Science.gov

Sample records for cell states spans

  1. Newborn screening for sickle cell diseases in the United States: A review of data spanning 2 decades.

    PubMed

    Therrell, Bradford L; Lloyd-Puryear, Michele A; Eckman, James R; Mann, Marie Y

    2015-04-01

    Sickle cell disease is a group of disorders, the majority of which are detected through state newborn screening programs. There is limited knowledge of disease prevalence in the U.S. We report 20 years of case finding and laboratory data for sickle cell disease and trait to assist in: planning for health services delivery; providing data for researchers; aiding in tracking health outcome trends; and assessing sickle gene prevalence in the newborn population. During the 20-year period, there were 39,422 confirmed cases of sickle cell disease among 76,527,627 newborn births screened (1:1941) and 1,107,875 laboratory reports of probable sickle trait among 73,951,175 newborn births screened (1:67). The highest sickle cell disease incidence during the 20 years was in the District of Columbia (1:437) followed by Mississippi (1:683) and South Carolina (1:771). For sickle cell trait, the highest incidences were in the District of Columbia (1:22), Mississippi (1:26), and South Carolina (1:31). Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Life span extension and neuronal cell protection by Drosophila nicotinamidase.

    PubMed

    Balan, Vitaly; Miller, Gregory S; Kaplun, Ludmila; Balan, Karina; Chong, Zhao-Zhong; Li, Faqi; Kaplun, Alexander; VanBerkum, Mark F A; Arking, Robert; Freeman, D Carl; Maiese, Kenneth; Tzivion, Guri

    2008-10-10

    The life span of model organisms can be modulated by environmental conditions that influence cellular metabolism, oxidation, or DNA integrity. The yeast nicotinamidase gene pnc1 was identified as a key transcriptional target and mediator of calorie restriction and stress-induced life span extension. PNC1 is thought to exert its effect on yeast life span by modulating cellular nicotinamide and NAD levels, resulting in increased activity of Sir2 family class III histone deacetylases. In Caenorhabditis elegans, knockdown of a pnc1 homolog was shown recently to shorten the worm life span, whereas its overexpression increased survival under conditions of oxidative stress. The function and regulation of nicotinamidases in higher organisms has not been determined. Here, we report the identification and biochemical characterization of the Drosophila nicotinamidase, D-NAAM, and demonstrate that its overexpression significantly increases median and maximal fly life span. The life span extension was reversed in Sir2 mutant flies, suggesting Sir2 dependence. Testing for physiological effectors of D-NAAM in Drosophila S2 cells, we identified oxidative stress as a primary regulator, both at the transcription level and protein activity. In contrast to the yeast model, stress factors such as high osmolarity and heat shock, calorie restriction, or inhibitors of TOR and phosphatidylinositol 3-kinase pathways do not appear to regulate D-NAAM in S2 cells. Interestingly, the expression of D-NAAM in human neuronal cells conferred protection from oxidative stress-induced cell death in a sirtuin-dependent manner. Together, our findings establish a life span extending the ability of nicotinamidase in flies and offer a role for nicotinamide-modulating genes in oxidative stress regulated pathways influencing longevity and neuronal cell survival.

  3. Properties of minimum spanning trees and fractional quantum Hall states

    NASA Astrophysics Data System (ADS)

    Jackson, Thomas Sundal

    This dissertation consists of work done on two disjoint problems. In the first two chapters I discuss fractal properties of average-case solutions to the random minimal spanning tree (MST) problem: given a graph with costs on the edges, the MST is the spanning tree minimizing the sum of the total cost of the chosen edges. In the random version the costs are quenched random variables. I solve the random MST problem on the Bethe lattice with appropriate boundary conditions and use the results to infer fractal dimensions in the mean-field approximation. I find that connected components of the MST in a window have dimension D=6, which establishes the upper critical dimension dc=6. This contradicts a value dc=8 proposed previously in the literature; I correct the argument that led to this value. I then develop an exact low-density expansion for the random MST on a finite graph and use it to develop an expansion for the MST on critical percolation clusters. I prove this perturbation expansion is renormalizable around dc=6. Using a renormalization-group approach, I calculate the fractal dimension Dp of paths on the latter MST to first order in epsilon=6-d for d≤6, with the result Dp˜2-epsilon/7. In the final chapter, I investigate the correspondence between wavefunctions in the fractional quantum Hall effect obtained as blocks of a conformal field theory (CFT) versus those defined as zero-energy eigenstates of projection Hamiltonians, specifically one which forbids three particles to come together in one of two linearly-independent states of relative angular momentum six and all states of lesser relative angular momentum. I construct zero-energy states from amplitudes of superconformal currents using a result due to Simon. The counting of edge excitations of these states agrees with the character formula for the superconformal Kac vacuum module at generic central charge c, which implies this Hamiltonian is gapless for all c. I attempt to obtain a rational theory by

  4. 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.

  5. 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.

  6. The Current State of Social Studies: A Report of Project SPAN.

    ERIC Educational Resources Information Center

    Social Science Education Consortium, Inc., Boulder, CO.

    This volume, one in a series resulting from Project SPAN (Social Studies/Social Science Education: Priorities, Practices, and Needs), reviews and analyzes the current state of K-12 social studies. A major purpose of the review and analysis was to form a basis for recommendations for future directions that might be taken to improve social studies.…

  7. 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.

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

    SciTech Connect

    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.

  9. 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. c1999 COSPAR. Published by Elsevier Science Ltd.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. Modular assembly of synthetic proteins that span the plasma membrane in mammalian cells.

    PubMed

    Qudrat, Anam; Truong, Kevin

    2016-12-09

    To achieve synthetic control over how a cell responds to other cells or the extracellular environment, it is important to reliably engineer proteins that can traffic and span the plasma membrane. Using a modular approach to assemble proteins, we identified the minimum necessary components required to engineer such membrane-spanning proteins with predictable orientation in mammalian cells. While a transmembrane domain (TM) fused to the N-terminus of a protein is sufficient to traffic it to the endoplasmic reticulum (ER), an additional signal peptidase cleavage site downstream of this TM enhanced sorting out of the ER. Next, a second TM in the synthetic protein helped anchor and accumulate the membrane-spanning protein on the plasma membrane. The orientation of the components of the synthetic protein were determined through measuring intracellular Ca(2+) signaling using the R-GECO biosensor and through measuring extracellular quenching of yellow fluorescent protein variants by saturating acidic and salt conditions. This work forms the basis of engineering novel proteins that span the plasma membrane to potentially control intracellular responses to extracellular conditions.

  15. Cell death, cell proliferation, and estimates of hair cell life spans in the vestibular organs of chicks.

    PubMed

    Kil, J; Warchol, M E; Corwin, J T

    1997-12-01

    We have examined the level of on-going cell death in the chick vestibular epithelia using the TUNEL method and compared this to the rate of on-going cell proliferation. Utricles contained 22.6 +/- 6.8 TUNEL-labeled cells (mean +/- s.e.m.) while saccules contained 15.1 +/- 4.0, with approximately 90% being labeled hair cells. In separate experiments, chicks were given a single injection of BrdU and killed 2 h later. Utricles contained 116.9 +/- 6.5 BrdU-labeled cells (mean +/- s.e.m.) and saccules contained 41.0 +/- 2.2. After 24 h in culture, utricles treated with 1 mM neomycin contained 115.5 +/- 38.9 TUNEL-labeled cells, an increase of 270% over controls. After 48 h, neomycin-treated saccules contained 40.9 +/- 7.8, an increase of 152% over controls. The majority of labeled cells were in the hair cell layer. Thus, neomycin exposure results in an apoptotic death of hair cells. The in vivo data measured here were used to estimate that the average life span of utricular hair cells in young chickens is approximately 20 days, in sharp contrast to the life spans assumed for hair cells in humans.

  16. STATE TRANSITIONS IN BRIGHT GALACTIC X-RAY BINARIES: LUMINOSITIES SPAN BY TWO ORDERS OF MAGNITUDE

    SciTech Connect

    Yu Wenfei; Yan Zhen

    2009-08-20

    Using X-ray monitoring observations with the All-Sky Monitor on board the Rossi X-Ray Timing Explorer and the Burst Alert Telescope on board the Swift, we are able to study the spectral state transitions occurred in about 20 bright persistent and transient black hole and neutron star binaries. We have confirmed that there is a correlation between the X-ray luminosity corresponding to the hard-to-soft transition and the X-ray luminosity of the following soft state. This correlation holds over a luminosity range spanning by 2 orders of magnitude, with no indication of a flux saturation or cutoff. We have also found that the transition luminosity correlates with the rate of increase in the X-ray luminosity during the rising phase of an outburst or flare, implying that the origin of the variation of the transition luminosity is associated with non-stationary accretion in both transient sources and persistent sources. The correlation between the luminosity corresponding to the end of the soft-to-hard transition and the peak luminosity of the preceding soft state is found insignificant. The results suggest that the hysteresis effect of spectral state transitions is primarily driven by non-stationary accretion when the mass accretion rate increases rather than the mass accretion rate decreases. Our results also imply that Galactic X-ray binaries can reach more luminous hard states during outbursts of higher luminosities and of similar rise timescales as those observed. Based on the correlations, we speculate that bright hard state beyond the Eddington luminosity will be observed in Galactic binaries in the next century. We also suggest that some ultra-luminous X-ray sources in nearby galaxies, which stay in the hard states during bright, short flares, harbor stellar-mass compact stars.

  17. Health Span-Extending Activity of Human Amniotic Membrane- and Adipose Tissue-Derived Stem Cells in F344 Rats

    PubMed Central

    Kim, Dajeong; Kyung, Jangbeen; Park, Dongsun; Choi, Ehn-Kyoung; Kim, Kwang Sei; Shin, Kyungha; Lee, Hangyoung; Shin, Il Seob; Kang, Sung Keun

    2015-01-01

    Aging brings about the progressive decline in cognitive function and physical activity, along with losses of stem cell population and function. Although transplantation of muscle-derived stem/progenitor cells extended the health span and life span of progeria mice, such effects in normal animals were not confirmed. Human amniotic membrane-derived mesenchymal stem cells (AMMSCs) or adipose tissue-derived mesenchymal stem cells (ADMSCs) (1 × 106 cells per rat) were intravenously transplanted to 10-month-old male F344 rats once a month throughout their lives. Transplantation of AMMSCs and ADMSCs improved cognitive and physical functions of naturally aging rats, extending life span by 23.4% and 31.3%, respectively. The stem cell therapy increased the concentration of acetylcholine and recovered neurotrophic factors in the brain and muscles, leading to restoration of microtubule-associated protein 2, cholinergic and dopaminergic nervous systems, microvessels, muscle mass, and antioxidative capacity. The results indicate that repeated transplantation of AMMSCs and ADMSCs elongate both health span and life span, which could be a starting point for antiaging or rejuvenation effects of allogeneic or autologous stem cells with minimum immune rejection. Significance This study demonstrates that repeated treatment with stem cells in normal animals has antiaging potential, extending health span and life span. Because antiaging and prolonged life span are issues currently of interest, these results are significant for readers and investigators. PMID:26315571

  18. Modified Matrix Method for Calculating Steady-State Span Loading on Flexible Wings in Subsonic Flight

    NASA Technical Reports Server (NTRS)

    Gainer, Patrick A.; Aiken, William S., Jr.

    1959-01-01

    A method is presented for shortening the computations required to determine the steady-state span loading on flexible wings in subsonic flight. The method makes use of tables of downwash factors to find the necessary aerodynamic-influence coefficients for the application of lifting-line theory. Explicit matrix equations of equilibrium are converted into a matrix power series with a finite number of terms by utilizing certain characteristic properties of matrices. The number of terms in the series is determined by a trial-and-error process dependent upon the required accuracy of the solution. Spanwise distributions of angle of attack, airload, shear, bending moment, and pitching moment are readily obtained as functions of qm(sub R) where q denotes the dynamic pressure and mR denotes the lift-curve slope of a rigid wing. This method is intended primarily to make it practical to solve steady-state aeroelastic problems on the ordinary manually operated desk calculators, but the method is also readily adaptable to automatic computing equipment.

  19. Resting-State Network Topology Differentiates Task Signals across the Adult Life Span

    PubMed Central

    Alhazmi, Fahd H.; Savalia, Neil K.

    2017-01-01

    Brain network connectivity differs across individuals. For example, older adults exhibit less segregated resting-state subnetworks relative to younger adults (Chan et al., 2014). It has been hypothesized that individual differences in network connectivity impact the recruitment of brain areas during task execution. While recent studies have described the spatial overlap between resting-state functional correlation (RSFC) subnetworks and task-evoked activity, it is unclear whether individual variations in the connectivity pattern of a brain area (topology) relates to its activity during task execution. We report data from 238 cognitively normal participants (humans), sampled across the adult life span (20–89 years), to reveal that RSFC-based network organization systematically relates to the recruitment of brain areas across two functionally distinct tasks (visual and semantic). The functional activity of brain areas (network nodes) were characterized according to their patterns of RSFC: nodes with relatively greater connections to nodes in their own functional system (“non-connector” nodes) exhibited greater activity than nodes with relatively greater connections to nodes in other systems (“connector” nodes). This “activation selectivity” was specific to those brain systems that were central to each of the tasks. Increasing age was accompanied by less differentiated network topology and a corresponding reduction in activation selectivity (or differentiation) across relevant network nodes. The results provide evidence that connectional topology of brain areas quantified at rest relates to the functional activity of those areas during task. Based on these findings, we propose a novel network-based theory for previous reports of the “dedifferentiation” in brain activity observed in aging. SIGNIFICANCE STATEMENT Similar to other real-world networks, the organization of brain networks impacts their function. As brain network connectivity patterns

  20. IKVAV-linked cell membrane-spanning peptide treatment induces neuronal reactivation following spinal cord injury

    PubMed Central

    Kazemi, Soheila; Baltzer, Wendy; Schilke, Karl; Mansouri, Hadi; Mata, John Enrique

    2015-01-01

    Spinal cord regeneration following treatment with a novel membrane-spanning peptide (MSP) expressing the isoleucine-lysine-valine-alanine-valine (IKVAV) epitope was assessed in Balb-c mice. After hemilaminectomy and compression injury, mice were treated with IKVAV, IKVAV-MSP, peptide or vehicle control. Functional improvement was assessed using modified Basso, Beattie, and Bresnahan Scale (mBBB) and spinal cord segments were studied histologically 28 days after injury. IKVAV-MSP group scores increased significantly compared with control groups after 4 weeks of observation (p < 0.05). The number of protoplasmic astrocytes, neurons and muscle bundle size in the IKVAV-MSP mice were significantly increased (p < 0.001; p < 0.05 and p < 0.007; respectively). This study demonstrates that it is possible to promote functional recovery after SCI using bioactive IKVAV presenting cell membrane-spanning peptides. PMID:28031930

  1. 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.

  2. 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

  3. GENERAL AERIAL VIEW OF WEST CHANNEL SPANS, SPANS 3, 4 ...

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

    GENERAL AERIAL VIEW OF WEST CHANNEL SPANS, SPANS 3, 4 AND 5 REMOVED, LOOKING EAST. - Walnut Street Bridge, Spanning Susquehanna River at Walnut Street (State Route 3034), Harrisburg, Dauphin County, PA

  4. Truncated span west of verticallift span, from SW. Pennsylvania ...

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

    Truncated span west of vertical-lift span, from SW. - Pennsylvania & New Jersey Railroad, Delaware River Bridge, Spanning Delaware River, south of Betsy Ross Bridge (State Route 90), Philadelphia, Philadelphia County, PA

  5. 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.

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

    PubMed Central

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

    2014-01-01

    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

  7. Association between life-span extension by caloric restriction and thiol redox state in two different strains of mice.

    PubMed

    Rebrin, Igor; Forster, Michael J; Sohal, Rajindar S

    2011-07-01

    The hypothesis that the life-extending effect of caloric restriction (CR) is associated with an attenuation of the age-related pro-oxidant shift in the thiol redox state was tested employing a novel experimental design. Amounts of GSH, GSSG, and protein mixed disulfides (Pr-SSG) in the skeletal muscle and liver were compared between two strains of mice that have similar life spans when fed ad libitum (AL), but different life spans under the standard CR regimen. The life span of one strain, C57BL/6, is extended under CR, whereas it remains unaffected in the other strain, DBA/2. Mice were fed AL or 40% less food starting at 4 months and compared at 6 and 24 months of age. The amounts of GSSG and Pr-SSG increased and the GSH:GSSG ratios decreased with age in both strains of AL-fed mice. CR prevented these age-related changes in the C57BL/6, whose life span is extended by CR, but not in the DBA/2 mice, in which it remains unaffected. CR enhanced the activity of glutamate-cysteine ligase in the C57BL/6, but not in the DBA/2 mice. The results suggest that longevity extension by CR may be associated with the attenuation of age-related pro-oxidizing shifts in the thiol redox state. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Generation and Characterization of Telomerase-Transfected Human Lymphatic Endothelial Cells with an Extended Life Span

    PubMed Central

    Nisato, Riccardo E.; Harrison, Jillian A.; Buser, Raphaele; Orci, Lelio; Rinsch, Chris; Montesano, Roberto; Dupraz, Philippe; Pepper, Michael S.

    2004-01-01

    The study of lymphatic endothelial cells and lymphangiogenesis has, in the past, been hampered by the lack of lymphatic endothelial-specific markers. The recent discovery of several such markers has permitted the isolation of lymphatic endothelial cells (LECs) from human skin. However, cell numbers are limited and purity is variable with the different isolation procedures. To overcome these problems, we have transfected human dermal microvascular endothelial cells (HDMVECs) with a retrovirus containing the coding region of human telomerase reverse transcriptase (hTERT), and have produced a cell line, hTERT-HDLEC, with an extended lifespan. hTERT-HDLEC exhibit a typical cobblestone morphology when grown in culture, are contact-inhibited, and express endothelial cell-specific markers. hTERT-HDLEC also express the recognized lymphatic markers, Prox-1, LYVE-1 and podoplanin, as well as integrin α9, but do not express CD34. They also form tube-like structures in three-dimensional collagen gels when stimulated with vascular endothelial growth factors -A and -C. Based on these currently recognized criteria, these cells are LEC. Surprisingly, we also found that the widely studied HMEC-1 cell line expresses recognized lymphatic markers; however, these cells are also CD34-positive. In summary, the ectopic expression of hTERT increases the life span of LECs and does not affect their capacity to form tube-like structures in a collagen matrix. The production and characterization of hTERT-HDLEC will facilitate the study of the properties of lymphatic endothelium in vitro. PMID:15215158

  9. 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…

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

    PubMed Central

    1981-01-01

    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. PMID:6454694

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

    PubMed Central

    Schneider, Stefan; Stone, Arthur A.

    2015-01-01

    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 two 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 three of the day's episodes. From these reports, three 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 lifespan. PMID:25894487

  12. Uncoupling of pathways that promote postmitotic life span and apoptosis from replicative immortality of Caenorhabditis elegans germ cells.

    PubMed

    Ahmed, Shawn

    2006-12-01

    A dichotomy exists between germ and somatic cells in most organisms, such that somatic cell lineages proliferate for a single generation, whereas the germ cell lineage has the capacity to proliferate from one generation to the next, indefinitely. Several theories have been proposed to explain the unlimited replicative life span of germ cells, including the elimination of damaged germ cells by apoptosis or expression of high levels of gene products that prevent aging in somatic cells. These theories were tested in the nematode Caenorhabditis elegans by examining the consequences of eliminating either apoptosis or the daf-16, daf-18 or sir-2.1 genes that promote longevity of postmitotic somatic cells. However, germ cells of strains deficient for these activities displayed an unlimited proliferative capacity. Thus, C. elegans germ cells retain their youthful character via alternative pathways that prevent or eliminate damage that accumulates as a consequence of cell proliferation.

  13. Temporal Variation in Single-Cell Power-Law Rheology Spans the Ensemble Variation of Cell Population.

    PubMed

    Cai, PingGen; Takahashi, Ryosuke; Kuribayashi-Shigetomi, Kaori; Subagyo, Agus; Sueoka, Kazuhisa; Maloney, John M; Van Vliet, Krystyn J; Okajima, Takaharu

    2017-08-08

    Changes in the cytoskeletal organization within cells can be characterized by large spatial and temporal variations in rheological properties of the cell (e.g., the complex shear modulus G(∗)). Although the ensemble variation in G(∗) of single cells has been elucidated, the detailed temporal variation of G(∗) remains unknown. In this study, we investigated how the rheological properties of individual fibroblast cells change under a spatially confined environment in which the cell translational motion is highly restricted and the whole cell shape remains unchanged. The temporal evolution of single-cell rheology was probed at the same measurement location within the cell, using atomic force microscopy-based oscillatory deformation. The measurements reveal that the temporal variation in the power-law rheology of cells is quantitatively consistent with the ensemble variation, indicating that the cell system satisfies an ergodic hypothesis in which the temporal statistics are identical to the ensemble statistics. The autocorrelation of G(∗) implies that the cell mechanical state evolves in the ensemble of possible states with a characteristic timescale. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  14. Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c.

    PubMed

    Cohen, Robert M; Franco, Robert S; Khera, Paramjit K; Smith, Eric P; Lindsell, Christopher J; Ciraolo, Peter J; Palascak, Mary B; Joiner, Clinton H

    2008-11-15

    Although red blood cell (RBC) life span is a known determinant of percentage hemoglobin A1c (HbA1c), its variation has been considered insufficient to affect clinical decisions in hematologically normal persons. However, an unexplained discordance between HbA1c and other measures of glycemic control can be observed that could be, in part, the result of differences in RBC life span. To explore the hypothesis that variation in RBC life span could alter measured HbA1c sufficiently to explain some of this discordance, we determined RBC life span using a biotin label in 6 people with diabetes and 6 nondiabetic controls. Mean RBC age was calculated from the RBC survival curve for all circulating RBCs and for labeled RBCs at multiple time points as they aged. In addition, HbA1c in magnetically isolated labeled RBCs and in isolated transferrin receptor-positivereticulocytes was used to determine the in vivo synthetic rate of HbA1c. The mean age of circulating RBCs ranged from 39 to 56 days in diabetic subjects and 38 to 60 days in nondiabetic controls. HbA1c synthesis was linear and correlated with mean whole blood HbA1c (R(2) = 0.91). The observed variation in RBC survival was large enough to cause clinically important differences in HbA1c for a given mean blood glucose.

  15. Karyotypic instability and centrosome aberrations in the progeny of finite life-span human mammary epithelial cells exposed to sparsely or densely ionizing radiation.

    PubMed

    Sudo, Hiroko; Garbe, James; Stampfer, Martha R; Barcellos-Hoff, Mary Helen; Kronenberg, Amy

    2008-07-01

    The human breast is sensitive to radiation carcinogenesis, and genomic instability occurs early in breast cancer development. This study tests the hypothesis that ionizing radiation elicits genomic instability in finite life-span human mammary epithelial cells (HMEC) and asks whether densely ionizing radiation is a more potent inducer of instability. HMEC in a non-proliferative state were exposed to X rays or 1 GeV/nucleon iron ions followed by delayed plating. Karyotypic instability and centrosome aberrations were monitored in expanded clonal isolates. Severe karyotypic instability was common in the progeny of cells that survived X-ray or iron-ion exposure. There was a lower dose threshold for severe karyotypic instability after iron-ion exposure. More than 90% of X-irradiated colonies and >60% of iron-ion-irradiated colonies showed supernumerary centrosomes at levels above the 95% upper confidence limit of the mean for unirradiated clones. A dose response was observed for centrosome aberrations for each radiation type. There was a statistically significant association between the incidence of karyotypic instability and supernumerary centrosomes for iron-ion-exposed colonies and a weaker association for X-irradiated colonies. Thus genomic instability occurs frequently in finite life-span HMEC exposed to sparsely or densely ionizing radiation and may contribute to radiation-induced breast cancer.

  16. HIV-1 dynamics in vivo: Virion clearance rate, infected cell life-span, and viral generation time

    SciTech Connect

    Perelson, A.S.; Neumann, A.U.; Markowitz, M.; Ho, D.D.; Leonard, J.M.

    1996-03-15

    A new mathematical model was used to analyze a detailed set of human immunodeficiency virus-type 1 (HIV-1) viral load data collected from five infected individuals after the administration of a potent inhibitor of HIV-1 protease. Productively infected cells were estimated to have, on average, a life-span of 2.2 days (half-life t{sub 1/2} = 1.6 days), and plasma virions were estimated to have, on average, a mean life-span of 0.3 days (t{sub 1/2} = 0.24 days). The estimated average total HIV-1 production was 10.3 x 10{sup 9}virions per day, which is substantially greater than previous minimum estimates. The results also suggest that the minimum duration of the HIV-1 life cycle in vivo is 1.2 days on average, and that the average HIV-1 generation time-defined as the time from release of a virion until it infects another cell and causes the release of a new generation of viral particles-is 2.6 days. These findings on viral dynamics provide not only a kinetic picture of HIV-1 pathogenesis, but also theoretical principles to guide the development of treatment strategies. 22 refs., 1 fig., 2 tabs.

  17. Ankyrin repeat-rich membrane spanning (ARMS)/Kidins220 scaffold protein regulates neuroblastoma cell proliferation through p21.

    PubMed

    Jung, Heekyung; Shin, Joo-Hyun; Park, Young-Seok; Chang, Mi-Sook

    2014-12-31

    Cell proliferation is tightly controlled by the cell-cycle regulatory proteins, primarily by cyclins and cyclin-dependent kinases (CDKs) in the G1 phase. The ankyrin repeat-rich membrane spanning (ARMS) scaffold protein, also known as kinase D-interacting substrate of 220 kDa (Kidins 220), has been previously identified as a prominent downstream target of neurotrophin and ephrin receptors. Many studies have reported that ARMS/Kidins220 acts as a major signaling platform in organizing the signaling complex to regulate various cellular responses in the nervous and vascular systems. However, the role of ARMS/Kidins220 in cell proliferation and cell-cycle progression has never been investigated. Here we report that knockdown of ARMS/Kidins220 inhibits mouse neuroblastoma cell proliferation by inducing slowdown of cell cycle in the G1 phase. This effect is mediated by the upregulation of a CDK inhibitor p21, which causes the decrease in cyclin D1 and CDK4 protein levels and subsequent reduction of pRb hyperphosphorylation. Our results suggest a new role of ARMS/Kidins220 as a signaling platform to regulate tumor cell proliferation in response to the extracellular stimuli.

  18. 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.

  19. 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.

  20. 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

  1. Single-spanning transmembrane domains in cell growth and cell-cell interactions: More than meets the eye?

    PubMed

    Hubert, Pierre; Sawma, Paul; Duneau, Jean-Pierre; Khao, Jonathan; Hénin, Jérôme; 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.

  2. Characterization of beta-adrenergic receptors through the replicative life span of IMR-90 cells

    SciTech Connect

    Scarpace, P.J.

    1987-01-01

    Beta-adrenergic receptor number and receptor affinity for isoproterenol were assessed at various in vitro ages of the human diploid fibroblast cell line IMR-90. From population doubling level (PDL) 33 to 44, there was a positive correlation between beta-adrenergic receptor density and PDL. Beta-adrenergic receptors, assessed by Scatchard analysis of (/sup 125/I)-iodocyanopindolol (ICYP) binding, increased from 15 fmol/mg protein at PDL 33 to 36 fmol/mg protein at PDL 44. In contrast, from PDL 44 to 59, there was a negative correlation between beta-adrenergic receptor density and PDL. Receptor density declined to 12 fmol/mg protein at PDL 59. When the density of beta-adrenergic receptors was expressed as receptor per cell, the findings were similar. Receptor agonist affinity for isoproterenol was determined from Hill plots of (/sup 125/I)-ICYP competition with isoproterenol. There was no change in the dissociation constant for isoproterenol with in vitro age. In humans, serum norepinephrine concentrations increase with age. This increase in serum norepinephrine may be partially responsible for the decreased beta-adrenergic receptor-agonist affinity observed with age in human lymphocytes and rat heart and lung. The present findings are consistent with the hypothesis that the decreases in receptor agonist affinity in rat and man with age are secondary to increases in catecholamine concentrations.

  3. What is SPAN?

    NASA Astrophysics Data System (ADS)

    SPAN is the Space Physics Analysis Network. This important research tool of the NASA scientific community links space researchers from over 50 institutions throughout the United States. The SPAN system is growing within the United States, and it also is expanding to connect NASA scientists with European and Japanese space research institutions.The SPAN system serves many functions. Its paramount purpose is to provide scientists with a tool that improves their productivity. SPAN has traditionally been used to exchange mail messages, to send data back and forth for scientific papers and analysis workshops, and to share scientific software. SPAN has played a crucial role by disseminating spacecraft data in near-real time during several recent NASA and ESA program successes, such as the International Cometary Explorer (ICE) spacecraft encounter with Comet Giacobini-Zinner (see “Behind the Scenes During a Comet Encounter” by J.L. Green and J.H. King, Eos, March 4, 1986, p. 105), the Voyager 2 encounter with Uranus, and the Giotto spacecraft encounter with Comet Halley (see “Networking Ground-Based Images of Comet Halley during the Giotto Encounter” by D. Rees et al., Eos, December 16, 1986, p. 1385). Of course, SPAN has served a variety of broader purposes. It has provided (and will continue to provide) an excellent testing ground for trying new technologies and for evaluating ideas about processing, storing, and transferring various kinds of information. Until the recent availability of computers sponsored by the National Science Foundation, the SPAN network provided one of the few opportunities for NASA researchers to have ready access to the supercomputers needed for large-scale numerical simulation of magnetospheric and ionospheric plasma systems. SPAN has also increased its usefulness substantially by the addition of the National Space Science Data Center (NSSDC) as a data node on the system. The network, which was originally based on a starshaped

  4. 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

  5. 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

    USDA-ARS?s Scientific Manuscript database

    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...

  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. 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

  8. 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

  9. Deconstructing sub-clinical psychosis into latent-state and trait variables over a 30-year time span.

    PubMed

    Rössler, Wulf; Hengartner, Michael P; Ajdacic-Gross, Vladeta; Haker, Helene; Angst, Jules

    2013-10-01

    Our aim was to deconstruct the variance underlying the expression of sub-clinical psychosis symptoms into portions associated with latent time-dependent states and time-invariant traits. We analyzed data of 335 subjects from the general population of Zurich, Switzerland, who had been repeatedly measured between 1979 (age 20/21) and 2008 (age 49/50). We applied two measures of sub-clinical psychosis derived from the SCL-90-R, namely schizotypal signs (STS) and schizophrenia nuclear symptoms (SNS). Variance was decomposed with latent state-trait analysis and associations with covariates were examined with generalized linear models. At ages 19/20 and 49/50, the latent states underlying STS accounted for 48% and 51% of variance, whereas for SNS those estimates were 62% and 50%. Between those age classes, however, expression of sub-clinical psychosis was strongly associated with stable traits (75% and 89% of total variance in STS and SNS, respectively, at age 27/28). Latent states underlying variance in STS and SNS were particularly related to partnership problems over almost the entire observation period. STS was additionally related to employment problems, whereas drug-use was a strong predictor of states underlying both syndromes at age 19/20. The latent trait underlying expression of STS and SNS was particularly related to low sense of mastery and self-esteem and to high depressiveness. Although most psychosis symptoms are transient and episodic in nature, the variability in their expression is predominantly caused by stable traits. Those time-invariant and rather consistent effects are particularly influential around age 30, whereas the occasion-specific states appear to be particularly influential at ages 20 and 50. © 2013.

  10. Effect of continuous irradiation with a very low dose of gamma rays on life span and the immune system in SJL mice prone to B-cell lymphoma.

    PubMed

    Lacoste-Collin, L; Jozan, S; Cances-Lauwers, V; Pipy, B; Gasset, G; Caratero, C; Courtade-Saïdi, M

    2007-12-01

    Ionizing radiation has been shown to have dose- and dose-rate-dependent carcinogenic effects on the hematopoietic and lymphoreticular systems. We report here that continuous exposure to a low dose of gamma rays influences the course of spontaneous B-cell lymphoma in SJL mice. We studied the biological effects of 10 cGy year(-1) gamma rays on the life span of 560 4-week-old SJL/J female mice and on various parameters of the cell-mediated immune response. Life span was slightly prolonged. The mean survival was 397 days for controls and 417 days for irradiated mice that died with lymphoma (P = 0.34). In lymph nodes and spleen, lower percentages of CD4+ and CD8+ T cells were observed in irradiated mice before 32 weeks. Interestingly, the percentages of CD49+ NK cells were increased in the spleens of irradiated mice at 28 weeks (0.61 +/- 0.08% compared to 0.43 +/- 0.12% in controls, P = 0.01) and at 32 weeks (0.62 +/- 0.24% compared to 0.33 +/- 0.09%, P = 0.02), while NK cell activity remained unchanged in exposed mice. These results provide further support for the absence of harmful effects of a continuous very low dose of radiation on life span and incidence of lymphoma in SJL mice.

  11. 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.

  12. 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.

  13. Data-driven Topological Filtering based on Orthogonal Minimal Spanning Trees: Application to Multi-Group MEG Resting-State Connectivity.

    PubMed

    Dimitriadis, Stavros I; Antonakakis, Marios; Simos, Panagiotis; Fletcher, Jack M; Papanicolaou, Andrew C

    2017-09-11

    In the present study a novel data-driven topological filtering technique is introduced to derive the backbone of functional brain networks relying on orthogonal minimal spanning trees (OMST). The method aims to identify the essential functional connections to ensure optimal information flow via the objective criterion of global efficiency minus the cost of surviving connections. The OMST technique was applied to multichannel, resting-state neuromagnetic recordings from four groups of participants: healthy adults (n=50), adults who have suffered mild traumatic brain injury (n=30), typically developing children (n=27), and reading-disabled children (n=25). Weighted interactions between network nodes (sensors) were computed using an integrated approach of dominant intrinsic coupling modes based on two alternative metrics (symbolic mutual information and phase lag index), resulting in excellent discrimination of individual cases according to their group membership. Classification results using OMST-derived functional networks were clearly superior to results using either relative power spectrum features or functional networks derived through the conventional minimal spanning trees algorithm.

  14. 8. VIEW OF SUPERSTRUCTURE OF MOVABLE SPAN TRUSS WORK AND ...

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

    8. VIEW OF SUPERSTRUCTURE OF MOVABLE SPAN TRUSS WORK AND ROADWAY OF MOVABLE SPAN, LOOKING NORTH (taken in December 1983) - Sharptown Bridge, Spanning Nanticoke River, State Route 313, Sharptown, Wicomico County, MD

  15. 13. VIEW TO WEST. DETAIL, WEST PIER, WEST APPROACH SPAN, ...

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

    13. VIEW TO WEST. DETAIL, WEST PIER, WEST APPROACH SPAN, LOCKING GEAR AT WEST END OF SWING SPAN. (photographed from boat) - Gianella Bridge, Spanning Sacramento River at State Highway 32, Hamilton City, Glenn County, CA

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. Budding yeast SSD1-V regulates transcript levels of many longevity genes and extends chronological life span in purified quiescent cells.

    PubMed

    Li, Lihong; Lu, Yong; Qin, Li-Xuan; Bar-Joseph, Ziv; Werner-Washburne, Margaret; Breeden, Linda L

    2009-09-01

    Ssd1 is an RNA-binding protein that affects literally hundreds of different processes and is polymorphic in both wild and lab yeast strains. We have used transcript microarrays to compare mRNA levels in an isogenic pair of mutant (ssd1-d) and wild-type (SSD1-V) cells across the cell cycle. We find that 15% of transcripts are differentially expressed, but there is no correlation with those mRNAs bound by Ssd1. About 20% of cell cycle regulated transcripts are affected, and most show sharper amplitudes of oscillation in SSD1-V cells. Many transcripts whose gene products influence longevity are also affected, the largest class of which is involved in translation. Ribosomal protein mRNAs are globally down-regulated by SSD1-V. SSD1-V has been shown to increase replicative life span currency and we show that SSD1-V also dramatically increases chronological life span (CLS). Using a new assay of CLS in pure populations of quiescent prototrophs, we find that the CLS for SSD1-V cells is twice that of ssd1-d cells.

  1. 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.

  2. 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.

  3. Visualizing Cell State Transition Using Raman Spectroscopy

    PubMed Central

    Ichimura, Taro; Chiu, Liang-da; Fujita, Katsumasa; Kawata, Satoshi; Watanabe, Tomonobu M.; Yanagida, Toshio; Fujita, Hideaki

    2014-01-01

    System level understanding of the cell requires detailed description of the cell state, which is often characterized by the expression levels of proteins. However, understanding the cell state requires comprehensive information of the cell, which is usually obtained from a large number of cells and their disruption. In this study, we used Raman spectroscopy, which can report changes in the cell state without introducing any label, as a non-invasive method with single cell capability. Significant differences in Raman spectra were observed at the levels of both the cytosol and nucleus in different cell-lines from mouse, indicating that Raman spectra reflect differences in the cell state. Difference in cell state was observed before and after the induction of differentiation in neuroblastoma and adipocytes, showing that Raman spectra can detect subtle changes in the cell state. Cell state transitions during embryonic stem cell (ESC) differentiation were visualized when Raman spectroscopy was coupled with principal component analysis (PCA), which showed gradual transition in the cell states during differentiation. Detailed analysis showed that the diversity between cells are large in undifferentiated ESC and in mesenchymal stem cells compared with terminally differentiated cells, implying that the cell state in stem cells stochastically fluctuates during the self-renewal process. The present study strongly indicates that Raman spectral morphology, in combination with PCA, can be used to establish cells' fingerprints, which can be useful for distinguishing and identifying different cellular states. PMID:24409302

  4. 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

  5. 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

  6. Reassessing the human immunodeficiency virus type 1 life cycle through age-structured modeling: life span of infected cells, viral generation time, and basic reproductive number, R0.

    PubMed

    Althaus, Christian L; De Vos, Anneke S; De Boer, Rob J

    2009-08-01

    The rapid decay of the viral load after drug treatment in patients infected with human immunodeficiency virus type 1 (HIV-1) has been shown to result from the rapid loss of infected cells due to their high turnover, with a generation time of around 1 to 2 days. Traditionally, viral decay dynamics after drug treatment is investigated using models of differential equations in which both the death rate of infected cells and the viral production rate are assumed to be constant. Here, we describe age-structured models of the viral decay dynamics in which viral production rates and death rates depend on the age of the infected cells. In order to investigate the effects of age-dependent rates, we compared these models with earlier descriptions of the viral load decay and fitted them to previously published data. We have found no supporting evidence that infected-cell death rates increase, but cannot reject the possibility that viral production rates increase, with the age of the cells. In particular, we demonstrate that an exponential increase in viral production with infected-cell age is perfectly consistent with the data. Since an exponential increase in virus production can compensate for the exponential loss of infected cells, the death rates of HIV-1-infected cells may be higher than previously anticipated. We discuss the implications of these findings for the life span of infected cells, the viral generation time, and the basic reproductive number, R0.

  7. Cell proliferation dynamics of somatic and germline tissues during zooidal life span in the colonial tunicate Botryllus primigenus.

    PubMed

    Kawamura, Kazuo; Tachibana, Miki; Sunanaga, Takeshi

    2008-07-01

    Botryllus primigenus is a colonial tunicate in which three successive generations develop synchronously. To identify proliferation centers and possible adult stem cells during asexual reproduction, somatic and germline cells were labeled with 5-bromo-2'-deoxyuridine (BrdU). In the youngest generation, multipotent epithelial cells exhibited an average labeling index (LI) of 30% 24 hr after BrdU injection. In the middle generation, the LI of organ rudiments decreased gradually and reached zero by the beginning of the eldest generation. Exceptionally, cells of specialized tissues such as the pharyngeal inner longitudinal vessel and the posterior end of the endostyle continued DNA synthesis and mitosis even in the eldest generation. Proliferating somatic and germline cells of younger generations expressed a Botryllus myc homolog (BpMyc), but adult tissues did not. This result strongly suggests that in B. primigenus undifferentiated progenitor cells are discernible from possible adult stem cells by the presence or absence of BpMyc.

  8. 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.

  9. January | 201span>6 | Space Station - NASA

    NASA Website

    August 201span>6; July 201span>6; June 201span>6; May 201span>6; April 201span>6; March 201span>6; February 201span>6; January 201span>6; December 2015; November 2015; October 2015; ...

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 63. VIEW OF THE SHOOFLY BRIDGE LIFT SPAN BEING FLOATED ...

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

    63. VIEW OF THE SHOOFLY BRIDGE LIFT SPAN BEING FLOATED INTO PLACE, LOOKING NORTH, January 29, 1935 - Sacramento River Bridge, Spanning Sacramento River at California State Highway 275, Sacramento, Sacramento County, CA

  19. Looking west over top of verticallift span. Pennsylvania & ...

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

    Looking west over top of vertical-lift span. - Pennsylvania & New Jersey Railroad, Delaware River Bridge, Spanning Delaware River, south of Betsy Ross Bridge (State Route 90), Philadelphia, Philadelphia County, PA

  20. Barrel view from east end, looking toward swing span. ...

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

    Barrel view from east end, looking toward swing span. - Pennsylvania & New Jersey Railroad, Delaware River Bridge, Spanning Delaware River, south of Betsy Ross Bridge (State Route 90), Philadelphia, Philadelphia County, PA

  1. Counterweight for verticallift span, from below. Pennsylvania & New ...

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

    Counterweight for vertical-lift span, from below. - Pennsylvania & New Jersey Railroad, Delaware River Bridge, Spanning Delaware River, south of Betsy Ross Bridge (State Route 90), Philadelphia, Philadelphia County, PA

  2. Barrel view at east end of swing span. Pennsylvania ...

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

    Barrel view at east end of swing span. - Pennsylvania & New Jersey Railroad, Delaware River Bridge, Spanning Delaware River, south of Betsy Ross Bridge (State Route 90), Philadelphia, Philadelphia County, PA

  3. Barrel view at east end of verticallift span. Pennsylvania ...

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

    Barrel view at east end of vertical-lift span. - Pennsylvania & New Jersey Railroad, Delaware River Bridge, Spanning Delaware River, south of Betsy Ross Bridge (State Route 90), Philadelphia, Philadelphia County, PA

  4. Hoist mechanism for verticallift span. Pennsylvania & New Jersey ...

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

    Hoist mechanism for vertical-lift span. - Pennsylvania & New Jersey Railroad, Delaware River Bridge, Spanning Delaware River, south of Betsy Ross Bridge (State Route 90), Philadelphia, Philadelphia County, PA

  5. Looking down to east from verticallift span hoist room. ...

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

    Looking down to east from vertical-lift span hoist room. - Pennsylvania & New Jersey Railroad, Delaware River Bridge, Spanning Delaware River, south of Betsy Ross Bridge (State Route 90), Philadelphia, Philadelphia County, PA

  6. Outer supports, bearing wheels, and rach ring of swing span. ...

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

    Outer supports, bearing wheels, and rach ring of swing span. - Pennsylvania & New Jersey Railroad, Delaware River Bridge, Spanning Delaware River, south of Betsy Ross Bridge (State Route 90), Philadelphia, Philadelphia County, PA

  7. 6. DETAIL VIEW OF INTERIOR OF NORTH SPAN, SHOWING LOWER ...

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

    6. DETAIL VIEW OF INTERIOR OF NORTH SPAN, SHOWING LOWER BRACING, LOOKING FROM NORTHEAST TO SOUTHWEST - Marathon City Bridge, Spanning Big Rib River, on state Trunk Highway 107, Marathon, Marathon County, WI

  8. 2. VIEW OF NORTH SPAN TRUSS, SHOWING CAUSEWAY BETWEEN NORTH ...

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

    2. VIEW OF NORTH SPAN TRUSS, SHOWING CAUSEWAY BETWEEN NORTH AND SOUTH TRUSS, LOOKING FROM SOUTHWEST TO NORTHEAST - Marathon City Bridge, Spanning Big Rib River, on state Trunk Highway 107, Marathon, Marathon County, WI

  9. 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

  10. 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

  11. 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

  12. Span efficiency in hawkmoths.

    PubMed

    Henningsson, Per; Bomphrey, Richard J

    2013-07-06

    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.

  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. 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

  15. 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

    2015-02-05

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. 16. Overall view of the swing span (Span G) turning ...

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

    16. Overall view of the swing span (Span G) turning drum, showing rollers and drive chains; looking W. (Ceronie) - Rock Island Arsenal, Rock Island Bridge, Fort Armstrong Avenue, Rock Island, Rock Island County, IL

  17. Homological Computation Using Spanning Trees

    NASA Astrophysics Data System (ADS)

    Molina-Abril, H.; Real, P.

    We introduce here a new mathbb{F}_2 homology computation algorithm based on a generalization of the spanning tree technique on a finite 3-dimensional cell complex K embedded in ℝ3. We demonstrate that the complexity of this algorithm is linear in the number of cells. In fact, this process computes an algebraic map φ over K, called homology gradient vector field (HGVF), from which it is possible to infer in a straightforward manner homological information like Euler characteristic, relative homology groups, representative cycles for homology generators, topological skeletons, Reeb graphs, cohomology algebra, higher (co)homology operations, etc. This process can be generalized to others coefficients, including the integers, and to higher dimension.

  18. 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

  19. Population dynamics of cancer cells with cell state conversions

    PubMed Central

    Zhou, Da; Wu, Dingming; Li, Zhe; Qian, Minping; Zhang, Michael Q.

    2015-01-01

    Cancer stem cell (CSC) theory suggests a cell-lineage structure in tumor cells in which CSCs are capable of giving rise to the other non-stem cancer cells (NSCCs) but not vice versa. However, an alternative scenario of bidirectional interconversions between CSCs and NSCCs was proposed very recently. Here we present a general population model of cancer cells by integrating conventional cell divisions with direct conversions between different cell states, namely, not only can CSCs differentiate into NSCCs by asymmetric cell division, NSCCs can also dedifferentiate into CSCs by cell state conversion. Our theoretical model is validated when applying the model to recent experimental data. It is also found that the transient increase in CSCs proportion initiated from the purified NSCCs subpopulation cannot be well predicted by the conventional CSC model where the conversion from NSCCs to CSCs is forbidden, implying that the cell state conversion is required especially for the transient dynamics. The theoretical analysis also gives the condition such that our general model can be equivalently reduced into a simple Markov chain with only cell state transitions keeping the same cell proportion dynamics. PMID:26085954

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. An Account of How Chinese Graduate Students in the United States View the Full Span of Their Educational Experiences: A Grounded Theory Investigation

    ERIC Educational Resources Information Center

    Tsai, Ming-Che

    2009-01-01

    Many teachers of international students in the United States are challenged to address cultural differences in a classroom. International students often experience psychological, physical and cultural stress when they study abroad, due mainly to unfamiliar environments and a diverse culture. The question this study asks is: Are there any…

  5. 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…

  6. 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…

  7. Characteristics of an infinite life span diploid human fibroblast cell strain and a near-diploid strain arising from a clone of cells expressing a transfected v-myc oncogene

    SciTech Connect

    Morgan, T.L.; Dajun Yang; Fry, D.G.; Hurlin, P.J.; Kohler, S.K.; Maher, V.M.; McCormick, J.J. )

    1991-11-01

    Diploid human fibroblasts were transfected with a plasmid carrying a v-myc oncogene linked to the neo gene or with a vector control carrying a neo gene. Drug-resistant clones were isolated and subcultured as needed. All populations went into crisis and eventually senesced. But while they were senescing, viable-appearing clones were noted among the progeny of a transfected population that expressed the v-myc oncogene. After several months, these cells began replicating more rapidly. Karyotype analysis indicated that they were clonally derived since all of them had 45 chromosomes, including 2 marker chromosomes. This cell strain was designated MSU-1.1. Similar analysis showed that cells from an earlier passage were diploid. These cells were designated MSU-1.0. The expression of v-myc is probably required for acquisition of an infinite life span, since this phenotype did not develop in populations not expressing this oncogene. However, expression of v-myc is clearly not sufficient, since all of the progeny of the clone that gave rise to the MSU-1.0 cells expressed this oncogene, but the vast majority of them senesced.

  8. Electrochemical cell assembled in discharged state

    DOEpatents

    Yao, Neng-Ping; Walsh, William J.

    1976-01-01

    A secondary, electrochemical cell is assembled in a completely discharged state within a sealed containment. As assembled, the cell includes a positive electrode separated from a negative electrode by a molten salt electrolyte. The positive electrode is contained within a porous structure, permitting passage of molten electrolyte, and includes one or more layers of a metallic mesh, e.g. iron, impregnated with an intimate mixture of lithium sulfide and the electrolyte. The negative electrode is a porous plaque of aluminum metal. Prior to using the cell, an electrical charge forms lithium-aluminum alloy within the negative electrode and metal sulfide within the positive electrode.

  9. 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.

  10. Yeast cells can access distinct quiescent states.

    PubMed

    Klosinska, Maja M; Crutchfield, Christopher A; Bradley, Patrick H; Rabinowitz, Joshua D; Broach, James R

    2011-02-15

    We conducted a phenotypic, transcriptional, metabolic, and genetic analysis of quiescence in yeast induced by starvation of prototrophic cells for one of three essential nutrients (glucose, nitrogen, or phosphate) and compared those results with those obtained with cells growing slowly due to nutrient limitation. These studies address two related questions: (1) Is quiescence a state distinct from any attained during mitotic growth, and (2) does the nature of quiescence differ depending on the means by which it is induced? We found that either limitation or starvation for any of the three nutrients elicits all of the physiological properties associated with quiescence, such as enhanced cell wall integrity and resistance to heat shock and oxidative stress. Moreover, the starvations result in a common transcriptional program, which is in large part a direct extrapolation of the changes that occur during slow growth. In contrast, the metabolic changes that occur upon starvation and the genetic requirements for surviving starvation differ significantly depending on the nutrient for which the cell is starved. The genes needed by cells to survive starvation do not overlap the genes that are induced upon starvation. We conclude that cells do not access a unique and discrete G(0) state, but rather are programmed, when nutrients are scarce, to prepare for a range of possible future stressors. Moreover, these survival strategies are not unique to quiescence, but are engaged by the cell in proportion to nutrient scarcity.

  11. Chromium oxidation state mapping in human cells

    NASA Astrophysics Data System (ADS)

    Ortega, R.; Fayard, B.; Salomé, M.; Devès, G.; Susini, J.

    2003-03-01

    The widespread use of chromium in industrial applications such as chemical production of pigments, refractory brick production, tanning, metallurgy, electroplating, and combustion of fuels has lead to human occupational exposure and to its increased introduction into the environment. Hexavalent chromium compounds are established carcinogens but their mechanism of cell transformation is not known. Up to now, no microanalytical technique was sensitive enough to allow the observation of chromium distribution, and oxidation state identification, within isolated cells at carcinogenic concentrations. In this experiment, we used successfully the ID-21 X-ray microscope to map Cr(VI) and total Cr distributions in cells exposed in vitro to soluble, and insoluble, Cr(VI) compounds. Exposure to soluble compounds, weak carcinogens, resulted in a homogeneous intracellular distribution of Cr, confirming by in situ measurement that Cr is present in the cell nucleus. Cr(VI) was never detected in cells which suggests a mechanism of rapid intracellular reducticn. On the other hand, exposure to insoluble compounds, strong carcinogens, also resulted in a homogeneous distribution of reduced forms of Cr in cells, and their nucleus. However, in this case, Cr(VI)-rich structures were observed into the cells suggesting that carcinogenicity is enhanced when oxidation reactions due to Cr(VI) chronic exposure are associated to Cr-DNA alterations.

  12. 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.

  13. January | 201span>6 | Ground Systems Development and Operations ...

    NASA Website

    August 201span>6; July 201span>6; June 201span>6; May 201span>6; April 201span>6; March 201span>6; February 201span>6; January 201span>6; December 2015; November 2015; October 2015; ...

  14. Using C-SPAN as a Research Tool To Analyze Cross-Cultural Relations.

    ERIC Educational Resources Information Center

    Schnell, Jim

    C-SPAN (Cable-Satellite Public Affairs Network) can be used for communications oriented research. A research project on reactions in the United States to the Chinese pro-democracy movement shows the use of C-SPAN as a representative forum. Primary funding for the project was obtained through grants from C-SPAN. Twenty-one C-SPAN programs since…

  15. 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

  16. 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

  17. 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

  18. 9. SEATING OF GIRDER SPAN AT SOUTH ABUTMENT. FABRICATOR'S PLATE ...

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

    9. SEATING OF GIRDER SPAN AT SOUTH ABUTMENT. FABRICATOR'S PLATE READS 'VIRGINIA BRIDGE COMPANY 1950,' ACCOMPANIED BY THE LOGO OF UNITED STATES STEEL. - George P. Coleman Memorial Bridge, Spanning York River at U.S. Route 17, Yorktown, York County, VA

  19. 30. DETAIL VIEW OF MOVABLE SPAN, UPPER TRUSS GUSSET PLATE, ...

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

    30. DETAIL VIEW OF MOVABLE SPAN, UPPER TRUSS GUSSET PLATE, JUNCTION OF VERTICAL AND HORIZONTAL MEMBERS, JUNCTION ALSO OF CENTER TRUSS SUPPORT AREA, LOOKING SOUTHEAST (taken in December 1983) - 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. 16. DETAIL VIEW OF DAMAGED AREA OF WEST APPROACH SPAN, ...

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

    16. DETAIL VIEW OF DAMAGED AREA OF WEST APPROACH SPAN, SHOWING REMAINING GRANITE OUTCROP BEING BROKEN UP BY HYDRAULIC HAMMER MOUNTED ON A BACKHOE, LOOKING EAST-NORTHEAST - Middle Fork Stanislaus River Bridge, Spans Middle Fork Stanislaus River at State Highway 108, Dardanelle, Tuolumne County, CA

  2. 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.

  3. 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

  4. 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

  5. July | 201span>6 | ISS On-Orbit Status Report

    NASA Website

    Monday, 08/01: Airway Monitoring Airlock ops, SPHERES, ... August 201span>6; July 201span>6; June 201span>6; May 201span>6; April 201span>6; March 201span>6; February 201span>6; January ...

  6. Solid-State Plasmonic Solar Cells.

    PubMed

    Ueno, Kosei; Oshikiri, Tomoya; Sun, Quan; Shi, Xu; Misawa, Hiroaki

    2017-07-24

    Metallic nanoparticles such as silver and gold show localized surface plasmon resonances (LSPRs), which are associated with near-field enhancement effects in the vicinity of nanoparticles. Therefore, strong light-matter interaction is induced by the near-field enhancement effects of LSPRs. Because the resonant wavelength of LSPRs can be easily controlled by the size and shape of the metallic nanoparticles in the visible and near-infrared wavelength range, LSPRs have received considerable attention as optical antennae for light energy conversion systems such as solar cells. LSPRs decay very quickly as a result of light scattering and excitation of electron-hole pairs in the metal itself. However, in addition to the near-field enhancement effect, this light scattering and electron-hole pair excitation, which are known to cause loss of LSPRs, can be utilized as a solar cell enhancement mechanism. Here, we focus on plasmonic solid-state solar cells. The mechanisms of the light scattering by LSPRs, near-field enhancement, and plasmon-induced charge separation based on electron-hole pair excitations can be clarified. We review the related studies from the viewpoint of these mechanisms rather than material science.

  7. Three-qubit entanglement witnesses with the full spanning properties

    NASA Astrophysics Data System (ADS)

    Kye, Seung-Hyeok

    2015-06-01

    We construct three-qubit entanglement witnesses with the full spanning property, by which we mean that all the partial transposes have the spanning properties. These witnesses determine faces for separable states whose interior lies in the interior of positive partial transposes (PPT) states, and so they detect sets of PPT entangled states with nonempty interiors. These witnesses also detect fully bi-separable states as well as all kinds of bi-separable pure product states. Our construction depends on the observation that multi-partite entanglement witnesses correspond to positive multi-linear maps.

  8. Suppression of NK and CD8(+) T cells reduces astrogliosis but accelerates cerebellar dysfunction and shortens life span in a mouse model of Sandhoff disease.

    PubMed

    White, Elizabeth J; Trigatti, Bernardo L; Igdoura, Suleiman A

    2017-05-15

    Sandhoff disease is an inherited lysosomal storage disease, resulting from the deficiency of lysosomal β-hexosaminidase A and B enzyme activity. The Hexb-/- mouse model recapitulates human disease and leads to fatal neurodegeneration and neuroinflammation. IL-15 is important for the proliferation of NK, NK T, and CD8(+) cytotoxic/memory T cells. In order to determine how changes to IL-15-dependent immune cell populations would alter the course of Sandhoff disease in mice, we generated a Hexb-/-Il-15-/- double knockout mouse and used motor behaviour tests, analyzed peripheral blood and brain leukocyte immunophenotypes, cytokine secretion, as well as examined markers of microgliosis, astrogliosis and apoptosis. Hexb-/-Il-15-/- mice had an accelerated neurodegenerative phenotype, and reached the humane endpoint at 118±3.5d, compared to Hexb-/- mice (127±2.2d). The performance of Hexb-/-Il-15-/- mice declined earlier than Hexb-/- mice on the rotarod and righting reflex motor behaviour tests. Hexb-/- mice had a significantly higher prevalence of pro-inflammatory monocytes in the blood relative to C57BL/6 mice, but this was unaltered by IL-15 deficiency. The prevalence of NK cells and CD8(+) T cells in Il-15-/- and Hexb-/-Il-15-/- mice was decreased compared to wild type and Hexb-/- mice. While Hexb-/- mice displayed an increase in the prevalence of CD4(+) and CD8(+) T cells in brain leukocytes compared to C57BL/6 mice, there was a decrease in CD8(+) T cells in Hexb-/-Il-15-/- compared to Hexb-/- mice. In addition, circulating IL-17 and IL-10 levels were significantly higher in Hexb-/-Il-15-/- mice, suggesting heightened inflammation compared to Hexb-/- mice. Interestingly, astrogliosis levels were significantly reduced in the cerebellum of Hexb-/-Il-15-/- mice compared to Hexb-/- mice while microgliosis was not affected in brains of Hexb-/-Il-15-/- mice. Our study demonstrated that IL-15 depletion dramatically reduced numbers of NK and CD8(+) T cells as well as

  9. 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.

  10. Damage assessment of a two-span RC slab using wavelet analysis

    NASA Astrophysics Data System (ADS)

    Zhu, X. Q.; Hao, H.

    2007-04-01

    A two-span RC slab that measures 6400mm×800mm×100mm with 3000mm spans and 200mm overhang on each end was tested to failure in the laboratory. UB sections were used as supports. The slab was designed according to the moment redistribution method with 11 N6 bars at 75mm centres for both positive and negative reinforcement. The slab was incrementally loaded at the middle of each span to different load levels to create crack damage using four-point loading. Twelve loading stages were performed with increasing maximum load level. Two load cells are used to record the static loads on left and right spans. The crack locations and lengths were monitored in addition to the displacement measurements. Four displacement transducers are located at two sides of the middle of each span to measure the deflection under the static load. Three sets of accelerometers with nine of them in each set are evenly distributed along the slab to measure the dynamic responses. The measured responses from the RC slab in different cracked damage states are analyzed using the wavelet transform (WT). The damping ratios and instantaneous frequency are extracted. The results show that the damping ratio and instantaneous frequency changes could be two good indicators of damage in the reinforced concrete structure.

  11. 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.

  12. 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.

  13. 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)…

  14. 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

  15. A YAC contig spanning the nevoid basal cell carcinoma syndrome, Fanconi anaemia group C, and xeroderma pigmentosum group A loci on chromosome 9q

    SciTech Connect

    Morris, D.J.; Reis, A.

    1994-09-01

    Nevoid basal cell carcinoma syndrome (NBCCS, Gorlin syndrome) is an autosomal dominant disorder, characterized primarily by multiple basal cell carcinomas, epithelium-lined jaw cysts, and palmar and plantar pits, as well as various other features. Loss of heterozygosity studies and linkage analysis have mapped the NBCCS gene to chromosome 9q and suggested that it is a tumor suppressor. The apparent sensitivity of NBCCS patients to UV and X-irradiation raises the possibility of hypersensitivity to DNA-damaging reagents or defective DNA repair being etiological in the disorder. The recent mapping of the Fanconi anaemia group C (FACC) and xeroderma pigmentosum complementing group A (XPAC) genes to the same region on 9q has led us to begin the molecular dissection of the 9q22-q31 region. PCR analysis of the presence or absence of 10 microsatellite markers and exons 3 and 4 of the XPAC and FACC genes, respectively, allowed us to order 12 YACs into an overlapping contig and to order the markers as follows: D9S151/D9S12P1-D9S12P2-D9S197-D9S196-D9S280-FACC-D9S287/XPAC-D9S180-D9S6-D9S176. Sizing of the YACs has provided an initial estimate of the size of the NBCCS candidate region between D9S12 and D9S180 to be less than 1.65 Mb. 45 refs., 1 fig., 1 tab.

  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. © 2016 American Society of Law, Medicine & Ethics.

  17. A Procedure-Spanning Analysis of Plasma Membrane Integrity for Assessment of Cell Viability in Sperm Cryopreservation of Zebrafish Danio rerio

    PubMed Central

    Daly, Jonathan; Carmichael, Carrie; Matthews, Jen; Varga, Zoltan M.; Tiersch, Terrence

    2016-01-01

    Abstract The goal of this study was to evaluate plasma membrane integrity and motility for zebrafish sperm quality assessment along the cryopreservation pathway—from sample collection through refrigerated storage, cryoprotectant equilibration, freezing, thawing, and fertilization. The objectives were to: (1) evaluate the effects of osmolality, extender, and refrigerated storage on sperm plasma membrane integrity and motility, and (2) compare cryopreservation of sperm from farm-raised and well-characterized research populations by evaluating motility and membrane integrity of fresh, post-equilibration (before freezing) and post-thaw sperm, and post-thaw fertility. Osmolality, extender, and storage time each influenced sperm motility and membrane integrity. Isotonic osmolality showed the best protection for motility and membrane integrity compared to hypotonic and hypertonic osmolalities. Of the four tested extenders, Hanks' balanced salt solution (HBSS) and Ca2+-free HBSS showed the best protection compared with NaCl and glucose, and sperm retained motility and membrane integrity for 24 h of refrigerated storage. Sperm cryopreservation of zebrafish from a farm population (n = 20) and an AB research line (n = 20) showed significant differences in post-thaw fertility (32% ± 18% vs. 73% ± 21%). No differences were found in post-thaw motility, although the farm-raised zebrafish possessed a larger body size, testis weight, and higher fresh motility. Correlation analysis of pooled data did not identify correlations among motility, flow cytometry analysis of membrane integrity and recognizable cells, and post-thaw sperm fertility (p ≥ 0.202). More research is needed to standardize the fertilization conditions especially sperm-to-egg ratio to avoid possible overabundance of sperm to obscure the differences. PMID:26859531

  18. A Procedure-Spanning Analysis of Plasma Membrane Integrity for Assessment of Cell Viability in Sperm Cryopreservation of Zebrafish Danio rerio.

    PubMed

    Yang, Huiping; Daly, Jonathan; Carmichael, Carrie; Matthews, Jen; Varga, Zoltan M; Tiersch, Terrence

    2016-04-01

    The goal of this study was to evaluate plasma membrane integrity and motility for zebrafish sperm quality assessment along the cryopreservation pathway-from sample collection through refrigerated storage, cryoprotectant equilibration, freezing, thawing, and fertilization. The objectives were to: (1) evaluate the effects of osmolality, extender, and refrigerated storage on sperm plasma membrane integrity and motility, and (2) compare cryopreservation of sperm from farm-raised and well-characterized research populations by evaluating motility and membrane integrity of fresh, post-equilibration (before freezing) and post-thaw sperm, and post-thaw fertility. Osmolality, extender, and storage time each influenced sperm motility and membrane integrity. Isotonic osmolality showed the best protection for motility and membrane integrity compared to hypotonic and hypertonic osmolalities. Of the four tested extenders, Hanks' balanced salt solution (HBSS) and Ca(2+)-free HBSS showed the best protection compared with NaCl and glucose, and sperm retained motility and membrane integrity for 24 h of refrigerated storage. Sperm cryopreservation of zebrafish from a farm population (n = 20) and an AB research line (n = 20) showed significant differences in post-thaw fertility (32% ± 18% vs. 73% ± 21%). No differences were found in post-thaw motility, although the farm-raised zebrafish possessed a larger body size, testis weight, and higher fresh motility. Correlation analysis of pooled data did not identify correlations among motility, flow cytometry analysis of membrane integrity and recognizable cells, and post-thaw sperm fertility (p ≥ 0.202). More research is needed to standardize the fertilization conditions especially sperm-to-egg ratio to avoid possible overabundance of sperm to obscure the differences.

  19. Plasmid accumulation reduces life span in Saccharomyces cerevisiae.

    PubMed

    Falcón, Alaric A; Aris, John P

    2003-10-24

    Aging in the yeast Saccharomyces cerevisiae is under the control of multiple pathways. The production and accumulation of extrachromosomal rDNA circles (ERCs) is one pathway that has been proposed to bring about aging in yeast. To test this proposal, we have developed a plasmid-based model system to study the role of DNA episomes in reduction of yeast life span. Recombinant plasmids containing different replication origins, cis-acting partitioning elements, and selectable marker genes were constructed and analyzed for their effects on yeast replicative life span. Plasmids containing the ARS1 replication origin reduce life span to the greatest extent of the plasmids analyzed. This reduction in life span is partially suppressed by a CEN4 centromeric element on ARS1 plasmids. Plasmids containing a replication origin from the endogenous yeast 2 mu circle also reduce life span, but to a lesser extent than ARS1 plasmids. Consistent with this, ARS1 and 2 mu origin plasmids accumulate in approximately 7-generation-old cells, but ARS1/CEN4 plasmids do not. Importantly, ARS1 plasmids accumulate to higher levels in old cells than 2 mu origin plasmids, suggesting a correlation between plasmid accumulation and life span reduction. Reduction in life span is neither an indirect effect of increased ERC levels nor the result of stochastic cessation of growth. The presence of a fully functional 9.1-kb rDNA repeat on plasmids is not required for, and does not augment, reduction in life span. These findings support the view that accumulation of DNA episomes, including episomes such as ERCs, cause cell senescence in yeast.

  20. 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.

  1. Physical Chemical State of Water in Living Cells.

    DTIC Science & Technology

    1985-05-01

    AD-A154 566 PHYSICAL CHEMICAL STATE OF WATER IN LIVING CELLS(J) / BAYLOR COLL OF MEDICINE HOUSTON TX DEPT OF PHYSIOLOGY C F HAZLEWOOD ET AL. MAY 85...N00014-76--C-0l0O Title: Physical Chemical State of Water in Living Cells Sub-Project A: Physical Chemical State of Water in Living Cells and Tissues Sub...provide the fundamental framework of our concepts of the living state. The following includes: (1) a statement of the rationale for this work; (2

  2. 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…

  3. 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…

  4. Non-label immune cell state prediction using Raman spectroscopy

    PubMed Central

    Ichimura, Taro; Chiu, Liang-da; Fujita, Katsumasa; Machiyama, Hiroaki; Yamaguchi, Tomoyuki; Watanabe, Tomonobu M.; Fujita, Hideaki

    2016-01-01

    The acquired immune system, mainly composed of T and B lymphocytes, plays a key role in protecting the host from infection. It is important and technically challenging to identify cell types and their activation status in living and intact immune cells, without staining or killing the cells. Using Raman spectroscopy, we succeeded in discriminating between living T cells and B cells, and visualized the activation status of living T cells without labeling. Although the Raman spectra of T cells and B cells were similar, they could be distinguished by discriminant analysis of the principal components. Raman spectra of activated T cells with anti-CD3 and anti-CD28 antibodies largely differed compared to that of naïve T cells, enabling the prediction of T cell activation status at a single cell level. Our analysis revealed that the spectra of individual T cells gradually change from the pattern of naïve T cells to that of activated T cells during the first 24 h of activation, indicating that changes in Raman spectra reflect slow changes rather than rapid changes in cell state during activation. Our results indicate that the Raman spectrum enables the detection of dynamic changes in individual cell state scattered in a heterogeneous population. PMID:27876845

  5. January | 201span>6 | Space Station | Page 2

    NASA Website

    Posted on January 7, 201span>6 at 12:00 pm by Mark Garcia. 1 Reply. ... August 201span>6; July 201span>6; June 201span>6; May 201span>6; April 201span>6; March 201span>6; February 201span>6; ...

  6. 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.

  7. Investigating transcriptional states at single-cell-resolution.

    PubMed

    Tischler, Julia; Surani, M Azim

    2013-02-01

    Gene expression analysis at single-cell-resolution is a powerful tool for uncovering individual cell differences within heterogeneous cell populations and complex tissues, which can provide invaluable insights into the extent of gene expression variability. Multi-dimensional information of gene expression at the level of the individual cell can help to identify distinct and rare molecular cell 'states' within populations and aid in unravelling genetic regulatory circuits. Gene expression analysis at the single-cell-level will also enhance our understanding of the molecular basis of aberrant cell states and disease development and holds great promise for the advancement of personalized medicine. We present approaches that provide large-scale views of gene expression at the level of the individual cell.

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

    PubMed

    Gordon, Natalie K; Gordon, Richard

    2016-03-10

    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).

  9. Multiplicity of Steady States in Glycolysis and Shift of Metabolic State in Cultured Mammalian Cells

    PubMed Central

    Grimm, Simon; Daoutidis, Prodromos; Hu, Wei-Shou

    2015-01-01

    Cultured mammalian cells exhibit elevated glycolysis flux and high lactate production. In the industrial bioprocesses for biotherapeutic protein production, glucose is supplemented to the culture medium to sustain continued cell growth resulting in the accumulation of lactate to high levels. In such fed-batch cultures, sometimes a metabolic shift from a state of high glycolysis flux and high lactate production to a state of low glycolysis flux and low lactate production or even lactate consumption is observed. While in other cases with very similar culture conditions, the same cell line and medium, cells continue to produce lactate. A metabolic shift to lactate consumption has been correlated to the productivity of the process. Cultures that exhibited the metabolic shift to lactate consumption had higher titers than those which didn’t. However, the cues that trigger the metabolic shift to lactate consumption state (or low lactate production state) are yet to be identified. Metabolic control of cells is tightly linked to growth control through signaling pathways such as the AKT pathway. We have previously shown that the glycolysis of proliferating cells can exhibit bistability with well-segregated high flux and low flux states. Low lactate production (or lactate consumption) is possible only at a low glycolysis flux state. In this study, we use mathematical modeling to demonstrate that lactate inhibition together with AKT regulation on glycolysis enzymes can profoundly influence the bistable behavior, resulting in a complex steady-state topology. The transition from the high flux state to the low flux state can only occur in certain regions of the steady state topology, and therefore the metabolic fate of the cells depends on their metabolic trajectory encountering the region that allows such a metabolic state switch. Insights from such switch behavior present us with new means to control the metabolism of mammalian cells in fed-batch cultures. PMID:25806512

  10. Multiplicity of steady states in glycolysis and shift of metabolic state in cultured mammalian cells.

    PubMed

    Mulukutla, Bhanu Chandra; Yongky, Andrew; Grimm, Simon; Daoutidis, Prodromos; Hu, Wei-Shou

    2015-01-01

    Cultured mammalian cells exhibit elevated glycolysis flux and high lactate production. In the industrial bioprocesses for biotherapeutic protein production, glucose is supplemented to the culture medium to sustain continued cell growth resulting in the accumulation of lactate to high levels. In such fed-batch cultures, sometimes a metabolic shift from a state of high glycolysis flux and high lactate production to a state of low glycolysis flux and low lactate production or even lactate consumption is observed. While in other cases with very similar culture conditions, the same cell line and medium, cells continue to produce lactate. A metabolic shift to lactate consumption has been correlated to the productivity of the process. Cultures that exhibited the metabolic shift to lactate consumption had higher titers than those which didn't. However, the cues that trigger the metabolic shift to lactate consumption state (or low lactate production state) are yet to be identified. Metabolic control of cells is tightly linked to growth control through signaling pathways such as the AKT pathway. We have previously shown that the glycolysis of proliferating cells can exhibit bistability with well-segregated high flux and low flux states. Low lactate production (or lactate consumption) is possible only at a low glycolysis flux state. In this study, we use mathematical modeling to demonstrate that lactate inhibition together with AKT regulation on glycolysis enzymes can profoundly influence the bistable behavior, resulting in a complex steady-state topology. The transition from the high flux state to the low flux state can only occur in certain regions of the steady state topology, and therefore the metabolic fate of the cells depends on their metabolic trajectory encountering the region that allows such a metabolic state switch. Insights from such switch behavior present us with new means to control the metabolism of mammalian cells in fed-batch cultures.

  11. Stress Proteins in Aging and Life Span

    PubMed Central

    Murshid, Ayesha; Eguchi, Takanori; Calderwood, Stuart K.

    2014-01-01

    Heat shock proteins (HSP) are molecular chaperones and have been implicated in longevity and aging in many species. Their major functions include, chaperoning misfolded or newly synthesized polypeptides, protecting cells from proteotoxic stress, and processing of immunogenic agents. These proteins are expressed constitutively and can be induced by stresses such as heat, oxidative stress and many more. The induction of HSP in aging could potentially maintain protein homeostasis and longevity by refolding the damaged proteins which accumulate during aging and are toxic to cells. HSP are shown to increase life span in model organisms such as C. elegans and decrease aging related proteotoxicity. Thus, decrease in HSP in aging is associated with disruption of cellular homeostasis which causes diseases such as cancer, cell senescence and neurodegeneration. HSP levels are decreased with aging in most organs including neurons. Aging also causes attenuation or alteration of many signaling pathways as well as the expression of transcription factors such as heat shock factor (HSF). The alteration in regulation and synthesis of Forkhead box O3a (FOXO3a) family of transcription factors as well as major antioxidant enzymes [manganese superoxide dismutase (MnSOD), catalase] are also seen in aging. Among many signaling mechanisms involved in altering longevity and aging, the insulin/IGF1 pathway and the Sir2 deacetylase are highly significant. This review inquires into the role of some of these pathways in longevity/aging along with HSP. PMID:23742046

  12. 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.

  13. Cell Fate Decision as High-Dimensional Critical State Transition.

    PubMed

    Mojtahedi, Mitra; Skupin, Alexander; Zhou, Joseph; Castaño, Ivan G; Leong-Quong, Rebecca Y Y; Chang, Hannah; Trachana, Kalliopi; Giuliani, Alessandro; Huang, Sui

    2016-12-01

    Cell fate choice and commitment of multipotent progenitor cells to a differentiated lineage requires broad changes of their gene expression profile. But how progenitor cells overcome the stability of their gene expression configuration (attractor) to exit the attractor in one direction remains elusive. Here we show that commitment of blood progenitor cells to the erythroid or myeloid lineage is preceded by the destabilization of their high-dimensional attractor state, such that differentiating cells undergo a critical state transition. Single-cell resolution analysis of gene expression in populations of differentiating cells affords a new quantitative index for predicting critical transitions in a high-dimensional state space based on decrease of correlation between cells and concomitant increase of correlation between genes as cells approach a tipping point. The detection of "rebellious cells" that enter the fate opposite to the one intended corroborates the model of preceding destabilization of a progenitor attractor. Thus, early warning signals associated with critical transitions can be detected in statistical ensembles of high-dimensional systems, offering a formal theory-based approach for analyzing single-cell molecular profiles that goes beyond current computational pattern recognition, does not require knowledge of specific pathways, and could be used to predict impending major shifts in development and disease.

  14. 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.

  15. Metric half-span model support system

    NASA Technical Reports Server (NTRS)

    Jackson, C. M., Jr.; Dollyhigh, S. M.; Shaw, D. S. (Inventor)

    1982-01-01

    A model support system used to support a model in a wind tunnel test section is described. The model comprises a metric, or measured, half-span supported by a nonmetric, or nonmeasured half-span which is connected to a sting support. Moments and forces acting on the metric half-span are measured without interference from the support system during a wind tunnel test.

  16. Two-carbon metabolites, polyphenols and vitamins influence yeast chronological life span in winemaking conditions

    PubMed Central

    2012-01-01

    Background Viability in a non dividing state is referred to as chronological life span (CLS). Most grape juice fermentation happens when Saccharomyces cerevisiae yeast cells have stopped dividing; therefore, CLS is an important factor toward winemaking success. Results We have studied both the physical and chemical determinants influencing yeast CLS. Low pH and heat shorten the maximum wine yeast life span, while hyperosmotic shock extends it. Ethanol plays an important negative role in aging under winemaking conditions, but additional metabolites produced by fermentative metabolism, such as acetaldehyde and acetate, have also a strong impact on longevity. Grape polyphenols quercetin and resveratrol have negative impacts on CLS under winemaking conditions, an unexpected behavior for these potential anti-oxidants. We observed that quercetin inhibits alcohol and aldehyde dehydrogenase activities, and that resveratrol performs a pro-oxidant role during grape juice fermentation. Vitamins nicotinic acid and nicotinamide are precursors of NAD+, and their addition reduces mean longevity during fermentation, suggesting a metabolic unbalance negative for CLS. Moreover, vitamin mix supplementation at the end of fermentation shortens CLS and enhances cell lysis, while amino acids increase life span. Conclusions Wine S. cerevisiae strains are able to sense changes in the environmental conditions and adapt their longevity to them. Yeast death is influenced by the conditions present at the end of wine fermentation, particularly by the concentration of two-carbon metabolites produced by the fermentative metabolism, such as ethanol, acetic acid and acetaldehyde, and also by the grape juice composition, particularly its vitamin content. PMID:22873488

  17. Social Studies in the 1980s. A Report of Project SPAN.

    ERIC Educational Resources Information Center

    Morrissett, Irving, Ed.

    Selected and condensed portions of five reports prepared by Project SPAN (Social Studies Priorities, Practices, and Needs) are presented. The purpose of Project SPAN was to describe and assess the current and recent state of social studies/social science education, designate desired states to which social studies might or should aspire, and shape…

  18. CSTEA: a webserver for the Cell State Transition Expression Atlas.

    PubMed

    Zhu, Guanghui; Yang, Hui; Chen, Xiao; Wu, Jun; Zhang, Yong; Zhao, Xing-Ming

    2017-05-09

    Cell state transition is one of the fundamental events in the development of multicellular organisms, and the transition trajectory path has recently attracted much attention. With the accumulation of large amounts of "-omics" data, it is becoming possible to get insights into the molecule mechanisms underlying the transitions between cell states. Here, we present CSTEA (Cell State Transition Expression Atlas), a webserver that organizes, analyzes and visualizes the time-course gene expression data during cell differentiation, cellular reprogramming and trans-differentiation in human and mouse. In particular, CSTEA defines gene signatures for uncharacterized stages during cell state transitions, thereby enabling both experimental and computational biologists to better understand the mechanisms of cell fate determination in mammals. To our best knowledge, CSTEA is the first webserver dedicated to the analysis of time-series gene expression data during cell state transitions. CSTEA is freely available at http://comp-sysbio.org/cstea/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Cell Fate Decision as High-Dimensional Critical State Transition

    PubMed Central

    Zhou, Joseph; Castaño, Ivan G.; Leong-Quong, Rebecca Y. Y.; Chang, Hannah; Trachana, Kalliopi; Giuliani, Alessandro; Huang, Sui

    2016-01-01

    Cell fate choice and commitment of multipotent progenitor cells to a differentiated lineage requires broad changes of their gene expression profile. But how progenitor cells overcome the stability of their gene expression configuration (attractor) to exit the attractor in one direction remains elusive. Here we show that commitment of blood progenitor cells to the erythroid or myeloid lineage is preceded by the destabilization of their high-dimensional attractor state, such that differentiating cells undergo a critical state transition. Single-cell resolution analysis of gene expression in populations of differentiating cells affords a new quantitative index for predicting critical transitions in a high-dimensional state space based on decrease of correlation between cells and concomitant increase of correlation between genes as cells approach a tipping point. The detection of “rebellious cells” that enter the fate opposite to the one intended corroborates the model of preceding destabilization of a progenitor attractor. Thus, early warning signals associated with critical transitions can be detected in statistical ensembles of high-dimensional systems, offering a formal theory-based approach for analyzing single-cell molecular profiles that goes beyond current computational pattern recognition, does not require knowledge of specific pathways, and could be used to predict impending major shifts in development and disease. PMID:28027308

  20. 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.

  1. Improved Fabrication Of Cathodes For Solid-State Li Cells

    NASA Technical Reports Server (NTRS)

    Nagasubramanian, Ganesan

    1995-01-01

    Utilization of cathode material increased. Improved composite-cathode/polymer-electrolyte units for solid-state lithium secondary electrochemical cells fabricated in modified version of original method of fabrication. Further development of units may lead to increases in energy and power densities and in cycle lives of rechargeable lithium cells.

  2. Electric impedance microflow cytometry for characterization of cell disease states.

    PubMed

    Du, E; Ha, Sungjae; Diez-Silva, Monica; Dao, Ming; Suresh, Subra; Chandrakasan, Anantha P

    2013-10-07

    The electrical properties of biological cells have connections to their pathological states. Here we present an electric impedance microflow cytometry (EIMC) platform for the characterization of disease states of single cells. This platform entails a microfluidic device for a label-free and non-invasive cell-counting assay through electric impedance sensing. We identified a dimensionless offset parameter δ obtained as a linear combination of a normalized phase shift and a normalized magnitude shift in electric impedance to differentiate cells on the basis of their pathological states. This paper discusses a representative case study on red blood cells (RBCs) invaded by the malaria parasite Plasmodium falciparum. Invasion by P. falciparum induces physical and biochemical changes on the host cells throughout a 48-h multi-stage life cycle within the RBC. As a consequence, it also induces progressive changes in electrical properties of the host cells. We demonstrate that the EIMC system in combination with data analysis involving the new offset parameter allows differentiation of P. falciparum infected RBCs from uninfected RBCs as well as among different P. falciparum intraerythrocytic asexual stages including the ring stage. The representative results provided here also point to the potential of the proposed experimental and analysis platform as a valuable tool for non-invasive diagnostics of a wide variety of disease states and for cell separation.

  3. Cloning and variation of ground state intestinal stem cells.

    PubMed

    Wang, Xia; Yamamoto, Yusuke; Wilson, Lane H; Zhang, Ting; Howitt, Brooke E; 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

    2015-06-11

    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 is likely to enforce the functional specificity of the adult intestinal tract. Using clonally derived colonic epithelia, we show that toxins A or B of the enteric pathogen Clostridium 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 modelling and regenerative medicine.

  4. 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. © 2015 Wiley Periodicals, Inc.

  5. Amyloid beta toxicity dependent upon endothelial cell state

    PubMed Central

    Balcells, Mercedes; Wallins, Joseph S.; Edelman, Elazer R.

    2008-01-01

    Amyloid beta (Aβ), a peptide family produced and deposited in neurons and endothelial cells (EC), is found at subnanomolar concentrations in the plasma of healthy individuals. Simple conformational changes produce a form of Aβ Aβ42, which creates toxic plaque in the brains of Alzheimer’s patients. Oxidative stress induced blood brain barrier degeneration has been proposed as a key factor for Aβ42 toxicity, but cannot account for lack of injury from the same peptide in healthy tissues. We hypothesized that cell state mediates Aβ effect. Thus, we examined the viability of aortic EC, vascular smooth muscle cells (SMC) and epithelial cells (EPI) in different states in the presence of Aβ secreted from transfected Chinese hamster ovary cells (CHO). Aβ was more toxic to all cell types when they were subconfluent. Subconfluent EC sprouted and SMC and EPI were inhibited by Aβ. Confluent EC were virtually resistant to Aβ and suppressed Aβ production by Aβ+CHO. Products of subconfluent EC overcame this resistant state, stimulating the production and toxicity of Aβ42. Confluent EC overgrew ~35% beyond their quiescent state in the presence of Aβ conditioned in media from subconfluent EC. These findings imply that Aβ42 may well be even more cytotoxic to cells in injured or growth states and potentially explain the variable and potent effects of this protein. One may now need to consider tissue and cell state in addition to local concentration of and exposure duration to Aβ. The specific interactions of Aβ and EC in a state-dependent fashion may help understand further the common and divergent forms of vascular and cerebral toxicity of Aβ and the spectrum of AD. PMID:18601976

  6. Omnidirectional Printing of Flexible, Stretchable, and Spanning Silver Microelectrodes

    NASA Astrophysics Data System (ADS)

    Ahn, Bok Y.; Duoss, Eric B.; Motala, Michael J.; Guo, Xiaoying; Park, Sang-Il; Xiong, Yujie; Yoon, Jongseung; Nuzzo, Ralph G.; Rogers, John A.; Lewis, Jennifer A.

    2009-03-01

    Flexible, stretchable, and spanning microelectrodes that carry signals from one circuit element to another are needed for many emerging forms of electronic and optoelectronic devices. We have patterned silver microelectrodes by omnidirectional printing of concentrated nanoparticle inks in both uniform and high-aspect ratio motifs with minimum widths of approximately 2 micrometers onto semiconductor, plastic, and glass substrates. The patterned microelectrodes can withstand repeated bending and stretching to large levels of strain with minimal degradation of their electrical properties. With this approach, wire bonding to fragile three-dimensional devices and spanning interconnects for solar cell and light-emitting diode arrays are demonstrated.

  7. U. S. (United States) Air Force Fuel Cell Application Analysis.

    DTIC Science & Technology

    1982-01-01

    FUEL CELL POWER UNIT PARAMETERS FOR UNATTENDED REMOTE UNIT - ETHANOL FUELED. . . . . . . . . . . . . . . . . . . . . . . . . 4-3 4-2 FUEL CELL POWER UNIT...4-20 4-4 STATE POINTS - 23 kW ETHANOL - FUELED FCPU. . . ...... 4-23 4 4-5 COMPARATIVE ANALYSIS MX POWER UNIT - DESIGN POINT SELECTION 4...DATA SUMMARY SHEET ETHANOL FUEL CELL POWER UNIT . .... 4-31 4-9 MAJOR COMPONENT DESIGN PARAMETERS - ETHANOL FCPU ........ 4-32 4-10 MAJOR CONTROL

  8. Epithelial neoplasia in Drosophila entails switch to primitive cell states

    PubMed Central

    Khan, Sumbul J.; Bajpai, Anjali; Alam, Mohammad Atif; Gupta, Ram P.; Harsh, Sneh; Pandey, Ravi K.; Goel-Bhattacharya, Surbhi; Nigam, Aditi; Mishra, Arati; Sinha, Pradip

    2013-01-01

    Only select cell types in an organ display neoplasia when targeted oncogenically. How developmental lineage hierarchies of these cells prefigure their neoplastic propensities is not yet well-understood. Here we show that neoplastic Drosophila epithelial cells reverse their developmental commitments and switch to primitive cell states. In a context of alleviated tissue surveillance, for example, loss of Lethal giant larvae (Lgl) tumor suppressor in the wing primordium induced epithelial neoplasia in its Homothorax (Hth)-expressing proximal domain. Transcriptional profile of proximally transformed mosaic wing epithelium and functional tests revealed tumor cooperation by multiple signaling pathways. In contrast, lgl− clones in the Vestigial (Vg)-expressing distal wing epithelium were eliminated by cell death. Distal lgl− clones, however, could transform when both tissue surveillance and cell death were compromised genetically and, alternatively, when the transcription cofactor of Hippo signaling pathway, Yorkie (Yki), was activated, or when Ras/EGFR signaling was up-regulated. Furthermore, transforming distal lgl− clones displayed loss of Vg, suggesting reversal of their terminal cell fate commitment. In contrast, reinforcing a distal (wing) cell fate commitment in lgl− clones by gaining Vg arrested their neoplasia and induced cell death. We also show that neoplasia in both distal and proximal lgl− clones could progress in the absence of Hth, revealing Hth-independent wing epithelial neoplasia. Likewise, neoplasia in the eye primordium resulted in loss of Elav, a retinal cell marker; these, however, switched to an Hth-dependent primitive cell state. These results suggest a general characteristic of “cells-of-origin” in epithelial cancers, namely their propensity for switch to primitive cell states. PMID:23708122

  9. Epithelial neoplasia in Drosophila entails switch to primitive cell states.

    PubMed

    Khan, Sumbul J; Bajpai, Anjali; Alam, Mohammad Atif; Gupta, Ram P; Harsh, Sneh; Pandey, Ravi K; Goel-Bhattacharya, Surbhi; Nigam, Aditi; Mishra, Arati; Sinha, Pradip

    2013-06-11

    Only select cell types in an organ display neoplasia when targeted oncogenically. How developmental lineage hierarchies of these cells prefigure their neoplastic propensities is not yet well-understood. Here we show that neoplastic Drosophila epithelial cells reverse their developmental commitments and switch to primitive cell states. In a context of alleviated tissue surveillance, for example, loss of Lethal giant larvae (Lgl) tumor suppressor in the wing primordium induced epithelial neoplasia in its Homothorax (Hth)-expressing proximal domain. Transcriptional profile of proximally transformed mosaic wing epithelium and functional tests revealed tumor cooperation by multiple signaling pathways. In contrast, lgl(-) clones in the Vestigial (Vg)-expressing distal wing epithelium were eliminated by cell death. Distal lgl(-) clones, however, could transform when both tissue surveillance and cell death were compromised genetically and, alternatively, when the transcription cofactor of Hippo signaling pathway, Yorkie (Yki), was activated, or when Ras/EGFR signaling was up-regulated. Furthermore, transforming distal lgl(-) clones displayed loss of Vg, suggesting reversal of their terminal cell fate commitment. In contrast, reinforcing a distal (wing) cell fate commitment in lgl(-) clones by gaining Vg arrested their neoplasia and induced cell death. We also show that neoplasia in both distal and proximal lgl(-) clones could progress in the absence of Hth, revealing Hth-independent wing epithelial neoplasia. Likewise, neoplasia in the eye primordium resulted in loss of Elav, a retinal cell marker; these, however, switched to an Hth-dependent primitive cell state. These results suggest a general characteristic of "cells-of-origin" in epithelial cancers, namely their propensity for switch to primitive cell states.

  10. Using ToxCast data to reconstruct dynamic cell state ...

    EPA Pesticide Factsheets

    AbstractBackground. High-throughput in vitro screening is an important tool for evaluating the potential biological activity of the thousands of existing chemicals in commerce and the hundreds more introduced each year. Among the assay technologies available, high-content imaging (HCI) allows multiplexed measurements of cellular phenotypic changes induced by chemical exposures. For a large chemical inventory having limited concentration-time series data, the deconvolution of cellular response profiles into transitive or irrevocable state trajectories is an important consideration. Objectives. Our goal was to analyze temporal and concentration-related cellular changes measured using HCI to identify the “tipping point” at which the cells did not show recovery towards a normal phenotypic state. Methods. The effects of 976 chemicals (ToxCast Phase I and II) were evaluated using HCI as a function of concentration and time in HepG2 cells over a 72-hr exposure period to concentrations ranging from 0.4- to 200 µM. The cellular endpoints included nuclear p53 accumulation, JNK, markers of oxidative stress, cytoskeletal changes, mitochondrial energization and density, cell viability and cell cycle progression. A novel computational model was developed to interpret dynamic multidimensional system responses as cell-state trajectories. Results. Analysis of cell-state trajectories showed that HepG2 cells were resilient to the effects of 178 chemicals up to the highest co

  11. Simultaneous prediction of protein secondary structure and transmembrane spans.

    PubMed

    Leman, Julia Koehler; Mueller, Ralf; Karakas, Mert; Woetzel, Nils; Meiler, Jens

    2013-07-01

    Prediction of transmembrane spans and secondary structure from the protein sequence is generally the first step in the structural characterization of (membrane) proteins. Preference of a stretch of amino acids in a protein to form secondary structure and being placed in the membrane are correlated. Nevertheless, current methods predict either secondary structure or individual transmembrane states. We introduce a method that simultaneously predicts the secondary structure and transmembrane spans from the protein sequence. This approach not only eliminates the necessity to create a consensus prediction from possibly contradicting outputs of several predictors but bears the potential to predict conformational switches, i.e., sequence regions that have a high probability to change for example from a coil conformation in solution to an α-helical transmembrane state. An artificial neural network was trained on databases of 177 membrane proteins and 6048 soluble proteins. The output is a 3 × 3 dimensional probability matrix for each residue in the sequence that combines three secondary structure types (helix, strand, coil) and three environment types (membrane core, interface, solution). The prediction accuracies are 70.3% for nine possible states, 73.2% for three-state secondary structure prediction, and 94.8% for three-state transmembrane span prediction. These accuracies are comparable to state-of-the-art predictors of secondary structure (e.g., Psipred) or transmembrane placement (e.g., OCTOPUS). The method is available as web server and for download at www.meilerlab.org. Copyright © 2013 Wiley Periodicals, Inc.

  12. 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. Copyright © 2016, American Association for the Advancement of Science.

  13. Node degree distribution in spanning trees

    NASA Astrophysics Data System (ADS)

    Pozrikidis, C.

    2016-03-01

    A method is presented for computing the number of spanning trees involving one link or a specified group of links, and excluding another link or a specified group of links, in a network described by a simple graph in terms of derivatives of the spanning-tree generating function defined with respect to the eigenvalues of the Kirchhoff (weighted Laplacian) matrix. The method is applied to deduce the node degree distribution in a complete or randomized set of spanning trees of an arbitrary network. An important feature of the proposed method is that the explicit construction of spanning trees is not required. It is shown that the node degree distribution in the spanning trees of the complete network is described by the binomial distribution. Numerical results are presented for the node degree distribution in square, triangular, and honeycomb lattices.

  14. Prospects for life span extension.

    PubMed

    Sierra, Felipe; Hadley, Evan; Suzman, Richard; Hodes, Richard

    2009-01-01

    Life expectancy has increased dramatically in the United States and in much of the world in recent years and decades. The factors underlying this increase are incompletely understood and are undoubtedly complex. A question that drives current research is whether life expectancy can be further extended using current knowledge of modifiable risk factors. A still more challenging research focus is on the possibility that life expectancy might be further increased through knowledge gained from studies of the basic biology of aging and its genetic and environmental modifiers.

  15. Accessing Data Resources in the Mouse Phenome Database for Genetic Analysis of Murine Life Span and Health Span

    PubMed Central

    Peters, Luanne L.; Paigen, Beverly; Korstanje, Ron; Yuan, Rong; Ackert-Bicknell, Cheryl; Grubb, Stephen C.; Churchill, Gary A.; Chesler, Elissa J.

    2016-01-01

    Understanding the source of genetic variation in aging and using this variation to define the molecular mechanisms of healthy aging require deep and broad quantification of a host of physiological, morphological, and behavioral endpoints. The murine model is a powerful system in which to understand the relations across age-related phenotypes and to identify research models with variation in life span and health span. The Jackson Laboratory Nathan Shock Center of Excellence in the Basic Biology of Aging has performed broad characterization of aging in genetically diverse laboratory mice and has placed these data, along with data from several other major aging initiatives, into the interactive Mouse Phenome Database. The data may be accessed and analyzed by researchers interested in finding mouse models for specific aging processes, age-related health and disease states, and for genetic analysis of aging variation and trait covariation. We expect that by placing these data in the hands of the aging community that there will be (a) accelerated genetic analyses of aging processes, (b) discovery of genetic loci regulating life span, (c) identification of compelling correlations between life span and susceptibility for age-related disorders, and (d) discovery of concordant genomic loci influencing life span and aging phenotypes between mouse and humans. PMID:25533306

  16. 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

  17. 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

  18. 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

  19. 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.

  20. Tracking the embryonic stem cell transition from ground state pluripotency.

    PubMed

    Kalkan, Tüzer; Olova, Nelly; Roode, Mila; Mulas, Carla; Lee, Heather J; Nett, Isabelle; Marks, Hendrik; Walker, Rachael; Stunnenberg, Hendrik G; Lilley, Kathryn S; Nichols, Jennifer; Reik, Wolf; Bertone, Paul; Smith, Austin

    2017-04-01

    Mouse embryonic stem (ES) cells are locked into self-renewal by shielding from inductive cues. Release from this ground state in minimal conditions offers a system for delineating developmental progression from naïve pluripotency. Here, we examine the initial transition process. The ES cell population behaves asynchronously. We therefore exploited a short-half-life Rex1::GFP reporter to isolate cells either side of exit from naïve status. Extinction of ES cell identity in single cells is acute. It occurs only after near-complete elimination of naïve pluripotency factors, but precedes appearance of lineage specification markers. Cells newly departed from the ES cell state display features of early post-implantation epiblast and are distinct from primed epiblast. They also exhibit a genome-wide increase in DNA methylation, intermediate between early and late epiblast. These findings are consistent with the proposition that naïve cells transition to a distinct formative phase of pluripotency preparatory to lineage priming.

  1. Slugging their way to immortality: driving mammary epithelial cells into a stem cell-like state.

    PubMed

    Soady, Kelly; Smalley, Matthew J

    2012-09-10

    Delineating the molecular factors that define and maintain the mammary stem cell state is vital for understanding normal development and tumourigenesis. A recent study by Guo and colleagues identifies two master transcriptional regulators of mammary stem cells, Slug and Sox9, ectopic expression of which confers stem cell attributes on differentiated mammary epithelial cells. Slug and Sox9 expression was also shown to determine in vivo metastatic potential of human breast cancer cell lines. Understanding these factors in the context of normal lineage differentiation is an important step toward elucidating the mammary epithelial cell hierarchy and the origins of cancer stem cells.

  2. NAAMES-II Expedition: June 1, 201span>6 : Notes from the Field ...

    NASA Website

    August 201span>6; July 201span>6; June 201span>6; May 201span>6; April 201span>6; March 201span>6; February 201span>6; January 201span>6; December 2015; November 2015; October 2015; ...

  3. NAAMES-II Expedition: May 31, 201span>6 : Notes from the Field ...

    NASA Website

    August 201span>6; July 201span>6; June 201span>6; May 201span>6; April 201span>6; March 201span>6; February 201span>6; January 201span>6; December 2015; November 2015; October 2015; ...

  4. Mode localization in multi-span beams

    NASA Technical Reports Server (NTRS)

    Lust, S. D.; Friedmann, P. P.; Bendiksen, O. O.

    1990-01-01

    The influence of numerous effects on mode localization in multi-span beams is investigated. Finite-element methods are used to study localization as a function of: Timoshenko beam effects; beam end conditions; span length, mass, and stiffness imperfection; viscous damping; axial force; transverse support and rotational coupling stiffness; and modeling resolution. Three configurations are studied, commencing with two different two-span models, and culminating in a ten-span configuration resembling lattice-type large space structures. Results indicate that, in addition to the ratio of imperfection to coupling stiffness being an important localization parameter, transverse support stiffness and Timoshenko beam effects greatly affect the tendency of a structure to exhibit localized modes.

  5. Anaesthesia in Sickle-cell States: A Plea for Simplicity

    PubMed Central

    Oduro, K. A.; Searle, J. F.

    1972-01-01

    505 patients with various haemoglobinopathies were given a general anaesthetic between January 1970 and February 1972. One patient with haemoglobin SC disease and one patient with sickle-cell trait (HbAS) died postoperatively. Four other patients who were sickling positive, but whose genotypes were unknown, died, one from sickle-cell crisis precipitated by haemorrhage. A simple anaesthetic technique together with good postoperative care can provide safe general anaesthesia for patients with sickle-cell states. A plea is made for simplicity in the anaesthetic management of these patients. PMID:4643397

  6. Dynamic Pluripotent Stem Cell States and Their Applications.

    PubMed

    Wu, Jun; Izpisua Belmonte, Juan Carlos

    2015-11-05

    Embryonic pluripotency can be recapitulated in vitro by a spectrum of pluripotent stem cell states stabilized with different culture conditions. Their distinct spatiotemporal characteristics provide an unprecedented tool for the study of early human development. The newly unveiled ability of some stem cell types for crossing xeno-barriers will facilitate the generation of interspecies chimeric embryos from distant species, including humans. When combined with efficient zygote genome editing technologies, xenogeneic human pluripotent stem cells may also open new frontiers for regenerative medicine applications, including the possibility of generating human organs in animals via interspecies chimeric complementation.

  7. Social network sampling using spanning trees

    NASA Astrophysics Data System (ADS)

    Jalali, Zeinab S.; Rezvanian, Alireza; Meybodi, Mohammad Reza

    2016-12-01

    Due to the large scales and limitations in accessing most online social networks, it is hard or infeasible to directly access them in a reasonable amount of time for studying and analysis. Hence, network sampling has emerged as a suitable technique to study and analyze real networks. The main goal of sampling online social networks is constructing a small scale sampled network which preserves the most important properties of the original network. In this paper, we propose two sampling algorithms for sampling online social networks using spanning trees. The first proposed sampling algorithm finds several spanning trees from randomly chosen starting nodes; then the edges in these spanning trees are ranked according to the number of times that each edge has appeared in the set of found spanning trees in the given network. The sampled network is then constructed as a sub-graph of the original network which contains a fraction of nodes that are incident on highly ranked edges. In order to avoid traversing the entire network, the second sampling algorithm is proposed using partial spanning trees. The second sampling algorithm is similar to the first algorithm except that it uses partial spanning trees. Several experiments are conducted to examine the performance of the proposed sampling algorithms on well-known real networks. The obtained results in comparison with other popular sampling methods demonstrate the efficiency of the proposed sampling algorithms in terms of Kolmogorov-Smirnov distance (KSD), skew divergence distance (SDD) and normalized distance (ND).

  8. Heat stress-induced life span extension in yeast.

    PubMed

    Shama, S; Lai, C Y; Antoniazzi, J M; Jiang, J C; Jazwinski, S M

    1998-12-15

    The yeast Saccharomyces cerevisiae has a limited life span that can be measured by the number of times individual cells divide. Several genetic manipulations have been shown to prolong the yeast life span. However, environmental effects that extend longevity have been largely ignored. We have found that mild, nonlethal heat stress extended yeast life span when it was administered transiently early in life. The increased longevity was due to a reduction in the mortality rate that persisted over many cell divisions (generations) but was not permanent. The genes RAS1 and RAS2 were necessary to observe this effect of heat stress. The RAS2 gene is consistently required for maintenance of life span when heat stress is chronic or in its extension when heat stress is transient or absent altogether. RAS1, on the other hand, appears to have a role in signaling life extension induced by transient, mild heat stress, which is distinct from its life-span-curtailing effect in the absence of stress and its lack of involvement in the response to chronic heat stress. This distinction between the RAS genes may be partially related to their different effects on growth-promoting genes and stress-responsive genes. The ras2 mutation clearly hindered resumption of growth and recovery from stress, while the ras1 mutation did not. The HSP104 gene, which is largely responsible for induced thermotolerance in yeast, was necessary for life extension induced by transient heat stress. An interaction between mitochondrial petite mutations and heat stress was found, suggesting that mitochondria may be necessary for life extension by transient heat stress. The results raise the possibility that the RAS genes and mitochondria may play a role in the epigenetic inheritance of reduced mortality rate afforded by transient, mild heat stress.

  9. 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

  10. 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

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

    PubMed

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

    2015-11-01

    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 are sparse, comprising on the order of 1,000 unique reads. However, by assaying thousands of ES cells, we identify a spectrum of subpopulations 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.

  12. 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.

  13. 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.

  14. Oxidative Stress Tolerance, Adenylate Cyclase, and Autophagy Are Key Players in the Chronological Life Span of Saccharomyces cerevisiae during Winemaking

    PubMed Central

    Orozco, Helena; Matallana, Emilia

    2012-01-01

    Most grape juice fermentation takes place when yeast cells are in a nondividing state called the stationary phase. Under such circumstances, we aimed to identify the genetic determinants controlling longevity, known as the chronological life span. We identified commercial strains with both short (EC1118) and long (CSM) life spans in laboratory growth medium and compared them under diverse conditions. Strain CSM shows better tolerance to stresses, including oxidative stress, in the stationary phase. This is reflected during winemaking, when this strain has an increased maximum life span. Compared to EC1118, CSM overexpresses a mitochondrial rhodanese gene-like gene, RDL2, whose deletion leads to increased reactive oxygen species production at the end of fermentation and a correlative loss of viability at this point. EC1118 shows faster growth and higher expression of glycolytic genes, and this is related to greater PKA activity due to the upregulation of the adenylate cyclase gene. This phenotype has been linked to the presence of a δ element in its promoter, whose removal increases the life span. Finally, EC1118 exhibits a higher level of protein degradation by autophagy, which might help achieve fast growth at the expense of cellular structures and may be relevant for long-term survival under winemaking conditions. PMID:22327582

  15. Component Analysis of Simple Span vs. Complex Span Adaptive Working Memory Exercises: A Randomized, Controlled Trial

    PubMed Central

    Gibson, Bradley S.; Kronenberger, William G.; Gondoli, Dawn M.; Johnson, Ann C.; Morrissey, Rebecca A.; Steeger, Christine M.

    2012-01-01

    There has been growing interest in using adaptive training interventions such as Cogmed-RM to increase the capacity of working memory (WM), but this intervention may not be optimally designed. For instance, Cogmed-RM can target the primary memory (PM) component of WM capacity, but not the secondary memory (SM) component. The present study hypothesized that Cogmed-RM does not target SM capacity because the simple span exercises it uses may not cause a sufficient amount of information to be lost from PM during training. To investigate, we randomly assigned participants to either a standard (simple span; N = 31) or a modified (complex span; N = 30) training condition. The main findings showed that SM capacity did not improve, even in the modified training condition. Hence, the potency of span-based WM interventions cannot be increased simply by converting simple span exercises into complex span exercises. PMID:23066524

  16. 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.

  17. Method of preparing an electrochemical cell in uncharged state

    DOEpatents

    Shimotake, Hiroshi; Bartholme, Louis G.; Arntzen, John D.

    1977-02-01

    A secondary electrochemical cell is assembled in an uncharged state for the preparation of a lithium alloy-transition metal sulfide cell. The negative electrode includes a material such as aluminum or silicon for alloying with lithium as the cell is charged. The positive electrode is prepared by blending particulate lithium sulfide, transition metal powder and electrolytic salt in solid phase. The mixture is simultaneously heated to a temperature in excess of the melting point of the electrolyte and pressed onto an electrically conductive substrate to form a plaque. The plaque is assembled as a positive electrode within the cell. During the first charge cycle lithium alloy is formed within the negative electrode and transition metal sulfide such as iron sulfide is produced within the positive electrode.

  18. Single-cell analysis of mixed-lineage states leading to a binary cell fate choice.

    PubMed

    Olsson, Andre; Venkatasubramanian, Meenakshi; Chaudhri, Viren K; Aronow, Bruce J; Salomonis, Nathan; Singh, Harinder; Grimes, H Leighton

    2016-09-29

    Delineating hierarchical cellular states, including rare intermediates and the networks of regulatory genes that orchestrate cell-type specification, are continuing challenges for developmental biology. Single-cell RNA sequencing is greatly accelerating such research, given its power to provide comprehensive descriptions of genomic states and their presumptive regulators. Haematopoietic multipotential progenitor cells, as well as bipotential intermediates, manifest mixed-lineage patterns of gene expression at a single-cell level. Such mixed-lineage states may reflect the molecular priming of different developmental potentials by co-expressed alternative-lineage determinants, namely transcription factors. Although a bistable gene regulatory network has been proposed to regulate the specification of either neutrophils or macrophages, the nature of the transition states manifested in vivo, and the underlying dynamics of the cell-fate determinants, have remained elusive. Here we use single-cell RNA sequencing coupled with a new analytic tool, iterative clustering and guide-gene selection, and clonogenic assays to delineate hierarchical genomic and regulatory states that culminate in neutrophil or macrophage specification in mice. We show that this analysis captured prevalent mixed-lineage intermediates that manifested concurrent expression of haematopoietic stem cell/progenitor and myeloid progenitor cell genes. It also revealed rare metastable intermediates that had collapsed the haematopoietic stem cell/progenitor gene expression programme, instead expressing low levels of the myeloid determinants, Irf8 and Gfi1 (refs 9, 10, 11, 12, 13). Genetic perturbations and chromatin immunoprecipitation followed by sequencing revealed Irf8 and Gfi1 as key components of counteracting myeloid-gene-regulatory networks. Combined loss of these two determinants 'trapped' the metastable intermediate. We propose that mixed-lineage states are obligatory during cell-fate specification

  19. Solid-state photogalvanic dye-sensitized solar cells.

    PubMed

    Berhe, Seare A; Gobeze, Habtom B; Pokharel, Sundari D; Park, Eunsol; Youngblood, W Justin

    2014-07-09

    Photogalvanic cells are photoelectrochemical systems wherein the semiconductor electrode is not a participant in primary photoinduced charge formation. The discovery of photoelectrochemical systems that successfully exploit secondary (thermal) electron injection at dye-semiconductor interfaces may enable studies of electron transfer at minimal driving force for electron injection into the semiconductor. In this study, we have examined thermal electron transfer from molecular sensitizers to nanostructured semiconductor electrodes composed of titanium dioxide nanorods by means of transient spectroscopy and the assembly and testing of photoelectrochemical cells. Electron-accepting molecular dyes have been studied alongside an arylamine electron donor. Thermal injection is estimated for a naphthacenequinone radical anion as a multiexponential decay process with initial decay lifetimes of 6 and 27 ps. The ambient electric field present during charge separation at a surface-adsorbed dye monolayer causes Stark shifts of the radical ion pair absorbance peaks that confounded kinetic estimation of thermal injection for a fullerene sensitizer. Electron-accepting dyes that operate by thermal injection into titanium dioxide function better in solid-state photoelectrochemical cells than in liquid-junction cells due to the kinetic advantage of solid-state cells with respect to photoinduced acceptor-quenching to form the necessary radical anion sensitizers.

  20. Life span extension and cancer risk: myths and reality.

    PubMed

    Anisimov, V N

    2001-07-01

    between the type of geroprotector-induced aging delay and the pattern of tumour development in the same population of animals. The first type of geroprotectors did not influence the incidence of tumour but increased tumour latency. The second type of geroprotectors was effective both in the inhibition of spontaneous carcinogenesis and the increase in tumour latency. Certain drugs of the third type raised tumour incidence in the exposed populations. According to the multistage model, geroprotectors either inhibit or accelerate the passage of carcinogen-exposed cells form one stage to another. Thus, the efficacy of geroprotectors as preventive means of cancer development will decrease with respect to the age of exposure onset. Recommendations of the available drugs and means of life span increase should be carefully reconsidered under the international scientific control.

  1. Phenotypic Profiling Reveals that Candida albicans Opaque Cells Represent a Metabolically Specialized Cell State Compared to Default White Cells

    PubMed Central

    Ene, Iuliana V.; Lohse, Matthew B.; Vladu, Adrian V.; Morschhäuser, Joachim; Johnson, Alexander D.

    2016-01-01

    ABSTRACT The white-opaque switch is a bistable, epigenetic transition affecting multiple traits in Candida albicans including mating, immunogenicity, and niche specificity. To compare how the two cell states respond to external cues, we examined the fitness, phenotypic switching, and filamentation properties of white cells and opaque cells under 1,440 different conditions at 25°C and 37°C. We demonstrate that white and opaque cells display striking differences in their integration of metabolic and thermal cues, so that the two states exhibit optimal fitness under distinct conditions. White cells were fitter than opaque cells under a wide range of environmental conditions, including growth at various pHs and in the presence of chemical stresses or antifungal drugs. This difference was exacerbated at 37°C, consistent with white cells being the default state of C. albicans in the mammalian host. In contrast, opaque cells showed greater fitness than white cells under select nutritional conditions, including growth on diverse peptides at 25°C. We further demonstrate that filamentation is significantly rewired between the two states, with white and opaque cells undergoing filamentous growth in response to distinct external cues. Genetic analysis was used to identify signaling pathways impacting the white-opaque transition both in vitro and in a murine model of commensal colonization, and three sugar sensing pathways are revealed as regulators of the switch. Together, these findings establish that white and opaque cells are programmed for differential integration of metabolic and thermal cues and that opaque cells represent a more metabolically specialized cell state than the default white state. PMID:27879329

  2. Differentiation state affects morphine induced cell regulation in neuroblastoma cultured cells.

    PubMed

    Fiore, Giovina; Ghelardini, Carla; Bruni, Giancarlo; Guarna, Massimo; Bianchi, Enrica

    2013-10-25

    Neuroblastoma (NB) is the most common extracranial solid cancer in childhood and the most common cancer in infancy. Our purpose was to investigate in vitro how cancer cell survival occurs in presence of morphine in undifferentiated and differentiated SHSY-5Y human neuroblastoma cultured cell line. Exposure of differentiated cells to morphine dose-dependently induced apoptosis in these cells through c-Jun N-terminal kinase (JNK)/caspase pathway. Otherwise, morphine induced activation for mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway, caused positive regulation of cell survival in undifferentiated cells. Therefore, cell differentiation state bimodally affects the cellular regulation activity triggered by morphine in isolated cultured neuroblastoma cells raising concerns about the application of morphine to this type of cancer patients.

  3. 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.

  4. Phenotypic Profiling Reveals that Candida albicans Opaque Cells Represent a Metabolically Specialized Cell State Compared to Default White Cells.

    PubMed

    Ene, Iuliana V; Lohse, Matthew B; Vladu, Adrian V; Morschhäuser, Joachim; Johnson, Alexander D; Bennett, Richard J

    2016-11-22

    The white-opaque switch is a bistable, epigenetic transition affecting multiple traits in Candida albicans including mating, immunogenicity, and niche specificity. To compare how the two cell states respond to external cues, we examined the fitness, phenotypic switching, and filamentation properties of white cells and opaque cells under 1,440 different conditions at 25°C and 37°C. We demonstrate that white and opaque cells display striking differences in their integration of metabolic and thermal cues, so that the two states exhibit optimal fitness under distinct conditions. White cells were fitter than opaque cells under a wide range of environmental conditions, including growth at various pHs and in the presence of chemical stresses or antifungal drugs. This difference was exacerbated at 37°C, consistent with white cells being the default state of C. albicans in the mammalian host. In contrast, opaque cells showed greater fitness than white cells under select nutritional conditions, including growth on diverse peptides at 25°C. We further demonstrate that filamentation is significantly rewired between the two states, with white and opaque cells undergoing filamentous growth in response to distinct external cues. Genetic analysis was used to identify signaling pathways impacting the white-opaque transition both in vitro and in a murine model of commensal colonization, and three sugar sensing pathways are revealed as regulators of the switch. Together, these findings establish that white and opaque cells are programmed for differential integration of metabolic and thermal cues and that opaque cells represent a more metabolically specialized cell state than the default white state. Epigenetic transitions are an important mechanism by which microbes adapt to external stimuli. For Candida albicans, such transitions are crucial for adaptation to complex, fluctuating environments, and therefore contribute to its success as a human pathogen. The white-opaque switch

  5. 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.

  6. 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.

  7. Identifying states along the hematopoietic stem cell differentiation hierarchy with single cell specificity via Raman spectroscopy

    PubMed Central

    Ilin, Yelena; Choi, Ji Sun; Harley, Brendan A. C.; Kraft, Mary L.

    2015-01-01

    A major challenge for expanding specific types of hematopoietic cells ex vivo for the treatment of blood cell pathologies is identifying the combinations of cellular and matrix cues that direct hematopoietic stem cells (HSC) to self-renew or differentiate into cell populations ex vivo. Microscale screening platforms enable minimizing the number of rare HSCs required to screen the effects of numerous cues on HSC fate decisions. These platforms create a strong demand for label-free methods that accurately identify the fate decisions of individual hematopoietic cells at specific locations on the platform. We demonstrate the capacity to identify discrete cells along the HSC differentiation hierarchy via multivariate analysis of Raman spectra. Notably, cell state identification is accurate for individual cells and independent of the biophysical properties of the functionalized polyacrylamide gels upon which these cells are cultured. We report partial least-squares discriminant analysis (PLS-DA) models of single cell Raman spectra enable identifying four dissimilar hematopoietic cell populations across the HSC lineage specification. Successful discrimination was obtained for a population enriched for long-term repopulating HSCs (LT-HSCs) versus their more differentiated progeny, including closely-related short-term repopulating HSCs (ST-HSCs), and fully differentiated lymphoid (B cells) and myeloid (granulocytes) cells. The lineage-specific differentiation states of cells from these four sub-populations were accurately identified independent of the stiffness of the underlying biomaterial substrate, indicating subtle spectral variations that discriminated these populations were not masked by features from the culture substrate. This approach enables identifying the lineage-specific differentiation stages of hematopoietic cells on biomaterial substrates of differing composition, and may facilitate correlating hematopoietic cell fate decisions with the extrinsic cues that

  8. Human mesenchymal stem cells promote survival of T cells in a quiescent state.

    PubMed

    Benvenuto, Federica; Ferrari, Stefania; Gerdoni, Ezio; Gualandi, Francesca; Frassoni, Francesco; Pistoia, Vito; Mancardi, Gianluigi; Uccelli, Antonio

    2007-07-01

    Mesenchymal stem cells (MSC) are part of the bone marrow that provides signals supporting survival and growth of bystander hematopoietic stem cells (HSC). MSC modulate also the immune response, as they inhibit proliferation of lymphocytes. In order to investigate whether MSC can support survival of T cells, we investigated MSC capacity of rescuing T lymphocytes from cell death induced by different mechanisms. We observed that MSC prolong survival of unstimulated T cells and apoptosis-prone thymocytes cultured under starving conditions. MSC rescued T cells from activation induced cell death (AICD) by downregulation of Fas receptor and Fas ligand on T cell surface and inhibition of endogenous proteases involved in cell death. MSC dampened also Fas receptor mediated apoptosis of CD95 expressing Jurkat leukemic T cells. In contrast, rescue from AICD was not associated with a significant change of Bcl-2, an inhibitor of apoptosis induced by cell stress. Accordingly, MSC exhibited a minimal capacity of rescuing Jurkat cells from chemically induced apoptosis, a process disrupting the mitochondrial membrane potential regulated by Bcl-2. These results suggest that MSC interfere with the Fas receptor regulated process of programmed cell death. Overall, MSC can inhibit proliferation of activated T cells while supporting their survival in a quiescent state, providing a model of their activity inside the HSC niche. Disclosure of potential conflicts of interest is found at the end of this article.

  9. 23 | September | 201span>6 | ISS On-Orbit Status Report

    NASA Website

    Opening of Lab MCA Hand Valve 01; HRF2 Supply Kit Resupply; ... August 201span>6; July 201span>6; June 201span>6; May 201span>6; April 201span>6; March 201span>6; February 201span>6; ...

  10. Essential role for autophagy in life span extension

    PubMed Central

    Madeo, Frank; Zimmermann, Andreas; Maiuri, Maria Chiara; Kroemer, Guido

    2015-01-01

    Life and health span can be prolonged by calorie limitation or by pharmacologic agents that mimic the effects of caloric restriction. Both starvation and the genetic inactivation of nutrient signaling converge on the induction of autophagy, a cytoplasmic recycling process that counteracts the age-associated accumulation of damaged organelles and proteins as it improves the metabolic fitness of cells. Here we review experimental findings indicating that inhibition of the major nutrient and growth-related signaling pathways as well as the upregulation of anti-aging pathways mediate life span extension via the induction of autophagy. Furthermore, we discuss mounting evidence suggesting that autophagy is not only necessary but, at least in some cases, also sufficient for increasing longevity. PMID:25654554

  11. 41. Detail showing meeting of two fixed land span segments, ...

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

    41. Detail showing meeting of two fixed land span segments, bridge land span at left, viaduct at right. VIEW NORTH - Broadway Bridge, Spanning Foundry Street, MBTA Yard, Fort Point Channel, & Lehigh Street, Boston, Suffolk County, MA

  12. 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

  13. 26. Central compression lock, north span facing north. Compression lock ...

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

    26. Central compression lock, north span facing north. Compression lock locks two spans together at highest point. There are three compression locks. - Henry Ford Bridge, Spanning Cerritos Channel, Los Angeles-Long Beach Harbor, Los Angeles, Los Angeles County, CA

  14. 5. LOOKING SOUTHEAST, VIEW OF CENTER TURN SPAN AND SOUTHWESTERNMOST ...

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

    5. LOOKING SOUTHEAST, VIEW OF CENTER TURN SPAN AND SOUTHWESTERNMOST SPAN FROM ADJACENT INTERSTATE 40 BRIDGE - St. Francis River Bridge, Spanning St. Francis River at U.S. Highway 70, Forrest City, St. Francis County, AR

  15. 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

  16. 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

  17. 20. Detail view of west swing span abutment through swing ...

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

    20. Detail view of west swing span abutment through swing span truss, looking north - India Point Railroad Bridge, Spanning Seekonk River between Providence & East Providence, Providence, Providence County, RI

  18. 20. DETAIL OF WEST ANCHOR SPAN, CANTILEVER ARMS AND WEST ...

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

    20. DETAIL OF WEST ANCHOR SPAN, CANTILEVER ARMS AND WEST HALF OF SUSPENDED SPAN OF THROUGH TRUSS. VIEW TO NORTHEAST. - MacArthur Bridge, Spanning Mississippi River on Highway 34 between IA & IL, Burlington, Des Moines County, IA

  19. The ground state of embryonic stem cell self-renewal

    PubMed Central

    Ying, Qi-Long; Wray, Jason; Nichols, Jennifer; Batlle-Morera, Laura; Doble, Bradley; Woodgett, James; Cohen, Philip; Smith, Austin

    2016-01-01

    In the three decades since pluripotent mouse embryonic stem (ES) cells were first described1,2 they have been derived and maintained by using various empirical combinations of feeder cells, conditioned media, cytokines, growth factors, hormones, fetal calf serum, and serum extracts1–7. Consequently ES-cell self-renewal is generally considered to be dependent on multifactorial stimulation of dedicated transcriptional circuitries, pre-eminent among which is the activation of STAT3 by cytokines (ref. 8). Here we show, however, that extrinsic stimuli are dispensable for the derivation, propagation and pluripotency of ES cells. Self-renewal is enabled by the elimination of differentiation-inducing signalling from mitogen-activated protein kinase. Additional inhibition of glycogen synthase kinase 3 consolidates biosynthetic capacity and suppresses residual differentiation. Complete bypass of cytokine signalling is confirmed by isolating ES cells genetically devoid of STAT3. These findings reveal that ES cells have an innate programme for self-replication that does not require extrinsic instruction. This property may account for their latent tumorigenicity. The delineation of minimal requirements for self-renewal now provides a defined platform for the precise description and dissection of the pluripotent state. PMID:18497825

  20. 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

  1. Direct reprogramming of adult cells: avoiding the pluripotent state.

    PubMed

    Kelaini, Sophia; Cochrane, Amy; Margariti, Andriana

    2014-01-01

    The procedure of using mature, fully differentiated cells and inducing them toward other cell types while bypassing an intermediate pluripotent state is termed direct reprogramming. Avoiding the pluripotent stage during cellular conversions can be achieved either through ectopic expression of lineage-specific factors (transdifferentiation) or a direct reprogramming process that involves partial reprogramming toward the pluripotent stage. Latest advances in the field seek to alleviate concerns that include teratoma formation or retroviral usage when it comes to delivering reprogramming factors to cells. They also seek to improve efficacy and efficiency of cellular conversion, both in vitro and in vivo. The final products of this reprogramming approach could be then directly implemented in regenerative and personalized medicine.

  2. 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

  3. 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.

  4. Analyzing Reaction in the U.S. to the Chinese Pro-Democracy Movement Using C-SPAN as a Data Base.

    ERIC Educational Resources Information Center

    Schnell, Jim

    This paper describes how videotapes of C-SPAN programs were used to aid research and teaching of cross-cultural issues related to United States-China relations. The specific focus of the C-SPAN programs discussed was the reaction in the United States to the Chinese pro-democracy movement. The use of C-SPAN resource can benefit student…

  5. 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…

  6. 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…

  7. 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…

  8. Complex Systems: Boundary-Spanning Training Techniques.

    ERIC Educational Resources Information Center

    Adler, Terry; Black, Janice A.; Loveland, John P.

    2003-01-01

    The complex system dynamics of organizations and the influence of information technology requires workers to have boundary-spanning skills and the ability to work in virtual teams. The integrated business core is an experiential graduate-level course designed to develop these skills; it is also adaptable for inservice training. (Contains 69…

  9. School Organization: Grade Span. Trends and Issues.

    ERIC Educational Resources Information Center

    Renchler, Ron

    This paper examines grade spans (grade configurations) and their importance in community school systems. Research has shown that geographic location often dictates the kind of grade configuration districts use. Furthermore, every grade configuration has strengths and weaknesses, and school officials must focus on developing the positive potential…

  10. 25. DETAIL VIEW OF COMMEMORATIVE NAMEPLATE PLAQUE, NORTH END SPAN ...

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

    25. DETAIL VIEW OF COMMEMORATIVE NAMEPLATE PLAQUE, NORTH END SPAN - East Bloomsburg Bridge, Spanning Susquehanna River at Pennsylvania Route 487 (Legislative Route 283), Bloomsburg, Columbia County, PA

  11. 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

  12. 22. Detail view of approach span, showing bottom chord construction, ...

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

    22. Detail view of approach span, showing bottom chord construction, looking east - India Point Railroad Bridge, Spanning Seekonk River between Providence & East Providence, Providence, Providence County, RI

  13. 13. View of swing span showing bridge operator's control cabin, ...

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

    13. View of swing span showing bridge operator's control cabin, looking northeast - India Point Railroad Bridge, Spanning Seekonk River between Providence & East Providence, Providence, Providence County, RI

  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. 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.

  16. Modeling of Cancer Stem Cell State Transitions Predicts Therapeutic Response

    PubMed Central

    Sehl, Mary E.; Shimada, Miki; Landeros, Alfonso; Lange, Kenneth; Wicha, Max S.

    2015-01-01

    Cancer stem cells (CSCs) possess capacity to both self-renew and generate all cells within a tumor, and are thought to drive tumor recurrence. Targeting the stem cell niche to eradicate CSCs represents an important area of therapeutic development. The complex nature of many interacting elements of the stem cell niche, including both intracellular signals and microenvironmental growth factors and cytokines, creates a challenge in choosing which elements to target, alone or in combination. Stochastic stimulation techniques allow for the careful study of complex systems in biology and medicine and are ideal for the investigation of strategies aimed at CSC eradication. We present a mathematical model of the breast cancer stem cell (BCSC) niche to predict population dynamics during carcinogenesis and in response to treatment. Using data from cell line and mouse xenograft experiments, we estimate rates of interconversion between mesenchymal and epithelial states in BCSCs and find that EMT/MET transitions occur frequently. We examine bulk tumor growth dynamics in response to alterations in the rate of symmetric self-renewal of BCSCs and find that small changes in BCSC behavior can give rise to the Gompertzian growth pattern observed in breast tumors. Finally, we examine stochastic reaction kinetic simulations in which elements of the breast cancer stem cell niche are inhibited individually and in combination. We find that slowing self-renewal and disrupting the positive feedback loop between IL-6, Stat3 activation, and NF-κB signaling by simultaneous inhibition of IL-6 and HER2 is the most effective combination to eliminate both mesenchymal and epithelial populations of BCSCs. Predictions from our model and simulations show excellent agreement with experimental data showing the efficacy of combined HER2 and Il-6 blockade in reducing BCSC populations. Our findings will be directly examined in a planned clinical trial of combined HER2 and IL-6 targeted therapy in HER2

  17. Perovskite enhanced solid state ZnO solar cells

    NASA Astrophysics Data System (ADS)

    Loh, L.; Briscoe, J.; Dunn, S.

    2013-12-01

    This paper will report on the design, fabrication and testing of a solid-state perovskite enhanced ZnO solar cell. The p-type perovskite material used is bismuth ferrite (BFO) which has an absorption range within the blue range of the visible light spectrum. The solid state solar cell, was sensitized with N719 dye and used a CuSCN hole conductor. A disadvantage of ZnO is its poor chemical stability in acidic and corrosive environments. As chemical solution techniques were used in depositing BFO, a buffer method using an aminosilane ((3-aminopropyltrimethoxysilane or H2N(CH2)3Si(OCH3)3)) coating was used to provide a protective coating on the ZnO nanorods before the BFO film was spin coated onto the ZnO nanorods. The photovoltaic performance of the solar cells were tested using a Keithley 2400 source meter under 100mW/cm2, AM 1.5G simulated sunlight, where improvements in Jsc and efficiency were observed. The BFO was able to harness more electrons and also acted as a buffer from electron recombination.

  18. 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.

  19. Cell-Type-Specific Chromatin States Differentially Prime Squamous Cell Carcinoma Tumor-Initiating Cells for Epithelial to Mesenchymal Transition.

    PubMed

    Latil, Mathilde; Nassar, Dany; Beck, Benjamin; Boumahdi, Soufiane; Wang, Li; Brisebarre, Audrey; Dubois, Christine; Nkusi, Erwin; Lenglez, Sandrine; Checinska, Agnieszka; Vercauteren Drubbel, Alizée; Devos, Michael; Declercq, Wim; Yi, Rui; Blanpain, Cédric

    2017-02-02

    Epithelial to mesenchymal transition (EMT) in cancer cells has been associated with metastasis, stemness, and resistance to therapy. Some tumors undergo EMT while others do not, which may reflect intrinsic properties of their cell of origin. However, this possibility is largely unexplored. By targeting the same oncogenic mutations to discrete skin compartments, we show that cell-type-specific chromatin and transcriptional states differentially prime tumors to EMT. Squamous cell carcinomas (SCCs) derived from interfollicular epidermis (IFE) are generally well differentiated, while hair follicle (HF) stem cell-derived SCCs frequently exhibit EMT, efficiently form secondary tumors, and possess increased metastatic potential. Transcriptional and epigenomic profiling revealed that IFE and HF tumor-initiating cells possess distinct chromatin landscapes and gene regulatory networks associated with tumorigenesis and EMT that correlate with accessibility of key epithelial and EMT transcription factor binding sites. These findings highlight the importance of chromatin states and transcriptional priming in dictating tumor phenotypes and EMT.

  20. 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.

  1. Increase in Testicular Germ Cell Tumor Incidence among Hispanic Adolescents and Young Adults in the United States

    PubMed Central

    Chien, Franklin L.; Schwartz, Stephen M.; Johnson, Rebecca H.

    2014-01-01

    Background While rising incidence rates of testicular germ cell tumors have been well documented in white men, relatively little is known about rates in men of Hispanic origin. In the current study, we compared germ cell tumor trends between men of Hispanic and non-Hispanic origin as a function of age at diagnosis. Methods We analyzed testicular germ cell tumor incidence trends in white men by Hispanic ethnicity in two datasets of the National Cancer Institute’s Surveillance, Epidemiology, and End Results program, spanning 1992 to 2010 and 2000 to 2010, and sampling 15% and 28% of the United States population, respectively. Rates were age-adjusted to the year 2000 United States standard population. Results Between 1992 and 2010, the annual incidence of testicular germ cell tumors in 15- to 39-year-old Hispanic whites increased 58% from 7.18 cases per 100,000 in 1992 to 11.34 cases per 100,000 by 2010 (p < 1×10−9). Their incidence rates increased in metropolitan areas for both seminoma and non-seminoma subtypes and for all stages at diagnosis. In the same 19-year interval, incidence among non-Hispanic white young adults increased 7%, from 12.41 to 13.22 per 100,000. During the 2000 to 2010 interval, no significant trends were observed in incidence among non-Hispanic whites. Conclusion There has been a recent substantial increase in testicular germ cell tumor incidence among Hispanic adolescents and young adults in the United States. Similar trends were not observed in non-Hispanic whites. PMID:25044313

  2. The cell-cycle state of stem cells determines cell fate propensity.

    PubMed

    Pauklin, Siim; Vallier, Ludovic

    2013-09-26

    Self-renewal and differentiation of stem cells are fundamentally associated with cell-cycle progression to enable tissue specification, organ homeostasis, and potentially tumorigenesis. However, technical challenges have impaired the study of the molecular interactions coordinating cell fate choice and cell-cycle progression. Here, we bypass these limitations by using the FUCCI reporter system in human pluripotent stem cells and show that their capacity of differentiation varies during the progression of their cell cycle. These mechanisms are governed by the cell-cycle regulators cyclin D1-3 that control differentiation signals such as the TGF-β-Smad2/3 pathway. Conversely, cell-cycle manipulation using a small molecule directs differentiation of hPSCs and provides an approach to generate cell types with a clinical interest. Our results demonstrate that cell fate decisions are tightly associated with the cell-cycle machinery and reveal insights in the mechanisms synchronizing differentiation and proliferation in developing tissues.

  3. Steady state peripheral blood provides cells with functional and metabolic characteristics of real hematopoietic stem cells.

    PubMed

    Bourdieu, Antonin; Avalon, Maryse; Lapostolle, Véronique; Ismail, Sadek; Mombled, Margaux; Debeissat, Christelle; Guérinet, Marianne; Duchez, Pascale; Chevaleyre, Jean; Vlaski-Lafarge, Marija; Villacreces, Arnaud; Praloran, Vincent; Ivanovic, Zoran; Brunet de la Grange, Philippe

    2018-01-01

    Hematopoietic stem cells (HSCs), which are located in the bone marrow, also circulate in cord and peripheral blood. Despite high availability, HSCs from steady state peripheral blood (SSPB) are little known and not used for research or cell therapy. We thus aimed to characterize and select HSCs from SSPB by a direct approach with a view to delineating their main functional and metabolic properties and the mechanisms responsible for their maintenance. We chose to work on Side Population (SP) cells which are highly enriched in HSCs in mouse, human bone marrow, and cord blood. However, no SP cells from SSBP have as yet been characterized. Here we showed that SP cells from SSPB exhibited a higher proliferative capacity and generated more clonogenic progenitors than non-SP cells in vitro. Furthermore, xenotransplantation studies on immunodeficient mice demonstrated that SP cells are up to 45 times more enriched in cells with engraftment capacity than non-SP cells. From a cell regulation point of view, we showed that SP activity depended on O2 concentrations close to those found in HSC niches, an effect which is dependent on both hypoxia-induced factors HIF-1α and HIF-2α. Moreover SP cells displayed a reduced mitochondrial mass and, in particular, a lower mitochondrial activity compared to non-SP cells, while they exhibited a similar level of glucose incorporation. These results provided evidence that SP cells from SSPB displayed properties of very primitive cells and HSC, thus rendering them an interesting model for research and cell therapy. © 2017 Wiley Periodicals, Inc.

  4. 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.

  5. Career development: a life span issue.

    PubMed

    Sterns, H L; Dorsett, J G

    1994-01-01

    One of the challenges for individuals pursuing a career throughout their life span is how to maintain a high level of professional competence. As the composition of the workforce changes, and new technologies are developed, workers are faced with changing job demands and pressures. A major issue for the 1990s is how long a worker's skills will remain current. With rapid technological changes, workers may find it necessary to update continually their knowledge, skills, and abilities or risk becoming obsolete. Factors such as individuals' motivation and attitudes and organizational climate can contribute to choices regarding career development. Current research on the factors that contribute to career development activities is reviewed, along with the impact of multiple career transitions throughout the life span. Interventions such as retraining and outplacement, which allow individuals in later life to continue work, change jobs, and further develop their careers, are also discussed.

  6. 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

  7. Spatial abilities across the adult life span.

    PubMed

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

    2014-02-01

    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 nonlinear age-related effects for spatial visualization and perspective taking but linear effects for mental rotation; few or no age-related effects were found for spatial self-assessments. Working memory accounted for only a small proportion of the variance in all spatial tasks and had no effect on spatial self-assessments. Overall, our findings suggest that the influence of age on spatial skills across the adult life span is considerable, but the effects of age change as a function of the spatial task considered, and the effect on spatial self-assessment is more marginal.

  8. 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…

  9. 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

  10. Improving Memory Span in Children with Down Syndrome

    ERIC Educational Resources Information Center

    Conners, F. A.; Rosenquist, C. J.; Arnett, L.; Moore, M. S.; Hume, L. E.

    2008-01-01

    Background: Down syndrome (DS) is characterized by impaired memory span, particularly auditory verbal memory span. Memory span is linked developmentally to several language capabilities, and may be a basic capacity that enables language learning. If children with DS had better memory span, they might benefit more from language intervention. The…

  11. 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

  12. Improving Memory Span in Children with Down Syndrome

    ERIC Educational Resources Information Center

    Conners, F. A.; Rosenquist, C. J.; Arnett, L.; Moore, M. S.; Hume, L. E.

    2008-01-01

    Background: Down syndrome (DS) is characterized by impaired memory span, particularly auditory verbal memory span. Memory span is linked developmentally to several language capabilities, and may be a basic capacity that enables language learning. If children with DS had better memory span, they might benefit more from language intervention. The…

  13. Extension of Health Span and Life Span in Drosophila by S107 Requires the calstabin Homologue FK506-BP2.

    PubMed

    Kreko-Pierce, Tabita; Azpurua, Jorge; Mahoney, Rebekah E; Eaton, Benjamin A

    2016-12-09

    The accumulation of oxidative damage is strongly linked to age-dependent declines in cell function, but the contribution of oxidative damage to morbidity is still debated. Many organisms seem to tolerate oxidative damage, and the extension of health span and life span by augmenting antioxidant activity has been inconsistent. Here we use the Drosophila model system to investigate the relationship among oxidative stress, health span, and life span. The oxidation-dependent dissociation of the Calstabin protein from the ryanodine receptor has been shown to result in reduced muscle function in mammals. The S107 molecule is able to reestablish this binding resulting in improved muscle function. We find that S107 is able to restore motor function in aging Drosophila to young levels, and this effect of S107 is absent in calstabin (FK506-BP2) mutants. Interestingly, FK506-BP2 mutant flies have reduced sensitivity to the effects of age and oxidative stress on motor function between 7 and 35 days of age. Muscle expression of FK506-BP2 in FK506-BP2 mutants completely restores the sensitivity of motor function to both age and oxidative stress, supporting the idea that the age-dependent decline in motor function in Drosophila requires FK506-BP2 function within the muscle. Although FK506-BP2 mutant flies are found to have less sensitivity to oxidative stress, FK506-BP2 mutants do not live longer than wild type. These results demonstrate that the deleterious effects of oxidation on motor function early in life are the result of a singular event that does not compromise survival.

  14. 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.

  15. 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

  16. Zeb2 Regulates Cell Fate at the Exit from Epiblast State in Mouse Embryonic Stem Cells.

    PubMed

    Stryjewska, Agata; Dries, Ruben; Pieters, Tim; Verstappen, Griet; Conidi, Andrea; Coddens, Kathleen; Francis, Annick; Umans, Lieve; van IJcken, Wilfred F J; Berx, Geert; van Grunsven, Leo A; Grosveld, Frank G; Goossens, Steven; Haigh, Jody J; Huylebroeck, Danny

    2017-03-01

    In human embryonic stem cells (ESCs) the transcription factor Zeb2 regulates neuroectoderm versus mesendoderm formation, but it is unclear how Zeb2 affects the global transcriptional regulatory network in these cell-fate decisions. We generated Zeb2 knockout (KO) mouse ESCs, subjected them as embryoid bodies (EBs) to neural and general differentiation and carried out temporal RNA-sequencing (RNA-seq) and reduced representation bisulfite sequencing (RRBS) analysis in neural differentiation. This shows that Zeb2 acts preferentially as a transcriptional repressor associated with developmental progression and that Zeb2 KO ESCs can exit from their naïve state. However, most cells in these EBs stall in an early epiblast-like state and are impaired in both neural and mesendodermal differentiation. Genes involved in pluripotency, epithelial-to-mesenchymal transition (EMT), and DNA-(de)methylation, including Tet1, are deregulated in the absence of Zeb2. The observed elevated Tet1 levels in the mutant cells and the knowledge of previously mapped Tet1-binding sites correlate with loss-of-methylation in neural-stimulating conditions, however, after the cells initially acquired the correct DNA-methyl marks. Interestingly, cells from such Zeb2 KO EBs maintain the ability to re-adapt to 2i + LIF conditions even after prolonged differentiation, while knockdown of Tet1 partially rescues their impaired differentiation. Hence, in addition to its role in EMT, Zeb2 is critical in ESCs for exit from the epiblast state, and links the pluripotency network and DNA-methylation with irreversible commitment to differentiation. Stem Cells 2017;35:611-625. © 2016 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  17. 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.

  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. Dietary restriction: critical co-factors to separate health span from life span benefits.

    PubMed

    Mendelsohn, Andrew R; Larrick, James W

    2012-10-01

    Dietary restriction (DR), typically a 20%-40% reduction in ad libitum or "normal" nutritional energy intake, has been reported to extend life span in diverse organisms, including yeast, nematodes, spiders, fruit flies, mice, rats, and rhesus monkeys. The magnitude of the life span enhancement appears to diminish with increasing organismal complexity. However, the extent of life span extension has been notoriously inconsistent, especially in mammals. Recently, Mattison et al. reported that DR does not extend life span in rhesus monkeys in contrast to earlier work of Colman et al. Examination of these papers identifies multiple potential confounding factors. Among these are the varied genetic backgrounds and composition of the "normal" and DR diets. In monkeys, the correlation of DR with increased health span is stronger than that seen with life span and indeed may be separable. Recent mechanistic studies in Drosophila implicate non-genetic co-factors such as level of physical activity and muscular fatty acid metabolism in the benefits of DR. These results should be followed up in mammals. Perhaps levels of physical activity among the cohorts of rhesus monkeys contribute to inconsistent DR effects. To understand the maximum potential benefits from DR requires differentiating fundamental effects on aging at the cellular and molecular levels from suppression of age-associated diseases, such as cancer. To that end, it is important that investigators carefully evaluate the effects of DR on biomarkers of molecular aging, such as mutation rate and epigenomic alterations. Several short-term studies show that humans may benefit from DR in as little as 6 months, by achieving lowered fasting insulin levels and improved cardiovascular health. Optimized health span engineering will require a much deeper understanding of DR.

  20. Cell Churches and Stem Cell Marketing in South Korea and the United States.

    PubMed

    Sipp, Douglas

    2016-05-23

    The commercial provision of putative stem cell-based medical interventions in the absence of conclusive evidence of safety and efficacy has formed the basis of an unregulated industry for more than a decade. Many clinics offering such supposed stem cell treatments include statements about the 'ethical' nature of somatic (often colloquially referred to as 'adult' stem cells) stem cells, in specific contrast to human embryonic stem cells (hESCs), which have been the subject of intensive political, legal, and religious controversy since their first derivation in 1998. Christian groups-both Roman Catholic and evangelical Protestant-in many countries have explicitly promoted the medical potential and current-day successes in the clinical application of somatic stem cells, lending indirect support to the activities of businesses marketing stem cells ahead of evidence. In this article, I make a preliminary examination of how the structures and belief systems of certain churches in South Korea and the United States, both of which are home to significant stem cell marketing industries, has complemented other factors, including national biomedical funding initiatives, international economic rivalries, permissive legal structures, which have lent impetus to a problematic and often exploitative sector of biomedical commerce.

  1. Mutant models of prolonged life span.

    PubMed

    Mahler, J F

    2001-01-01

    Aging is an important biological process that affects all creatures. For humans, age-related diseases and the question of why we age and die also have tremendous social and philosophical impact. We can therefore expect that models to study mechanisms of the aging process will always attract much interest. Until recently, the mutant model approach to study molecular mechanisms of aging has been limited to lower animals such as yeast, worms, and flies. However, given the current power of genetic technology in mammals, we can expect that phenotypes of prolonged life span will increasingly be seen in mice and subject to evaluation by pathologists. A brief review of current models is presented.

  2. 01 | February | 201span>6 | ISS On-Orbit Status Report

    NASA Website

    February 201span>6; S M T W T F S « Jan : ... August 201span>6; July 201span>6; June 201span>6; May 201span>6; April 201span>6; March 201span>6; February 201span>6; January 201span>6; December ...

  3. 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

  4. 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.

  5. Drivers' use of handheld cell phones before and after New York State's cell phone law.

    PubMed

    McCartt, Anne T; Braver, Elisa R; Geary, Lori L

    2003-05-01

    In response to public concern about driver distraction from cellular telephones, New York became the first state to ban handheld cell phone use while driving. The law, accompanied by considerable publicity, included a warning phase (November 2001), after which violators could be fined. Until March 2002, fines could be waived if motorists provided proof of purchase of hands-free accessories. Daytime cell phone use among passenger vehicle drivers was observed at controlled intersections 1 month before the law's implementation, after fines could be issued (December 2001), and after waivers were not allowed (March 2002). Use was observed for 37,462 vehicles in four New York communities and 21,315 vehicles in two central Connecticut communities. Driver gender, estimated age, and vehicle type were recorded for cell phone users and a sample of passing motorists. The use rate in New York declined significantly from 2.3% before the law to 1.1% after the law (P < 0.05). Use rates in Connecticut, an adjacent state without a law, did not change. In both states, use was higher among drivers of sport utility vehicles (P < 0.05) and minimal among drivers ages 60 or older. In New York, observed use declined among drivers younger than 60, male and female drivers, and all vehicle types. A well-publicized law restricting drivers' use of handheld cell phones had a strong effect on behavior. Whether compliance will remain high is unknown.

  6. 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

  7. Densely interconnected transcriptional circuits control cell states in human hematopoiesis

    PubMed Central

    Novershtern, Noa; Subramanian, Aravind; Lawton, Lee N.; Mak, Raymond H.; Haining, W. Nicholas; McConkey, Marie E.; Habib, Naomi; Yosef, Nir; Chang, Cindy Y.; Shay, Tal; Frampton, Garrett M.; Drake, Adam C. B.; Leskov, Ilya; Nilsson, Bjorn; Preffer, Fred; Dombkowski, David; Evans, John W.; Liefeld, Ted; Smutko, John S.; Chen, Jianzhu; Friedman, Nir; Young, Richard A.; Golub, Todd R.; Regev, Aviv; Ebert, Benjamin L.

    2011-01-01

    While many individual transcription factors are known to regulate hematopoietic differentiation, major aspects of the global architecture of hematopoiesis remain unknown. Here, we profiled gene expression in 38 distinct purified populations of human hematopoietic cells and used probabilistic models of gene expression and analysis of cis-elements in gene promoters to decipher the general organization of their regulatory circuitry. We identified modules of highly co-expressed genes, some of which are restricted to a single lineage, but most are expressed at variable levels across multiple lineages. We found densely interconnected cis-regulatory circuits and a large number of transcription factors that are differentially expressed across hematopoietic states. These findings suggest a more complex regulatory system for hematopoiesis than previously assumed. PMID:21241896

  8. The dihydrolipoamide acetyltransferase is a novel metabolic longevity factor and is required for calorie restriction-mediated life span extension.

    PubMed

    Easlon, Erin; Tsang, Felicia; Dilova, Ivanka; Wang, Chen; Lu, Shu-Ping; Skinner, Craig; Lin, Su-Ju

    2007-03-02

    Calorie restriction (CR) extends life span in a wide variety of species. Recent studies suggest that an increase in mitochondrial metabolism mediates CR-induced life span extension. Here we present evidence that Lat1 (dihydrolipoamide acetyltransferase), the E2 component of the mitochondrial pyruvate dehydrogenase complex, is a novel metabolic longevity factor in the CR pathway. Deleting the LAT1 gene abolishes life span extension induced by CR. Overexpressing Lat1 extends life span, and this life span extension is not further increased by CR. Similar to CR, life span extension by Lat1 overexpression largely requires mitochondrial respiration, indicating that mitochondrial metabolism plays an important role in CR. Interestingly, Lat1 overexpression does not require the Sir2 family to extend life span, suggesting that Lat1 mediates a branch of the CR pathway that functions in parallel to the Sir2 family. Lat1 is also a limiting longevity factor in nondividing cells in that overexpressing Lat1 extends cell survival during prolonged culture at stationary phase. Our studies suggest that Lat1 overexpression extends life span by increasing metabolic fitness of the cell. CR may therefore also extend life span and ameliorate age-associated diseases by increasing metabolic fitness through regulating central metabolic enzymes.

  9. Linguistic Agency and Life-Span Longevity.

    PubMed

    Robinson, Michael D; Bair, Jessica L; Persich, Michelle R; Moen, Nicholas R

    2016-09-01

    Agency has been conceptualized as a drive toward mastery, control, and effective self-management. Such an agentic approach to life and its challenges may be life-prolonging, a hypothesis not previously investigated. In four studies, individual differences in agency were assessed in terms of the frequency with which agency-related words (e.g., "achieve," "fix," and "control") were mentioned in archived interviews or speeches (N = 210). Higher levels of linguistic agency predicted longer life-spans among prominent physicists (study 1: n = 60, β = .30, t = 2.30, p = .025), historians (study 2: n = 69, β = .29, t = 2.47, p = .016), psychologists (study 3: n = 45, β = .32, t = 2.35, p = .024), and American presidents (study 4: n = 36, β = .75, t = 2.74, p = .010) when adjusting for birth year. Considered from another angle, life-span longevity averaged 8 years longer at a high (+1 standard deviation) relative to low (-1 standard deviation) level of the linguistic agency continuum, a marked difference. Follow-up analyses indicated that these results could not be attributed to covarying levels of positive emotion, negative emotion, or social connection, as quantified in terms of other linguistic categories. The investigation provides unique support for agentic perspectives on health, and several potential mechanisms are discussed.

  10. 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

  11. Dynamics of embryonic stem cell differentiation inferred from single-cell transcriptomics show a series of transitions through discrete cell states.

    PubMed

    Jang, Sumin; Choubey, Sandeep; Furchtgott, Leon; Zou, Ling-Nan; Doyle, Adele; Menon, Vilas; Loew, Ethan B; Krostag, Anne-Rachel; Martinez, Refugio A; Madisen, Linda; Levi, Boaz P; Ramanathan, Sharad

    2017-03-15

    The complexity of gene regulatory networks that lead multipotent cells to acquire different cell fates makes a quantitative understanding of differentiation challenging. Using a statistical framework to analyze single-cell transcriptomics data, we infer the gene expression dynamics of early mouse embryonic stem (mES) cell differentiation, uncovering discrete transitions across nine cell states. We validate the predicted transitions across discrete states using flow cytometry. Moreover, using live-cell microscopy, we show that individual cells undergo abrupt transitions from a naïve to primed pluripotent state. Using the inferred discrete cell states to build a probabilistic model for the underlying gene regulatory network, we further predict and experimentally verify that these states have unique response to perturbations, thus defining them functionally. Our study provides a framework to infer the dynamics of differentiation from single cell transcriptomics data and to build predictive models of the gene regulatory networks that drive the sequence of cell fate decisions during development.

  12. 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

  13. 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

  14. 11. VIEW OF SPAN 8, SHOWING WESTERN POST (UPPER SECTION) ...

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

    11. VIEW OF SPAN 8, SHOWING WESTERN POST (UPPER SECTION) OF BENT 8, LOOKING NORTHWEST - West End-North Side Bridge, Spanning Ohio River, approximately 1 mile downstream from confluence of Monongahela & Allegheny rivers, Pittsburgh, Allegheny County, PA

  15. 12. VIEW OF SPAN 8, SHOWING WESTERN POST (LOWER SECTION) ...

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

    12. VIEW OF SPAN 8, SHOWING WESTERN POST (LOWER SECTION) OF BENT 8, LOOKING NORTHWEST - West End-North Side Bridge, Spanning Ohio River, approximately 1 mile downstream from confluence of Monongahela & Allegheny rivers, Pittsburgh, Allegheny County, PA

  16. 8. General view of truss geometry at center of span ...

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

    8. General view of truss geometry at center of span from lower parking lot, looking northwest - Lower Rollstone Street Bridge, Spanning Nashua River on Rollstone Street, Fitchburg, Worcester County, MA

  17. 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

  18. 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

  19. 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

  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. 35. CRAWFORD AVENUE BRIDGE SPANNING PLUM RUN, ELEVATION. NOTE ORIGINAL ...

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

    35. CRAWFORD AVENUE BRIDGE SPANNING PLUM RUN, ELEVATION. NOTE ORIGINAL IRON RAILS AND REPLACEMENT CONCRETE SPAN (ORIGINALLY METAL BEAMS). VIEW W. - Gettysburg National Military Park Tour Roads, Gettysburg, Adams County, PA

  2. 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

  3. 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

  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 VIEW OF NORTH ABUTMENT SPANS WITH END PAIR OF ...

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

    DETAIL VIEW OF NORTH ABUTMENT SPANS WITH END PAIR OF LIGHT STANDARDS. NOTE THE DECORATIVE PANELS CAST INTO THE SPANDREL COLUMN - Ash Avenue Bridge, Spanning Salt River at Foot of Ash Avenue, Tempe, Maricopa County, AZ

  6. 98. George Newman Photographer. VIEW OF THE NEBRASKA SWING SPAN ...

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

    98. George Newman Photographer. VIEW OF THE NEBRASKA SWING SPAN OPEN FOR RIVER PASSAGE. APRIL 13, 1945. - Pacific Shortline Bridge, U.S. Route 20,spanning Missouri River, Sioux City, Woodbury County, IA

  7. 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

  8. 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

  9. 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

  10. 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

  11. 17. Historic view of north elevation spans 3 and 2. ...

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

    17. Historic view of north elevation spans 3 and 2. Photoengraving from Artwork of Rhode Island (Chicago: W.H. Parish Publishing Co., 1896), view south - Court Street Bridge, Court Street spanning Blackstone River & Truman Drive, Woonsocket, Providence County, RI

  12. 39. SUPERSTRUCTUREAPPROACH SPANS, EXPANSION DETAILS (Sheet 4 of 28 sheets), ...

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

    39. SUPERSTRUCTURE-APPROACH SPANS, EXPANSION DETAILS (Sheet 4 of 28 sheets), September 8, 1930 - West End-North Side Bridge, Spanning Ohio River, approximately 1 mile downstream from confluence of Monongahela & Allegheny rivers, Pittsburgh, Allegheny County, PA

  13. 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

  14. 4. VIEW, LOOKING SOUTHWEST, SHOWING TIMBER PILL APPROACH SPAN AND ...

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

    4. VIEW, LOOKING SOUTHWEST, SHOWING TIMBER PILL APPROACH SPAN AND BRIDGE IN OPEN POSITION - New York, New Haven & Hartford Railroad, Shaw's Cove Bridge, Spanning Shaw's Cove, New London, New London County, CT

  15. 43. Detail, subdeck, east bridge land span showing typical structural ...

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

    43. Detail, sub-deck, east bridge land span showing typical structural connections and relationship to stone pier. - Broadway Bridge, Spanning Foundry Street, MBTA Yard, Fort Point Channel, & Lehigh Street, Boston, Suffolk County, MA

  16. 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

  17. 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

  18. 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

  19. 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

  20. 52. Fixed Span, Top Chord at Panel Point 6; diagonal ...

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

    52. Fixed Span, Top Chord at Panel Point 6; diagonal member goes to intermediate connection 7 & then to bottom chord at 8; looking ESE. - Pacific Shortline Bridge, U.S. Route 20,spanning Missouri River, Sioux City, Woodbury County, IA

  1. 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

  2. 1. VIEW NORTHWEST, THROUGH CENTER SPAN OF EASTBOUND BRIDGE, WESTBOUND ...

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

    1. VIEW NORTHWEST, THROUGH CENTER SPAN OF EASTBOUND BRIDGE, WESTBOUND BRIDGE IN BACKGROUND - Willow Run Expressway Bridge No. R01, Spanning Conrail Railway, eastbound, at US-10, Ypsilanti, Washtenaw County, MI

  3. 7. View of first panel point, bottom chord. Span 1 ...

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

    7. View of first panel point, bottom chord. Span 1 is showing pin connection and eye bar construction around pin. - Bridge No. 33.3, Spanning Elk River at Milepost JC-33.3, Fayetteville, Lincoln County, TN

  4. 7. INTERIOR OF SOUTH SPAN: DETAIL OF UPPER CHORD INTERSECTION ...

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

    7. INTERIOR OF SOUTH SPAN: DETAIL OF UPPER CHORD INTERSECTION WITH SWAY BRACING, VERTICALS, AND DIAGONALS; LOOKING NORTHWEST - Shaw Farm Bridge, Spanning Chippewa River at County Trunk Highway E, Island Lake, Rusk County, WI

  5. 10. VIEW OF NORTH END SPAN, SHOWING FLOOR BEAM AND ...

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

    10. VIEW OF NORTH END SPAN, SHOWING FLOOR BEAM AND STRINGERS AT PANEL POINT L1 - East Bloomsburg Bridge, Spanning Susquehanna River at Pennsylvania Route 487 (Legislative Route 283), Bloomsburg, Columbia County, PA

  6. 11. VIEW, LOOKING NORTHEAST, SHOWING SOUTH END SPAN, WEST SIDE, ...

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

    11. VIEW, LOOKING NORTHEAST, SHOWING SOUTH END SPAN, WEST SIDE, AT FLOOR LEVEL - East Bloomsburg Bridge, Spanning Susquehanna River at Pennsylvania Route 487 (Legislative Route 283), Bloomsburg, Columbia County, PA

  7. 15. VIEW OF SOUTH END SPAN, SHOWING SWAY BRACING FRAME ...

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

    15. VIEW OF SOUTH END SPAN, SHOWING SWAY BRACING FRAME AT PANEL POINTS 2 AND 4, TOP LATERAL BRACING - East Bloomsburg Bridge, Spanning Susquehanna River at Pennsylvania Route 487 (Legislative Route 283), Bloomsburg, Columbia County, PA

  8. 8. VIEW, LOOKING SOUTHWEST, SHOWING NORTH END SPAN, SIDE AND ...

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

    8. VIEW, LOOKING SOUTHWEST, SHOWING NORTH END SPAN, SIDE AND FLOOR SYSTEM - East Bloomsburg Bridge, Spanning Susquehanna River at Pennsylvania Route 487 (Legislative Route 283), Bloomsburg, Columbia County, PA

  9. 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

  10. 16. Span 1, view across at traffic level, showing all ...

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

    16. Span 1, view across at traffic level, showing all three upper lateral struts; view to east. - Fifth Street Bridge, Spanning MBTA Fitchburg Commuter Rail Line tracks, Conrail Fitchburg Secondary Line & North Nashua River, Fitchburg, Worcester County, MA

  11. 15. Span 1, view across at traffic level; view to ...

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

    15. Span 1, view across at traffic level; view to west. - Fifth Street Bridge, Spanning MBTA Fitchburg Commuter Rail Line tracks, Conrail Fitchburg Secondary Line & North Nashua River, Fitchburg, Worcester County, MA

  12. 56. View below deck of Manhattan side span showing ramps ...

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

    56. View below deck of Manhattan side span showing ramps to East Side Expressway. Jet Lowe, photographer, 1982. - Brooklyn Bridge, Spanning East River between Park Row, Manhattan and Sands Street, Brooklyn, New York County, NY

  13. 51. View below deck superstructure of Manhattan side span showing ...

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

    51. View below deck superstructure of Manhattan side span showing connection between main center cable and deck superstructure. Jet Lowe, photographer, 1982. - Brooklyn Bridge, Spanning East River between Park Row, Manhattan and Sands Street, Brooklyn, New York County, NY

  14. 13. VIEW OF SPAN 8, SHOWING FIXED SHOE AND ROLLER ...

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

    13. VIEW OF SPAN 8, SHOWING FIXED SHOE AND ROLLER PIN, LOOKING WEST - West End-North Side Bridge, Spanning Ohio River, approximately 1 mile downstream from confluence of Monongahela & Allegheny rivers, Pittsburgh, Allegheny County, PA

  15. 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

  16. 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

  17. 33. View of swing span floor framing, looking east from ...

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

    33. View of swing span floor framing, looking east from pivot pier - Macombs Dam Bridge, Spanning Harlem River Between 155th Street Viaduct, Jerome Avenue, & East 162nd Street, Bronx, Bronx County, NY

  18. 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

  19. 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

  20. 7. DETAIL VIEW OF NORTHWEST WEB OF THE SOUTHEAST SPAN, ...

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

    7. DETAIL VIEW OF NORTHWEST WEB OF THE SOUTHEAST SPAN, SHOWING DECK, BRACING AND PANEL, LOOKING NORTHEAST - Linden Avenue Bridge, Spanning Purgatoire River on Linden Avenue, Trinidad, Las Animas County, CO

  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. 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

  3. 6. East elevation of center span showing detail of secondhand ...

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

    6. East elevation of center span showing detail of second-hand girder, looking west. - Allender Road Bridge, Spanning CSX Transportation railroad tracks at Allender Road, White Marsh, Baltimore County, MD

  4. 5. West elevation of center span showing detail of secondhand ...

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

    5. West elevation of center span showing detail of second-hand girder, looking east. - Allender Road Bridge, Spanning CSX Transportation railroad tracks at Allender Road, White Marsh, Baltimore County, MD

  5. 15. View north. Detail of west end of link span, ...

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

    15. View north. Detail of west end of link span, north chord, showing expansion joint and typical scupper inside of plate, girder web. - Walpole-Westminster Bridge, Spanning Connecticut River between Walpole, NH & Westminster, VT, Walpole, Cheshire County, NH

  6. 9. View southwest. Typical bearing detail (northwest corner. Walpole span) ...

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

    9. View southwest. Typical bearing detail (northwest corner. Walpole span) showing slip plate and bolted anchorage. - Walpole-Westminster Bridge, Spanning Connecticut River between Walpole, NH & Westminster, VT, Walpole, Cheshire County, NH

  7. 15. Perspective view of bascule and vertical lift spans, each ...

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

    15. Perspective view of bascule and vertical lift spans, each in open position, facing east - Sault Ste. Marie International Railroad Bridge, Spanning Soo Locks at St. Marys Falls Canal, Sault Ste. Marie, Chippewa County, MI

  8. DETAIL OF SOUTH SAN GABRIEL RIVER BRIDGE, CANTILEVER SPAN CONNECTION, ...

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

    DETAIL OF SOUTH SAN GABRIEL RIVER BRIDGE, CANTILEVER SPAN CONNECTION, LOOKING NORTHWEST. - South San Gabriel River Bridge, Spanning South Fork of San Gabriel River at Georgetown at Business Route 35, Georgetown, Williamson County, TX

  9. GENERAL VIEW OF SOUTH SAN GABRIEL RIVER BRIDGE, RIVER SPAN, ...

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

    GENERAL VIEW OF SOUTH SAN GABRIEL RIVER BRIDGE, RIVER SPAN, LOOKING NORTHWEST. - South San Gabriel River Bridge, Spanning South Fork of San Gabriel River at Georgetown at Business Route 35, Georgetown, Williamson County, TX

  10. DETAIL OF NORTH SAN GABRIEL RIVER BRIDGE, CANTILEVER SPAN CONNECTION, ...

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

    DETAIL OF NORTH SAN GABRIEL RIVER BRIDGE, CANTILEVER SPAN CONNECTION, LOOKING SOUTHEAST. - North San Gabriel River Bridge, Spanning North Fork of San Gabriel River at Business Route 35, Georgetown, Williamson County, TX

  11. Detail, lower joint L, at truss span 6, from below, ...

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

    Detail, lower joint L, at truss span 6, from below, showing member connections and floor system - Breslau Bridge, Spanning North Branch of Susquehanna River at Hannover Street, Plymouth, Luzerne County, PA

  12. 16. Detail view of swing span track manual alignment and ...

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

    16. Detail view of swing span track manual alignment and locking mechanisms, looking southwest - India Point Railroad Bridge, Spanning Seekonk River between Providence & East Providence, Providence, Providence County, RI

  13. 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

  14. 18. WEST DECK TRUSS APPROACH SPAN AND PIERS NO. 1 ...

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

    18. WEST DECK TRUSS APPROACH SPAN AND PIERS NO. 1 AND 2, FROM WEST RIVERBANK. VIEW TO NORTHEAST. - MacArthur Bridge, Spanning Mississippi River on Highway 34 between IA & IL, Burlington, Des Moines County, IA

  15. 19. WEST ANCHOR SPAN OF THROUGH TRUSS AND PIERS NO. ...

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

    19. WEST ANCHOR SPAN OF THROUGH TRUSS AND PIERS NO. 2 AND 3, FROM WEST RIVERBANK. VIEW TO NORTH. - MacArthur Bridge, Spanning Mississippi River on Highway 34 between IA & IL, Burlington, Des Moines County, IA

  16. 15. DETAIL OF EAST DECK GIRDER APPROACH SPANS AND STEEL ...

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

    15. DETAIL OF EAST DECK GIRDER APPROACH SPANS AND STEEL CYLINDER PIERS, FROM EAST RIVERBANK. VIEW TO NORTHWEST. - MacArthur Bridge, Spanning Mississippi River on Highway 34 between IA & IL, Burlington, Des Moines County, IA

  17. 12. DETAIL OF THROUGH TRUSS SPANS AND PIERS NO. 3, ...

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

    12. DETAIL OF THROUGH TRUSS SPANS AND PIERS NO. 3, 4 AND 5, FROM WEST RIVERBANK. VIEW TO NORTHEAST. - MacArthur Bridge, Spanning Mississippi River on Highway 34 between IA & IL, Burlington, Des Moines County, IA

  18. 16. DETAIL OF EAST DECK GIRDER APPROACH SPANS AND STEEL ...

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

    16. DETAIL OF EAST DECK GIRDER APPROACH SPANS AND STEEL CYLINDER PIERS, FROM EAST RIVERBANK. VIEW TO WEST. - MacArthur Bridge, Spanning Mississippi River on Highway 34 between IA & IL, Burlington, Des Moines County, IA

  19. 45. Bridge land span detail showing typical steel post to ...

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

    45. Bridge land span detail showing typical steel post to beam cross brace connection. - Broadway Bridge, Spanning Foundry Street, MBTA Yard, Fort Point Channel, & Lehigh Street, Boston, Suffolk County, MA

  20. The states "race" with the federal government for stem cell research.

    PubMed

    Sax, Joanna K

    2006-01-01

    This article presents an innovative study of the effect of individual states and private institutes in pushing forward stem cell research despite a federal ban on creating new stem cell lines. The author analyzes the impact of state legislation, proposing that states are reacting to federal policy by serving as laboratories for what is traditionally federally funded biomedical research.

  1. 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.

  2. 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.

  3. Hierarchical clustering in minimum spanning trees

    NASA Astrophysics Data System (ADS)

    Yu, Meichen; Hillebrand, Arjan; Tewarie, Prejaas; Meier, Jil; van Dijk, Bob; Van Mieghem, Piet; Stam, Cornelis Jan

    2015-02-01

    The identification of clusters or communities in complex networks is a reappearing problem. The minimum spanning tree (MST), the tree connecting all nodes with minimum total weight, is regarded as an important transport backbone of the original weighted graph. We hypothesize that the clustering of the MST reveals insight in the hierarchical structure of weighted graphs. However, existing theories and algorithms have difficulties to define and identify clusters in trees. Here, we first define clustering in trees and then propose a tree agglomerative hierarchical clustering (TAHC) method for the detection of clusters in MSTs. We then demonstrate that the TAHC method can detect clusters in artificial trees, and also in MSTs of weighted social networks, for which the clusters are in agreement with the previously reported clusters of the original weighted networks. Our results therefore not only indicate that clusters can be found in MSTs, but also that the MSTs contain information about the underlying clusters of the original weighted network.

  4. 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

  5. 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.

  6. Mitigating the Impact of Nurse Manager Large Spans of Control.

    PubMed

    Simpson, Brenda Baird; Dearmon, Valorie; Graves, Rebecca

    Nurse managers are instrumental in achievement of organizational and unit performance goals. Greater spans of control for managers are associated with decreased satisfaction and performance. An interprofessional team measured one organization's nurse manager span of control, providing administrative assistant support and transformational leadership development to nurse managers with the largest spans of control. Nurse manager satisfaction and transformational leadership competency significantly improved following the implementation of large span of control mitigation strategies.

  7. 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.

  8. Chromatin states define tumour-specific T cell dysfunction and reprogramming.

    PubMed

    Philip, Mary; Fairchild, Lauren; Sun, Liping; Horste, Ellen L; Camara, Steven; Shakiba, Mojdeh; Scott, Andrew C; Viale, Agnes; Lauer, Peter; Merghoub, Taha; Hellmann, Matthew D; Wolchok, Jedd D; Leslie, Christina S; Schietinger, Andrea

    2017-05-25

    Tumour-specific CD8 T cells in solid tumours are dysfunctional, allowing tumours to progress. The epigenetic regulation of T cell dysfunction and therapeutic reprogrammability (for example, to immune checkpoint blockade) is not well understood. Here we show that T cells in mouse tumours differentiate through two discrete chromatin states: a plastic dysfunctional state from which T cells can be rescued, and a fixed dysfunctional state in which the cells are resistant to reprogramming. We identified surface markers associated with each chromatin state that distinguished reprogrammable from non-reprogrammable PD1(hi) dysfunctional T cells within heterogeneous T cell populations from tumours in mice; these surface markers were also expressed on human PD1(hi) tumour-infiltrating CD8 T cells. Our study has important implications for cancer immunotherapy as we define key transcription factors and epigenetic programs underlying T cell dysfunction and surface markers that predict therapeutic reprogrammability.

  9. 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

  10. 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

  11. Final report on the United States phase I clinical trial of the hypoxic cell radiosensitizer, misonidazole (Ro-07-0582; NSC No. 261037

    SciTech Connect

    Phillips, T.L.; Wasserman, T.H.; Johnson, R.J.; Levin, V.A.; VanRaalte, G.

    1981-10-15

    The hypoxic cell sensitizer misonidazole began phase I evaluation in the United States in July 1977. One hundred two patients received 104 individual courses of drug. Drug was administered from once to five times per week over time spans from one to six weeks. The individual doses ranged 1 to 5 g/m. The major toxicity noted was neurologic; 49% of evaluable courses showed peripheral neuropathy, and 9% of evaluable courses showed central nervous system effects and/or ototoxicity. In addition, 48 of 102 patients exhibited some degree of nausea and vomiting. The concomitant administration of dexamethasone and phenytoin sodium appeared to lower the incidence of neuropathy. Observations of efficacy were made comparatively in five patients who had multiple lesions treated with and without misonidazole. All five showed increased response in the lesions treated with misonidazole. It is concluded that misonidazole is a reasonably safe and potentially effective hypoxic cell sensitizer whose dose-limiting toxicity is neurologic.

  12. 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

  13. Photonic density of states of cholesteric liquid crystal cells

    NASA Astrophysics Data System (ADS)

    Gevorgyan, A. H.; Oganesyan, K. B.; Vardanyan, G. A.; Matinyan, G. K.

    2014-11-01

    Using the exact analytical expressions for the reflection and transmission matrices for the finite thickness cholesteric liquid crystal (CLC) layer, we calculated its photonic density of states (PDS) of the eigen polarizations (EPs). We investigated the influence of absorption and gain, as well as the CLC cell thickness and CLC local dielectric anisotropy on PDS. We presented the full picture of distribution of total field in the CLC layer and outside it for two EPs. The possibility of connections between the PDS and the density of the light energy accumulated in the medium was investigated, and it was shown that these characteristics had analogous spectra and, besides, the influences of the problem parameters on these characteristics were also analogous. We showed that there existed a critical value of the parameter characterizing the gain beyond which the lasing mode was quenched and the feedback vanished. We showed that in the presence of gain there existed a critical value of numbers of pitches in the CLC layer beyond which the lasing mode was again quenched and the feedback vanished, too. It is shown that the subject system can work as a low-threshold laser or a multi-position trigger.

  14. 08 | December | 201span>6 | ISS On-Orbit Status Report

    NASA Website

    JPM1F0-01 CLOSEOUT PANEL FASTENER LOOSEN; ... August 201span>6; July 201span>6; June 201span>6; May 201span>6; April 201span>6; March 201span>6; February 201span>6; January 201span>6; ...

  15. 09/02/201span>6 | ISS On-Orbit Status Report - blogs.nasa.gov

    NASA Website

    ← ISS Daily Summary Report – 09/01/201span>6 ISS Daily Summary Report – 09/05/201span>6 ... August 201span>6; July 201span>6; June 201span>6; May 201span>6; April 201span>6; March 201span>6; ...

  16. Reliability based calibration of partial safety factors for design of free pipeline spans

    SciTech Connect

    Ronold, K.O.; Nielsen, N.J.R.; Tura, F.; Bryndum, M.B.; Smed, P.F.

    1995-12-31

    This paper demonstrates how a structural reliability method can be applied as a rational means to analyze free spans of submarine pipelines with respect to failure in ultimate loading, and to establish partial safety factors for design of such free spans against this failure mode. It is important to note that the described procedure shall be considered as an illustration of a structural reliability methodology, and that the results do not represent a set of final design recommendations. A scope of design cases, consisting of a number of available site-specific pipeline spans, is established and is assumed representative for the future occurrence of submarine pipeline spans. Probabilistic models for the wave and current loading and its transfer to stresses in the pipe wall of a pipeline span is established together with a stochastic representation of the material resistance. The event of failure in ultimate loading is considered as based on a limit state which is reached when the maximum stress over the design life of the pipeline exceeds the yield strength of the pipe material. The yielding limit state is considered an ultimate limit state (ULS).

  17. 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.

  18. Stem cells, telomerase regulation and the hypoxic state.

    PubMed

    Mathews, Juanita; Davy, Philip M C; Gardner, Lauren H; Allsopp, Richard C

    2016-01-01

    The cellular response to a hypoxic environment is regulated by hypoxia inducible factors. Hypoxia inducible factor 1 alpha (Hif1alpha) in particular, is tightly regulated by the hypoxic environment in most cells, and plays an important role in regulating the stress response of cells to hypoxia. Interestingly, substantial observations are now emerging that point to an important role for Hif1alpha in stem cells, including embryonic stem cells, neuronal stem cells and hematopoietic stem cells. Notably, Hif1alpha has been shown to enhance self renewal of stem cells, mediate a shift to glycolytic metabolism, and promote telomerase expression.

  19. 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

  20. 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.

  1. Differentiation state determines neural effects on microvascular endothelial cells

    PubMed Central

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

    2012-01-01

    Growing evidence indicates that nerves and capillaries interact paracrinely in uninjured skin and cutaneous wounds. Although mature neurons are the predominant neural cell in the skin, neural progenitor cells have also been detected in uninjured adult skin. The aim of this study was to characterize differential paracrine effects of neural progenitor cells and mature sensory neurons on dermal microvascular endothelial cells. Our results suggest that neural progenitor cells and mature sensory neurons have unique secretory profiles and distinct effects on dermal microvascular endothelial cell proliferation, migration, and nitric oxide production. Neural progenitor cells and dorsal root ganglion neurons secrete different proteins related to angiogenesis. Specific to neural progenitor cells were dipeptidyl peptidase-4, IGFBP-2, pentraxin-3, serpin f1, TIMP-1, TIMP-4 and VEGF. In contrast, endostatin, FGF-1, MCP-1 and thrombospondin-2 were specific to dorsal root ganglion neurons. Microvascular endothelial cell proliferation was inhibited by dorsal root ganglion neurons but unaffected by neural progenitor cells. In contrast, microvascular endothelial cell migration in a scratch wound assay was inhibited by neural progenitor cells and unaffected by dorsal root ganglion neurons. In addition, nitric oxide production by microvascular endothelial cells was increased by dorsal root ganglion neurons but unaffected by neural progenitor cells. PMID:22683922

  2. Low auxotrophy-complementing amino acid concentrations reduce yeast chronological life span.

    PubMed

    Gomes, Pedro; Sampaio-Marques, Belém; Ludovico, Paula; Rodrigues, Fernando; Leão, Cecília

    2007-01-01

    In the yeast Saccharomyces cerevisiae, interventions resembling caloric restriction, either by reduction of glucose or non-essential amino acid content in the medium, prolong life span and retard aging. Here we have examined the role of auxotrophy-complementing amino acid supplementation of S. cerevisiae strains in determining yeast chronological life span and stress resistance. The results obtained from cells cultured in standard amino acid concentrations revealed a reduced final biomass yield and premature aging phenotypes. These included shorter life span and indicators of oxidative stress, together with a G2/M cell cycle arrest and the appearance of a sub-G0/G1 population pointing to the occurrence of a specific cell death programme under starvation of essential amino acids. In order to overcome this starvation, five times higher amino acid concentrations were supplied to the medium as has already been commonly used by few laboratories. Such cultures reached more than five-fold higher final biomass yield in stationary phase and the early aging phenotypes were abrogated. Furthermore, in a long-lived yeast strain lacking TOR1, there was no positive effect of amino acid supplementation on longevity. On the contrary, amino acid supply had a positive effect on chronological life span of RAS2 deleted cells. This study may provide novel insights into the role of essential nutrients and their effect on aging process and raises the warning that the positive effects of caloric restriction on life span maybe restricted to non-essential nutrients. Moreover, the severe consequences on cell physiology, life span and stress resistance induced by essential amino acid imbalances presents a note of caution for those still using standard amino acid concentrations for studies with auxotrophic yeast strains.

  3. Genetic Determinants of Human Health Span and Life Span: Progress and New Opportunities

    PubMed Central

    Martin, George M; Bergman, Aviv; Barzilai, Nir

    2007-01-01

    We review three approaches to the genetic analysis of the biology and pathobiology of human aging. The first and so far the best-developed is the search for the biochemical genetic basis of varying susceptibilities to major geriatric disorders. These include a range of progeroid syndromes. Collectively, they tell us much about the genetics of health span. Given that the major risk factor for virtually all geriatric disorders is biological aging, they may also serve as markers for the study of intrinsic biological aging. The second approach seeks to identify allelic contributions to exceptionally long life spans. While linkage to a locus on Chromosome 4 has not been confirmed, association studies have revealed a number of significant polymorphisms that impact upon late-life diseases and life span. The third approach remains theoretical. It would require longitudinal studies of large numbers of middle-aged sib-pairs who are extremely discordant or concordant for their rates of decline in various physiological functions. We can conclude that there are great opportunities for research on the genetics of human aging, particularly given the huge fund of information on human biology and pathobiology, and the rapidly developing knowledge of the human genome. PMID:17677003

  4. 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

  5. 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

  6. Naturally processed peptides spanning the HPA-1a polymorphism are efficiently generated and displayed from platelet glycoprotein by HLA-DRB3*0101-positive antigen-presenting cells.

    PubMed

    Anani Sarab, Gholamreza; Moss, Michael; Barker, Robert N; Urbaniak, Stanislaw J

    2009-08-27

    In neonatal alloimmune thrombocytopenia, almost all human platelet antigen (HPA)-1b1b mothers who produce anti-HPA-1a antibody through carrying an HPA-1a fetus are human histocompatibility leukocyte antigen (HLA)-DRB3*0101 positive. It is predicted that the HPA-1a Leu(33) polymorphism forms part of an HLA-DRB3*0101-restricted T-helper epitope, and acts as an anchor residue for binding this class II molecule. However, it is not known whether any corresponding peptides are naturally processed and presented from platelet glycoprotein. In this study, peptides displayed by a homozygous HLA-DRB3*0101 antigen-presenting cell line were identified after pulsing with recombinant HPA-1a (Leu(33) plexin-semaphorin-integrin domain). The peptides were eluted from HLA-DR molecules, fractionated by high performance liquid chromatography, and analyzed by tandem mass spectrometry. A "nested set" of naturally presented HPA-1a-derived peptides, each containing the Trp(25)-Leu(33) core epitope, was identified, with the most abundant member being the 16-mer Met(22)-Arg(37). These peptides may provide the basis for novel treatments to tolerize the corresponding T-helper response in women at risk of neonatal alloimmune thrombocytopenia.

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. Solid-state NMR on bacterial cells: selective cell wall signal enhancement and resolution improvement using dynamic nuclear polarization.

    PubMed

    Takahashi, Hiroki; Ayala, Isabel; Bardet, Michel; De Paëpe, Gaël; Simorre, Jean-Pierre; Hediger, Sabine

    2013-04-03

    Dynamic nuclear polarization (DNP) enhanced solid-state nuclear magnetic resonance (NMR) has recently emerged as a powerful technique for the study of material surfaces. In this study, we demonstrate its potential to investigate cell surface in intact cells. Using Bacillus subtilis bacterial cells as an example, it is shown that the polarizing agent 1-(TEMPO-4-oxy)-3-(TEMPO-4-amino)propan-2-ol (TOTAPOL) has a strong binding affinity to cell wall polymers (peptidoglycan). This particular interaction is thoroughly investigated with a systematic study on extracted cell wall materials, disrupted cells, and entire cells, which proved that TOTAPOL is mainly accumulating in the cell wall. This property is used on one hand to selectively enhance or suppress cell wall signals by controlling radical concentrations and on the other hand to improve spectral resolution by means of a difference spectrum. Comparing DNP-enhanced and conventional solid-state NMR, an absolute sensitivity ratio of 24 was obtained on the entire cell sample. This important increase in sensitivity together with the possibility of enhancing specifically cell wall signals and improving resolution really opens new avenues for the use of DNP-enhanced solid-state NMR as an on-cell investigation tool.

  12. 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…

  13. Metformin supplementation and life span in Fischer-344 rats.

    PubMed

    Smith, Daniel L; Elam, Calvin F; Mattison, Julie A; Lane, Mark A; Roth, George S; Ingram, Donald K; Allison, David B

    2010-05-01

    Calorie restriction (CR) has been known for more than 70 years to extend life span and delay disease in rodent models. Metformin administration in rodent disease models has been shown to delay cancer incidence and progression, reduce cardiovascular disease and extend life span. To more directly test the potential of metformin supplementation (300 mg/kg/day) as a CR mimetic, life-span studies were performed in Fischer-344 rats and compared with ad libitum feeding and CR (30%). The CR group had significantly reduced food intake and body weight throughout the study. Body weight was significantly reduced in the metformin group compared with control during the middle of the study, despite similar weekly food intake. Although CR significantly extended early life span (25th quantile), metformin supplementation did not significantly increase life span at any quantile (25th, 50th, 75th, or 90th), overall or maximum life span (p > .05) compared with control.

  14. All-solid-state, semiconductor-sensitized nanoporous solar cells.

    PubMed

    Hodes, Gary; Cahen, David

    2012-05-15

    Despite the rapid increase in solar cell manufacturing capacity (~50 GW(p) in 2011), maintaining this continued expansion will require resolving some major fabrication issues. Crystalline Si, the most common type of cell, requires a large energy input in the manufacturing process, which results in an energy payback time of years. CdTe/CdS thin film cells, which have captured around 10% of the global market, may not be sustainable for very large-scale use because of limited Te availability. Thus, research in this field is emphasizing cells that are energy efficient and inexpensive and use readily available materials. The extremely thin absorber (ETA) cell, the subject of this Account, is one of these new generation cells. Since the active light absorber in an ETA cell is no more than tens of nanometers thick, the direct recombination of photogenerated electrons and holes in the absorber should not compete as much with charge removal in the form of photocurrent as in thicker absorber materials. As a result, researchers expect that poorer quality semiconductors can be used in an ETA cell, which would expand the choice of semiconductors over those currently in use. We first describe the ETA cell, comparing and contrasting it to the dye-sensitized cell (DSC) from which it developed and describing its potential advantages and disadvantages. We then explain the mechanism(s) of operation of the ETA cell, which remain controversial: different ETA cells most likely operate by different mechanisms, particularly in their photovoltage generation. We then present a general description of how we prepare ETA cells in our laboratory, emphasizing solution methods to form the various layers and solution treatments of these layers to minimize manufacturing costs. This is followed by a more specific discussion of the various layers and treatments used to make and complete a cell with emphasis on solution treatments that are important in optimizing cell performance and explaining the

  15. 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

  16. 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…

  17. 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…

  18. 01 | September | 201span>6 | ISS On-Orbit Status Report

    NASA Website

    ISS Daily Summary Report – 09/01/201span>6. Posted on September 1, 201span>6 at 4:00 pm by HQ. ... August 201span>6; July 201span>6; June 201span>6; May 201span>6; April 201span>6; ...

  19. Longitudinal Section AA; Lower Chord Plan Powerscourt Bridge, Spanning ...

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

    Longitudinal Section A-A; Lower Chord Plan - Powerscourt Bridge, Spanning Chateauguay River, First Concession Road, Elgin/Hichinbrooke, Huntingdon County, Quebec, Canada, Chateaugay, Franklin County, NY

  20. 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.

  1. Cells in human milk: state of the science.

    PubMed

    Hassiotou, Foteini; Geddes, Donna T; Hartmann, Peter E

    2013-05-01

    Reflecting millions of years of adaptation and optimization, milk is unique to the species that produces it and for the young of which it is intended, with large variations in both lactation strategies and milk composition existing among different mammalian species. Despite this, milk has the consistent function of providing nourishment, protection, and developmental programming to the young, with short- and long-term effects. Among its components that confer these functions, breast milk contains maternal cells, from leukocytes to epithelial cells of various developmental stages that include stem cells, progenitor cells, lactocytes, and myoepithelial cells. Although in the first 150 years since their discovery, breast milk cells were mostly studied for their morphological traits, technological advances in the last decade have allowed characterization of breast milk cell types at the protein and messenger RNA levels. This is now paving the way for investigation of the functions of these cells in the breastfed infant and the use of breast milk as a tool to understand the normal biology of the breast and its pathologies. This review summarizes the current knowledge of breast milk cellular heterogeneity and discusses future prospects and potential applications.

  2. Study on Remote Monitoring System of Crossing and Spanning Tangent Tower

    NASA Astrophysics Data System (ADS)

    Chen, Da-bing; Zhang, Nai-long; Zhang, Meng-ge; Wang, Ze-hua; Zhang, Yan

    2017-05-01

    In order to grasp the vibration state of overhead transmission line and ensure the operational security of transmission line, the remote monitoring system of crossing and spanning tangent tower was studied. By use of this system, the displacement, velocity and acceleration of the tower, and the local weather data are collected automatically, displayed on computer of remote monitoring centre through wireless network, real-time collection and transmission of vibration signals are realized. The applying results show that the system is excellent in reliability and accuracy and so on. The system can be used to remote monitoring of transmission tower of UHV power transmission lines and in large spanning areas.

  3. 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.

  4. Consequence for dairy herds in the United States of imposing different standards for somatic cell count

    USDA-ARS?s Scientific Manuscript database

    New European Union (E.U.) regulations may require that a somatic cell count (SCC) limit of 400,000 cells/mL for milk be met by every farm that contributes to pooled milk exported to Europe. In the United States, the standard is 750,000 cells/mL. Because bulk tank SCC is not readily available through...

  5. 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

  6. Semi-span model testing in the national transonic facility

    NASA Astrophysics Data System (ADS)

    Chokani, Ndaona

    1994-05-01

    The present work was motivated by an ongoing research program at NASA Langley Research Center to develop a semi-span testing capability for the National Transonic Facility (NTF). This test technique is being investigated as a means to design and optimize high-lift devices at flight Reynolds numbers in a ground test facility. Even though the freestream Mach numbers of interest are around .20, the flow around a transport wing with high lift devices deployed may contain regions of compressible flow. Thus to properly model the flow physics, a compressible flow solver may be required. However, the application of a compressible flow solver at low Mach numbers can be problematic. The objective of this phase of the project is to directly compare the performance of two widely used three-dimensional compressible Navier-Stokes solvers at low Mach numbers to both experimental data and to results obtained from an incompressible Navier-Stokes solver. The geometries of interest are two isolated wings with different leading edge sweep angles. The compressible Navier-Stokes solvers chosen, TLNS3D-MB and CFL3D, which were developed at NASA Langley Research Center (LaRC), represent the current state-of-the-art in compressible 3-D Navier-Stokes solvers. The incompressible Navier-Stokes solver, INS3D-UP, developed recently at NASA Ames Research Center (ARC), represents the current state-of-the-art in incompressible Navier-Stokes solvers.

  7. State-Dependent Function of Neocortical Chandelier Cells

    PubMed Central

    Woodruff, Alan R.; McGarry, Laura M.; Vogels, Tim P.; Inan, Melis; Anderson, Stewart A.; Yuste, Rafael

    2013-01-01

    Chandelier (axoaxonic) cells (ChCs) are a distinct group of GABAergic interneurons that innervate the axon initial segments of pyramidal cells. However, their circuit role and the function of their clearly defined anatomical specificity remain unclear. Recent work has demonstrated that chandelier cells can produce depolarizing GABAergic PSPs, occasionally driving postsynaptic targets to spike. On the other hand, other work suggests that ChCs are hyperpolarizing and may have an inhibitory role. These disparate functional effects may reflect heterogeneity among ChCs. Here, using brain slices from transgenic mouse strains, we first demonstrate that, across different neocortical areas and genetic backgrounds, upper Layer 2/3 ChCs belong to a single electrophysiologically and morphologically defined population, extensively sampling Layer 1 inputs with asymmetric dendrites. Consistent with being a single cell type, we find electrical coupling between ChCs. We then investigate the effect of chandelier cell activation on pyramidal neuron spiking in several conditions, ranging from the resting membrane potential to stimuli designed to approximate in vivo membrane potential dynamics. We find that under quiescent conditions, chandelier cells are capable of both promoting and inhibiting spike generation, depending on the postsynaptic membrane potential. However, during in vivo-like membrane potential fluctuations, the dominant postsynaptic effect was a strong inhibition. Thus, neocortical chandelier cells, even from within a homogeneous population, appear to play a dual role in the circuit, helping to activate quiescent pyramidal neurons, while at the same time inhibiting active ones. PMID:22159102

  8. Individuals with low working memory spans show greater interference from irrelevant information because of poor source monitoring, not greater activation.

    PubMed

    Lilienthal, Lindsey; Rose, Nathan S; Tamez, Elaine; Myerson, Joel; Hale, Sandra

    2015-04-01

    Although individuals with high and low working memory (WM) span appear to differ in the extent to which irrelevant information interferes with their performance on WM tasks, the locus of this interference is not clear. The present study investigated whether, when performing a WM task, high- and low-span individuals differ in the activation of formerly relevant, but now irrelevant items, and/or in their ability to correctly identify such irrelevant items. This was done in two experiments, both of which used modified complex WM span tasks. In Experiment 1, the span task included an embedded lexical decision task designed to obtain an implicit measure of the activation of both currently and formerly relevant items. In Experiment 2, the span task included an embedded recognition judgment task designed to obtain an explicit measure of both item and source recognition ability. The results of these experiments indicate that low-span individuals do not hold irrelevant information in a more active state in memory than high-span individuals, but rather that low-span individuals are significantly poorer at identifying such information as irrelevant at the time of retrieval. These results suggest that differences in the ability to monitor the source of information, rather than differences in the activation of irrelevant information, are the more important determinant of performance on WM tasks.

  9. 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.

  10. 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.

  11. Extended life-span conferred by cotransporter gene mutations in Drosophila.

    PubMed

    Rogina, B; Reenan, R A; Nilsen, S P; Helfand, S L

    2000-12-15

    Aging is genetically determined and environmentally modulated. In a study of longevity in the adult fruit fly, Drosophila melanogaster, we found that five independent P-element insertional mutations in a single gene resulted in a near doubling of the average adult life-span without a decline in fertility or physical activity. Sequence analysis revealed that the product of this gene, named Indy (for I'm not dead yet), is most closely related to a mammalian sodium dicarboxylate cotransporter-a membrane protein that transports Krebs cycle intermediates. Indy was most abundantly expressed in the fat body, midgut, and oenocytes: the principal sites of intermediary metabolism in the fly. Excision of the P element resulted in a reversion to normal life-span. These mutations may create a metabolic state that mimics caloric restriction, which has been shown to extend life-span.

  12. Towards a Threat Assessment Framework for Ecosystem Servicespan>s.

    PubMed

    Maron, Martine; Mitchell, Matthew G E; Runting, Rebecca K; Rhodes, Jonathan R; Mace, Georgina M; Keith, David A; Watson, James E M

    2017-04-01

    How can we tell if the ecosystem servicespan>s upon which we rely are at risk of being lost, potentially permanently? Ecosystem servicespan>s underpin human well-being, but we lack a consistent approach for categorizing the extent to which they are threatened. We present an assessment framework for assessing the degree to which the adequate and sustainable provision of a given ecosystem service is threatened. Our framework combines information on the states and trends of both ecosystem service supply and demand, with reference to two critical thresholds: demand exceeding supply and ecosystem service 'extinction'. This framework can provide a basis for global, national, and regional assessments of threat to ecosystem servicespan>s, and accompany existing assessments of threat to species and ecosystems.

  13. Solid oxide fuel cell commercialization in the United States

    SciTech Connect

    Williams, M.C.

    1995-03-01

    This paper discusses aspects of solid oxide fuel cell (SOFC) technology commercialization in the US. It provides the status of the major SOFC developments occurring in the US by addressing both intermediate- and high-temperature SOFC`s, several SOFC designs, including both planar and tubular, and SOFC system configurations. This paper begins with general characteristics, proceeds with designs and system configurations, and finishes with a discussion of commercialization, funding, and policies. The US Department of Energy`s (DOE) Morgantown Energy Technology Center (METC) is the lead US DOE center for the implementation of a Research, Development, and Demonstration Program to develop fuel cells for stationary power. METC`s stakeholders include the electric power and gas industries, as well as fuel cell developers and others. This paper offers some new perspectives on SOFC development and commercialization which come from the broad consideration of the commercialization efforts of the entire fuel cell industry.

  14. Mitochondria-mediated hormetic response in life span extension of calorie-restricted Saccharomyces cerevisiae.

    PubMed

    Sharma, Praveen Kumar; Agrawal, Vineet; Roy, Nilanjan

    2011-06-01

    Calorie restriction (CR) is the only proven regimen, which confers lifespan extension benefits across the various phyla right from unicellular organisms like yeast to primates. In a bid to elucidate the mechanism of calorie-restriction-mediated life span extension, the role of mitochondria in the process was investigated. In this study, we found that the mitochondrial content in CR cells remains unaltered as compared to cells grown on nonrestricted media. However, mitochondria isolated from CR cells showed increased respiration and elevated reactive oxygen species levels without augmenting adenosine triphosphate (ATP) generation. The antioxidant defense system was amplified in CR mitochondria, and in CR cells a cross protection to hydrogen-peroxide-induced stress was also observed. Moreover, we also documented that a functional electron transport chain was vital for the life span extension benefits of calorie restriction. Altogether, our results indicate that calorie restriction elicits mitohormetic effect, which ultimately leads to longevity benefit.

  15. Life-span extension by a metacaspase in the yeast Saccharomyces cerevisiae.

    PubMed

    Hill, Sandra Malmgren; Hao, Xinxin; Liu, Beidong; Nyström, Thomas

    2014-06-20

    Single-cell species harbor ancestral structural homologs of caspase proteases, although the evolutionary benefit of such apoptosis-related proteins in unicellular organisms is unclear. Here, we found that the yeast metacaspase Mca1 is recruited to the insoluble protein deposit (IPOD) and juxtanuclear quality-control compartment (JUNQ) during aging and proteostatic stress. Elevating MCA1 expression counteracted accumulation of unfolded proteins and aggregates and extended life span in a heat shock protein Hsp104 disaggregase- and proteasome-dependent manner. Consistent with a role in protein quality control, genetic interaction analysis revealed that MCA1 buffers against deficiencies in the Hsp40 chaperone YDJ1 in a caspase cysteine-dependent manner. Life-span extension and aggregate management by Mca1 was only partly dependent on its conserved catalytic cysteine, which suggests that Mca1 harbors both caspase-dependent and independent functions related to life-span control.

  16. 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.

  17. Molecular pathway and cell state responsible for dissociation-induced apoptosis in human pluripotent stem cells.

    PubMed

    Ohgushi, Masatoshi; Matsumura, Michiru; Eiraku, Mototsugu; Murakami, Kazuhiro; Aramaki, Toshihiro; Nishiyama, Ayaka; Muguruma, Keiko; Nakano, Tokushige; Suga, Hidetaka; Ueno, Morio; Ishizaki, Toshimasa; Suemori, Hirofumi; Narumiya, Shuh; Niwa, Hitoshi; Sasai, Yoshiki

    2010-08-06

    Human embryonic stem cells (hESCs), unlike mouse ones (mESCs), are vulnerable to apoptosis upon dissociation. Here, we show that the apoptosis, which is of a nonanoikis type, is caused by ROCK-dependent hyperactivation of actomyosin and efficiently suppressed by the myosin inhibitor Blebbistatin. The actomyosin hyperactivation is triggered by the loss of E-cadherin-dependent intercellular contact and also observed in dissociated mouse epiblast-derived pluripotent cells but not in mESCs. We reveal that Abr, a unique Rho-GEF family factor containing a functional Rac-GAP domain, is an indispensable upstream regulator of the apoptosis and ROCK/myosin hyperactivation. Rho activation coupled with Rac inhibition is induced in hESCs upon dissociation, but not in Abr-depleted hESCs or mESCs. Furthermore, artificial Rho or ROCK activation with Rac inhibition restores the vulnerability of Abr-depleted hESCs to dissociation-induced apoptosis. Thus, the Abr-dependent "Rho-high/Rac-low" state plays a decisive role in initiating the dissociation-induced actomyosin hyperactivation and apoptosis in hESCs. Copyright 2010 Elsevier Inc. All rights reserved.

  18. Gender-related differences in the oxidant state of cells in Fanconi anemia heterozygotes.

    PubMed

    Petrovic, Sandra; Leskovac, Andreja; Kotur-Stevuljevic, Jelena; Joksic, Jelena; Guc-Scekic, Marija; Vujic, Dragana; Joksic, Gordana

    2011-07-01

    Abstract Fanconi anemia (FA) is a rare cancer-prone genetic disorder characterized by progressive bone marrow failure, chromosomal instability and redox abnormalities. There is much biochemical and genetic data, which strongly suggest that FA cells experience increased oxidative stress. The present study was designed to elucidate if differences in oxidant state exist between control, idiopathic bone marrow failure (idBMF) and FA cells, and to analyze oxidant state of cells in FA heterozygous carriers as well. The results of the present study confirm an in vivo prooxidant state of FA cells and clearly indicate that FA patients can be distinguished from idBMF patients based on the oxidant state of cells. Female carriers of FA mutation also exhibited hallmarks of an in vivo prooxidant state behaving in a similar manner as FA patients. On the other hand, the oxidant state of cells in FA male carriers and idBMF families failed to show any significant difference vs. controls. We demonstrate that the altered oxidant state influences susceptibility of cells to apoptosis in both FA patients and female carriers. The results highlight the need for further research of the possible role of mitochondrial inheritance in the pathogenesis of FA.

  19. 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.

  20. 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…

  1. Detail of counterweight wire rope attachment to lift span at ...

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

    Detail of counterweight wire rope attachment to lift span at southwest corner. The plates with three pins serve to equalize the forces on the counterweight ropes. - Potomac Edison Company, Chesapeake & Ohio Canal Bridge, Spanning C & O Canal South of U.S. 11, Williamsport, Washington County, MD

  2. 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

  3. 41. Photocopy of engineering drawing titled 'Existing Bridge, Two Span ...

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

    41. Photocopy of engineering drawing titled 'Existing Bridge, Two Span Continuous Through Truss' (original in files of District 3-0, Pennsylvania Department of Transportation, Montoursville), 1984 PLAN AND SOUTH ELEVATION - Memorial Avenue Bridge, Spanning Lycoming Creek, Williamsport, Lycoming County, PA

  4. 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…

  5. Developmental Dyslexia: The Visual Attention Span Deficit Hypothesis

    ERIC Educational Resources Information Center

    Bosse, Marie-Line; Tainturier, Marie Josephe; Valdois, Sylviane

    2007-01-01

    The visual attention (VA) span is defined as the amount of distinct visual elements which can be processed in parallel in a multi-element array. Both recent empirical data and theoretical accounts suggest that a VA span deficit might contribute to developmental dyslexia, independently of a phonological disorder. In this study, this hypothesis was…

  6. 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 bridge...

  7. 23 CFR 650.809 - Movable span bridges.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 23 Highways 1 2012-04-01 2012-04-01 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 bridge...

  8. 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 bridge...

  9. 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 bridge...

  10. 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 bridge...

  11. 9. VIEW OF BRIDGE NEAR CENTER SPAN, LOOKING NORTH FROM ...

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

    9. VIEW OF BRIDGE NEAR CENTER SPAN, LOOKING NORTH FROM THE ARROYO SECO. THE PARKER-MAYBERRY BRIDGE IS BELOW THE COLORADO STREET BRIDGE, THE PIONEER BRIDGE IS IN THE BACKGROUND. - Colorado Street Bridge, Spanning Arroyo Seco at Colorado Boulevard, Pasadena, Los Angeles County, CA

  12. 11. DETAIL NEAR CENTER OF SPAN, LOOKING SOUTH FROM THE ...

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

    11. DETAIL NEAR CENTER OF SPAN, LOOKING SOUTH FROM THE ARROYO SECO. DETAIL VIEW OF THE PARKER-MAYBERRY BRIDGE, THE ARROYO CHANNEL, AND THE LOWER PORTION OF THE COLORADO STREET BRIDGE. - Colorado Street Bridge, Spanning Arroyo Seco at Colorado Boulevard, Pasadena, Los Angeles County, CA

  13. 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

  14. 4. General view, Span 1, from southerly end of Railroad ...

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

    4. General view, Span 1, from southerly end of Railroad Street Lane; view to south. (Note roadway grade rising to east.) - Fifth Street Bridge, Spanning MBTA Fitchburg Commuter Rail Line tracks, Conrail Fitchburg Secondary Line & North Nashua River, Fitchburg, Worcester County, MA

  15. 10. DETAIL NEAR CENTER OF SPAN, LOOKING NORTH FROM THE ...

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

    10. DETAIL NEAR CENTER OF SPAN, LOOKING NORTH FROM THE ARROYO SECO. THIS VIEW IS EAST OF THE PARKER-MAYBERRY BRIDGE, WITH THE PIONEER BRIDGE IN THE BACKGROUND. - Colorado Street Bridge, Spanning Arroyo Seco at Colorado Boulevard, Pasadena, Los Angeles County, CA

  16. 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…

  17. 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

  18. Spanning trees of lattices embedded on the Klein bottle.

    PubMed

    Lu, Fuliang

    2014-01-01

    The problem of enumerating spanning trees in lattices with Klein bottle boundary condition is considered here. The exact closed-form expressions of the numbers of spanning trees for 4.8.8 lattice, hexagonal lattice, and 3(3) · 4(2) lattice on the Klein bottle are presented.

  19. Sir2 blocks extreme life-span extension.

    PubMed

    Fabrizio, Paola; Gattazzo, Cristina; Battistella, Luisa; Wei, Min; Cheng, Chao; McGrew, Kristen; Longo, Valter D

    2005-11-18

    Sir2 is a conserved deacetylase that modulates life span in yeast, worms, and flies and stress response in mammals. In yeast, Sir2 is required for maintaining replicative life span, and increasing Sir2 dosage can delay replicative aging. We address the role of Sir2 in regulating chronological life span in yeast. Lack of Sir2 along with calorie restriction and/or mutations in the yeast AKT homolog, Sch9, or Ras pathways causes a dramatic chronological life-span extension. Inactivation of Sir2 causes uptake and catabolism of ethanol and upregulation of many stress-resistance and sporulation genes. These changes while sufficient to extend chronological life span in wild-type yeast require severe calorie restriction or additional mutations to extend life span of sir2Delta mutants. Our results demonstrate that effects of SIR2 on chronological life span are opposite to replicatve life span and suggest that the relevant activities of Sir2-like deacetylases may also be complex in higher eukaryotes.

  20. 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…

  1. 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…

  2. 5. LOOKING NORTH AT FIXED PLATE GIRDER SPAN ON WESTERN ...

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

    5. LOOKING NORTH AT FIXED PLATE GIRDER SPAN ON WESTERN APPROACH. STONE PIER AT CENTER OF FRAME DATES TO PREVIOUS SWING BRIDGE ON THIS SITE. - Chicago, Milwaukee & St. Paul Railway, Bridge No. Z-6, Spanning North Branch of Chicago River, South of Cortland Street, Chicago, Cook County, IL

  3. 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

  4. 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…

  5. 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

  6. 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

  7. 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…

  8. 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

  9. 38. Reconstruction of roadway; view looking west on swing span, ...

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

    38. Reconstruction of roadway; view looking west on swing span, showing new concrete foundation and new design of curb angels and covers over bottom chord. December 15, 1925 photograph - University Heights Bridge, Spanning Harlem River at 207th Street & West Harlem Road, New York County, NY

  10. 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…

  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. 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

  13. 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

  14. 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…

  15. 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

  16. 1. Threefourths view showing relation of span to creek with ...

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

    1. Three-fourths view showing relation of span to creek with timber trestle approaches. North approach on timber piling, south approach on concrete bents. Note stone piers - Bridge No. 2.4, Spanning Boiling Fork Creek at Railroad Milepost JC-2.4, Decherd, Franklin County, TN

  17. High-density P300 enhancers control cell state transitions.

    PubMed

    Witte, Steven; Bradley, Allan; Enright, Anton J; Muljo, Stefan A

    2015-11-06

    Transcriptional enhancers are frequently bound by a set of transcription factors that collaborate to activate lineage-specific gene expression. Recently, it was appreciated that a subset of enhancers comprise extended clusters dubbed stretch- or super-enhancers (SEs). These SEs are located near key cell identity genes, and enriched for non-coding genetic variations associated with disease. Previously, SEs have been defined as having the highest density of Med1, Brd4 or H3K27ac by ChIP-seq. The histone acetyltransferase P300 has been used as a marker of enhancers, but little is known about its binding to SEs. We establish that P300 marks a similar SE repertoire in embryonic stem cells as previously reported using Med1 and H3K27ac. We also exemplify a role for SEs in mouse T helper cell fate decision. Similarly, upon activation of macrophages by bacterial endotoxin, we found that many SE-associated genes encode inflammatory proteins that are strongly up-regulated. These SEs arise from small, low-density enhancers in unstimulated macrophages. We also identified expression quantitative trait loci (eQTL) in human monocytes that lie within such SEs. In macrophages and Th17 cells, inflammatory SEs can be perturbed either genetically or pharmacologically thus revealing new avenues to target inflammation. Our findings support the notion that P300-marked SEs can help identify key nodes of transcriptional control during cell fate decisions. The SE landscape changes drastically during cell differentiation and cell activation. As these processes are crucial in immune responses, SEs may be useful in revealing novel targets for treating inflammatory diseases.

  18. 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.

  19. 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.

  20. Boundary spanning and health: invitation to a learning community.

    PubMed

    Aungst, Heide; Ruhe, Mary; Stange, Kurt C; Allan, Terry M; Borawski, Elaine A; Drummond, Colin K; Fischer, Robert L; Fry, Ronald; Kahana, Eva; Lalumandier, James A; Mehlman, Maxwell; Moore, Shirley M

    2012-01-01

    Boundaries, which are essential for the healthy functioning of individuals and organisations, can become problematic when they limit creative thought and action. In this article, we present a framework for promoting health across boundaries and summarise preliminary insights from experience, conversations and reflection on how the process of boundary spanning may affect health. Boundary spanning requires specific individual qualities and skills. It can be facilitated or thwarted by organisational context. Boundary spanning often involves risk, but may reap abundant rewards. Boundary spanning is necessary to optimise health and health care. Exploring the process, the landscape and resources that enable boundary spanning may yield new opportunities for advancing health. We invite boundary spanners to join in a learning community to advance understanding and health.

  1. 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.

  2. Independent control of natural killer cell responsiveness and homeostasis at steady-state by CD11c+ dendritic cells

    PubMed Central

    Luu, Thuy Thanh; Ganesan, Sridharan; Wagner, Arnika Kathleen; Sarhan, Dhifaf; Meinke, Stephan; Garbi, Natalio; Hämmerling, Günter; Alici, Evren; Kärre, Klas; Chambers, Benedict J.; Höglund, Petter; Kadri, Nadir

    2016-01-01

    During infection and inflammation, dendritic cells (DC) provide priming signals for natural killer (NK) cells via mechanisms distinct from their antigen processing and presentation functions. The influence of DC on resting NK cells, i.e. at steady-state, is less well studied. We here demonstrate that as early as 1 day after DC depletion, NK cells in naïve mice downregulated the NKG2D receptor and showed decreased constitutive phosphorylation of AKT and mTOR. Subsequently, apoptotic NK cells appeared in the spleen concomitant with reduced NK cell numbers. At 4 days after the onset of DC depletion, increased NK cell proliferation was seen in the spleen resulting in an accumulation of Ly49 receptor-negative NK cells. In parallel, NK cell responsiveness to ITAM-mediated triggering and cytokine stimulation dropped across maturation stages, suggestive of a functional deficiency independent from the homeostatic effect. A role for IL-15 in maintaining NK cell function was supported by a gene signature analysis of NK cell from DC-depleted mice as well as by in vivo DC transfer experiments. We propose that DC, by means of IL-15 transpresentation, are required to maintain not only homeostasis, but also function, at steady-state. These processes appear to be regulated independently from each other. PMID:27905484

  3. C. elegans VANG-1 Modulates Life Span via Insulin/IGF-1-Like Signaling

    PubMed Central

    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. PMID:22359667

  4. High resolution imaging reveals heterogeneity in chromatin states between cells that is not inherited through cell division.

    PubMed

    Dickerson, David; Gierliński, Marek; Singh, Vijender; Kitamura, Etsushi; Ball, Graeme; Tanaka, Tomoyuki U; Owen-Hughes, Tom

    2016-09-08

    Genomes of eukaryotes exist as chromatin, and it is known that different chromatin states can influence gene regulation. Chromatin is not a static structure, but is known to be dynamic and vary between cells. In order to monitor the organisation of chromatin in live cells we have engineered fluorescent fusion proteins which recognize specific operator sequences to tag pairs of syntenic gene loci. The separation of these loci was then tracked in three dimensions over time using fluorescence microscopy. We established a work flow for measuring the distance between two fluorescently tagged, syntenic gene loci with a mean measurement error of 63 nm. In general, physical separation was observed to increase with increasing genomic separations. However, the extent to which chromatin is compressed varies for different genomic regions. No correlation was observed between compaction and the distribution of chromatin markers from genomic datasets or with contacts identified using capture based approaches. Variation in spatial separation was also observed within cells over time and between cells. Differences in the conformation of individual loci can persist for minutes in individual cells. Separation of reporter loci was found to be similar in related and unrelated daughter cell pairs. The directly observed physical separation of reporter loci in live cells is highly dynamic both over time and from cell to cell. However, consistent differences in separation are observed over some chromosomal regions that do not correlate with factors known to influence chromatin states. We conclude that as yet unidentified parameters influence chromatin configuration. We also find that while heterogeneity in chromatin states can be maintained for minutes between cells, it is not inherited through cell division. This may contribute to cell-to-cell transcriptional heterogeneity.

  5. Dynamics of embryonic stem cell differentiation inferred from single-cell transcriptomics show a series of transitions through discrete cell states

    PubMed Central

    Jang, Sumin; Choubey, Sandeep; Furchtgott, Leon; Zou, Ling-Nan; Doyle, Adele; Menon, Vilas; Loew, Ethan B; Krostag, Anne-Rachel; Martinez, Refugio A; Madisen, Linda; Levi, Boaz P; Ramanathan, Sharad

    2017-01-01

    The complexity of gene regulatory networks that lead multipotent cells to acquire different cell fates makes a quantitative understanding of differentiation challenging. Using a statistical framework to analyze single-cell transcriptomics data, we infer the gene expression dynamics of early mouse embryonic stem (mES) cell differentiation, uncovering discrete transitions across nine cell states. We validate the predicted transitions across discrete states using flow cytometry. Moreover, using live-cell microscopy, we show that individual cells undergo abrupt transitions from a naïve to primed pluripotent state. Using the inferred discrete cell states to build a probabilistic model for the underlying gene regulatory network, we further predict and experimentally verify that these states have unique response to perturbations, thus defining them functionally. Our study provides a framework to infer the dynamics of differentiation from single cell transcriptomics data and to build predictive models of the gene regulatory networks that drive the sequence of cell fate decisions during development. DOI: http://dx.doi.org/10.7554/eLife.20487.001 PMID:28296635

  6. Simulation of solid-state dye solar cells based on organic and Perovskite sensitizers

    NASA Astrophysics Data System (ADS)

    Di Carlo, Aldo; Gentilini, Desireé; Gagliardi, Alessio

    2015-03-01

    In this work we present a multiscale numerical simulation of solid-state Dye and Perovskite Solar Cells where the real morphology of the mesoporous active layer is taken into account. Band alignment and current densities are computed using the drift-diffusion model. In the case of Dye cells, a portion of the real interface is merged between two regions described using the effective medium approximation, casting light on the role of trapped states at the interface between TiO2 / Dye / hole transporting materials. A second case of study is the simulation of Perovskite Solar Cell where the performances of cells based on Alumina and Titania mesoporous layer are compared.

  7. Discovering sparse transcription factor codes for cell states and state transitions during development

    PubMed Central

    Furchtgott, Leon A; Melton, Samuel; Menon, Vilas; Ramanathan, Sharad

    2017-01-01

    Computational analysis of gene expression to determine both the sequence of lineage choices made by multipotent cells and to identify the genes influencing these decisions is challenging. Here we discover a pattern in the expression levels of a sparse subset of genes among cell types in B- and T-cell developmental lineages that correlates with developmental topologies. We develop a statistical framework using this pattern to simultaneously infer lineage transitions and the genes that determine these relationships. We use this technique to reconstruct the early hematopoietic and intestinal developmental trees. We extend this framework to analyze single-cell RNA-seq data from early human cortical development, inferring a neocortical-hindbrain split in early progenitor cells and the key genes that could control this lineage decision. Our work allows us to simultaneously infer both the identity and lineage of cell types as well as a small set of key genes whose expression patterns reflect these relationships. DOI: http://dx.doi.org/10.7554/eLife.20488.001 PMID:28296636

  8. Using measures of single-cell physiology and physiological state to understand organismic aging.

    PubMed

    Mendenhall, Alexander; Driscoll, Monica; Brent, Roger

    2016-02-01

    Genetically identical organisms in homogeneous environments have different lifespans and healthspans. These differences are often attributed to stochastic events, such as mutations and 'epimutations', changes in DNA methylation and chromatin that change gene function and expression. But work in the last 10 years has revealed differences in lifespan- and health-related phenotypes that are not caused by lasting changes in DNA or identified by modifications to DNA or chromatin. This work has demonstrated persistent differences in single-cell and whole-organism physiological states operationally defined by values of reporter gene signals in living cells. While some single-cell states, for example, responses to oxygen deprivation, were defined previously, others, such as a generally heightened ability to make proteins, were, revealed by direct experiment only recently, and are not well understood. Here, we review technical progress that promises to greatly increase the number of these measurable single-cell physiological variables and measureable states. We discuss concepts that facilitate use of single-cell measurements to provide insight into physiological states and state transitions. We assert that researchers will use this information to relate cell level physiological readouts to whole-organism outcomes, to stratify aging populations into groups based on different physiologies, to define biomarkers predictive of outcomes, and to shed light on the molecular processes that bring about different individual physiologies. For these reasons, quantitative study of single-cell physiological variables and state transitions should provide a valuable complement to genetic and molecular explanations of how organisms age.

  9. Alternative splicing regulates pluripotent state in pluripotent stem cells.

    PubMed

    He, Ling; Bai, Qiang; Tang, Liling

    2015-01-01

    Alternative splicing (AS) generates multiple mature mRNAs from a single pre-mRNA, so AS is the main contributor for the diversity of the proteins, participating in most of the cellular processes. For pluripotent stem cells (PSCs), great effort has been made to search for pluripotency-related genes and their regulatory mechanisms. However, the sophisticated regulation still remains to be clear. Recent studies indicate that stem cells undergo a unique AS pattern and have a different protein expression profile from differentiated cells, giving a new clue that AS switching or AS itself may play a significant role in the processes of differentiation and somatic reprogramming. Indeed, accumulating evidences prove that AS plays critical roles in maintaining pluripotent homeostasis in PSCs. In this review, we summarized recent researches on AS in ESCs and iPSCs, including some distinct AS events in pluripotent cells, and then discussed the new progress on mechanisms for AS in ESCs and iPSCs differentiation and somatic reprogramming.

  10. 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.

  11. 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…

  12. Ground-state properties of hcp helium-4 on the basis of a cell model

    NASA Technical Reports Server (NTRS)

    Jacobi, N.; Zmuidzinas, J. S.

    1977-01-01

    A simple cell model is used to compute the ground-state energy and the volume-pressure relation for hcp He-4, in good agreement with experiments and with more sophisticated quantum mechanical calculations.

  13. 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.

  14. Ground-state properties of hcp helium-4 on the basis of a cell model

    NASA Technical Reports Server (NTRS)

    Jacobi, N.; Zmuidzinas, J. S.

    1977-01-01

    A simple cell model is used to compute the ground-state energy and the volume-pressure relation for hcp He-4, in good agreement with experiments and with more sophisticated quantum mechanical calculations.

  15. Ovariectomy shortens the life span of female mice

    PubMed Central

    Benedusi, Valeria; Martini, Elisa; Kallikourdis, Marinos; Villa, Alessandro; Meda, Clara; Maggi, Adriana

    2015-01-01

    This study shows that lack of ovarian activity has a negative impact on the life span of female mice. The extent to which this phenomenon could be associated with the anti-inflammatory effect of estrogens was analyzed in metabolic organs and aorta, by quantitative analysis of mRNAs encoding proteins in the inflammatory cascade. We demonstrate that the TNFα, IL-1β, MCP-1, MIP-2 and IL-6 mRNA contents are increased in the liver, adipose tissue and aorta 7 months after ovariectomy (ovx) and this increased basal inflammation is maintained as the mice aged. In contrast, the extent of inflammatory gene expression is directly proportional to age in sham-operated mice. As a consequence, at 22 months, most of the inflammatory parameters examined were higher in the sham-operated group compared with the ovx group. These observations led us to propose that the decreased longevity of ovx mice may be due to an acceleration of the basal state of inflammation in metabolic organs, which is likely driven by the combination of a lack of estrogen-mediated anti-inflammatory activity and the loss of gonadal control of energy metabolism. PMID:25719423

  16. Embedded fiber-optic sensing for accurate internal monitoring of cell state in advanced battery management systems part 2: Internal cell signals and utility for state estimation

    NASA Astrophysics Data System (ADS)

    Ganguli, Anurag; Saha, Bhaskar; Raghavan, Ajay; Kiesel, Peter; Arakaki, Kyle; Schuh, Andreas; Schwartz, Julian; Hegyi, Alex; Sommer, Lars Wilko; Lochbaum, Alexander; Sahu, Saroj; Alamgir, Mohamed

    2017-02-01

    A key challenge hindering the mass adoption of Lithium-ion and other next-gen chemistries in advanced battery applications such as hybrid/electric vehicles (xEVs) has been management of their functional performance for more effective battery utilization and control over their life. Contemporary battery management systems (BMS) reliant on monitoring external parameters such as voltage and current to ensure safe battery operation with the required performance usually result in overdesign and inefficient use of capacity. More informative embedded sensors are desirable for internal cell state monitoring, which could provide accurate state-of-charge (SOC) and state-of-health (SOH) estimates and early failure indicators. Here we present a promising new embedded sensing option developed by our team for cell monitoring, fiber-optic (FO) sensors. High-performance large-format pouch cells with embedded FO sensors were fabricated. This second part of the paper focuses on the internal signals obtained from these FO sensors. The details of the method to isolate intercalation strain and temperature signals are discussed. Data collected under various xEV operational conditions are presented. An algorithm employing dynamic time warping and Kalman filtering was used to estimate state-of-charge with high accuracy from these internal FO signals. Their utility for high-accuracy, predictive state-of-health estimation is also explored.

  17. Computational analysis of semi-span model test techniques

    NASA Technical Reports Server (NTRS)

    Milholen, William E., II; Chokani, Ndaona

    1996-01-01

    A computational investigation was conducted to support the development of a semi-span model test capability in the NASA LaRC's National Transonic Facility. This capability is required for the testing of high-lift systems at flight Reynolds numbers. A three-dimensional Navier-Stokes solver was used to compute the low-speed flow over both a full-span configuration and a semi-span configuration. The computational results were found to be in good agreement with the experimental data. The computational results indicate that the stand-off height has a strong influence on the flow over a semi-span model. The semi-span model adequately replicates the aerodynamic characteristics of the full-span configuration when a small stand-off height, approximately twice the tunnel empty sidewall boundary layer displacement thickness, is used. Several active sidewall boundary layer control techniques were examined including: upstream blowing, local jet blowing, and sidewall suction. Both upstream tangential blowing, and sidewall suction were found to minimize the separation of the sidewall boundary layer ahead of the semi-span model. The required mass flow rates are found to be practicable for testing in the NTF. For the configuration examined, the active sidewall boundary layer control techniques were found to be necessary only near the maximum lift conditions.

  18. Study of Semi-Span Model Testing Techniques

    NASA Technical Reports Server (NTRS)

    Gatlin, Gregory M.; McGhee, Robert J.

    1996-01-01

    An investigation has been conducted in the NASA Langley 14- by 22-Foot Subsonic Tunnel in order to further the development of semi-span testing capabilities. A twin engine, energy efficient transport (EET) model with a four-element wing in a takeoff configuration was used for this investigation. Initially a full span configuration was tested and force and moment data, wing and fuselage surface pressure data, and fuselage boundary layer measurements were obtained as a baseline data set. The semi-span configurations were then mounted on the wind tunnel floor, and the effects of fuselage standoff height and shape as well as the effects of the tunnel floor boundary layer height were investigated. The effectiveness of tangential blowing at the standoff/floor juncture as an active boundary-layer control technique was also studied. Results indicate that the semi-span configuration was more sensitive to variations in standoff height than to variations in floor boundary layer height. A standoff height equivalent to 30 percent of the fuselage radius resulted in better correlation with full span data than no standoff or the larger standoff configurations investigated. Undercut standoff leading edges or the use of tangential blowing in the standoff/ floor juncture improved correlation of semi-span data with full span data in the region of maximum lift coefficient.

  19. Relationship between heat shock protein 70 expression and life span in Daphnia

    PubMed Central

    Schumpert, Charles; Handy, Indhira; Dudycha, Jeffry L.; Patel, Rekha C.

    2014-01-01

    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 ageing 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. D. pulicaria, the long lived ecotype, showed a robust Hsp70 induction as compared to the shorter lived D. 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

  20. 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. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Basal p21 controls population heterogeneity in cycling and quiescent cell cycle states

    PubMed Central

    Overton, K. Wesley; Spencer, Sabrina L.; Noderer, William L.; Meyer, Tobias; Wang, Clifford L.

    2014-01-01

    Phenotypic heterogeneity within a population of genetically identical cells is emerging as a common theme in multiple biological systems, including human cell biology and cancer. Using live-cell imaging, flow cytometry, and kinetic modeling, we showed that two states—quiescence and cell cycling—can coexist within an isogenic population of human cells and resulted from low basal expression levels of p21, a Cyclin-dependent kinase (CDK) inhibitor (CKI). We attribute the p21-dependent heterogeneity in cell cycle activity to double-negative feedback regulation involving CDK2, p21, and E3 ubiquitin ligases. In support of this mechanism, analysis of cells at a point before cell cycle entry (i.e., before the G1/S transition) revealed a p21–CDK2 axis that determines quiescent and cycling cell states. Our findings suggest a mechanistic role for p21 in generating heterogeneity in both normal tissues and tumors. PMID:25267623

  2. Study of upscaling possibilities for antimony sulfide solid state sensitized solar cells

    NASA Astrophysics Data System (ADS)

    Nikolakopoulou, Archontoula; Raptis, Dimitrios; Dracopoulos, Vasilios; Sygellou, Lamprini; Andrikopoulos, Konstantinos S.; Lianos, Panagiotis

    2015-03-01

    Solid state solar cells of inverted structure were constructed by successive deposition of nanoparticulate titania, antimony sulfide sensitizer and P3HT on FTO electrodes with PEDOT:PSS:Ag as counter electrode. Sensitized photoanode electrodes were characterized by XRD, Raman, XPS, FESEM and UV-vis. Small laboratory scale cells were first constructed and optimized. Functional cells were obtained by annealing the antimony sulfide film either in air or in inert atmosphere. High short-circuit currents were recorded in both cases with air-annealed sample producing more current but lower voltage. Small unit cells were combined to form cell modules. Connection of unit cells in parallel increased current but not proportionally to that of the unit cell. Connection in series preserved current and generated voltage multiplication. Cells were constructed and studied under ambient conditions, without encapsulation. The results encourage upscaling of antimony sulfide solar cells.

  3. Universal Relationship in Gene-Expression Changes for Cells in Steady-Growth State

    NASA Astrophysics Data System (ADS)

    Kaneko, Kunihiko; Furusawa, Chikara; Yomo, Tetsuya

    2015-01-01

    Cells adapt to different conditions by altering a vast number of components, which is measurable using transcriptome analysis. Given that a cell undergoing steady growth is constrained to sustain each of its internal components, the abundance of all the components in the cell has to be roughly doubled during each cell-division event. From such steady-growth constraint, expression of all genes is shown to change along a one-parameter curve in the state space in response to the environmental stress. This conclusion leads to a global relationship that governs the cellular state: By considering a relatively moderate change around a steady state, logarithmic changes in expression are shown to be proportional across all genes, upon alteration of stress strength, with the proportionality coefficient given by the change in the growth rate of the cell. This theory is confirmed by transcriptome analysis of Escherichia coli in response to several stresses.

  4. Cyanine dyes in solid state organic heterojunction solar cells

    NASA Astrophysics Data System (ADS)

    Heier, Jakob; Peng, Chuyao; Véron, Anna C.; Hany, Roland; Geiger, Thomas; Nüesch, Frank A.; Vismara, Marcus V. G.; Graeff, Carlos F. O.

    2014-10-01

    Today numerous cyanine dyes that are soluble in organic solvents are available, driven by more than a century of research and development of the photographic industry. Several properties specific to cyanine dyes suggest that this material class can be of interest for organic solar cell applications. The main absorption wavelength can be tuned from the ultra-violet to the near-infrared. The unparalleled high absorption coefficients allow using very thin films for harvesting the solar photons. Furthermore, cyanines are cationic polymethine dyes, offering the possibility to modify the materials by defining the counteranion. We here show specifically how counterions can be utilized to tune the bulk morphology when blended with fullerenes. We compare the performance of bilayer heterojunction and bulk heterojunction solar cells for two different dyes absorbing in the visible and the near-infrared. Light-induced Electron Spin Resonance (LESR) was used to study the charge transfers of light induced excitons between cyanine dyes and the archetype fullerene C60. LESR results show good correlation with the cell performance.

  5. CELL STATE AS AFFECTING SUSCEPTIBILITY TO A VIRUS

    PubMed Central

    Friedewald, William F.

    1942-01-01

    Rabbit skin can be rendered abnormally susceptible to papilloma virus infection by preliminary treatments with a variety of agents. The most effective agents thus far found are 0.3 per cent methylcholanthrene in benzene and a mixture in equal parts of turpentine and acetone, applied four or five times at 2 day intervals. When virus is inoculated into skin altered by these agents, either intradermally or by inunction after scarification, papillomas appear earlier and in greater number than on normal skin, and much higher dilutions give rise to growths. The method provides a means of detecting amounts of virus which cause no papillomas upon inoculation into normal skin. Papilloma virus material which is rubbed into scarified normal or hyperplastic skin is largely lost in the scabbing which ensues, and nearly all of it fails to reach susceptible cells. The preparatory agents which increase the effectiveness of the virus bring about marked epidermal hyperplasia, and the hyperplastic tissue regenerates with greater rapidity when scarified. The agents evidently act in large part by providing young epidermal cells in quantity to the virus, as also by inducing a richer vascularization than ordinary in support of the papillomatous proliferation. It is possible that they also act by providing especially susceptible cells. The implications of the findings are discussed. PMID:19871177

  6. Stem cell-based regenerative opportunities for the liver: State of the art and beyond

    PubMed Central

    Tsolaki, Eleftheria; Yannaki, Evangelia

    2015-01-01

    The existing mismatch between the great demand for liver transplants and the number of available donor organs highlights the urgent need for alternative therapeutic strategies in patients with acute or chronic liver failure. The rapidly growing knowledge on stem cell biology and the intrinsic repair processes of the liver has opened new avenues for using stem cells as a cell therapy platform in regenerative medicine for hepatic diseases. An impressive number of cell types have been investigated as sources of liver regeneration: adult and fetal liver hepatocytes, intrahepatic stem cell populations, annex stem cells, adult bone marrow-derived hematopoietic stem cells, endothelial progenitor cells, mesenchymal stromal cells, embryonic stem cells, and induced pluripotent stem cells. All these highly different cell types, used either as cell suspensions or, in combination with biomaterials as implantable liver tissue constructs, have generated great promise for liver regeneration. However, fundamental questions still need to be addressed and critical hurdles to be overcome before liver cell therapy emerges. In this review, we summarize the state-of-the-art in the field of stem cell-based therapies for the liver along with existing challenges and future perspectives towards a successful liver cell therapy that will ultimately deliver its demanding goals. PMID:26604641

  7. C-SPAN in the High School Classroom: A Guide for Educators.

    ERIC Educational Resources Information Center

    C-SPAN, Washington, DC.

    Intended for middle and high school educators, the publication provides information about the C-SPAN networks and facilitates the use of the network's programming as a teaching resource. The section on the C-SPAN cable networks contains information on C-SPAN, C-SPAN 2, C-SPAN Audio 1, and C-SPAN Audio 2, regularly scheduled programs, ways to…

  8. PROGRESSION OF REGULATORY GENE EXPRESSION STATES IN FETAL AND ADULT PRO-T CELL DEVELOPMENT

    PubMed Central

    David-Fung, Elizabeth-Sharon; Yui, Mary A.; Morales, Marissa; Wang, Hua; Taghon, Tom; Diamond, Rochelle A.; Rothenberg, Ellen V.

    2014-01-01

    Precursors entering the T-cell developmental pathway traverse a progression of states characterized by distinctive patterns of gene expression. Of particular interest are regulatory genes, which ultimately control the dwell time of cells in each state and establish the mechanisms that propel them forward to subsequent states. Under particular genetic and developmental circumstances, the transitions between these states occur with different timing, and environmental feedbacks may shift the steady-state accumulations of cells in each state. The fetal transit through pro-T cell stages is faster than in the adult, and subject to somewhat different genetic requirements. To explore causes of such variation, this review presents previously unpublished data on differentiation gene activation in pro-T cells of pre-TCR deficient mutant mice, and a quantitative comparison of the profiles of transcription factor gene expression in pro-T cell subsets of fetal and adult wildtype mice. Against a background of consistent gene expression, several regulatory genes show marked differences between fetal and adult expression profiles, including those encoding two bHLH antagonist Id factors, the Ets family factor SpiB, and the Notch target gene Deltex1. The results also reveal global differences in regulatory alterations triggered by the first TCR-dependent selection events in fetal and adult thymopoiesis. PMID:16448545

  9. MicroRNAs 221 and 222 regulate the undifferentiated state in mammalian male germ cells.

    PubMed

    Yang, Qi-En; Racicot, Karen E; Kaucher, Amy V; Oatley, Melissa J; Oatley, Jon M

    2013-01-15

    Continuity of cycling cell lineages relies on the activities of undifferentiated stem cell-containing subpopulations. Transition to a differentiating state must occur periodically in a fraction of the population to supply mature cells, coincident with maintenance of the undifferentiated state in others to sustain a foundational stem cell pool. At present, molecular mechanisms regulating these activities are poorly defined for most cell lineages. Spermatogenesis is a model process that is supported by an undifferentiated spermatogonial population and transition to a differentiating state involves attained expression of the KIT receptor. We found that impaired function of the X chromosome-clustered microRNAs 221 and 222 (miR-221/222) in mouse undifferentiated spermatogonia induces transition from a KIT(-) to a KIT(+) state and loss of stem cell capacity to regenerate spermatogenesis. Both Kit mRNA and KIT protein abundance are influenced by miR-221/222 function in spermatogonia. Growth factors that promote maintenance of undifferentiated spermatogonia upregulate miR-221/222 expression; whereas exposure to retinoic acid, an inducer of spermatogonial differentiation, downregulates miR-221/222 abundance. Furthermore, undifferentiated spermatogonia overexpressing miR-221/222 are resistant to retinoic acid-induced transition to a KIT(+) state and are incapable of differentiation in vivo. These findings indicate that miR-221/222 plays a crucial role in maintaining the undifferentiated state of mammalian spermatogonia through repression of KIT expression.

  10. The state of T cells before cryopreservation: Effects on post-thaw proliferation and function.

    PubMed

    Luo, Ying; Wang, Peng; Liu, Hui; Zhu, Zhengyan; Li, Chenglong; Gao, Yingtang

    2017-08-31

    We aim to assess the effect of the state of T cells before cryopreservation on the post-thaw proliferative capacity, phenotype and functional response. Peripheral blood mononuclear cells (PBMCs) were isolated from a hepatocellular carcinoma (HCC) patient, and the T cells were frozen during cell culture according to our experimental design. After a period of re-culture, the proliferative capacity of the cryopreserved cells, the expression of T cell surface markers and the secretion of IFN-γ and IL-10 were assayed. There was >90% cell viability after thaw in every group. Lymphocytes cryopreserved at day 4, 8 or 12 during the cell culture were allowed to recover for 24 h, whereas lymphocytes cryopreserved while freshly isolated were allowed to recover for 72 h. After the period of re-culture, cryopreservation at day 4, 8 or 12 during T cell culture was not found to alter the T cell subpopulation. The proportions of NKT and Treg cells were unchanged when cells were cryopreserved at day 12 during T cell culture. IFN-γ secretion was not impacted by cryopreservation, and IL-10 secretion was significantly decreased when cells were cryopreserved at day 8 or 12 during T cell culture. The state of T cells before cryopreservation has effects on the post-thaw proliferation capacity, the phenotype and the secretion of IFN-γ and IL-10. Cryopreservation of lymphocytes at day 8 or 12 during the cell culture may be the best choice for T cell immunotherapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Improving digit span assessment of short-term verbal memory.

    PubMed

    Woods, David L; Kishiyamaa, Mark M; Lund, E William; Herron, Timothy J; Edwards, Ben; Poliva, Oren; Hink, Robert F; Reed, Bruce

    2011-01-01

    We measured digit span (DS) in two experiments that used computerized presentation of randomized auditory digits with performance-adapted list length adjustment. A new mean span (MS) metric of DS was developed that showed reduced variance, improved test-retest reliability, and higher correlations with the results of other neuropsychological test results when compared to traditional DS measures. The MS metric also enhanced the sensitivity of forward versus backward span comparisons, enabled the development of normative performance criteria with subdigit precision, and elucidated changes in DS performance with age and education level. Computerized stimulus delivery and improved scoring metrics significantly enhance the precision of DS assessments of short-term verbal memory.

  12. Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway | Office of Cancer Genomics

    Cancer.gov

    Plasticity of the cell state has been proposed to drive resistance to multiple classes of cancer therapies, thereby limiting their effectiveness. A high-mesenchymal cell state observed in human tumors and cancer cell lines has been associated with resistance to multiple treatment modalities across diverse cancer lineages, but the mechanistic underpinning for this state has remained incompletely understood.

  13. Chicken leukemia inhibitory factor maintains chicken embryonic stem cells in the undifferentiated state.

    PubMed

    Horiuchi, Hiroyuki; Tategaki, Airo; Yamashita, Yusuke; Hisamatsu, Hikaru; Ogawa, Mari; Noguchi, Takashi; Aosasa, Masayoshi; Kawashima, Tsuyoshi; Akita, Sachiko; Nishimichi, Norihisa; Mitsui, Naoko; Furusawa, Shuichi; Matsuda, Haruo

    2004-06-04

    Mouse embryonic stem (ES) cells can be maintained in an undifferentiated state in the presence of leukemia inhibitory factor (LIF), a member of the interleukin-6 cytokine family. In other mammals, this is not possible with LIF alone. Chicken ES-like cells (blastodermal cells) have only been cultured with mouse LIF because chicken LIF was not available. However the culture system is imperfect and chicken ES-like cells equivalent to mouse ES cells were not observed. In the present study, we cloned the cDNA-encoding chicken LIF using mRNA subtraction and RACE methodology. The chicken LIF cDNA encodes a protein with approximately 40% sequence identity to mouse LIF. It has 211 amino acids including a putative N-terminal signal peptide of 24 residues. Chicken blastodermal cells were cultured in the presence of bacterially expressed chicken LIF or mouse LIF. The expression of alkaline phosphatase and embryonal carcinoma cell monoclonal antibody-1 and stage-specific embryonic antigen-1 and the activation of STAT3 were examined, all of which are indices of the undifferentiated state. Exposure in the blastodermal cells to recombinant chicken LIF but not to mouse LIF maintained the expression of these various markers. After 9 days of incubation, the blastodermal cells formed cystic embryoid bodies in the presence of mouse LIF but not in the presence of recombinant chicken LIF. We conclude that chicken LIF is able to maintain chicken ES cell cultures in the undifferentiated state.

  14. A resolution designating July 9, 201span>0, as "Collector Car Appreciation Day" and recognizing that the collection and restoration of historic and classic cars is an important part of preserving the technological achievements and cultural heritage of the United States.

    THOMAS, 111th Congress

    Sen. Tester, Jon [D-MT

    05/04/201span>0 Submitted in the Senate, considered, and agreed to without amendment and with a preamble by Unanimous Consent. (consideration: CR S3091, S3116-3117; text as passed Senate: CR S3116; text of measure as introduced: CR S3099) (All Actions) Tracker: This bill has the status Passed SenateHere are the steps for Status of Legislation:

  15. Two distinct states of Escherichia coli cells that overexpress recombinant heterogeneous β-galactosidase.

    PubMed

    Zhao, Yun; He, Wei; Liu, Wei-Feng; Liu, Chun-Chun; Feng, Li-Kui; Sun, Lei; Yan, Yong-Bin; Hang, Hai-Ying

    2012-03-16

    The mechanism by which inclusion bodies form is still not well understood, partly because the dynamic processes of the inclusion body formation and its solubilization have hardly been investigated at an individual cell level, and so the important detailed information has not been acquired for the mechanism. In this study, we investigated the in vivo folding and aggregation of Aspergillus phoenicis β-D-galactosidase fused to a red fluorescence protein in individual Escherichia coli cells. The folding status and expression level of the recombinant β-D-galactosidase at an individual cell level was analyzed by flow cytometry in combination with transmission electron microscopy and Western blotting. We found that individual E. coli cells fell into two distinct states, one containing only inclusion bodies accompanied with low galactosidase activity and the other containing the recombinant soluble galactosidase accompanied with high galactosidase activity. The majority of the E. coli cells in the later state possessed no inclusion bodies. The two states of the cells were shifted to a cell state with high enzyme activity by culturing the cells in isopropyl 1-thio-β-D-galactopyranoside-free medium after an initial protein expression induction in isopropyl 1-thio-β-D-galactopyranoside-containing medium. This shift of the cell population status took place without the level change of the β-D-galactosidase protein in individual cells, indicating that the factor(s) besides the crowdedness of the recombinant protein play a major role in the cell state transition. These results shed new light on the mechanism of inclusion body formation and will facilitate the development of new strategies in improving recombinant protein quality.

  16. 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.

  17. High-resolution solution-state NMR of unfractionated plant cell walls

    Treesearch

    John Ralph; Fachuang Lu; Hoon Kim; Dino Ress; Daniel J. Yelle; Kenneth E. Hammel; Sally A. Ralph; Bernadette Nanayakkara; Armin Wagner; Takuya Akiyama; Paul F. Schatz; Shawn D. Mansfield; Noritsugu Terashima; Wout Boerjan; Bjorn Sundberg; Mattias Hedenstrom

    2009-01-01

    Detailed structural studies on the plant cell wall have traditionally been difficult. NMR is one of the preeminent structural tools, but obtaining high-resolution solution-state spectra has typically required fractionation and isolation of components of interest. With recent methods for dissolution of, admittedly, finely divided plant cell wall material, the wall can...

  18. Correlation of nonlinear noises from different spans in 100 Gb/s multi-span fiber optic lines

    NASA Astrophysics Data System (ADS)

    Konyshev, V. A.; Leonov, A. V.; Nanii, O. E.; Novikov, A. G.; Treshchikov, V. N.; Ubaydullaev, R. R.

    2016-12-01

    The accumulation of nonlinear noise in multi-span communication lines was investigated by numerical modeling and experimentally for different values of accumulated dispersion at input of each span. One coherent 100G channel was investigated (wavelength 1549.32 nm, DWDM channel C35). It has been established that interaction of nonlinear noises from two different spans can be described by a correlation function that depends only on values of input dispersion for these spans. It confirms the idea that the nonlinear noise in a fiber optic line is formed mainly due to signal to signal interaction, and the influence of the signal to noise interaction can be neglected. The shape of correlation function was investigated by numerical modeling and experimentally, and its simple approximation was offered. The nonlinear noise in any multi-span line with arbitrary dispersion plan can be calculated based on the investigated correlation function for two spans. It was shown that in a compensated line the offered theoretical model based on correlation function corresponds well to simpler theoretical model based on superlinear dependence of total noise on number of spans.

  19. Renal cell cancer: state of the art in adjuvant therapy.

    PubMed

    Buti, Sebastiano; Rovere, Rodrigo K

    2010-11-01

    Renal cell cancer is fastly growing in incidence worldwide. No adjuvant therapy has been unarguably proven feasible so far, although an autologous vaccine has achieved a significant benefit. An effective agent in adjuvant therapy against renal cell cancer must achieve several goals. It should be relatively non toxic, have estabilished efficacy in the metastatic setting, and have demonstrated efficacy against the standard of care in randomized phase III trials. The development of adjuvant therapy requires the properly identification of patients at highest risk of relapse, as potential benefactors of adjuvant therapy development. Our ability to predict when and where patients will recur has much room for improvement. Therefore several models and nomograms including the most important prognostic and predictive factors have been developed. Nevertheless, during the past few years, major advances have been made concerning the metastatic setting of the disease with the arrival of new drug classes such as tyrosine kinase inhibitors and monoclonal antibodies, strongly improving overall and progression free survivals, renewing hopes on activity regarding the adjuvant therapy. Several trials are today in progress to evaluate the effectiveness of antiangiogenic agents in this area. An overall review of the completed and upcoming trials and patents shall be discussed here.

  20. 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.

  1. Characterization of nonderivatized plant cell walls using high-resolution solution-state NMR spectroscopy

    Treesearch

    Daniel J. Yelle; John Ralph; Charles R. Frihart

    2008-01-01

    A recently described plant cell wall dissolution system has been modified to use perdeuterated solvents to allow direct in-NMR-tube dissolution and high-resolution solution-state NMR of the whole cell wall without derivatization. Finely ground cell wall material dissolves in a solvent system containing dimethylsulfoxide-d6 and 1-methylimidazole-d6 in a ratio of 4:1 (v/...

  2. 22. WEST CONFEDERATE AVENUE BRIDGE SPANNING SPANGLER'S RUN. NOTE MORE ...

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

    22. WEST CONFEDERATE AVENUE BRIDGE SPANNING SPANGLER'S RUN. NOTE MORE RANDOM ASHLAR COURSING AND ARCH TO PARAPET. BRIDGE WAS WIDENED BY NPS USING CCC LABOR. VIEW SSE. - Gettysburg National Military Park Tour Roads, Gettysburg, Adams County, PA

  3. 4. Span support bent from underneath. Monongahela Connecting Railroad ...

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

    4. Span support bent from underneath. - Monongahela Connecting Railroad Company, Y Trestle, South side of Monongahela River between Thirty-fourth & Twenty-ninth Streets, Pittsburgh, Allegheny County, PA

  4. A Motivational Theory of Life-Span Development

    PubMed Central

    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 action-phase model of developmental regulation with their original life-span theory of control to present a comprehensive theory of development. Third, they reviewed the relevant empirical literature testing key propositions of the Motivational Theory of Life-Span Development. Finally, because the conceptual reach of their theory goes far beyond the current empirical base, they pointed out areas that deserve further and more focused empirical inquiry. PMID:20063963

  5. How Genes Influence Life Span: The Biodemography of Human Survival

    PubMed Central

    Wu, Deqing; Arbeev, Konstantin G.; Stallard, Eric; Land, Kenneth C.; Ukraintseva, Svetlana V.

    2012-01-01

    Abstract Background In genome-wide association studies (GWAS) of human life span, none of the genetic variants has reached the level of genome-wide statistical significance. The roles of such variants in life span regulation remain unclear. Data and Method A biodemographic analyses was done of genetic regulation of life span using data on low-significance longevity alleles selected in the earlier GWAS of the original Framingham cohort. Results Age-specific survival curves considered as functions of the number of longevity alleles exhibit regularities known in demography as “rectangularization” of survival curves. The presence of such pattern confirms observations from experimental studies that regulation of life span involves genes responsible for stress resistance. Conclusion Biodemographic analyses could provide important information about the properties of genes affecting phenotypic traits. PMID:22607627

  6. 10. General oblique view of steel pedestrian bridge spanning mouth ...

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

    10. General oblique view of steel pedestrian bridge spanning mouth of raceway; view to northwest. - Champion-International Paper Company, West bank of Spicket River at Canal Street, Lawrence, Essex County, MA

  7. View of movable span and point truss (to right), from ...

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

    View of movable span and point truss (to right), from navy land, looking west, showing bridge in context of navigational channel. - Naval Supply Annex Stockton, Rough & Ready Island, Stockton, San Joaquin County, CA

  8. View of movable span and point truss (to right), from ...

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

    View of movable span and point truss (to right), from navy land, looking west, showing bridge in context of navigational channel. - Naval Supply Annex Stockton, Daggett Road Bridge, Daggett Road traversing Burns Cut Off, Stockton, San Joaquin County, CA

  9. Detail, starpattern balustrade of north span, from northwest, showing row ...

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

    Detail, star-pattern balustrade of north span, from northwest, showing row of four star-pattern railing slabs bracketed by simple molded concrete balusters - Horner Street Bridge, Horner Street over Stonycreek River, Johnstown, Cambria County, PA

  10. 15. Stress Sheet, Truss number 2, span number 6, Superior ...

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

    15. Stress Sheet, Truss number 2, span number 6, Superior Avenue viaduct. Drawing courtesy Engineering Dept., City of Cleveland. - Superior Avenue Viaduct, Cleveland East & West side, Cuyahoga Valley Vicinity, Cleveland, Cuyahoga County, OH

  11. Study Looks At Parkinson's Effect on Life Span

    MedlinePlus

    ... gov/news/fullstory_165589.html Study Looks at Parkinson's Effect on Life Span 2-year difference seen ... HealthDay News) -- People with brain diseases such as Parkinson's and dementia with Lewy bodies die about two ...

  12. Detail of west end of movable span. Shows lattice beams. ...

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

    Detail of west end of movable span. Shows lattice beams. Latticed portal. Adjustable tension members connecting top chords, and metal floor beams looking south from navy land. - Naval Supply Annex Stockton, Rough & Ready Island, Stockton, San Joaquin County, CA

  13. Effect of deleterious mutations on life span in Drosophila melanogaster.

    PubMed

    Gong, Yi; Thompson, James N; Woodruff, R C

    2006-12-01

    Evolutionary theories of aging assume that the accumulation of deleterious mutations will reduce life span. We tested this assumption in Drosophila melanogaster by a newly designed mating scheme, in which mutations accumulate on the Binscy balancer X chromosome in heterozygous females in the absence of selection and recombination. We found that the life span of Binscy/RY(L) males from this cross decreased faster than the life span of their sibling controls over time in two of three runs, and that there was an age-specific increase in mortality in the Binscy/RY(L) males with time in one of three runs. Therefore, the accumulation of deleterious mutations can decrease life span by increasing fragility and can cause age-specific changes in mortality. These results support the evolutionary theory of aging.

  14. Detail, north span, from east, showing concrete "rainbow" arch rigidly ...

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

    Detail, north span, from east, showing concrete "rainbow" arch rigidly fixed at center pier and north abutment, and hangers linking arch rib and bridge deck - Horner Street Bridge, Horner Street over Stonycreek River, Johnstown, Cambria County, PA

  15. Detail, north span, abutment and pier, from southwest, showing northwest ...

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

    Detail, north span, abutment and pier, from southwest, showing northwest arch rib rigidly fixed at center pier and north abutment, and hangers and floorbeams supporting bridge deck - Horner Street Bridge, Horner Street over Stonycreek River, Johnstown, Cambria County, PA

  16. 14. Detail, typical approach span fixed bearing atop stone masonry ...

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

    14. Detail, typical approach span fixed bearing atop stone masonry pier, view to northwest, 210mm lens. - Southern Pacific Railroad Shasta Route, Bridge No. 210.52, Milepost 210.52, Tehama, Tehama County, CA

  17. View of one half of movable span, showing truss and ...

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

    View of one half of movable span, showing truss and tension bars, from navy land looking southwest. - Naval Supply Annex Stockton, Daggett Road Bridge, Daggett Road traversing Burns Cut Off, Stockton, San Joaquin County, CA

  18. View of deck of pony truss approach span. Deck system ...

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

    View of deck of pony truss approach span. Deck system has failed at northwest corner. Looking south. - Naval Supply Annex Stockton, Daggett Road Bridge, Daggett Road traversing Burns Cut Off, Stockton, San Joaquin County, CA

  19. 6. DETAIL OF DRIVE TRUCK ASSEMBLY. MOBILE SERVICE STRUCTURE SPANNING ...

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

    6. DETAIL OF DRIVE TRUCK ASSEMBLY. MOBILE SERVICE STRUCTURE SPANNING LAUNCHER BUILDING WITH FLAME DUCT FAR RIGHT; VIEW TO NORTHWEST. - Cape Canaveral Air Station, Launch Complex 17, Facility 28416, East end of Lighthouse Road, Cape Canaveral, Brevard County, FL

  20. Detail, east truss of south span, showing railing, vertical UL, ...

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

    Detail, east truss of south span, showing railing, vertical U-L, diagonal eyebar U-L with turnbuckle - Castle Garden Bridge, Township Route 343 over Bennetts Branch of Sinnemahoning Creek, Driftwood, Cameron County, PA