments, and continuum in space. The step-wise approach allows detailed characterization of properties of the steady state of the system, providing more insights for biological regulations during cell polarization. For cases without membrane diffusion, our study reveals that increasing the number of spatial compartments results in an increase in the number of steady-state solutions, in particular, the number of stable steady-state solutions, with the continuum models possessing infinitely many steady-state solutions. Through both analysis and simulations, we find that stronger positive feedback, reduced diffusion, and a shallower ligand gradient all result in more steady-state solutions, although most of these are not optimally aligned with the gradient. We explore in the different settings the relationship between the number of steady-state solutions and the extent and accuracy of the polarization. Taken together

  11. Span load distribution for tapered wings with partial-span flaps

    NASA Technical Reports Server (NTRS)

    Pearson, H A

    1937-01-01

    Tables are given for determining the load distribution of tapered wings with partial-span flaps placed either at the center or at the wing tips. Seventy-two wing-flap combinations, including two aspect ratios, four taper ratios, and nine flap lengths, are included. The distributions for the flapped wing are divided into two parts, one a zero lift distribution due primarily to the flaps and the other an additional lift distribution due to an angle of attack of the wing as a whole. Comparison between theoretical and experimental results for wings indicate that the theory may be used to predict the load distribution with sufficient accuracy for structural purposes.

  12. Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease

    PubMed Central

    Acloque, Hervé; Adams, Meghan S.; Fishwick, Katherine; Bronner-Fraser, Marianne; Nieto, M. Angela

    2009-01-01

    The events that convert adherent epithelial cells into individual migratory cells that can invade the extracellular matrix are known collectively as epithelial-mesenchymal transition (EMT). Throughout evolution, the capacity of cells to switch between these two cellular states has been fundamental in the generation of complex body patterns. Here, we review the EMT events that build the embryo and further discuss two prototypical processes governed by EMT in amniotes: gastrulation and neural crest formation. Cells undergo EMT to migrate and colonize distant territories. Not surprisingly, this is also the mechanism used by cancer cells to disperse throughout the body. PMID:19487820

  13. The state of the union: the cell biology of fertilization.

    PubMed

    Evans, Janice P; Florman, Harvey M

    2002-10-01

    Fertilization is the process by which sperm and egg unite. An expanded understanding of the mechanisms that underlie these events has provided insights into an important aspect of early development and also has proven to be a valuable model in which to study cellular function. In addition, many emerging strategies for contraception and for the treatment of infertility are based on the mechanism of gamete interaction. Here, we discuss the cell and molecular biology of mammalian fertilization, highlight selected recent breakthroughs and attempt to identify key unanswered questions.

  14. Sickle cell in Latin America and the United States [corrected].

    PubMed

    Huttle, Alexandra; Maestre, Gladys E; Lantigua, Rafael; Green, Nancy S

    2015-07-01

    Latin Americans are an underappreciated population affected by sickle cell disease (SCD). Sickle trait and SCD exist throughout Latin America and U.S. Latino communities. We describe the epidemiology and genetic heterogeneity of SCD among Latin Americans, and fetal hemoglobin expression. National population-based newborn screening for SCD is limited to Brazil, Costa Rica, and the U.S. Available and extrapolated data suggest that over 6,000 annual births and 100,000-150,000 Latin Americans are affected by SCD. This comprehensive review highlights the substantial numbers and population distribution of SCD and sickle trait in Latin America, and where national newborn screening programs for SCD exist.

  15. Tequila Regulates Insulin-Like Signaling and Extends Life Span in Drosophila melanogaster.

    PubMed

    Huang, Cheng-Wen; Wang, Horng-Dar; Bai, Hua; Wu, Ming-Shiang; Yen, Jui-Hung; Tatar, Marc; Fu, Tsai-Feng; Wang, Pei-Yu

    2015-12-01

    The aging process is a universal phenomenon shared by all living organisms. The identification of longevity genes is important in that the study of these genes is likely to yield significant insights into human senescence. In this study, we have identified Tequila as a novel candidate gene involved in the regulation of longevity in Drosophila melanogaster. We have found that a hypomorphic mutation of Tequila (Teq(f01792)), as well as cell-specific downregulation of Tequila in insulin-producing neurons of the fly, significantly extends life span. Tequila deficiency-induced life-span extension is likely to be associated with reduced insulin-like signaling, because Tequila mutant flies display several common phenotypes of insulin dysregulation, including reduced circulating Drosophila insulin-like peptide 2 (Dilp2), reduced Akt phosphorylation, reduced body size, and altered glucose homeostasis. These observations suggest that Tequila may confer life-span extension by acting as a modulator of Drosophila insulin-like signaling.

  16. The de-adhesive activity of matricellular proteins: is intermediate cell adhesion an adaptive state?

    PubMed

    Murphy-Ullrich, J E

    2001-04-01

    The process of cellular de-adhesion is potentially important for the ability of a cell to participate in morphogenesis and to respond to injurious stimuli. Cellular de-adhesion is induced by the highly regulated matricellular proteins TSP1 and 2, tenascin-C, and SPARC. These proteins induce a rapid transition to an intermediate state of adhesiveness characterized by loss of actin-containing stress fibers and restructuring of the focal adhesion plaque that includes loss of vinculin and alpha-actinin, but not of talin or integrin. This process involves intracellular signaling mediators, which are engaged in response to matrix protein-receptor interactions. Each of these proteins employs different receptors and signaling pathways to achieve this common morphologic endpoint. What is the function of this intermediate adhesive state and what is the physiologic significance of this action of the matricellular proteins? Given that matricellular proteins are expressed in response to injury and during development, one can speculate that the intermediate adhesive state is an adaptive condition that facilitates expression of specific genes that are involved in repair and adaptation. Since cell shape is maintained in weakly adherent cells, this state might induce survival signals to prevent apoptosis due to loss of strong cell adhesion, but yet allow for cell locomotion. The three matricellular proteins considered here might each preferentially facilitate one or more aspects of this adaptive response rather than all of these equally. Currently, we have only preliminary data to support the specific ideas proposed in this article. It will be interesting in the next several years to continue to elucidate the biological roles of the intermediate adhesive state induced by these matricellular proteins. and focal adhesions in a cell that nevertheless maintains a spread, extended morphology and integrin clustering. TSP1, tenascin-C, and SPARC induce the intermediate adhesive state, as

  17. Buckling mode localization in a multi-span periodic structure with a disorder in a single span

    NASA Technical Reports Server (NTRS)

    Li, Y. W.; Elishakoff, Isaac; Starnes, J. H., Jr.

    1998-01-01

    This paper investigates the buckling mode localization in the periodic multi-span beam with disorder occurring in an arbitrary single span. The analytical finite difference calculus is used in conjunction with the conventional displacement method to derive the transcendental equations from which buckling load is calculated. The underlying treatment is general and the solution thus obtained is exact. Numerical results show that the buckling mode is highly localized in the vicinity of the disordered span of the beam.

  18. SOLID STATE ENERGY CONVERSION ALLIANCE DELPHI SOLID OXIDE FUEL CELL

    SciTech Connect

    Steven Shaffer; Sean Kelly; Subhasish Mukerjee; David Schumann; Gail Geiger; Kevin Keegan; John Noetzel; Larry Chick

    2003-12-08

    The objective of Phase I under this project is to develop a 5 kW Solid Oxide Fuel Cell power system for a range of fuels and applications. During Phase I, the following will be accomplished: Develop and demonstrate technology transfer efforts on a 5 kW stationary distributed power generation system that incorporates steam reforming of natural gas with the option of piped-in water (Demonstration System A). Initiate development of a 5 kW system for later mass-market automotive auxiliary power unit application, which will incorporate Catalytic Partial Oxidation (CPO) reforming of gasoline, with anode exhaust gas injected into an ultra-lean burn internal combustion engine. This technical progress report covers work performed by Delphi from January 1, 2003 to June 30, 2003, under Department of Energy Cooperative Agreement DE-FC-02NT41246. This report highlights technical results of the work performed under the following tasks: Task 1 System Design and Integration; Task 2 Solid Oxide Fuel Cell Stack Developments; Task 3 Reformer Developments; Task 4 Development of Balance of Plant (BOP) Components; Task 5 Manufacturing Development (Privately Funded); Task 6 System Fabrication; Task 7 System Testing; Task 8 Program Management; and Task 9 Stack Testing with Coal-Based Reformate.

  19. Allogeneic hematopoietic cell transplantation: the state of the art

    PubMed Central

    Gyurkocza, Boglarka; Rezvani, Andrew; Storb, Rainer F

    2010-01-01

    Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative procedure for a variety of hematologic malignancies. The field has evolved substantially over the past decade, with advances in patient and donor selection, stem cell sources, supportive care, prevention of complications and reduced-toxicity preparative regimens. As a result, the indications for HCT and the pool of eligible patients have expanded significantly. In this article, we provide an overview of the major aspects of allogeneic HCT, and focus specifically on areas of active research and on novel approaches to challenges in the field. Specifically, we will discuss approaches to reduce the toxicity of the preparative regimen, with the goal of increasing the safety and applicability of HCT. The availability of suitable donors may be an obstacle to wider application of HCT. We review three major approaches to broadening the donor pool: the use of HLA-mismatched unrelated donors, umbilical cord blood and HLA-haploidentical family donors. Graft-versus-host disease remains a major cause of morbidity and mortality after HCT. We review recent advances in the understanding of this phenomenon, and novel prophylactic and therapeutic approaches that hold the promise of further improving the safety of the procedure. We conclude with a speculative outline of the next 5 years of research in the field of HCT. PMID:20871781

  20. Biomanufacturing of Therapeutic Cells: State of the Art, Current Challenges, and Future Perspectives.

    PubMed

    Roh, Kyung-Ho; Nerem, Robert M; Roy, Krishnendu

    2016-06-01

    Stem cells and other functionally defined therapeutic cells (e.g., T cells) are promising to bring hope of a permanent cure for diseases and disorders that currently cannot be cured by conventional drugs or biological molecules. This paradigm shift in modern medicine of using cells as novel therapeutics can be realized only if suitable manufacturing technologies for large-scale, cost-effective, reproducible production of high-quality cells can be developed. Here we review the state of the art in therapeutic cell manufacturing, including cell purification and isolation, activation and differentiation, genetic modification, expansion, packaging, and preservation. We identify current challenges and discuss opportunities to overcome them such that cell therapies become highly effective, safe, and predictively reproducible while at the same time becoming affordable and widely available. PMID:27276552

  1. Life span variation in 13 Drosophila species: a comparative study on life span, environmental variables and stress resistance.

    PubMed

    Wit, J; Loeschcke, V; Kellermann, V

    2015-10-01

    Recently, heterogeneity of the environment has been suggested as an important player in the evolution of life span variation. Established ageing theories propose that life span variation is the result of coevolution with other traits, such as stress resistance. This study aimed to compare these alternative hypotheses by examining the relationship between four environmental variables and different types of stress resistance traits with life span in 13 Drosophila species originating from tropical, subtropical and temperate environments (ecotypes). Average life span was found to differ significantly both between species and sexes, but only male life span correlated with the environment and cold resistance. While controlling for phylogeny, the environmental variable precipitation seasonality and resistance against cold-induced stress explained most variation in male life span. Furthermore, male life span varied between species in a manner represented by environmental variables linked to the different ecotypes, such that tropical species lived longer and were less cold resistant. The current results suggest that general mechanisms underlying stress resistance and life span are unlikely. In addition, our results point to the environment independently shaping variation in life span and cold resistance rather than genetic interactions.

  2. Multiple steady states with distinct cellular metabolism in continuous culture of mammalian cells.

    PubMed

    Europa, A F; Gambhir, A; Fu, P C; Hu, W S

    2000-01-01

    Mammalian cells have the ability to proliferate under different nutrient environments by utilizing different combinations of the nutrients, especially glucose and the amino acids. Under the conditions often used in in vitro cultivation, the cells consume glucose and amino acids in great excess of what is needed for making up biomass and products. They also produce large amounts of metabolites with lactate, ammonia, and some non-essential amino acids such as alanine as the most dominant ones. By controlling glucose and glutamine at low levels, cellular metabolism can be altered and can result in reduced glucose and glutamine consumption as well as in reduced metabolite formation. Using a fed-batch reactor to manipulate glucose at a low level (as compared to a typical batch culture), cell metabolism was altered to a state with substantially reduced lactate production. The culture was then switched to a continuous mode and allowed to reach a steady-state. At this steady-state, the concentrations of cells and antibody were substantially higher than a control culture that was initiated from a batch culture without first altering cellular metabolism. The lactate and other metabolite concentrations were also substantially reduced as compared to the control culture. This newly observed steady-state was achieved at the same dilution rate and feed medium as the control culture. The paths leading to the two steady-states, however, were different. These results demonstrate steady-state multiplicity. At this new steady-state, not only was glucose metabolism altered, but the metabolism of amino acids was altered as well. The amino acid metabolism in the new steady-state was more balanced, and the excretion of non-essential amino acids and ammonia was substantially lower. This approach of reaching a more desirable steady-state with higher concentrations of cells and product opens a new avenue for high-density- and high-productivity-cell culture.

  3. Reconstructing and analysing cellular states, space and time from gene expression profiles of many cells and single cells.

    PubMed

    Francesconi, Mirko; Lehner, Ben

    2015-10-01

    Genome-wide gene expression profiling is a fast, cheap and standardised analysis that provides a high dimensional measurement of the state of a biological sample. In this review we describe computational methods that can be applied to identify and interpret sources of variance in gene expression in whole organisms, organs, tissues or single cells. This allows the identification of constituent cell types and states in complex mixtures, the reconstruction of temporal trajectories of development, differentiation and progression, and the reconstruction of spatial patterning. When applied to genetically variable samples, these methods allow the efficient investigation of how genetic variation influences gene expression and biological processes in space and time.

  4. C. elegans VANG-1 modulates life span via insulin/IGF-1-like signaling.

    PubMed

    Honnen, Sebastian J; Büchter, Christian; Schröder, Verena; Hoffmann, Michael; Kohara, Yuji; Kampkötter, Andreas; Bossinger, Olaf

    2012-01-01

    The planar cell polarity (PCP) pathway is highly conserved from Drosophila to humans and a PCP-like pathway has recently been described in the nematode Caenorhabditis elegans. The developmental function of this pathway is to coordinate the orientation of cells or structures within the plane of an epithelium or to organize cell-cell intercalation required for correct morphogenesis. Here, we describe a novel role of VANG-1, the only C. elegans ortholog of the conserved PCP component Strabismus/Van Gogh. We show that two alleles of vang-1 and depletion of the protein by RNAi cause an increase of mean life span up to 40%. Consistent with the longevity phenotype vang-1 animals also show enhanced resistance to thermal- and oxidative stress and decreased lipofuscin accumulation. In addition, vang-1 mutants show defects like reduced brood size, decreased ovulation rate and prolonged reproductive span, which are also related to gerontogenes. The germline, but not the intestine or neurons, seems to be the primary site of vang-1 function. Life span extension in vang-1 mutants depends on the insulin/IGF-1-like receptor DAF-2 and DAF-16/FoxO transcription factor. RNAi against the phase II detoxification transcription factor SKN-1/Nrf2 also reduced vang-1 life span that might be explained by gradual inhibition of insulin/IGF-1-like signaling in vang-1. This is the first time that a key player of the PCP pathway is shown to be involved in the insulin/IGF-1-like signaling dependent modulation of life span in C. elegans.

  5. SOLID STATE ENERGY CONVERSION ALLIANCE DELPHI SOLID OXIDE FUEL CELL

    SciTech Connect

    Steven Shaffer; Sean Kelly; Subhasish Mukerjee; David Schumann; Gail Geiger; Kevin Keegan; Larry Chick

    2004-05-07

    The objective of this project is to develop a 5 kW Solid Oxide Fuel Cell power system for a range of fuels and applications. During Phase I, the following will be accomplished: Develop and demonstrate technology transfer efforts on a 5 kW stationary distributed power generation system that incorporates steam reforming of natural gas with the option of piped-in water (Demonstration System A). Initiate development of a 5 kW system for later mass-market automotive auxiliary power unit application, which will incorporate Catalytic Partial Oxidation (CPO) reforming of gasoline, with anode exhaust gas injected into an ultra-lean burn internal combustion engine. This technical progress report covers work performed by Delphi from July 1, 2003 to December 31, 2003, under Department of Energy Cooperative Agreement DE-FC-02NT41246. This report highlights technical results of the work performed under the following tasks: Task 1 System Design and Integration; Task 2 Solid Oxide Fuel Cell Stack Developments; Task 3 Reformer Developments; Task 4 Development of Balance of Plant (BOP) Components; Task 5 Manufacturing Development (Privately Funded); Task 6 System Fabrication; Task 7 System Testing; Task 8 Program Management; Task 9 Stack Testing with Coal-Based Reformate; and Task 10 Technology Transfer from SECA CORE Technology Program. In this reporting period, unless otherwise noted Task 6--System Fabrication and Task 7--System Testing will be reported within Task 1 System Design and Integration. Task 8--Program Management, Task 9--Stack Testing with Coal Based Reformate, and Task 10--Technology Transfer from SECA CORE Technology Program will be reported on in the Executive Summary section of this report.

  6. Cell Wall Chemical Composition of Enterococcus faecalis in the Viable but Nonculturable State

    PubMed Central

    Signoretto, Caterina; del Mar Lleò, Maria; Tafi, Maria Carla; Canepari, Pietro

    2000-01-01

    The viable but nonculturable (VBNC) state is a survival mechanism adopted by many bacteria (including those of medical interest) when exposed to adverse environmental conditions. In this state bacteria lose the ability to grow in bacteriological media but maintain viability and pathogenicity and sometimes are able to revert to regular division upon restoration of normal growth conditions. The aim of this work was to analyze the biochemical composition of the cell wall of Enterococcus faecalis in the VBNC state in comparison with exponentially growing and stationary cells. VBNC enterococcal cells appeared as slightly elongated and were endowed with a wall more resistant to mechanical disruption than dividing cells. Analysis of the peptidoglycan chemical composition showed an increase in total cross-linking, which rose from 39% in growing cells to 48% in VBNC cells. This increase was detected in oligomers of a higher order than dimers, such as trimers (24% increase), tetramers (37% increase), pentamers (65% increase), and higher oligomers (95% increase). Changes were also observed in penicillin binding proteins (PBPs), the enzymes involved in the terminal stages of peptidoglycan assembly, with PBPs 5 and 1 being prevalent, and in autolytic enzymes, with a threefold increase in the activity of latent muramidase-1 in E. faecalis in the VBNC state. Accessory wall polymers such as teichoic acid and lipoteichoic acid proved unchanged and doubled in quantity, respectively, in VBNC cells in comparison to dividing cells. It is suggested that all these changes in the cell wall of VBNC enterococci are specific to this particular physiological state. This may provide indirect confirmation of the viability of these cells. PMID:10788366

  7. Solid state photovoltaic cells based on localized surface plasmon-induced charge separation

    NASA Astrophysics Data System (ADS)

    Takahashi, Yukina; Tatsuma, Tetsu

    2011-10-01

    Charge separation induced by localized surface plasmon resonance (LSPR) of gold and silver nanoparticles (AuNPs and AgNPs) are applied to various devices and photoelectrochemical functionalities. Here, we develop all solid state In/TiO2/MNPs/ITO photovoltaic cells (MNP = AuNP or AgNP) by using two-dimensional MNP ensembles. Their quantum efficiencies are higher than those of previously reported solid state cells with hole-transport materials (HTMs) (ITO/TiO2/AuNPs/HTM/Au). The photoresponses from cells without HTMs suggest that the photovoltage generates at the TiO2-MNP interface.

  8. Effect of letter spacing on visual span and reading speed.

    PubMed

    Yu, Deyue; Cheung, Sing-Hang; Legge, Gordon E; Chung, Susana T L

    2007-01-01

    S. T. L. Chung (2002) has shown that rapid serial visual presentation (RSVP) reading speed varies with letter spacing, peaking near the standard letter spacing for text and decreasing for both smaller and larger spacings. In this study, we tested the hypothesis that the dependence of reading speed on letter spacing is mediated by the size of the visual span-the number of letters recognized with high accuracy without moving the eyes. If so, the size of the visual span and reading speed should show a similar dependence on letter spacing. We tested this prediction for RSVP reading and asked whether it generalizes to the reading of blocks of text requiring eye movements. We measured visual-span profiles and reading speeds as a function of letter spacing. Visual-span profiles, measured with trigrams (strings of three random letters), are plots of letter-recognition accuracy as a function of letter position left or right of fixation. Size of the visual span was quantified by a measure of the area under the visual-span profile. Reading performance was measured using two presentation methods: RSVP and flashcard (a short block of text on four lines). We found that the size of the visual span and the reading speeds measured by the two presentation methods showed a qualitatively similar dependence on letter spacing and that they were highly correlated. These results are consistent with the view that the size of the visual span is a primary visual factor that limits reading speed.

  9. 41. Reconstruction of roadway; view of swing span looking northwest ...

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

    41. Reconstruction of roadway; view of swing span looking northwest from Bronx approach, showing new apron under construction-concrete foundation partly built. Note trolley in background and broken asphalt in roadway bed. December 15, 1925 photograph. - University Heights Bridge, Spanning Harlem River at 207th Street & West Harlem Road, New York County, NY

  10. Community Engagement and Boundary-Spanning Roles at Research Universities

    ERIC Educational Resources Information Center

    Weerts, David J.; Sandmann, Lorilee R.

    2010-01-01

    Over the past decade, community engagement has emerged as an important priority among many colleges and universities. This study employs a multi-case study design to examine boundary spanning practices of research universities that have adopted a community engagement agenda. A model is advanced to conceptualize spanning behaviors and to inform…

  11. 9. VIEW OF INTAKE PIER AND MAIN SPAN OF ACCESS ...

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

    9. VIEW OF INTAKE PIER AND MAIN SPAN OF ACCESS BRIDGE FROM WATER LEVEL, LOOKING NORTHWEST. - Sacramento River Water Treatment Plant Intake Pier & Access Bridge, Spanning Sacramento River approximately 175 feet west of eastern levee on river; roughly .5 mile downstream from confluence of Sacramento & American Rivers, Sacramento, Sacramento County, CA

  12. 2. AERIAL VIEW OF THE VERTICAL LIFT BRIDGES SPANNING THE ...

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

    2. AERIAL VIEW OF THE VERTICAL LIFT BRIDGES SPANNING THE HACKENSACK RIVER, LOOKING NORTHEAST. THE PATH TRANSIT BRIDGE IS IN THE FOREGROUND, WITH THE CONRAIL (HAER No. NJ-43), NEWARK TURNPIKE, AND ERIE & LACKAWANNA RAILROAD (HAER No. NJ-42) BRIDGES BEHIND IT - Path Transit System Bridge, Spanning Hackensack River, Kearny, Hudson County, NJ

  13. Developmental Regulation across the Life Span: Toward a New Synthesis

    ERIC Educational Resources Information Center

    Haase, Claudia M.; Heckhausen, Jutta; Wrosch, Carsten

    2013-01-01

    How can individuals regulate their own development to live happy, healthy, and productive lives? Major theories of developmental regulation across the life span have been proposed (e.g., dual-process model of assimilation and accommodation; motivational theory of life-span development; model of selection, optimization, and compensation), but they…

  14. 23 CFR 650.809 - Movable span bridges.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Movable span bridges. 650.809 Section 650.809 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS BRIDGES, STRUCTURES, AND HYDRAULICS Navigational Clearances for Bridges § 650.809 Movable span bridges. A fixed...

  15. 23 CFR 650.809 - Movable span bridges.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 23 Highways 1 2013-04-01 2013-04-01 false Movable span bridges. 650.809 Section 650.809 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS BRIDGES, STRUCTURES, AND HYDRAULICS Navigational Clearances for Bridges § 650.809 Movable span bridges. A fixed...

  16. 23 CFR 650.809 - Movable span bridges.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 23 Highways 1 2014-04-01 2014-04-01 false Movable span bridges. 650.809 Section 650.809 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS BRIDGES, STRUCTURES, AND HYDRAULICS Navigational Clearances for Bridges § 650.809 Movable span bridges. A fixed...

  17. 23 CFR 650.809 - Movable span bridges.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 23 Highways 1 2011-04-01 2011-04-01 false Movable span bridges. 650.809 Section 650.809 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS BRIDGES, STRUCTURES, AND HYDRAULICS Navigational Clearances for Bridges § 650.809 Movable span bridges. A fixed...

  18. 11. DETAIL: OBLIQUE VIEW FROM SOUTHWEST OF TYPICAL SPAN SHOWING ...

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

    11. DETAIL: OBLIQUE VIEW FROM SOUTHWEST OF TYPICAL SPAN SHOWING ART DECO RELIEFS AND REMAINS OF BRACKETS FOR SUPPORTING STEEL SIDEWALKS. - Puente de la Marina, San Lorenzo-Florida & Cerro Gordo Neighborhoods, spanning Rio Grande de Loiza River at Narciso Varona-Suarez Street, San Lorenzo, San Lorenzo Municipio, PR

  19. An improved spatial span test of visuospatial memory.

    PubMed

    Woods, David L; Wyma, John M; Herron, Timothy J; Yund, E William

    2016-09-01

    In the widely used Corsi Block Test and Wechsler Spatial Span Tests, participants must reproduce sequences of blocks in the order touched by the examiner until two trials are missed at the same sequence length. The examiner records either the maximum number of blocks correctly reported or the total number of correct lists. Here, we describe a computerized spatial span test (C-SST) that uses psychophysical procedures to quantify visuospatial mean span (MnS) with sub-digit precision. Results from 187 participants ranging in age from 18 to 82 years showed that accuracy declined gradually with list length around the MnS (by ∼30% per item). Simulation studies revealed high variance and biases in CBT and Wechsler measures, and demonstrated that the C-SST provided the most accurate estimate of true span (i.e., the sequence length producing 50% correct). MnS declined more rapidly with age than mean digit span (MnDS) measured in the same participants. Response times correlated with both MnS and MnDS scores. Error analysis showed that omission and transposition errors predominated, with weaker primacy and recency effects in spatial span than digit span testing. The C-SST improves the precision of spatial span testing and reveals significant differences between visuospatial and verbal working memory.

  20. Detail of west span showing connection of superstructure to granite ...

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

    Detail of west span showing connection of superstructure to granite pier at low tide. Photograph articulates subdeck support members. View southeast - New York, New Haven & Hartford Railroad, Fort Point Channel Rolling Lift Bridge, Spanning Fort Point Channel, Boston, Suffolk County, MA

  1. The Effect of Orthographic Neighborhood in the Reading Span Task

    ERIC Educational Resources Information Center

    Robert, Christelle; Postal, Virginie; Mathey, Stéphanie

    2015-01-01

    This study aimed at examining whether and to what extent orthographic neighborhood of words influences performance in a working memory span task. Twenty-five participants performed a reading span task in which final words to be memorized had either no higher frequency orthographic neighbor or at least one. In both neighborhood conditions, each…

  2. C-Span in the Classroom. Teacher's Guide.

    ERIC Educational Resources Information Center

    Carey, Helen H.; Greenberg, Judith E.

    This teacher's guide is designed to show how Cable-Satellite Public Affairs Network (C-SPAN) can be used as a primary source in the secondary education classroom to teach citizenship education for concept and skill development. Subject areas that C-SPAN can supplement are global education, government, public speaking, economics education, law…

  3. Detail, view, underside of halfthrough girder span over entrance to ...

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

    Detail, view, underside of half-through girder span over entrance to scrap yard at western end of trestle. Note that abutment is slightly skewed. - Pennsylvania Railroad, French Creek Trestle, Spanning French Creek, north of Paradise Street, Phoenixville, Chester County, PA

  4. 7. View west. East pier and underside of Walpole span, ...

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

    7. View west. East pier and underside of Walpole span, showing deck beams, stringers, and wind bracing rods. Structure on pier is a stream level gauge station. - Walpole-Westminster Bridge, Spanning Connecticut River between Walpole, NH & Westminster, VT, Walpole, Cheshire County, NH

  5. A Motivational Theory of Life-Span Development

    ERIC Educational Resources Information Center

    Heckhausen, Jutta; Wrosch, Carsten; Schulz, Richard

    2010-01-01

    This article had four goals. First, the authors identified a set of general challenges and questions that a life-span theory of development should address. Second, they presented a comprehensive account of their Motivational Theory of Life-Span Development. They integrated the model of optimization in primary and secondary control and the…

  6. 3. DETAIL VIEW OF ONE ARCH SPAN, LOOKING NW ALONG ...

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

    3. DETAIL VIEW OF ONE ARCH SPAN, LOOKING NW ALONG EAST BANK OF SUSQUEHANNA RIVER. NOTE FLOOD STAGE MARKINGS ON PIER, ALSO LONGITUDINAL CONSTRUCTION JOINT IN ARCH BARREL. - Philadelphia & Reading Railroad, Susquehanna River Bridge, Spanning Susquehanna River, North of I-83 Bridge, Harrisburg, Dauphin County, PA

  7. Paternal smoking habits affect the reproductive life span of daughters.

    PubMed

    Fukuda, Misao; Fukuda, Kiyomi; Shimizu, Takashi; Nobunaga, Miho; Andersen, Elisabeth Wreford; Byskov, Anne Grete; Andersen, Claus Yding

    2011-06-30

    The present study assessed whether the smoking habits of fathers around the time of conception affected the period in which daughters experienced menstrual cycles (i.e., the reproductive life span). The study revealed that the smoking habits of the farther shortened the daughters' reproductive life span compared with daughters whose fathers did not smoke.

  8. View of West end of central lift span truss web ...

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

    View of West end of central lift span truss web of Tensaw River Bridge, showing operator's ladder and platform, diagonals and posts, looking southwest - Tensaw River Lift Bridge, Spanning Tensaw River at U.S. Highway 90, Mobile, Mobile County, AL

  9. 42. Fixed Span; General View of the Floor Beam, Stringer, ...

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

    42. Fixed Span; General View of the Floor Beam, Stringer, & Lateral Bracing System; looking S. (from near to far: 6L & R, 5L & R, 4 L & R). - Pacific Shortline Bridge, U.S. Route 20,spanning Missouri River, Sioux City, Woodbury County, IA

  10. View of pony truss approach span, showing metal caissons and ...

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

    View of pony truss approach span, showing metal caissons and deck system, including metal floor beams and timber stringers. The same decking system was used on movable span. Looking north from civilian land. - Naval Supply Annex Stockton, Daggett Road Bridge, Daggett Road traversing Burns Cut Off, Stockton, San Joaquin County, CA

  11. View of pony truss approach span, showing metal caissons and ...

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

    View of pony truss approach span, showing metal caissons and deck system, including metal floor beams and timber stringers. The same decking system was used on movable span. Looking north from civilian land. - Naval Supply Annex Stockton, Rough & Ready Island, Stockton, San Joaquin County, CA

  12. Spending, Size, and Grade Span in K-8 Schools

    ERIC Educational Resources Information Center

    Rubenstein, Ross; Schwartz, Amy Ellen; Stiefel, Leanna; Zabel, Jeffrey

    2009-01-01

    Reorganizing primary school grade spans is a tractable and relatively inexpensive school reform. However, assessing the effects of reorganization requires also examining other organizational changes that may accompany grade span reforms. Using data on New York City public schools from 1996 to 2002 and exploiting within-school variations, we…

  13. Synergies between Processing and Memory in Children's Reading Span

    ERIC Educational Resources Information Center

    Towse, John N.; Hitch, Graham J.; Horton, Neil; Harvey, Katarina

    2010-01-01

    Previous research has established the relevance of working memory for cognitive development. Yet the factors responsible for shaping performance in the complex span tasks used to assess working memory capacity are not fully understood. We report a study of reading span in 7- to 11-year-old children that addresses several contemporary theoretical…

  14. Measuring Boundary-Spanning Behaviors in Community Engagement

    ERIC Educational Resources Information Center

    Sandmann, Lorilee R.; Jordan, Jenny W.; Mull, Casey D.; Valentine, Thomas

    2014-01-01

    Community engagement professionals and partners serve as, work with, study, and build the capacity of boundary spanners. To augment knowledge about these functions, the Weerts-Sandmann Boundary Spanning Conceptual Framework (2010) has been operationalized through a survey instrument to examine community engagement boundary-spanning behaviors by…

  15. 41. Fixed Span, Floor Beam 1, showing the cantilever; looking ...

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

    41. Fixed Span, Floor Beam 1, showing the cantilever; looking N. (The splice between the original beam and the 1960 extension (widening) is between the two stringers to the left of the bottom chord tension members). - Pacific Shortline Bridge, U.S. Route 20,spanning Missouri River, Sioux City, Woodbury County, IA

  16. Children's Working Memory: Investigating Performance Limitations in Complex Span Tasks

    ERIC Educational Resources Information Center

    Conlin, J.A.; Gathercole, S.E.; Adams, J.W.

    2005-01-01

    Three experiments investigated the roles of resource-sharing and intrinsic memory demands in complex working memory span performance in 7- and 9-year-olds. In Experiment 1, the processing complexity of arithmetic operations was varied under conditions in which processing times were equivalent. Memory span did not differ as a function of processing…

  17. 2. Threefourths view of bridge showing truss spans 1, 2, ...

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

    2. Three-fourths view of bridge showing truss spans 1, 2, and 3 timber approach on south end, and relation of bridge to stream an adjoining terrain - Bridge No. 33.3, Spanning Elk River at Milepost JC-33.3, Fayetteville, Lincoln County, TN

  18. 8. East portal of 1898 swing span of Bridge Number ...

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

    8. East portal of 1898 swing span of Bridge Number 210.52, view to east, 210mm lens. Note the difference in the latticed portal strut as compared to that of the 1929 approach span in the previous photo. - Southern Pacific Railroad Shasta Route, Bridge No. 210.52, Milepost 210.52, Tehama, Tehama County, CA

  19. An improved spatial span test of visuospatial memory.

    PubMed

    Woods, David L; Wyma, John M; Herron, Timothy J; Yund, E William

    2016-09-01

    In the widely used Corsi Block Test and Wechsler Spatial Span Tests, participants must reproduce sequences of blocks in the order touched by the examiner until two trials are missed at the same sequence length. The examiner records either the maximum number of blocks correctly reported or the total number of correct lists. Here, we describe a computerized spatial span test (C-SST) that uses psychophysical procedures to quantify visuospatial mean span (MnS) with sub-digit precision. Results from 187 participants ranging in age from 18 to 82 years showed that accuracy declined gradually with list length around the MnS (by ∼30% per item). Simulation studies revealed high variance and biases in CBT and Wechsler measures, and demonstrated that the C-SST provided the most accurate estimate of true span (i.e., the sequence length producing 50% correct). MnS declined more rapidly with age than mean digit span (MnDS) measured in the same participants. Response times correlated with both MnS and MnDS scores. Error analysis showed that omission and transposition errors predominated, with weaker primacy and recency effects in spatial span than digit span testing. The C-SST improves the precision of spatial span testing and reveals significant differences between visuospatial and verbal working memory. PMID:26357906

  20. 9. OBLIQUE VIEW, PARTIAL WEST SPAN, FROM SOUTHWEST, SHOWING TRUSS ...

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

    9. OBLIQUE VIEW, PARTIAL WEST SPAN, FROM SOUTHWEST, SHOWING TRUSS PANELS AND SOLID CONFIGURATION OF TRUSS MEMBERS, INCLUDING POLYGONAL TOP CHORD, VERTICAL AND DIAGONAL MEMBERS, AND CROSS-STRUTS - Glendale Road Bridge, Spanning Deep Creek Lake on Glendale Road, McHenry, Garrett County, MD

  1. Underside of Span No. 1, with pier no. 2 in ...

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

    Underside of Span No. 1, with pier no. 2 in background, showing floor beams, stringers, lower chords, lower lateral braces and underside of deck slab, view to west - Gillespie Dam Bridge, Spanning Gila River on Old US 80 Highway, south of Gillespie Dam, Arlington, Maricopa County, AZ

  2. Boundary Spanning in Higher Education: How Universities Can Enable Success

    ERIC Educational Resources Information Center

    Skolaski, Jennifer Pauline

    2012-01-01

    Purpose: The purpose of this research is to better understand the identity and work of academic and extension staff who have boundary spanning responsibilities. The results will help universities, especially public land-grant universities with an outreach mission, to create stronger policies and systems to support boundary spanning staff members…

  3. Rhesus Monkey Cumulus Cells Revert to a Mural Granulosa Cell State After an Ovulatory Stimulus

    PubMed Central

    Chaffin, Charles L.; Lee, Young S.; Patel, Bela G.; Latham, Keith E.

    2012-01-01

    Follicular somatic cells (mural granulosa cells and cumulus cells) and the oocyte communicate through paracrine interactions and through direct gap junctions between oocyte and cumulus cells. Considering that mural and cumulus cells arise through a common developmental pathway and that their differentiation is essential to reproductive success, understanding how these cells differ is a key aspect to understanding their critical functions. Changes in global gene expression before and after an ovulatory stimulus were compared between cumulus and mural granulosa cells to test the hypothesis that mural and cumulus cells are highly differentiated at the time of an ovulatory stimulus and further differentiate during the periovulatory interval. The transcriptomes of the two cell types were markedly different (>1500 genes) before an ovulatory hCG bolus but converged after ovulation to become completely overlapping. The predominant transition was for the cumulus cells to become more like mural cells after hCG. This indicates that the differentiated phenotype of the cumulus cell is not stable and irreversibly established but may rather be an ongoing physiological response to the oocyte. PMID:23008515

  4. Rhesus monkey cumulus cells revert to a mural granulosa cell state after an ovulatory stimulus.

    PubMed

    Chaffin, Charles L; Lee, Young S; VandeVoort, Catherine A; Patel, Bela G; Latham, Keith E

    2012-11-01

    Follicular somatic cells (mural granulosa cells and cumulus cells) and the oocyte communicate through paracrine interactions and through direct gap junctions between oocyte and cumulus cells. Considering that mural and cumulus cells arise through a common developmental pathway and that their differentiation is essential to reproductive success, understanding how these cells differ is a key aspect to understanding their critical functions. Changes in global gene expression before and after an ovulatory stimulus were compared between cumulus and mural granulosa cells to test the hypothesis that mural and cumulus cells are highly differentiated at the time of an ovulatory stimulus and further differentiate during the periovulatory interval. The transcriptomes of the two cell types were markedly different (>1500 genes) before an ovulatory hCG bolus but converged after ovulation to become completely overlapping. The predominant transition was for the cumulus cells to become more like mural cells after hCG. This indicates that the differentiated phenotype of the cumulus cell is not stable and irreversibly established but may rather be an ongoing physiological response to the oocyte.

  5. Effects of defect states on the performance of perovskite solar cells

    NASA Astrophysics Data System (ADS)

    Fengjuan, Si; Fuling, Tang; Hongtao, Xue; Rongfei, Qi

    2016-07-01

    We built an ideal perovskite solar cell model and investigated the effects of defect states on the solar cell's performance. The verities of defect states with a different energy level in the band gap and those in the absorption layer CH3NH3PbI3 (MAPbI3), the interface between the buffer layer/MAPbI3, and the interface between the hole transport material (HTM) and MAPbI3, were studied. We have quantitatively analyzed these effects on perovskite solar cells' performance parameters. They are open-circuit voltage, short-circuit current, fill factor, and photoelectric conversion efficiency. We found that the performances of perovskite solar cells change worse with defect state density increasing, but when defect state density is lower than 1016 cm‑3, the effects are small. Defect states in the absorption layer have much larger effects than those in the adjacent interface layers. The perovskite solar cells have better performance as its working temperature is reduced. When the thickness of MAPbI3 is about 0.3 μm, perovskite solar cells show better comprehensive performance, while the thickness 0.05 μm for Spiro-OMeTAD is enough. Project supported by the National Natural Science Foundation of China (Nos. 11164014, 11364025), the Gansu Science and Technology Pillar Program (No. 1204GKCA057), and the Gansu Supercomputer Center.

  6. Effects of defect states on the performance of perovskite solar cells

    NASA Astrophysics Data System (ADS)

    Fengjuan, Si; Fuling, Tang; Hongtao, Xue; Rongfei, Qi

    2016-07-01

    We built an ideal perovskite solar cell model and investigated the effects of defect states on the solar cell's performance. The verities of defect states with a different energy level in the band gap and those in the absorption layer CH3NH3PbI3 (MAPbI3), the interface between the buffer layer/MAPbI3, and the interface between the hole transport material (HTM) and MAPbI3, were studied. We have quantitatively analyzed these effects on perovskite solar cells' performance parameters. They are open-circuit voltage, short-circuit current, fill factor, and photoelectric conversion efficiency. We found that the performances of perovskite solar cells change worse with defect state density increasing, but when defect state density is lower than 1016 cm-3, the effects are small. Defect states in the absorption layer have much larger effects than those in the adjacent interface layers. The perovskite solar cells have better performance as its working temperature is reduced. When the thickness of MAPbI3 is about 0.3 μm, perovskite solar cells show better comprehensive performance, while the thickness 0.05 μm for Spiro-OMeTAD is enough. Project supported by the National Natural Science Foundation of China (Nos. 11164014, 11364025), the Gansu Science and Technology Pillar Program (No. 1204GKCA057), and the Gansu Supercomputer Center.

  7. DEVELOPMENT OF SOLID-STATE DRIVERS FOR THE NIF PLASMA ELECTRODE POCKELS CELL

    SciTech Connect

    Barbosa, F; Arnold, P A; McHale, G B; James, G; Brown, G; Cook, E G; Hickman, B C

    2008-05-14

    Large aperture Plasma Electrode Pockels Cells (PEPC) are an enabling technology in the National Ignition Facility (NIF) at the Lawrence Livermore National Laboratory. The Pockels cell allows the NIF laser to take advantage of multipass amplifier architecture, thus reducing costs and physical size of the facility. Each Pockels cell comprises four 40-cm x 40-cm apertures arranged in a 4 x 1 array. The combination of the Pockels cell and a thin-film polarizer, configured in a 4 x 1 array, form an optical switch that is key to achieving multi-pass operation. Solid-state Plasma Pulse Generators (PPGs) and high current high voltage solid-state Switch Pulse Generators (SPGs) have been developed for use in the PEPC. The solid-state plasma pulse generators initiate and maintain plasma within the cells; each pulser is capable of delivering 60J of energy to each plasma channel. Deployment of the solid-state PPGs has been completed in NIF. The MOSFET-switched SPG is capable of delivering a requisite fast rise time, 17kV flattop pulse to the cells nonlinear crystals. A complete software and hardware control system has been developed and is currently being tested for use on the solid-state SPGs. Also a transmission line modeling, development, and testing effort is in process, in support of NIFs Advanced Radiographic Capabilities (ARC). Work is scheduled for completion by the end of the calendar year.

  8. Dissociation between recency and span: neuropsychological and experimental evidence.

    PubMed

    Della Sala, S; Logie, R H; Trivelli, C; Cubelli, R; Marchetti, C

    1998-10-01

    This article reports dissociations between verbal span and the recency portion of the serial position curve in immediate free recall, in 2 neuropsychological case studies and in 3 experiments with normal participants. Patient A. N. presented with an impaired serial verbal span while showing an intact recency effect. The opposite pattern was observed in patient G. C., who despite a poor recency showed normal span in verbal serial recall tasks. Experiments 1 and 2 showed a recency effect with visually and auditory presented lists and written recall was resistant to the effects of articulatory suppression and of irrelevant speech, but was disrupted by the suffix effect. Experiment 3 showed that in contrast with recency, memory span was affected by articulatory suppression and irrelevant speech during presentation but not by a suffix. These findings are not consistent with the idea that span and recency measure aspects of the same memory system. Moreover, in clinical practice, they should not be used as equivalent alternatives.

  9. Introduction to the Space Physics Analysis Network (SPAN)

    NASA Technical Reports Server (NTRS)

    Green, J. L. (Editor); Peters, D. J. (Editor)

    1985-01-01

    The Space Physics Analysis Network or SPAN is emerging as a viable method for solving an immediate communication problem for the space scientist. SPAN provides low-rate communication capability with co-investigators and colleagues, and access to space science data bases and computational facilities. The SPAN utilizes up-to-date hardware and software for computer-to-computer communications allowing binary file transfer and remote log-on capability to over 25 nationwide space science computer systems. SPAN is not discipline or mission dependent with participation from scientists in such fields as magnetospheric, ionospheric, planetary, and solar physics. Basic information on the network and its use are provided. It is anticipated that SPAN will grow rapidly over the next few years, not only from the standpoint of more network nodes, but as scientists become more proficient in the use of telescience, more capability will be needed to satisfy the demands.

  10. Fuzzy α-minimum spanning tree problem: definition and solutions

    NASA Astrophysics Data System (ADS)

    Zhou, Jian; Chen, Lu; Wang, Ke; Yang, Fan

    2016-04-01

    In this paper, the minimum spanning tree problem is investigated on the graph with fuzzy edge weights. The notion of fuzzy ? -minimum spanning tree is presented based on the credibility measure, and then the solutions of the fuzzy ? -minimum spanning tree problem are discussed under different assumptions. First, we respectively, assume that all the edge weights are triangular fuzzy numbers and trapezoidal fuzzy numbers and prove that the fuzzy ? -minimum spanning tree problem can be transformed to a classical problem on a crisp graph in these two cases, which can be solved by classical algorithms such as the Kruskal algorithm and the Prim algorithm in polynomial time. Subsequently, as for the case that the edge weights are general fuzzy numbers, a fuzzy simulation-based genetic algorithm using Prüfer number representation is designed for solving the fuzzy ? -minimum spanning tree problem. Some numerical examples are also provided for illustrating the effectiveness of the proposed solutions.

  11. CD24 tracks divergent pluripotent states in mouse and human cells

    PubMed Central

    Shakiba, Nika; White, Carl A.; Lipsitz, Yonatan Y.; Yachie-Kinoshita, Ayako; Tonge, Peter D; Hussein, Samer M. I.; Puri, Mira C.; Elbaz, Judith; Morrissey-Scoot, James; Li, Mira; Munoz, Javier; Benevento, Marco; Rogers, Ian M.; Hanna, Jacob H.; Heck, Albert J. R.; Wollscheid, Bernd; Nagy, Andras; Zandstra, Peter W

    2015-01-01

    Reprogramming is a dynamic process that can result in multiple pluripotent cell types emerging from divergent paths. Cell surface protein expression is a particularly desirable tool to categorize reprogramming and pluripotency as it enables robust quantification and enrichment of live cells. Here we use cell surface proteomics to interrogate mouse cell reprogramming dynamics and discover CD24 as a marker that tracks the emergence of reprogramming-responsive cells, while enabling the analysis and enrichment of transgene-dependent (F-class) and -independent (traditional) induced pluripotent stem cells (iPSCs) at later stages. Furthermore, CD24 can be used to delineate epiblast stem cells (EpiSCs) from embryonic stem cells (ESCs) in mouse pluripotent culture. Importantly, regulated CD24 expression is conserved in human pluripotent stem cells (PSCs), tracking the conversion of human ESCs to more naive-like PSC states. Thus, CD24 is a conserved marker for tracking divergent states in both reprogramming and standard pluripotent culture. PMID:26076835

  12. Dendritic cell function in vivo during the steady state: a role in peripheral tolerance.

    PubMed

    Steinman, Ralph M; Hawiger, Daniel; Liu, Kang; Bonifaz, Laura; Bonnyay, David; Mahnke, Karsten; Iyoda, Tomonori; Ravetch, Jeffrey; Dhodapkar, Madhav; Inaba, Kayo; Nussenzweig, Michel

    2003-04-01

    The avoidance of autoimmunity requires mechanisms to actively silence or tolerize self reactive T cells in the periphery. During infection, dendritic cells are not only capturing microbial antigens, but also are processing self antigens from dying cells as well as innocuous environmental proteins. Since the dendritic cells are maturing in response to microbial and other stimuli, peptides will be presented from both noxious and innocuous antigens. Therefore it would be valuable to have mechanisms whereby dendritic cells, prior to infection, establish tolerance to those self and environmental antigens that can be processed upon pathogen encounter. In the steady state, prior to acute infection and inflammation, dendritic cells are in an immature state and not fully differentiated to carry out their known roles as inducers of immunity. These immature cells are not inactive, however. They continuously circulate through tissues and into lymphoid organs, capturing self antigens as well as innocuous environmental proteins. Recent experiments have provided direct evidence that antigen-loaded immature dendritic in vivo silence T cells either by deleting them or by expanding regulatory T cells. In this way, it is proposed that the immune system overcomes at least some of the risk of developing autoimmunity and chronic inflammation. It is proposed that dendritic cells play a major role in defining immunologic self, not only centrally in the thymus but also in the periphery.

  13. A XEN-like State Bridges Somatic Cells to Pluripotency during Chemical Reprogramming.

    PubMed

    Zhao, Yang; Zhao, Ting; Guan, Jingyang; Zhang, Xu; Fu, Yao; Ye, Junqing; Zhu, Jialiang; Meng, Gaofan; Ge, Jian; Yang, Susu; Cheng, Lin; Du, Yaqin; Zhao, Chaoran; Wang, Ting; Su, Linlin; Yang, Weifeng; Deng, Hongkui

    2015-12-17

    Somatic cells can be reprogrammed into pluripotent stem cells (PSCs) by using pure chemicals, providing a different paradigm to study somatic reprogramming. However, the cell fate dynamics and molecular events that occur during the chemical reprogramming process remain unclear. We now show that the chemical reprogramming process requires the early formation of extra-embryonic endoderm (XEN)-like cells and a late transition from XEN-like cells to chemically-induced (Ci)PSCs, a unique route that fundamentally differs from the pathway of transcription factor-induced reprogramming. Moreover, precise manipulation of the cell fate transition in a step-wise manner through the XEN-like state allows us to identify small-molecule boosters and establish a robust chemical reprogramming system with a yield up to 1,000-fold greater than that of the previously reported protocol. These findings demonstrate that chemical reprogramming is a promising approach to manipulate cell fates.

  14. Single Cell RNA-Sequencing of Pluripotent States Unlocks Modular Transcriptional Variation

    PubMed Central

    Kolodziejczyk, Aleksandra A.; Kim, Jong Kyoung; Tsang, Jason C.H.; Ilicic, Tomislav; Henriksson, Johan; Natarajan, Kedar N.; Tuck, Alex C.; Gao, Xuefei; Bühler, Marc; Liu, Pentao; Marioni, John C.; Teichmann, Sarah A.

    2015-01-01

    Summary Embryonic stem cell (ESC) culture conditions are important for maintaining long-term self-renewal, and they influence cellular pluripotency state. Here, we report single cell RNA-sequencing of mESCs cultured in three different conditions: serum, 2i, and the alternative ground state a2i. We find that the cellular transcriptomes of cells grown in these conditions are distinct, with 2i being the most similar to blastocyst cells and including a subpopulation resembling the two-cell embryo state. Overall levels of intercellular gene expression heterogeneity are comparable across the three conditions. However, this masks variable expression of pluripotency genes in serum cells and homogeneous expression in 2i and a2i cells. Additionally, genes related to the cell cycle are more variably expressed in the 2i and a2i conditions. Mining of our dataset for correlations in gene expression allowed us to identify additional components of the pluripotency network, including Ptma and Zfp640, illustrating its value as a resource for future discovery. PMID:26431182

  15. Cell transcriptional state alters genomic patterns of DNA double-strand break repair in human astrocytes.

    PubMed

    Yong, Raymund L; Yang, Chunzhang; Lu, Jie; Wang, Huaien; Schlaff, Cody D; Tandle, Anita; Graves, Christian A; Elkahloun, Abdel G; Chen, Xiaoyuan; Zhuang, Zhengping; Lonser, Russell R

    2014-01-01

    The misrepair of DNA double-strand breaks in close spatial proximity within the nucleus can result in chromosomal rearrangements that are important in the pathogenesis of haematopoietic and solid malignancies. It is unknown why certain epigenetic states, such as those found in stem or progenitor cells, appear to facilitate neoplastic transformation. Here we show that altering the transcriptional state of human astrocytes alters patterns of DNA damage repair from ionizing radiation at a gene locus-specific and genome-wide level. Astrocytes induced into a reactive state exhibit increased DNA repair, compared with non-reactive cells, in actively transcribed chromatin after irradiation. In mapping these repair sites, we identify misrepair events and repair hotspots that are unique to each state. The precise characterization of genomic regions susceptible to mutation in specific transcriptional states provides new opportunities for addressing clonal evolution in solid cancers, in particular those where double-strand break induction is a cornerstone of clinical intervention. PMID:25517576

  16. Malingering in Toxic Exposure. Classification Accuracy of Reliable Digit Span and WAIS-III Digit Span Scaled Scores

    ERIC Educational Resources Information Center

    Greve, Kevin W.; Springer, Steven; Bianchini, Kevin J.; Black, F. William; Heinly, Matthew T.; Love, Jeffrey M.; Swift, Douglas A.; Ciota, Megan A.

    2007-01-01

    This study examined the sensitivity and false-positive error rate of reliable digit span (RDS) and the WAIS-III Digit Span (DS) scaled score in persons alleging toxic exposure and determined whether error rates differed from published rates in traumatic brain injury (TBI) and chronic pain (CP). Data were obtained from the files of 123 persons…

  17. Constitutive stabilization of hypoxia-inducible factor alpha selectively promotes the self-renewal of mesenchymal progenitors and maintains mesenchymal stromal cells in an undifferentiated state.

    PubMed

    Park, In-Ho; Kim, Kwang-Ho; Choi, Hyun-Kyung; Shim, Jae-Seung; Whang, Soo-Young; Hahn, Sang June; Kwon, Oh-Joo; Oh, Il-Hoan

    2013-01-01

    With the increasing use of culture-expanded mesenchymal stromal cells (MSCs) for cell therapies, factors that regulate the cellular characteristics of MSCs have been of major interest. Oxygen concentration has been shown to influence the functions of MSCs, as well as other normal and malignant stem cells. However, the underlying mechanisms of hypoxic responses and the precise role of hypoxia-inducible factor-1α (Hif-1α), the master regulatory protein of hypoxia, in MSCs remain unclear, due to the limited span of Hif-1α stabilization and the complex network of hypoxic responses. In this study, to further define the significance of Hif-1α in MSC function during their self-renewal and terminal differentiation, we established adult bone marrow (BM)-derived MSCs that are able to sustain high level expression of ubiquitin-resistant Hif-1α during such long-term biological processes. Using this model, we show that the stabilization of Hif-1α proteins exerts a selective influence on colony-forming mesenchymal progenitors promoting their self-renewal and proliferation, without affecting the proliferation of the MSC mass population. Moreover, Hif-1α stabilization in MSCs led to the induction of pluripotent genes (oct-4 and klf-4) and the inhibition of their terminal differentiation into osteogenic and adipogenic lineages. These results provide insights into the previously unrecognized roles of Hif-1α proteins in maintaining the primitive state of primary MSCs and on the cellular heterogeneities in hypoxic responses among MSC populations. PMID:24071737

  18. Relationship between heat shock protein 70 expression and life span in Daphnia.

    PubMed

    Schumpert, Charles; Handy, Indhira; Dudycha, Jeffry L; Patel, Rekha C

    2014-07-01

    The longevity of an organism is directly related to its ability to effectively cope with cellular stress. Heat shock response (HSR) protects the cells against accumulation of damaged proteins after exposure to elevated temperatures and also in aging cells. To understand the role of Hsp70 in regulating life span of Daphnia, we examined the expression of Hsp70 in two ecotypes that exhibit strikingly different life spans. Daphnia pulicaria, the long lived ecotype, showed a robust Hsp70 induction as compared to the shorter lived Daphnia pulex. Interestingly, the short-lived D. pulex isolates showed no induction of Hsp70 at the mid point in their life span. In contrast to this, the long-lived D. pulicaria continued to induce Hsp70 expression at an equivalent age. We further show that the Hsp70 expression was induced at transcriptional level in response to heat shock. The transcription factor responsible for Hsp70 induction, heat shock factor-1 (HSF-1), although present in aged organisms did not exhibit DNA-binding capability. Thus, the decline of Hsp70 induction in old organisms could be attributed to a decline in HSF-1's DNA-binding activity. These results for the first time, present a molecular analysis of the relationship between HSR and life span in Daphnia. PMID:24814302

  19. Jun‐Mediated Changes in Cell Adhesion Contribute to Mouse Embryonic Stem Cell Exit from Ground State Pluripotency

    PubMed Central

    Veluscek, Giulia; Li, Yaoyong; Yang, Shen‐Hsi

    2016-01-01

    Abstract Embryonic stem cells (ESC) are able to give rise to any somatic cell type. A lot is known about how ESC pluripotency is maintained, but comparatively less is known about how differentiation is promoted. Cell fate decisions are regulated by interactions between signaling and transcriptional networks. Recent studies have shown that the overexpression or downregulation of the transcription factor Jun can affect the ESC fate. Here we have focussed on the role of the Jun in the exit of mouse ESCs from ground state pluripotency and the onset of early differentiation. Transcriptomic analysis of differentiating ESCs reveals that Jun is required to upregulate a programme of genes associated with cell adhesion as ESCs exit the pluripotent ground state. Several of these Jun‐regulated genes are shown to be required for efficient adhesion. Importantly this adhesion is required for the timely regulated exit of ESCs from ground state pluripotency and the onset of early differentiation events. Stem Cells 2016;34:1213–1224 PMID:26850660

  20. An ES-Like Pluripotent State in FGF-Dependent Murine iPS cells

    PubMed Central

    Ungaro, Federica; Prigione, Alessandro; Chen, Hsu-Hsin; Welling, Maaike; Eijpe, Maureen; Mostoslavsky, Gustavo; Tesar, Paul; Adjaye, James; Geijsen, Niels; Broccoli, Vania

    2010-01-01

    Recent data demonstrates that stem cells can exist in two morphologically, molecularly and functionally distinct pluripotent states; a naïve LIF-dependent pluripotent state which is represented by murine embryonic stem cells (mESCs) and an FGF-dependent primed pluripotent state represented by murine and rat epiblast stem cells (EpiSCs). We find that derivation of induced pluripotent stem cells (iPSCs) under EpiSC culture conditions yields FGF-dependent iPSCs from hereon called FGF-iPSCs) which, unexpectedly, display naïve ES-like/ICM properties. FGF-iPSCs display X-chromosome activation, multi-lineage differentiation, teratoma competence and chimera contribution in vivo. Our findings suggest that in 129 and Bl6 mouse strains, iPSCs can dominantly adopt a naive pluripotent state regardless of culture growth factor conditions. Characterization of the key molecular signalling pathways revealed FGF-iPSCs to depend on the Activin/Nodal and FGF pathways, while signalling through the JAK-STAT pathway is not required for FGF-iPS cell maintenance. Our findings suggest that in 129 and Bl6 mouse strains, iPSCs can dominantly adopt a naive pluripotent state regardless of culture growth factor conditions. PMID:21209851